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The potential heart risk of psychedelics*

The Psychedelic Scientist | 6 Dec 2019

An important part of building a healthy psychedelic community is being fully aware of the risks of psychedelics.

This includes both being educated about the risk of trauma and injury from challenging psychedelic experiences, but also the potential physiological harm they can do to us.
It appears that occasional large doses of psychedelics don’t do much harm to healthy individuals, as long as they are properly looked after to prevent really damaging traumatic experiences (sometimes called “Bad Trips”). But we don’t have any evidence yet that regular microdosing is safe.

There are reports of people microdosing for many months in succession, with no ill effects aside from tiredness. But there is always the chance that with longer term microdosing regimens, unwanted physiological side effects could start building up. Ingesting any substance over a long period, no matter how harmless they are in single doses, could cause significant changes in your body.

Here’s what we know so far about the potential risks of taking frequent doses of psychedelics…

MDMA and Heart Disease

Various studies have shown that there is a link between regular, high-dose MDMA use and heart defects. Although the conclusion of this research is that the occasional dose of MDMA will not harm you, it has potential implications for frequent, long-term psychedelic use – especially microdosing – and I’ll explain how.

MDMA’s harmful effects on the heart are due to its activation of the 5-HT2B receptor. This receptor is present all over the heart, and convincing evidence suggests that the long-term activation of this receptor leads to the formation of ‘valvular strands’, which can lead to Valvular Heart Disease (VHD) in extreme cases.
Classic psychedelics, including LSD and psilocybin, also activate this 5-HT2B receptor.

Again – cases of VHD are only found in people who use MDMA very frequently (several times a week) and at high doses. The question we want to answer is: do the classic psychedelics (LSD and psilocybin) activate the 5-HT2B receptors in our hearts as much as MDMA? And – is there a risk of VHD with long-term usage, like microdosing?

LSD, psilocybin, and the 5-HT2B Receptor

LSD and psilocybin work by mimicking the effect of our natural neurotransmitter, serotonin. Therefore both these psychedelics activate a wide range of serotonin receptors, including the 5-HT2B receptor. The real question is, are these psychedelics activating the 5-HT2B receptor enough to cause damage to the heart?

Unfortunately, we don’t have a clear answer to that question yet. We know that LSD and psilocybin bind strongly to the 5-HT2B receptor, but we don’t know how comparable this is to the way that MDMA (and other cardiotoxic molecules) binds to 5-HT2B. So right now, there is no way of knowing for sure if there is any risk.
We can, however, make some educated speculation.

We can look at a previous study of a compound that definitely causes heart damage through the 5-HT2B receptor: fenfluramine. This was a weight-loss drug that was withdrawn in the 90s after a small percentage of people developed heart disease after using it.

Studies found that fenfluramine roughly doubled the risk of developing VHD after a 90-day treatment course, at a dose of around 30mg/day (Sachdev et al, 2002). Fenfluramine has an affinity (Ki) for the 5-HT2B receptor of around 30nM (Rothman & Baumann, 2009).

LSD has a similar affinity for the 5-HT2B receptor as fenfluramine, a Ki of around 30nM (Passie et al, 2008). However, when we take a dose of LSD, it is several hundred times less than a single dose of fenfluramine (100ug compared to 30mg). So it’s highly unlikely that a single dose of LSD, even if it’s a high dose, would have any immediate cardiotoxicity.

With microdosing, it’s a different story. A typical microdosing regimen involves taking the equivalent of around 3ug/day, several thousand times less than fenfluramine. However, the main reason that fenfluramine is cardiotoxic is because it is taken every day in a continuous regimen.

The comparison to fenfluramine isn’t great – it’s quite possible that a daily dose of fenfluramine affects the 5-HT2B receptor in a vastly more harmful way than intermittent microdoses.

Overall, it seems reasonable to assume that microdosing probably has nowhere near the heart risk associated with fenfluramine. At the same time, it’s also very possible that even very minor, but frequent activation of the 5-HT2B receptor could slightly increase our risk of heart disease.

Conclusions

It seems likely that single large dose psychedelic experiences, and short-term microdosing routines, are relatively safe for your body. Decades of anecdotal reports and epidemiological studies back this up.

What remains to be seen is whether long-term microdosing regimens (i.e. for many months or even years) have a potential to damage the heart. This is why it is sensible to microdose for no longer than 90 days, and spread out your microdosing regimens throughout the year. If you have a pre-existing heart condition, it is especially important to avoid extended periods of microdosing.

It’s important for the community to be aware of these potential risks. I often come under fire for “scaremongering” when I bring up this research. But the reality is that educating ourselves about the science, and showing that we have a firm understanding of psychedelic safety, gives us the best chance of defeating the authorities hell-bent on shutting down our movement.

*From the article here :
 
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LSD side-effects: Risks to be aware of when consuming LSD

by Edan Armas | 21 Apr 2021

Over the last 15 years, the hallucinogenic drug lysergic acid diethylamide, or LSD, has reemerged in public conversation as a powerful healing tool, a productivity and creativity catalyst, and a vehicle for collective spiritual transformation.

This article is your comprehensive introduction to the neurological, perceptual, and psychological effects of LSD, and it aims to quell the LSD-makes-you-jump-out-of-a-window anxiety that has permeated the collective consciousness since the seventies. Here, we explore the true risks to LSD users (spoiler: no window-jumping involved) and how to mitigate them. Additionally, while the field of psychedelic science is still in its relative infancy, we review some data on LSD’s long-term effects.

General short-term effects of LSD

In the context of LSD’s use in psychotherapy and psychiatry, LSD does not really fit the standard psychopharmacology label of a “drug” with “effects”. Unlike antidepressants, for example, LSD is a facilitator of an experience.

The details of that experience depend heavily on various factors, including the dose of LSD, the environment the LSD is taken in, the psychological state of the person taking it, and the cosmological and theoretical background of the guide or therapist holding the space. These factors are summarized as set and setting.

Because of the wide diversity of set and setting, no two LSD “trips” are alike. Consumed on a piece of blotter paper, gelatin tabs, or in sugar cubes, you might have visual hallucinations, or experience synesthesia—the blending of the senses—as you hear the color purple or see the sound of music. At higher doses (200-500 mcg), you might experience your own birth, travel through time, or dissolve into oneness with the entire universe.

LSD journeys can feel ecstatic and liberating, but they can also be challenging and uncomfortable. That’s why it’s always a good idea to prepare well and have a guide present to keep yourself safe and mitigate “bad trips” or experiences.

Physical side effects can include fluctuating blood pressure and body temperature, increased heart rate, dry mouth, and a loss of appetite, yet these are usually manageable and pass quickly.

But what is happening in the brain during all of this? How can such powerful experiences such as “dissolving into oneness” occur as a result of ingesting 0.0002 of a gram of one little molecule?

Effects on the neurotransmitter serotonin

LSD is a “classic” psychedelic, which means, like the hallucinogens DMT, psilocybin (magic mushrooms), peyote, and ayahuasca, its primary mechanism of action is to bind to the 5-HT2A serotonin receptor.

Activation of these serotonin receptors is thought to produce the “psychedelic”, subjective effects of LSD, because when researchers give participants LSD but block the 5-HT2A receptors, the participants don’t experience any subjective effects.

What’s most interesting about LSD is that not only does it bind to the 5-HT2A receptor more strongly than any of the other classic psychedelics, it binds more strongly than serotonin itself. Part of the receptor folds over the LSD molecule like a lid, keeping it in place—possibly explaining the long duration of LSD experiences (8-12 hrs), as well as its strong binding affinity.

In addition, LSD’s transformational capacity makes sense when you consider that the 5-HT2A receptor is expressed at high levels in the prefrontal cortex (PFC). The PFC is the most recently evolved part of the brain, responsible for higher order functioning like complex cognitive behavior and personality expression. So the fact that LSD has such a powerful neurological presence in this area sheds light on why journeyers can come out of an LSD experience with new insight and a shift in who they think they are.

Effects on dopamine

Although LSD does directly activate several dopamine receptors in rats, the exact pharmacology in humans is unclear. However, it is known that LSD does not increase the amount of dopamine in the human brain, which makes it (and the other classic psychedelic drugs) physiologically non-addictive.

Effects on the central nervous system and nerve pathways

Before going into how LSD affects the brain on a systems level, it will be helpful to understand a few things first.

Right now, life probably feels normal. You’re reading these words, you might feel the handle of a coffee mug in your hand, and you might be dimly aware of a sense of “you” processing everything.

But how can this be? Light from the sun or the ceiling is bouncing like crazy on every surface. You have trillions of bacteria churning away your lunch in your digestive system. Receptors all over your body are sending electrical signals to your 86 billion neurons about your sitting position, the movement of your pancreas, and the feelings of your memories. How are you not rolling haphazardly on the floor exploding with information?

The answer is: you’re hallucinating.

Everyday waking consciousness is the first hallucinogen, because our brains synthesize millions of bits of random information every second into a cohesive picture we call “reality”. That synthesis is primarily performed by an interconnected group of brain regions called the Default Mode Network (DMN), which acts like an orchestra conductor for your brain, managing the furiously complex electrical signaling in the brain so you can experience an orderly, predictable reality.

So where does LSD fit into all of this? Put simply, LSD kicks the orchestra conductor off the stage. In other words, it quiets down signaling in the DMN, allowing regions of your brain that don’t normally signal to each other to leap into new electrical harmonies. This is why “LSD changed everything I thought I knew about the world” is such a common response to a journey, because it dramatically disrupts the network in your brain responsible for creating your normal reality.

In addition, the DMN is often referred to as the “me network”, because the most basic component of everyday reality it creates is a sense of “me” experiencing it. When you take LSD, the quieting down of the DMN can lead to ego-dissolution, where that sense of “me” dissolves and a more primal, interconnected consciousness is revealed.

For a scientific breakdown of the nature of that primal consciousness, check out neuroscientist Robin Carhart-Harris’s “Entropic Brain” hypothesis. For a more spiritual account, check out LSD and the Mind of the Universe by philosopher Christopher Bach.

Effects on anxiety

Since LSD can radically shift the hallucination of reality that we’re used to, it’s understandable that some anxiety is often a part of the experience. This is why preparation is key: an active practice in surrender through meditation or Holotropic Breathwork and a trained guide can help significantly in mitigating any anxiety during a journey.

In fact, one seminal study actually used LSD to help terminally ill patients cope with their debilitating anxiety surrounding their impending passing. However, this study was small and contained no placebo group, so further research is still needed.

Does LSD damage your brain?

But LSD seems so intense, surely there must be some life-threatening damage to the brain, right?

Short answer: nope.

After LSD wears off, the DMN returns to its normal functioning, and LSD has been shown to be physiologically non-toxic. If anything, LSD helps your brain—it promotes neural plasticity, which means it increases the amount of synaptic connections between neurons as well as promoting the growth of new neurons.

LSD risks & when not to take LSD

However, there are risks associated with LSD.

First and foremost, LSD is still illegal in every country, with the only quasi-exception being Portugal. Read our LSD legality blog post to learn about the specifics concerning decriminalization in some countries.

Then there’s the matter of purity. As is the case with most synthetic compounds, it’s hard to tell what you have by just looking at it, so practice responsible drug use and test your LSD before using it.

For example, a drug called DOI is frequently sold as LSD. DOI is much more intense. It can last for 16 to 30+ hours, and effects of the drug include trouble sleeping, pronounced visual effects, and a heavy body load. Having a DOI experience when you were expecting an LSD experience can be unpleasant, so again, always make sure testing is part of your substance use.

Once you’ve accounted for legality and purity, the remaining risks are psychological and spiritual.

If you have a family history of psychosis or schizophrenia, you should not take LSD, because there is a risk of triggering a psychotic episode or developing severe depression. If you have a severe mental illness—like depression, panic attacks, or substance abuse—you should absolutely journey with a guide or therapist who will be able to create a container of healing and integration. And in general, for anyone experimenting with hallucinogens or dissociative drugs, you should make sure to have some sort of support—an online integration group, a close friend, or even literature about the psychedelic experience—to ground your experiences in everyday life and prevent spiritual or existential emergencies.

For folks without a family history of psychosis or schizophrenia who still wonder if there are cases when they should not take LSD, it might be helpful to return to the idea that we hallucinate our everyday reality.

We’ve established that, when taken in a proper setting with a guide, LSD can be very safe. Your brain returns to DMN functionality after the experience, there is little risk of addiction, and proper integration can help ensure minimal psychological suffering or other adverse effects.

So the best barometer of whether or not you should take LSD is one question: Am I prepared to, in some capacity, let go of what I currently think is true about myself, the world, and my relationship to it?

Long-term effects

Although Swiss chemist Albert Hofmann synthesized LSD all the way back in 1938, science doesn’t yet definitively know the long-term effects of LSD, only because there have not been many longitudinal studies on its long-term effects. However, we do know some things.

On the negative side, a condition called hallucinogen persisting perception disorder (HPPD) can occur. HPPD is characterized by a continual presence of sensory disturbances, most often visual, sometimes continuing for months or years following psychedelic use. This is different from flashbacks. HPPD is rare and most likely a result of drug abuse, for it has not been seen in psychotherapy settings.

On the positive side, there is one recent study that found no correlation between use of LSD and mental health problems or suicidal behavior. In addition, although the psychiatry studies from the ’50s and ’60s don’t meet current standards for the validity of scientific research because of a lack of placebo groups, many found no lasting brain damage in participants. This would make sense considering that, as we learned above, LSD doesn’t harm the brain in the first place.

But while Western science moves to legitimize the safety of psychedelics in future clinical trials, we should keep in mind that intense serotonergic psychedelics have been around for a long time. Psilocybin mushrooms and ayahuasca, which both act on the 5-HT2A receptor and quiet down the DMN like LSD, have been used safely and with transformative intent in indigenous cultures for thousands of years.

Of course, these medicines are of the earth and while LSD is derived from the ergot fungus, it was made in a lab, so the comparison is not a completely viable indication of LSD’s long-term safety profile.

Regardless, LSD is on the path to revolutionize psychiatry, mental healthcare, and how we as a people see ourselves. But with great power comes great responsibility. If the last half-century of illegality represented the ashes of LSD’s potential to help people, then we must be responsible, well-informed, and conscientious as the phoenix of psychedelic therapy rises.

 
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Ibogaine and the heart: A delicate relation*

Xaver Koenig, Karlheinz Hilber

Ibogaine has shown promising anti-addictive properties in humans as the drug alleviates drug craving and impedes relapse of drug use. Though unlicensed as therapeutic drug, and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases associated with the administration of ibogaine have been accumulating. These reactions are hypothesized to be associated with ibogaine’s propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine’s effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti-addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener, are also considered.

The mechanisms by which ibogaine exerts its psychoactive effects in the brain are only poorly understood, which is attributable to the alkaloid’s complex pharmacology. Effects on multiple neurotransmitter systems via numerous brain targets have been reported. Among those, ibogaine interacts with neurotransmitter transporters, opioid receptors, sigma receptors, glutamate receptors, and nicotinic receptors in low micromolar concentrations. Long-lasting effects after ibogaine intake are attributed to the alkaloid’s long-lived active metabolite, noribogaine.

Although all efforts to clinically approve ibogaine have failed as yet, NIDA has recently committed financial support for preclinical testing and chemical manufacturing, as well as control work intended to enable clinical trials to develop the synthetic ibogaine congener 18-methoxycoronaridine (18-MC) as a pharmacotherapy for addiction. 18-MC also exhibits anti-addictive effects, and is less toxic in animals than ibogaine.

Ibogaine’s complex pharmacology has a considerable potential to generate adverse effects. Besides neurotoxic actions, ibogaine also affects the cardiovascular system, and, in recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of the alkaloid, have been accumulating. It was hypothesised that the above-mentioned sudden deaths cases in humans were related to cardiac arrhythmias. These are most probably associated with ibogaine’s propensity to induce a QT interval prolongation in the electrocardiogram (ECG), which is known to enhance the risk for life-threatening Torsade de pointes (TdP) arrhythmia generation.

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Effects on the cardiovascular system

Several indole alkaloids exert effects on the cardiovascular system, and have been or are still used as therapeutic drugs. Among those reserpine has a history as antihypertensive drug, and ajmaline is still approved as an antiarrhythmic medicine. Cardiovascular effects of iboga alkaloids have been known for many years. For example, Tabernanthine, contained in Tabernanthe iboga root bark extracts, induced bradycardia and hypotension in rats and dogs. Low doses of ibogaine didn't change the resting heart rate or blood pressure, but at higher doses ibogaine decreased the heart rate without affecting blood pressure.

In contrast, a significant decrease in heart rate was found in rats already at low ibogaine doses. 18-MC, even at high doses, did not show any apparent effects on either heart rate or blood pressure. Besides these findings on animals, anecdotal evidence suggests that ibogaine can also slow the heart rate in humans. Mash et al. performed intensive cardiac monitoring in 39 human subjects who received single doses of ibogaine for the treatment of cocain/heroin addiction. With dosages in the range of 500–1000 mg, six out of 39 subjects showed a significant bradycardia, and one subject a significant hypotension.

Ibogaine's effects on heart rate

A drug modulating several neurotransmitter systems, such as ibogaine, may generate effects on the cardiovascular system related to its central nervous activity. Further, ibogaine was shown to inhibit voltage-gated calcium channels in rat sympathetic and parasympathetic neurons via sigma receptor activation. This may influence cell-to-cell signalling in autonomic ganglia, and thus the regulation of heart rate by the peripheral nervous system. Interestingly, compared to ibogaine, 18-MC shows significantly less affinity to sigma receptors. If the heart rate is indeed affected by sigma receptor activation, 18-MC will be less effective in this regard.

Ibogaine’s bradycardic action is often related to stimulatory effects of the drug on the cholinergic system. Here, two possible mechanisms were proposed: (1) inhibition of acetylcholinesterase by the drug; and (2) an agonistic action on muscarinic acetylcholine receptors. 18-MC’s affinity for muscarinic receptors is at least two-fold less than that of ibogaine.

A further postulated mechanism by which ibogaine could induce bradycardia is a blockade of voltage-gated sodium channels. Indeed, ibogaine has low micromolar affinity for sodium channels in the brain, and cardiac sodium channel blockers can exert a bradycardic effect. We recently tested ibogaine’s effects on human cardiac sodium channels heterologously expressed in TSA -201 cells. To our surprise we found that low micromolar ibogaine (18-MC) concentrations did not affect Nav1.5 channel currents at all. Consequently, it is unlikely that cardiac sodium channel inhibition by ibogaine significantly contributes to bradycardia generation. However, in this context, the modulation of ion channels, representing major physiological determinants of the heart rate, deserves special consideration.

Ibogaine's effects on cardiac ion channels

Cases of ibogaine-induced QT interval prolongation and associated life-threatening TdP arrhythmias have been accumulating in recent years. The most common reasons for QT prolongation and arrhythmia induction by drugs are modulatory effects on cardiac ion channels. It is therefore noteworthy to look at ibogaine’s effects on ion channels with major importance for electrical impulse conduction in the heart. In this context, we have recently studied the effects of ibogaine and its congener 18-MC on cardiac sodium, L-type calcium, and "human ether-a-go-go-related gene" (hERG), and we found that cardiac sodium and calcium currents are not significantly modulated by ibogaine and its congener 18-MC in a regime of doses normally used to treat human addicts.

The described effects of ibogaine and noribogaine: prolongation and flattening of the human cardiac AP, and relative selective hERG channel inhibition as triggers of QT interval prolongation must be considered proarrhythmic. Moreover, ibogaine’s effects on in vitro cardiac electrophysiology within the drug’s therapeutic plasma concentration range, closely resemble the cardiac actions of formerly approved drugs like cisapride or astemizole, which have been withdrawn from the market because of their propensity to induce TdP arrhythmias.

Here we want to emphasize that not only QT prolongation itself, but also and especially a flattening of the repolarization phase in the AP is considered a proarrhythmic characteristic. Moreover, ibogaine’s effects on in vitro cardiac electrophysiology within the drug’s therapeutic plasma concentration range closely resemble the cardiac actions of formerly approved drugs like cisapride or astemizole, which are known to be unsafe, and have been withdrawn from the market because of their pronounced propensity to induce TdP arrhythmias. Thus, ibogaine, at the doses currently used in humans, must be classified an unsafe drug! Because of its considerably longer half-life in human plasma, ibogaine’s metabolite noribogaine might represent the major proarrhythmic factor. This clearly challenges the idea of noribogaine being considered a potentially safer alternative to ibogaine for anti-addiction medication development.

Risk factors

Based on the findings of the above described experimental studies and case reports on ibogaine’s cardiovascular actions, this section deals with risk factors and their practical impacts for the future application of ibogaine and 18-MC as anti-addiction drugs. First, application of ibogaine, should be done under strict medical observation and continuous electrocardiographic monitoring for an extended time period, which carefully takes noribogaine’s longevity in human plasma into account.

Secondly, prior to ibogaine application one must carefully consider additional risk factors for drug-induced TdP arrhythmias in a patient including female gender, prolonged baseline QT interval, bradycardia, abnormal electrolyte levels, pre-existing cardiovascular disease, ion channel mutations, drug-drug interactions, and genetic variants influencing drug metabolism.

For anti-addiction treatment with ibogaine, two risk factors deserve special attention: bradycardia and hypokalemia. Ibogaine itself induces bradycardia, and hypokalemia is frequent in drug users. Compared with the large number of people who have received ibogaine treatments over many years worldwide, comparably few fatality cases have occurred or have been reported. In addition, drug safety studies on human addicts performed under well-controlled conditions revealed no significant adverse effects.

Baseline screening should include a medical evaluation, physical examination, ECG recording, blood chemistries, haematological workup, and psychiatric and chemical dependency evaluations. In some cases more extensive evaluations should be performed to rule out cardiac risk factors and to exclude subjects for study entry.

Drug-drug interactions

Addicts often have a long history of substance abuse. Alcohol, heroin, cocaine, benzodiazepines, and methadone are among the abused substances, frequently also combinations thereof. Methadone is also prescribed for opioid substitution therapy. When ibogaine is administered to addicts, the presence of other substances in the patient’s blood plasma is not uncommon. This paves the way for adverse drug interactions.

Concerning the heart, alcohol, cocaine and methadone have been associated with QT interval prolongation. If relevant concentrations of such substances are still residing in the plasma when ibogaine is applied, the drug’s QT prolonging effect, and thus the risk of TdP arrhythmias will be raised. Here, methadone deserves special attention because it additionally has an exceptionally long plasma half-life.

Given that noribogaine has a long half-life in human plasma (1–2 days), the inhibition of its metabolism by other drugs will have strong impacts. Thus, cardiotoxic effects may persist for weeks after intake of a single dose of ibogaine. Therefore, we strongly encourage researchers to determine the pathways involved in the metabolic conversion of noribogaine.

Conclusions

Due to the longevity of noribogaine—ibogaine’s active metabolite—in human plasma, cardiac adverse events may also occur several days, in some cases weeks after intake of a single dose of ibogaine. Noribogaine, on the other hand, may also convey long-lasting anti-addictive efficacy after ibogaine application.

Future administration of ibogaine to treat addiction may be justified by the urgent medical need for an effective anti-addiction drug. Thus, the use of a drug known to prolong the QT interval must be based on risk-benefit analysis in individual patients. Where benefit outweighs risk, QT prolongation should not limit necessary therapy. Recommendations on prevention and guidelines for the management of drug-induced QT prolongation and TdP in hospital settings can be found in. Two things need to be carefully considered:

(1) Ibogaine application should only take place under strict medical observation and continuous electrocardiographic monitoring over a sufficiently long period of time.

(2) Additional risk factors for drug-induced TdP arrhythmias must be clarified prior to ibogaine application. Eventually, informed consent should be received from drug addicts, in which the risk of ibogaine-induced sudden cardiac death is appropriately highlighted. Based on the rapidly accumulating knowledge about the potentially harmful cardiotoxicity of ibogaine, the responsible medical authorities are now requested to define respective standards and exclusion criteria to allow for a safer ibogaine anti-addiction therapy in the future.

*From the study here:
https://www.ncbi.nlm.nih.gov/pmc/art...emss-62840.pdf
 
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Ann and Sasha Shulgin

How to have a safe psychedelic trip

A psychedelic experience can be deeply rewarding, but also carries real risks. Here’s how to avoid a bad trip.

by Christian Jarrett | PSYCH | May 2021

Humans have consumed substances with consciousness-altering properties for millennia. Traditional societies used them in healing rituals, initiation ceremonies and to make contact with the gods and the dead, among other practices. Today they are known as psychedelics, and include the naturally occurring compounds psilocybin (found in ‘magic mushrooms’), DMT and mescaline; the hallucinogenic tea Ayahuasca, used by indigenous peoples in the Amazon basin; and the hallucinogenic shrub iboga, found in West Africa.

Synthetic hallucinogenic compounds, most famously LSD, emerged in the 20th century. The synthetic ‘party drugs’ MDMA (also known as ecstasy) and ketamine (used in medicine as an anaesthetic) are not technically classified as psychedelics, but they also produce consciousness-altering effects and are often considered under the same broad umbrella as the classic psychedelics.

In the industrialised West, psychedelic substances, especially LSD and magic mushrooms, burst on to the scene in the 1950s and ’60s with intense research interest in their therapeutic potential. However, an establishment backlash began in the late-1960s as the drugs became associated with the counterculture movement and opposition to the Vietnam War.

Fermenting the eventual clampdown, the psychedelics-researcher-turned-evangelist Timothy Leary exhorted American youth to ‘turn on, tune in, drop out’. Tales spread of ‘bad trips’ and associated suicides, and the field of psychedelic research fell silent for decades.

We are now living through what’s been described as a ‘psychedelic renaissance’ that began in the 1990s. Research groups around the world, notably at Imperial College London and Johns Hopkins University in Baltimore, have been pumping out studies uncovering the neural basis of the drugs’ effects and exploring their apparent therapeutic benefits, especially when used as an adjunct to psychotherapy.

Research trials suggest that, when used as part of psychotherapy, the benefits of psychedelics include, but are not limited to, alleviating depression and anxiety (including for people who have not benefited from other forms of therapy or drug treatment), tackling longstanding symptoms of post-traumatic stress disorder, treating addiction, and calming existential distress in people with terminal illnesses.

Superior trial outcomes correlate with participants’ reports of having a mystical or transcendent experience during their psychedelic session. In fact, many people who take a psychedelic drug describe the experience as among the most personally meaningful of their lives. Many are changed by their trip, displaying greater open-mindedness, humility and feelings of connectedness with humanity and the wider world.

Although they can lead to subjectively similar experiences, different psychedelic drugs exert their effects in the brain via different mechanisms. For instance, psilocybin, mescaline and LSD act principally via the 5-HT2A receptor system (5-HT, also known as serotonin, is a neurotransmitter involved in mood and perception), whereas DMT acts on the 5-HT2A system and sigma-1 receptors involved in neuronal signalling. Meanwhile, ketamine interacts with another brain chemical called glutamate by blocking the NMDA receptors that this neurotransmitter usually binds with.

At a global level, psychedelic drugs have in common that they increase levels of entropy in the brain by allowing for communication between neural regions that don’t usually interact, and reducing the activity of a group of neural areas known collectively as the ‘default mode network’, which is involved in self-conscious thought. It’s believed that these neural changes lead to ‘ego dissolution’ and facilitate the mystical feelings of oneness and transcendence that are common to many trips.

The upsurge in research interest in psychedelic drugs and reports of their transcendent, life-changing effects have led to a steady flow of newspaper stories documenting their potential, and the publication of a spate of popular books about psychedelics. As curiosity about these drugs and their beneficial effects continues to grow, it raises the question of whether it’s possible for individuals to take these substances safely – and, if so, how?

Safety and legal issues

There are certain physical and mental health conditions that make it inadvisable to experiment with psychedelics, including heart problems and a history of psychosis or bipolar disorder. Antidepressant or antipsychotic medication could also interact unpredictably with the psychedelic. ‘Chronically, SSRIs [a form of antidepressant] may reduce the effect of psychedelics while other antidepressants may have other effects. But at this point there’s just not enough known about the effect of other psychoactive drugs on psychedelics,’ explains Sandeep Nayak, a psychiatrist at Johns Hopkins who has trained as a facilitator in psychedelic research studies.

‘If you have underlying mental health concerns or are experiencing depression, anxiety, or any medical issues, talk to a psychedelic-friendly therapist or doctor before taking substances,’ advises Sara Gael, director of harm reduction at the Multidisciplinary Association for Psychedelic Studies (MAPS) in the United States.

Even if you are fully fit and healthy, experts unanimously say that it’s a bad idea to take a psychedelic drug on your own, especially if it’s your first time. Ben Sessa is a psychiatrist, based in the United Kingdom, who has been researching the therapeutic effects of psychedelics for more than 15 years. He rejects the framing of the question in terms of whether it is possible to have a safe trip. ‘It’s like: “Is a knife safe or dangerous?”, it’s a ridiculous question. It’s about risk/benefit analysis.’ But he, like others, warns against journeying solo.

‘There are more risk factors [on your own] because there isn’t somebody there to manage your feelings or your behaviour,’ he says. ‘More importantly, you could be disorientated, and try to get in your car and drive away. Anything from the most benign behaviour – going online and buying 200 kg of avocados – to much more dangerous, there’s nobody who is not high who is able to temper your behaviour and make sure things are okay.’ Psychedelics have a pround effect on cognition, perception and coordination and you should take care to be in a physically safe, controlled environment. You should not plan to be driving, walking in traffic, be in high places or other dangerous environments which require you to be alert and coordinated.

Ideally you should identify an experienced and trusted guide or therapist to work with you before, during and after your psychedelic experience. Many cities in the US, Europe and elsewhere have psychedelics societies and these can be a good place to begin your search for a guide. At a minimum, make sure you are with a trusted and competent friend to keep you as safe as possible for the duration of the drug’s effects (consider, for instance, that the mind-altering effects of LSD can typically last up to 12 hours).

Another glaring practical issue is that, in most jurisdictions around the world, psychedelic drugs are illegal and if you are caught in possession, you will face criminal charges. This also has important implications for sourcing drugs safely. Françoise Bourzat, who has worked as a psychedelics guide in California for decades and is the author of the book Consciousness Medicine (2019), says that to source the drugs you will have little option other than to rely on word of mouth. ‘Always test your drugs,’ adds Gael. ‘Test kits are available on the DanceSafe website.’

If you decide to go ahead and it’s your first time, it’s sensible to start out with a weaker dose and, as mentioned, to pay due attention to the duration of the drug’s effects. The PsychonautWiki community encyclopaedia has information on dosing, duration and other practical issues.

However, even if you take these practical precautions, other experts urge an even more cautious stance. ‘I can’t and don’t endorse the use of psychedelics outside of research settings,’ says Nayak.

Fortunately, the physiological risks from the classic psychedelics are low to zero. ‘LSD and psilocybin are virtually inert physically – they have very low physical toxicity profiles so there are minimal physical risks,’ says Sessa. ‘They’re also not moreish,’ he explains. ‘You can see this in animal trials, they won’t repeatedly self-administer psychedelic drugs, they’ll take a single dose and then just largely ignore options to redose. So, the risk of addiction to psychedelics is low. Taking MDMA repeatedly long-term can be more harmful, but studies show that the physical risks go down after stopping.’

The main risks are psychological, and this is why preparation is so important. As safety guidelines for psychedelics trials from Johns Hopkins University put it: ‘The most likely risk associated with hallucinogen administration is commonly known as a “bad trip” and is characterised by anxiety, fear/panic, dysphoria, and/or paranoia.’

What to do

The most effective way to minimise the risk of a bad trip occurring is to prepare well. The Johns Hopkins advice is for guides and therapists to discuss the broad range of psychological effects that can be experienced under the influence of a psychedelic, including out-of-body sensations, the evocation of powerful memories, distortions to time and space, and feelings of oneness with the world, to name but a few. It’s also important to pay due attention to what Leary called ‘set and setting’. Most relevant to the preparation phase, ‘set’ describes the mindset and intention you bring to the psychedelic journey, and an experienced guide will work on this with you. The ‘setting’ refers to the physical, social and cultural environment in which the user takes a psychedelic drug.

‘Are you entering the experience with a certain need in your life? Do you want to explore something? Do you need healing? Do you have an emotional relationship that is problematic, burdened by childhood issues?’ asks Bourzat. "Do you want to be connected more with spirits or explore your relationship with nature? You don’t have to have a pathology to have an experience, but it’s a good idea to know why you’re doing it. What are you looking for in the journey? That’s the preparation. Other basic aspects of preparation," she adds, "include writing a journal and preparing the body by fasting and avoiding alcohol."

The journey

Researchers have known about the importance of the ‘setting’ in the psychedelic experience for decades. In a series of studies published in 1960, Robert Hyde, a doctor at Boston Psychopathic Hospital, spent three years observing how the effects of LSD varied in different contexts. For instance, in the second year of his research, volunteers were treated as ‘research objects’ and given structured tasks to complete, whereas in the final year, the experience involved more chance for relaxation and personal support from and rapport with the researchers. Needless to say, the final year was generally associated with positive psychedelic experiences whereas the second year led to more unpleasant outcomes.

If you take a psychedelic drug at a party, even the attitude – the ‘set’ – of your friends could influence the ‘setting’ and thereby make a difference to your own experience. A field study in 2002 found that, on the rare occasions when people taking MDMA/ecstasy at parties reported bad experiences, this usually coincided with the user’s friends having pessimistic expectations or concerns about the trip. "A sense that another user, particularly a friend or acquaintance who is part of the collective, is not having a pleasant experience may have a deleterious effect on the group as a whole," the researchers said.

When it comes to a more formal, guided psychedelic journey, Bourzat explains that the setting is literally where the journey is happening: "What is the location? Who is sitting with you? Who is helping? What is the expertise and style of the guide? It also includes the length of time … What is guiding the work? Is it nature? Is it someone singing for you? Is there music playing? Is it quiet? All these different elements create the setting."

She adds that commonsense steps to take include ensuring that the room is comfortable with soft furnishings and that any music is conducive to a pleasant experience. "I wouldn’t play rock and roll or house music. It should be expansive, not just classical but also more contemporary, or new age or tribal, African, Tibetan – anything ambient that’s conducive to introspection," says Bourzat.

If you have any frightening experiences or difficult overwhelming emotions, the usual advice is to surrender to these rather than trying to suppress them or run away from them. "Whether the disturbance consists of frightening illusions or internal imagery, difficult thoughts and feelings about some past or present personal issue, or anxiety related to a radical change in sense of self (eg, temporary loss of self-identity), the volunteer is encouraged to mentally surrender to the experience, trusting that her or his usual state of consciousness will return when the drug effects resolve," state the safety guidelines from Johns Hopkins University.

Integration

Following your psychedelic journey, it’s critical that you process the meaning of your experience with a guide or therapist. This ‘integration’ should take place during the two to three months after your experience. "When people take drugs recreationally, like just go to a festival and take LSD and then go home, that’s where they tend to run into problems because there’s a lack of integration of the experience," says Sessa.

One of the key aims of integration, Bourzat explains, is to carry the beneficial aspects of the psychedelic journey into everyday life. "If someone had a beautiful experience of nature, and in the journey they experienced beautiful birds, a meadow, then I would say you actually need to do that in your life. You need to cultivate that experience, and maintain that goodness that you connected with in the journey," she says. "Or say someone connected with a loved one they had lost, and felt love and tenderness and dealt with unfinished business in the journey, then I would suggest some ritual in real life – writing to the deceased person or beginning a journal and making that part of their life."

Gael notes that integration therapists have different approaches and backgrounds. It’s important to find a guide or therapist whom you trust and who is nonjudgmental. "One helpful resource for finding integration support is the Psychedelic Support network," she says.

Key points
  • Remember that psychedelic substances are illegal in most jurisdictions.​
  • If you have physical or mental health issues, speak to a sympathetic doctor before experimenting with psychedelics. People with a history of psychosis or bipolar disorder are usually not allowed to participate in psychedelic research trials because they face heightened risks.​
  • Ensure you are in a physically safe, controlled environment. Always start with a low dose.​
  • Don’t take psychedelic drugs on your own. Find an experienced guide or therapist whom you trust.​
  • Use word of mouth at psychedelic societies and elsewhere to source psychedelic substances safely, and use online testing kits to ensure their quality. Alternatively, for greater safety, consider signing up to a research trial conducted at a university.​
  • Remember the importance of set and setting. Work with a guide who will help you prepare for your psychedelic journey, sit with you during the experience, and conduct integration with you for several weeks or months afterwards.​

Learn more

The main safety challenges confronting anyone who wishes to experiment with psychedelics stem from their illegality, meaning that there is no formal regulation of the training of psychedelic guides, nor is there a reliable way to source the drugs safely. Many researchers in the field, including Sessa, have been campaigning for drug-law reforms for decades. ‘The current situation is a total practical folly and extremely dangerous, utterly immoral and totally unpoliceable,’ he says. ‘It’s putting our heads in the sand and not addressing the fact that many people will take these drugs. It’s like the prohibition era in the States but on a much larger scale. The only way to control potentially dangerous drugs is through appropriate regulation. Imagine if scuba diving were outlawed – people would still do it, but now there were would be poor training, poor equipment and loads of people dying.’

Until the laws are changed, and outside of a research environment, the best route to a safe experience lies in finding a suitably trustworthy and experienced guide – someone who is vouched for by others. And it’s key that this guide will work with you before and after your psychedelic journey.

‘There’s lots of underground therapists in this country and elsewhere, these so-called healer/shaman/guru-type people who will quite happily take you down to Totnes and take four grand off you and take you into their yurt and give you a bag of mushrooms, but they won’t give you the other stuff; they won’t do the preparation and they won’t do the integration, so people are left hanging high and dry,’ says Sessa. "I always say to people who’ve found a so-called shaman or healer: 'Ask this guy if he will see you for three weeks before and three weeks afterwards, and I bet he won’t.' That’s the bit that’s missing, not only from recreational use, but also from underground use."

Until the laws change, signing up to a research trial is probably the least risky way to experience a psychedelic trip. These are being conducted at various research institutions around the world, principally: the University of Bristol, Imperial College London, Newcastle University and Manchester University in the UK; and at Johns Hopkins University in the US.

Links & books

Erowid is a US-based organisation that provides ‘reliable, nonjudgmental information about psychoactive plants, chemicals, and related issues.’

Bluelight is the ‘international, online, harm-reduction community committed to reducing the harms associated with drug use.’

The Multidisciplinary Association for Psychedelic Studies (MAPS) is a US-based ‘non-profit research and educational organisation that develops medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana.’

DanceSafe is a public health organisation, founded in California, that provides ‘a nonjudgmental perspective to help support people who use drugs in making informed decisions about their health and safety.’

PsychonautWiki is a ‘community-driven online encyclopaedia that aims to document the field of psychonautics in a comprehensive, scientifically grounded manner.’

The Psychedelic Renaissance (2nd ed, 2017) by Ben Sessa is an excellent introductory textbook that describes the cultural history of psychedelics, and is the most up-to-date review of contemporary work in the field.

Consciousness Medicine: Indigenous Wisdom, Entheogens, and Expanded States of Consciousness for Healing and Growth (2019) by Françoise Bourzat with Kristina Hunter is a ‘comprehensive guide to the safe and ethical application of expanded states of consciousness for therapists, healing practitioners, and sincere explorers.’

How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence by Michael Pollan is a ‘brilliant and brave investigation into the medical and scientific revolution taking place around psychedelic drugs – and the spellbinding story of his own life-changing psychedelic experiences.’

 
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Safely Exploring High Doses of Psychedelics

by John Robertson | Maps of the Mind | 13 Aug 2021

As I begin to get feedback from readers about what they would like to explore next on their psychedelic journey, one thing I’ve noticed is that quite a few people want to take higher doses. People are interested in experiences of ego dissolution or oneness. I understand this perspective because it’s something I would like to explore myself more too. Something myself and my readers have in common.

One of the problems with exploring high doses is that the experiences can be very intense and difficult to handle. This can make people apprehensive about doing it, especially on their own, which they might feel comfortable doing on lower doses. In this post I’d like to look at possible solutions to this problem.

Start low and go slow

One possible solution, which is a common piece of advice, is to start on a low-dose and slowly work your way up, increasing the dose that you take on each subsequent session.

This is a generally good tact, however, many of us don’t have the time or the inclination to be doing sessions that often to steadily work our way up. Maybe we only have the time to do a single high dose session once within the next year, and we want to be sure one that counts.

If that’s the case, and we only have one session planned, this isn’t much of a solution. In which case, there are a couple of other options.

Attend a retreat

One option is to attend a psychedelic retreat. Psychedelic retreats are typically run by experienced guides and offer a held space for people to explore higher doses and more intense experiences that they would not feel comfortable with doing outside that setting. I am a co-founder of one such retreat company, and I think it’s an excellent way for first timers to have their first psychedelic experience.

The context provides a structured container, a safe space and built-in preparation and integration. The level of support and information is as good as it’s going to get, and I would say it’s the best way for someone to have their first experience on site, with a professional. I think it’s also an excellent way for a beginner to learn about taking psychedelics.

However, retreats are not always the most attractive, or especially these days, convenient option. OPur retreat company has not actually been able to facilitate any retreats since the start of corona, though we do hope to return next year. Retreats are also a more expensive option because of all the costs that go into organising and running them.

If you’ve already been on a retreat, you may want to explore psychedelic trips outside of that context, and without all the extra travel costs and logistical concerns involved.

It may also be that you’ve not been on a retreat but already have some psychedelic experiences yourself and retreats don’t appeal to you.

It can be nice to try psychedelics in a different setting, and a group context can add a different dimension to the experience. Many people report that the group dimension is one of the most beneficial and healing aspects of the entire experience.

Self-organised session

Conversely, journeying outside of the retreat setting can also bring new dimensions to the experience. Your own home or apartment might well be the most psychologically safe space for you, which would make it an excellent choice to go on a deep exploration. Other people may also like to explore tripping in natural environments.

The benefits of a sitter

If organising your own high dose session, it can be very beneficial to have a trip sitter or facilitator. Having a trip sitter can be reassuring and help ease feelings of anxiety and nervousness. Having one can help one approach the session feeling more comfortable, as they know someone will be there to watch over them and ensure their physical safety, and offer reassurance for them in any challenging moments. That kind of support can go a long way in a session. It might be as simple as a chance reminder that they are safe and what they are going through is a temporary experience, and though it may be challenging, it will pass.

Finding a sitter

The question is then about finding a trip sitter. With the current legal status of psychedelics, that is of course very difficult as you cannot just search people openly online and hire someone. In this case your options would be to see if there’s anyone you know who could do it. If going this route, the ideal candidate would be someone who has their own experience with plant medicines, and is generally able to hold space and has the attributes of a good sitter.

It might be a friend who already has some experience with psychedelics or a member of a community. The most important thing is that you are able to trust them. If deciding to work with someone for the first time I would recommend that you spend at least a few hours talking with that person beforehand so you have some familiarity and basic level of relationship with them. You should feel open to sharing with them and it is important for the sitter to have a non-judgemental stance. You also want to talk about more logistical things such as music, setting, and what kind of role the tripsitter will have. You might also want to come to some agreements, which can also be not as ground rules, for the session.

Exploring options

If a high dose experience is something you know that you would like to explore but are currently unable to, ask yourself what would it take for you to be able to do that. What would you need to do to accommodate that?

This might mean opening up to someone close to you about your intention, with an honest request for help in your endeavor. You needn’t necessarily ask someone to sit you as a favor, as that would be quite a big favor to ask. You might ask if they would consider it, and explain that you could do something in return for that. You could explain that it’s something you would really like to do and that you’d really appreciate it if they would consider doing that for you.

Do you know anyone who might be a possible person that you could talk to? What might you be able to do for them that would make it a win-win deal? You might even ask your friend that very question. Of course you can explain that there is no pressure and that you are just exploring your options, and if it doesn’t work out then no worries.

Physical safety

Unless you are using mushrooms, or have tested your substance, I would caution against going for high doses, just for the fact that you don’t know exactly what you are taking. Pure LSD is non toxic, meaning that you can’t physically overdose, but unless you have drug tested it, you can’t be sure. The same is true of ketamine and 2cb. If wanting to go for higher doses with them the only reasonable thing to do would be to make sure it is tested well for purity.

Ideally, you’d grow your own mushrooms, then you can be sure of their source. Then on higher doses, even if you think you’re dissolving or dying (a not uncommon experience), you can be reassured that you are not, and can go ahead and allow yourself to dissolve and surrender into that experience of (ego) death.

Private session

If lack of a reliable source is a problem, an option that you might consider is traveling to the Netherlands. Psilocybin truffles are legal there, and easily bought in shops. If you take care of most of the logistics such as accommodation and food, you could hire a tripsitter privately. If traveling there for this kind of experience, you might decide to go for two sessions in a row stepping up your dose, going from a low dose on the first day to familiarize yourself with effects, and stepping up to a high dose on the second day. I think this is a pretty solid approach personally.

Final thoughts

Last year I had one of my highest doses with psilocybin truffles. It was an incredible experience, and I was fortunate to be able to have a friend tripsit for me. I’m grateful that I was able to have that experience, but it’s not always so easy. I would like to have another high-dose experience but to be honest tripsitters are not so easy to come by and it’s not always that easy to just ask a friend to take out the whole day to look after you.

Until we have decriminalization or legalization, organising high dose sessions will continue to be a problem. If you have any solutions or things that you have found to help with this issue, please, I would love to hear them. And otherwise I wish you best of luck, safe and wondrous journeys.

 
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Mixing Psychedelics and SSRIs is Generally Safe, with Significant Exceptions

by Jon Kelvey | LUCID News | 14 Aug 2021

Psychedelics such as psilocybin and MDMA continue to show increasing promise for the treatment of major depression, post-traumatic stress disorder and other conditions, and could soon enter medical practice more generally. Outside the clinic, meanwhile, many people seek healing and spiritual experiences at psychedelic retreat centers. Altogether, it’s a situation that could soon lead to many more people, and a wider variety of people, taking psychedelics than ever before.

That’s potentially a cause for concern, according to Kelan Thomas, a psychiatric pharmacist with Touro University in California. That’s because many of the conditions people may use psychedelics to treat are currently treated with psychiatric medications such as serotonin reuptake inhibitor (SSRI) antidepressants, and little research has been done on their potential interactions with psychedelics. So far, most clinical trials have focused on the safety and efficacy of a single psychedelic compound alone, not its interactions with other medications.

“I didn’t see anyone in the field doing that sort of work,” Thomas says. “I wanted to review the existing literature that’s out there to think about, what is the level of risk?”

In a new review paper in the journal Psychopharmacology, Thomas and his colleague Benjamin Malcolm take a look at the available evidence for potential hazards in combining psychedelics with existing psychiatric medications, and largely come to a heartening conclusion: With a few notable exceptions, most potential psychiatric drug and psychedelics combinations pose mild to modest risks.

But the exceptions are important to understand.

The paper focuses on the risk of serotonin toxicity from the combination of medications and psychedelics. Serotonin toxicity, or serotonin syndrome, can occur when drugs increase levels of the neurotransmitter serotonin between nerve cells beyond a safe level. Serotonin plays a wide variety of roles in the brain, from regulating gut motility to appetite, but is perhaps most well known for its role in mood and mood disorders. Lower levels of serotonin are associated with depression for instance, and antidepressant medications attempt to raise those levels through a variety of pharmacological mechanisms.

But there can be too much of a good thing, and symptoms of serotonin toxicity from too much of the neurotransmitter can range from nausea and anxiety up to life-threatening reactions such as delirium, coma and even death. However, Thomas and Malcom point out in the paper that serotonin toxicity is generally very rare.

But since many psychedelics and psychiatric medications alike modify the neurotransmission of serotonin, it’s important to analyze which drugs and drug combinations could increase the risk for serotonin toxicity, according to Thomas.

Classic psychedelics bind and cause their effects at the serotonin 2A receptor, while MDMA causes the release of serotonin from nerve cells. SSRIs, meanwhile, prevent nerve cells from reabsorbing serotonin once it is released, and other medications, such as monoamine oxidase inhibitors, known as MAOIs, prevent the body from breaking serotonin — and psychedelic drugs — down.

Looking at the available evidence, Thomas said, most traditional tryptamines such as psilocybin and LSD present a very low risk for serotonin toxicity alone or in combination with most medications such as SSRIs. "Psychostimulants such as MDMA and the many phenethylamines discovered by psychedelic chemist Alexander Shulgin — drugs such as 2C-B, or 2C-T-7 — are slightly higher risk," says Thomas, "because they are actually spilling serotonin out into the synapse.”

Where things get dicier is with the addition of MAOIs, which can come from multiple sources. Although prescribed more rarely than they once were, Thomas said, MAOIs are sometimes prescribed for the treatment of depression, says Thomas. At the same time, the psychedelic brew ayahuasca also contains MAOIs from plant sources, which are what make the DMT in such concoctions orally available. If you are taking a prescription MAOI and combine that with ayahuasca, “That to me is where the risk starts to escalate,” he says. “Whereas MAOIs with something like LSD or psilocybin, I’m not really too concerned. It’s just going to extend the time the effects of those drugs have, maybe slightly increase the intensity.”

One particular tryptamine psychedelic may present a higher risk for serotonin toxicity than others, even without interactions with prescription drugs, according to Thomas, and that is 5-MeO-DMT. “There is some evidence that 5-MeO-DMT might have even stronger activity than serotonin itself at the [serotonin] 2A receptor,” he says. “There have been a few case reports of ayahuasca with 5-MeO DMT leading to what appeared to be a fatal serotonin toxicity.” These cases are rare, but significant.

Another potential drug interaction that concerns Thomas is microdosing, or the practice of taking regular, small, sub-psychotropic doses of a psychedelic such as LSD to improve mood or creativity. “Anything where you are consistently dosing a drug again and again inherently has a different risk profile than a single dose of something,” he says. “But that is not so much serotonin toxicity, it’s an aspect of the drug triggering certain receptors.”

"There’s evidence for instance that LSD can trigger serotonin 2B receptors that regulate the heart’s valves,"
Thomas notes, "and medications have been pulled from the market for that sort of activity. Moreover, We don’t know if there’s a benefit from microdosing. There’s a lot of people who swear by it, but there is no clinical evidence in the way we do have actual clinical evidence for macrodosing,” he says.

Evidence for psychedelic drug interactions is also limited, and so Thomas intends the paper to serve as a starting point for further research and discussion. “There have been a few case reports of deaths with ayahuasca and antidepressants,” he says, but other epidemiological studies suggest more people are doing ayahuasca more frequently without any such toxicities showing up. “It’s really an area of clinical controversy and it’s not real clear right now.”

The takeaway for clinicians, researchers and those who may be using psychedelics illicitly is to be very wary of combining MAOIs with psychedelics, especially ayahuasca, says Thomas, and that there will be more to come from the field of psychedelic drug interactions as time goes on.

“It becomes very important from a harm reduction standpoint to have the best information and education out there about what are more risky things,” says Thomas.

 
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Drug Interactions between Stimulants and Psychedelics

by Dr. Ben Malcolm | Spirit Pharmacist | Apr 26, 2021

For some they are about focus, productivity, and being ‘smart’…it seems that many are searching for an edge when it comes to task accomplishment, goal-oriented activity, or management of attention deficit disorders. For others, they have become disordered habits or even addictions and they are stuck in cycles of binging and crashing. Others still, use them to boost energy associated with depression or fatigue syndromes, manage weight loss or binge-eating, avoid narcoleptic episodes, and to ‘power through’ congestion and colds. As psychedelic use becomes a dinner table conversation in millions of households, more and more people are attracted to them for management of clinical conditions in larger doses or even boosting focus and productivity in microdoses.

But what are the risks of using stimulants with psychedelics? Can it be counterproductive?

Physical risks seem mostly related to additive stress on the cardiovascular system, while psychological risks are more theoretical, but do include potential for counterproductive effects. In this article, we’ll explore these questions with a focus on combinations of psychedelics with traditional prescription stimulants used by mouth.

What are stimulants?

Psychostimulants (stimulants) have long histories of use and are commonly used for both recreational and therapeutic purposes. They have been used since time immemorial for increased stamina, wakefulness, or euphoric effects. Examples of plants with naturally occurring stimulants are coffee and tea (caffeine), Ma Huang (ephedrine), Khat (cathinone), and Coca (cocaine).

The most common therapeutic stimulants are various forms of amphetamine (Adderall; Dexedrine; Lisdexamfetamine; Desoxyn; several other brand products) and methylphenidate (Ritalin; Concerta; several other brand products). These stimulants will be referred to as ‘traditional stimulants’ throughout the rest of this article and serve as the focus of discussion when it comes to combining stimulants with psychedelics. Traditional stimulants provide a stimulating effect to the central and sympathetic nervous systems. They promote the release of neurotransmitters such as norepinephrine and dopamine which lead to wakefulness, increased energy, decreased fatigue, and euphoria. They also activate ‘fight or flight’ responses to increase blood pressure and heart rate as well as dilate airways.

Other stimulants include modafanil (Provigil) and Armodafanil (Nuvigil). These are utilized less than traditional stimulants, although are becoming popular for use as ‘neurohacking’ agents to boost cognitive performance in persons without attention deficit disorders. Stimulants can be used as decongestants (pseudoephedrine), anorectic weight loss aides (phentermine), or antidepressants (bupropion). In addition, supplements that make claims of being ‘metabolism boosting’ frequently contain either natural or synthetic stimulants.

Can psychedelics also be stimulants?

Yes they can, and some stimulants are indeed dually categorized as psychedelics and stimulants. For example, the phenylethylamine chemical backbone of MDMA and mescaline is shared with d-amphetamine and methamphetamine. There are myriad Novel Psychoactive Substances (NPS) derived from phenyethylamine such 2Cx, DOx, NBOMe compounds. Other NPS use a cathinone chemical backbone and are collectively referred to as ‘bath salts’. Substances like methylone or mephedrone are psychedelic cathinones reported to mimic effects of MDMA. Generally, phenylethylamine or cathinone psychedelics have predominately serotonergic activity along with norepinephrine and dopamine activity, whereas stimulants like dextroamphetamine (d-amphetamine) or methamphetamine have predominately norepinephrine and dopamine activity with relatively minor effects on serotonin. This general rule may not apply in all cases of NPS as each of these substances has a distinct pharmacologic profile that may alter risks in combination with other drugs including stimulants. For example, the stimulant para-methoxyamphetamine (PMA) features monoamine oxidase inhibition (MAOI) as part of its pharmacologic profile, which can increase the risk of serious toxicity and death. It is outside the scope of this article to discuss all NPS, and MDMA will serve as the focus of discussion of combinations of traditional and psychedelic stimulants due to having the most data available and being the farthest along in clinical development.

Overview of stimulant structures:

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How does stimulant use pattern and route of administration interface with intentions of psychedelic healing?

Stimulants tend to be habit forming, carry the potential risk of developing substance use disorders, and many are regulated as controlled or illicit substances. When stimulants are used in large quantities, increased frequency, or by a route of administration (ROA) such as insufflation (snorting), inhalation (smoking), or injection they cause immediate and intense effects that carry considerable cardiovascular and psychological risks in and of themselves. Common recreational stimulants used by these ROA include amphetamine, methamphetamine, and cocaine. Physical adverse effects include stroke, heart attacks, seizures, muscle breakdown, or kidney failure while psychologically, paranoia, psychotic symptoms, agitated and aggressive behavior, craving and dependence can occur. If you are seeking to use psychedelics for management of a stimulant use disorder then ibogaine has the best evidence for benefit, although ayahuasca and 5-MeO-DMT have also been touted as helpful. Comprehensive review of psychedelics for treatment of stimulant use disorders is outside the scope of this article. While cognitive liberty supports the psychonaut’s right to explore these ROA, it seems unlikely that these methods of stimulant use are aligned with intentions of using psychedelics to facilitate healing processes. Therefore, the duration of the article will explore potential risks and management strategies of combining traditional stimulants used by mouth for therapeutic purposes with psychedelics.

What physical risks are there when combining stimulants and psychedelics?

The main (acute or short-term) physical responses of combining stimulants with psychedelics are additive increases in blood pressures, heart rates, and thermodynamic responses (increased body temperatures). These could lead to risks of adverse events such as arrhythmias, heart attacks, stroke, kidney failure, or seizures. How severe these risks are likely depend on a number of factors including characteristics of the user, route of administration (ROA), dose, and particular combination used. When it comes to adverse effects as a result of stimulants our old friend Paracelsus is insightful:

“What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison” – Paracelsus

Persons that are elderly or have existing cardiovascular conditions such as high blood pressure, arrhythmias, or histories of heart attack and stroke would be at the greatest risk of physical adverse effects of psychedelic stimulants such as MDMA as well as combinations between stimulants and psychedelics. In phase II clinical trials, doses of MDMA (75-125 + booster 37.5-62.5mg) increased systolic blood pressure (SBP) by an average of 25 mmHg, diastolic blood pressure (DBP) by 12mmHg and heart rate (HR) by 28bpm. Therefore, these values may be helpful in guiding potential cardiovascular responses to MDMA. If blood pressures, heart rates, or other aspects of cardiovascular function are a concern, beyond avoiding use, antihypertensive drugs such as clonidine and carvedilol have been shown to attenuate cardiovascular responses to MDMA without interfering with subjective effects.

Is there a hierarchy to risk when it comes to combining stimulants and psychedelics?

As far as psychedelics commonly used with healing intentions, those that contain a MAOI such as ayahuasca are likely the highest risk followed by psychedelic stimulants like MDMA. Tryptamines appear to have lower physical risks in combination with stimulants, although can still elevate blood pressures and heart rates. We’ll explore various risks of these combinations now:

Stimulants + MAOI containing psychedelics (Ayahuasca)

These combinations can carry risks of severe physical toxicities including hypertensive crisis and Serotonin Syndrome. The most dangerous drugs to take in combination with MAOIs are drugs that block serotonin reuptake as well as drugs that release serotonin. Neither methylphenidate nor amphetamine do this to a significant extent and slow introduction of stimulants to MAOI regimens have been used historically with expert oversight. However, risk of extreme hypertensive responses to the combination of stimulants and MAOIs has occurred and cases of harm have typically featured intracranial bleeding as result of very high blood pressures rather than Serotonin Syndrome. Risk of developing Serotonin Syndrome is higher when combining psychedelic stimulants that release serotonin such as MDMA opposed to traditional stimulants.

Bottom Line: Stimulants can be hazardous with MAOIs and discontinuation is the safest practice.

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Stimulants + phenylethylamine psychedelics (MDMA)

Since phenylethylamine psychedelics such as MDMA and mescaline are themselves psychostimulants, there may risks of additive stimulant effects when combined with amphetamine or methylphenidate products.

One study investigated differences between placebo, methylphenidate, MDMA and the combination of methylphenidate and MDMA in healthy volunteers. They found that methylphenidate (60mg) did not enhance psychoactive effects of MDMA (125mg) or have additive effects on core temperature increases when used in combination. The hemodynamic response (combination of blood pressure and heart rate effects) was significantly higher when MDMA and methylphenidate were combined compared to each drug alone. They also found higher rates of subjectively reported adverse effects, however no severe adverse effects were observed. There is very little research on the effects of combining amphetamines with MDMA from a laboratory setting since most studies have aimed at comparing them to elucidate potential differences. However, similar to methylphenidate, there is a high degree of plausibility that there are additive effects on the cardiovascular system. MDMA and amphetamines are not uncommon to combine in recreational settings either via separate drug ingestions or due to impurities in ecstasy tablets. It is likely that impurities in ecstasy tablets or combination with other psychostimulants has contributed to situations in which toxic effects including death have been reported. For a number of reasons results from recreational literature are not likely very generalizable to persons taking therapeutic doses of traditional stimulants who wish to use psychedelics for healing. Nonetheless, the body of literature from recreational settings could be used as a harbinger of potential dangers when psychedelics and stimulants are combined in high doses or unsafe environments.

Bottom line: Given higher cardiovascular stress, increased reports of adverse effects, and lack of enhancement of psychedelic effects, it appears there is little to gain by combining stimulants with MDMA and potential for increased risks.

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Stimulants + tryptamine psychedelics (Psilocybin, LSD)

Classic tryptamine psychedelics like psilocybin or LSD appear to be the least risky to combine since there is no mechanistic overlap in release of neurotransmitters or blockade of neurotransmitter reuptake. Tryptamine psychedelics do cause some amount of vasoconstriction and are associated with increased blood pressures or heart rates so some risk likely still exists. There is little (if any) research from clinical settings observing effects of combining stimulants with psychedelics. Some tryptamines, such as 5-MeO-DMT, lack basic studies characterizing cardiovascular responses to administration and are difficult to predict risk with for this reason. Recreationally, psychedelic psychostimulants like MDMA are often combined with psilocybin mushrooms or LSD and referred to as a ‘hippy flip’ or ‘candy flip’. There is little literature supporting combinations drastically increase physical risks, although do lead to intensified psychological experiences, and should be approached with caution.

Bottom Line: Stimulant discontinuation should be considered based upon intentions of use and individual risk assessment.

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Are there psychological risks of combining stimulants with psychedelics?

There are some interesting differences found in psychological tests and rating scales between traditional stimulants and psychedelics as well as pharmacologic observations that may carry implications for healing effects. The emphasis is on may here due to the largely theoretical nature of this discussion and the reader is encouraged to approach the section with healthy skepticism.

Focus, psychosis, and surrender

Traditional stimulants boost dopamine and norepinephrine levels, which has been associated with the therapeutic effects of increased focus, concentration, motivation, and energy. There is often much emphasis placed on allowing non-linear modes of thinking, non-directive therapeutic approaches, periods of silence, and ‘surrendering’ to the effects psychedelics when discussing optimal navigation of psychedelic states in psychedelic assisted psychotherapy. This may lead one to wonder if drugs that enhance aspects of logical or rational cognitive abilities would affect the healing mental processes that are active under the influence of psychedelics. It is unclear if a drug that increases focus could modulate an individual’s ability to ‘surrender’ or interfere with non-linear thinking.

In addition, traditional stimulants are often used as a pharmacologic model of psychosis due to psychotic symptoms caused by excessive dopamine signaling. Among neuroscientists, psychedelics have also held long-time interest as potential pharmacologic probes in models of psychosis. Originally, psychedelics were termed ‘psychotomimetic’ due to the observation that the user appeared to be in a psychotic state while under their influence. Emotional discomfort, panic, paranoia, and delusional states often occur transiently with psychedelics and have been reported in clinical trials. It is unknown if stimulant and psychedelic combinations may increase risk of transient psychotic symptoms like paranoia at low-moderate doses in controlled settings.

Facial recognition

Psychedelic stimulants such as MDMA have been found to decrease the ability of an individual to accurately identify faces displaying negative emotions leading to positive emotion misclassification. Conversely, the traditional stimulant methylphenidate increases recognition of faces displaying negative emotion and misclassification of faces displaying positive emotion. The effects of MDMA on facial recognition is postulated to be a favorable component of the drug’s pharmacologic profile as it may be related to its pro-social effects or therapeutic effects in PTSD or social anxiety in autistic adults. It is unknown how these seemingly opposed effects on facial recognition tests may effect therapeutic uses of psychedelics.

Stimulants, psychedelics and the ego

The ego can be defined as a person’s sense of ‘who they think they are’ and is thought to correlate with the portion of the mind that is self-referential and constructive of a sense of personal identity. In contemporary neuroscience, this is often mapped to a set of functionally interconnected neural circuits collectively termed the Default Mode Network (DMN). The effects of several tryptamine psychedelics such as ayahuasca, LSD, and psilocybin have demonstrated that they globally diminish DMN activity and that this effect is correlated with a subjective sense of ‘ego-dissolution’ and spiritual or mystical experience. In turn, mystical experiences have been linked to improvements in mindfulness and longer term psychosocial functioning. On the flip side, stimulants are known to increase self-confidence or a sense of superiority and have been classified as ‘ego-inflating’ drugs. A two factor scale termed the Ego Dissolution Inventory (EDI) was designed to discriminate between drugs with ‘ego-dissolving’ vs. ‘ego-inflating’ characteristics. When tested in a large online sample it was found that psychedelics are strongly correlated with ego-dissolution while cocaine was strongly correlated with ego-inflation. These observations may carry implications for interactions between psychedelics and stimulants. If the intention is use of a tryptamine psychedelic to create a state of consciousness in which the ego is dissolved, then it may not be favorable to combine them with stimulant drugs with ego-inflating properties. However, MDMA has demonstrated therapeutic properties in several phase II trials and has pharmacologic properties of both stimulants and psychedelics. It is unknown if the overall effects of MDMA are ego-dissolving or ego-inflating. The fact that MDMA can offer healing and exist as both a stimulant and a psychedelic may render the perspective that ego-dissolving and ego-inflating drugs are incompatible in healing processes as reductionist or inaccurate.

Harm reduction with psychedelics and stimulants

Use of concurrent stimulants have not been permitted in studies of MDMA- or psilocybin-assisted psychotherapies to date. Therefore, research has set a precedent of discontinuing stimulants prior to therapeutic psychedelic use. This is likely done for two reasons: The first is fear of introducing risks discussed above and the second is to keep the experiment pure and prevent confounding their results with other drugs. It appears that psychedelics largely retain their effects when combined with stimulants and cross-tolerance has not been observed in laboratory settings. Thus it is conceivable that stimulants and psychedelics may not be considered absolute contraindications if psychedelic-assisted psychotherapy became Food and Drug Administration (FDA) approved (especially with psilocybin). That being said, the most reassuring method of reducing risk and optimizing potential benefit is discontinuation of stimulants.

Stimulants have withdrawal syndromes characterized by low mood, irritability, fatigue, and lowered motivation. Typically this last 7-14 days, although can be persistent beyond this time frame. Many persons taking stimulants for therapeutic purposes do not take them on a daily basis. For adults with attention deficit disorders, it is common to take a stimulant during the workweek and take a ‘drug holiday’ each weekend. For persons taking relatively low doses of stimulants whom do not report severe withdrawal syndromes or those accustomed to taking drug holidays, it is relatively simple to discontinue stimulants. For persons accustomed to everyday use, taking higher doses, or those that experience severe discontinuation syndromes, then tapering the dose of stimulant would reduce discontinuation symptoms and risk of clinical decompensation. It is recommended to not discontinue psychotropics without support and oversight from your providing prescriber. Recruitment of additional support systems such as friends, family, community, a therapist, or a psychedelic integration coach is desirable.

Stimulants are rapidly eliminated from the body and it is predicted that methylphenidate would be completely eliminated after 24-48 hours (half-life ~2-6 hours), while amphetamine products completely eliminated after 48-72 hours (half-life ~12 hours). Depending on intentions of psychedelic use and the individual’s relationship to stimulants, consideration of longer discontinuation times prior to use may be reasonable. When prominent withdrawal effects are present, it may be best to wait until the withdrawal symptoms have run their course before engaging with psychedelics. If desired and aligned with intentions of psychedelic use, it is predicted to be safe to resume stimulants 24 hours after using a psychedelic without a MAOI and 48 hours after psychedelics containing a MAOI (ayahuasca).

Summary & conclusions

Combinations of psychedelics and stimulants are somewhat less clear cut than drugs that directly interfere with psychedelic effects like antidepressants. Research in psychedelic-assisted psychotherapy has set a precedent for stimulant discontinuation prior to psychedelic use, while stimulant and psychedelic combinations are common in recreational settings. There is mechanistic overlap between some psychedelics and stimulants, although differences are also apparent. Stimulant management with psychedelic use is likely personal and multifaceted. The users’ baseline cardiovascular status, particular drug combination planned, doses of drugs, and intentions for psychedelic use are important principles in guiding decision making when it comes to navigating psychedelics and stimulants.

Dr. Ben Malcolm is a doctor of pharmacy, master of public health, and Board Certified Psychiatric Pharmacist. He provides consultation services, courses focused on psychedelic healing and pharmacology.

*From the article here :
 
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Now test the potency of your psilocybin at home

The Miraculix test kit shows the percentage of psilocybin in your mushrooms.

by Dr. K Mandrake | DoubleBlind | 1 Jun 2021

nswering questions about the potency of magic mushrooms has been mostly done through self-experimentation, with subjective factors like set and setting blurring the objectivity of those making their measurements. Until recently, accurate testing of psilocybin content in magic mushrooms was something that could only be done in a laboratory by comparing samples to known quantities of a pure reference compound.

Enter miraculix, a company based in Jena, Germany, which has recently developed portable psilocybin “QTest” kits that can be used by anyone to give fast and accurate potency information, allowing people to easily standardize their doses and figure out when their mushrooms might have lost potency.

Dr. Felix Blei, lead scientist at miraculix, has published a number of papers on the biochemistry of psilocybin production in mushrooms, and was the first to discover the presence of β‐carboline monoamine oxidase inhibitors (MAOI) in the fungal genus Psilocybe, which are also produced in Banisteriopsis caapi, the vine often used as part of traditional ayahuasca brews. The discovery of these MAOI compounds in Psilocybe raises some interesting questions around their potential entourage effect with psilocybin and other alkaloids during a whole-mushroom psychedelic experience.

We recently got to chat with chief science officer and founder of Miraculix, Roxana Preuß, and the team to learn more about the QTests, the story behind their creation, and the science of psilocybin mushrooms.

Tell us about the team at miraculix, who are the team and how did you come together?

RP: The team is made up of Dr. Felix Blei, Frank Junger and myself. Following his doctoral thesis, our lead scientist Dr. Felix Blei developed an innovative rapid test method for determining the concentration of psilocybin, the main active ingredient in magic mushrooms.

Recognizing the potential of this process and the need for such a simple test, Dr. Blei wrote applications and managed to get a grant to work in the laboratory at Friedrich Schiller University in Germany.

However, understanding that it takes a diverse team to turn an idea into reality, we held interviews at the university to grow our knowledge base. Frank Junger and I recently joined the team, and we’ve been working together for almost a year. I have a background in business management and Frank has years of experience in the events industry.

We’re really focused on joint teamwork, and have recently become registered as a spin-off company from the university we started in.

What made you decide to make the QTests?

As we mentioned, Dr. Blei’s PhD thesis was focused on the investigation, characterization and biosynthesis of various chemical compounds from psychedelic mushrooms in the genus Psilocybe. While undertaking this work, media interest along with inquiries from the internet made it clear that many people were curious about testing the potency of a variety of psychedelic mushrooms outside of the lab.

At the same time, given the sensational therapeutic successes with psilocybin and the beginnings of magic mushroom decriminalization, we realized there was no easy analytical method to check potency to help inform the therapeutic use of psilocybin from natural sources. From our work in the lab, we saw that the proportion of active ingredients in psychedelic substances varies greatly and accurate quantification is both time-consuming and expensive.

Realizing there is a need for measurement of active ingredients, we applied for a federal grant for funding to conduct research, and developed simple quantitative test kits for not only psilocybin, but also MDMA and LSD. We now have a proof-of-concept method that we hope will act as the starting point for quantifying many more active ingredients in the future.

How do the QTests work? What can the results tell people?

With our tests, it is now possible for the first time to determine the concentrations of psychedelic substances easily, without the need for a complex laboratory or technical equipment. The QTests are low-cost and can detect compounds like psilocybin at low thresholds, providing precise results within a few minutes. The QTest uses a chemical color reaction to detect potency, with the color intensity being proportional to the concentration of the active ingredient, and evaluation can be done by eye or with our smartphone app. The process is basically the same whether you’re using our QTests to detect psilocybin, MDMA or LSD.

With decriminalization coming to many US states, how does the perception of psilocybin mushrooms and other drugs differ in Germany, and have you had any problems trying to develop your company?

In Germany, much like in the US, there has been a slow change in political discourse in recent years. Here a health policy focus has gained influence, and although drug testing and harm reduction are anchored in a coalition agreement between many German federal states, such approaches are difficult to carry out in practice due to the legal situation and lack of on-site testing.

We are the first company to change this with our QTests, as venues can now perform testing directly on-site. We’ve worked in cooperation with addiction services in our federal state to start the first german pilot project, which combines on-site drug testing with drug prevention work to provide harm reduction and options for safer use.

More broadly, the medical benefits of these substances are beginning to be recognized and medical studies are now underway. We hope that we can further strengthen scientific perspectives with our work and thus make a meaningful contribution to the discourse, while rejecting some of the cliches around these substances from past misinformation.

The psilocybin “Psilo-QTest” kit is particularly interesting. Are there any other psilocybin test kits currently available from other companies?

The Psilo-QTests are the first quantitative test kits for psilocybin worldwide on the market. Until now there were only qualitative test kits that let you know if psilocybin is present, but not how much is there. We tried these kits on different Psilocybe species and found that they work very badly—sometimes only successfully detecting psilocybin in 50 percent of our samples, which we knew all contained the compound through cross-validating using more reliable testing.

Are the Psilo-QTests easy to use? Do people need any other special equipment to test their mushroom material?

The Psilo-QTests are very easy to use, and each one includes almost everything you need. We’ve created a how to video, with English subtitles that can guide you through the process. Besides the QTest, you only need a scale (that can weigh 0.15g) to weigh the mushrooms, hot water for the test incubation, which you can get from a kettle, or even a camping stove if you’re out and about. The whole process takes 30 minutes, with just two to three minutes of work; the rest is just waiting time.

If you’re checking potency by eye, we recommend you do this in natural daylight as artificial lights have different wavelengths and can sometimes make colors look different. However we also developed a smartphone app that uses your phone’s camera and takes some of the personal judgement out of the process.

Will the Psilo-QTest work on all mushroom species? Will they also work for sclerotia/truffles?

We have access to a broad range of mushroom species that contain psilocybin, which we either grew in our lab or collected outdoors. We’ve already tried the QTests with different fruiting bodies or mycelium for not only a range of Psilocybe cubensis strains, but also for Psilocybe cyanescens (Wavy Caps) and Psilocybe semilanceata (Liberty Caps). We’ve also tested the mushrooms and sclerotia of Psilocybe mexicana and Psilocybe tampanensis. We also tried with psilocybin-containing fungi of other genera like Pluteus salicinus, and can confirm it works on every one we’ve tested!

How dry do the mushroom samples need to be for analysis? How do you best prepare mushroom samples for analysis using the Psilo-QTests?

We calibrated our Psilo-QTests for normal air-dried mushrooms, though we find they grind best if they’re cracker-dry (i.e. they snap rather than bend). The best way to prepare the mushrooms would be to grind up several whole specimens using a mortar and pestle, but you can also use scissors and a glass beaker (like we show in the how-to video). Once you have your prepared mushroom material, only 0.15g are needed for the analysis.

Your QTests can be analyzed with a smartphone app; how does this work? Are there any considerations people need to give to lighting or background color in order to get the most accurate results?

We’re constantly improving our smartphone app. The first version is very simple to use: The sample vial is placed in front of the reference color sheet, using the manual to provide a standard white background. Simply take a picture of both the vial and the color sheet, and the app will calibrate between these images to calculate the amount of psilocybin that is present. We find the app works best if the photographs are taken in good amount of natural daylight, but our next update should allow the app to work completely independent of external light conditions.

How accurate are the QTests compared to the equipment you might use in a laboratory?

The accuracy of the QTests ultimately depends on how you chose to analyse the results. As the supplied color sheets have around 10 reference measurements each spaced 0.3 percent apart, making it very easy to figure out the concentration of psilocybin based on the color of the sample. Using this method, the maximum difference between our QTests and measurements we’ve performed in our lab is no more than 10 percent, which is very impressive for such an easy and fast test.

As mentioned earlier we’re working on an updated version of our smartphone app, which will make analysis even more accurate, reducing this difference down to around one to five percent. We’re hoping an added advantage of the updated app is that the QTests could be used to test batch-to-batch quality in commercial production, or to standardise doses in therapeutic applications as natural products.

Do you ship the QTests internationally?

Shipping ultimately depends on the legal framework in each country. Shipping is currently limited to the USA and Europe, but we are constantly working on making these available for everyone.

What sorts of psilocybin concentrations have you found in your lab work? Does it vary a lot between mushrooms?

Interesting question! Felix has analyzed a lot of mushrooms during his studies and when developing these test kits, including both cultivated or wild-grown species. Psilocybin concentration varies a lot, not only between different species, but also if the same species are just grown under different conditions. The best example is some local Psilocybe cyanescens which we collected near the university in Jena, Germany, which had content of around one percent psilocybin. We compared these to the same species collected in the neighboring town of Leipzig, and found these samples contained over two percent psilocybin.

Felix also analyzed different Psilocybe cubensis strains which vary both within and between strains. For example, the Huautla strain we analysed always contained less psilocybin content than the Albino A+ strain when grown in the same exact setup. In addition we found that Albino A+ potency ranges between 1.1 and 1.8 percent psilocybin.

What’s the oldest sample you’ve still been able to detect psilocybin in?

The oldest samples we have are a few years old, and we keep them in our laboratory freezer; they still contain high amounts of psilocybin.

What do you suggest is the best way for people to prepare and store their mushrooms to retain potency?

For best potency the crucial point is the fast removal of the water from the mushrooms. In the lab we find the best way is to freeze dry them, but as psilocybin is very heat stable a good alternative at home is to dry your mushrooms using a dehydrator or an oven set to a low heat. Once the mushrooms are fully cracker dry, store them frozen in an airtight container in the dark.

 
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Alexander Shulgin

Can you overdose on LSD? This is what to know

by Karla Ilicic | Healing Maps | 22 Oct 2021

When you think of LSD, it’s most likely in the party drug context, not the potential psychedelic therapy treatment. Still, it’s one of the most sought after hallucinogens of today, with many people still wondering, can you overdose on LSD?

LSD, or Lysergic Acid Diethylamide, is a very potent, hallucinogenic drug that can produce changes in perception, mood, and a sense of time and space. On the federal level, it’s classified as Schedule I of the Controlled Substances Act. This means it has a high potential for abuse — with no currently acceptable medical use.

LSD is not a natural psychedelic, meaning it is not from nature. Instead, it’s a synthetic psychedelic.

Swiss chemist Albert Hofmann is responsible for discovering and synthesizing the drug in a lab. While using lysergic acid, and with the hydrolysis of ergotamine, an alkaloid found in a fungus that infects rye was created.

Hofmann began experimenting on himself and experienced the LSD (or acid) trip. His diary made the following claims.​
“Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.” He later went on to explain how “everything in his field of vision wavered and was distorted as if seen in a curved mirror, and that he also had the sensation of being unable to move from the spot.”

He collaborated with many psychologists of the time, who began experimenting with small doses of LSD on their own patients. The results were positive shifts in their mood and behavior, often lowering stress and anxiety. Unfortunately, all research stopped when the United States officially banned the drug in 1967.

It wasn’t until 15 years ago that the interest in this psychedelic began to grow. That’s when doctors, again, began exploring the potential behind its incredible stress-relieving and anxiety-reducing effects.

LSD as a party drug

In the 1990s, LSD started circulating around popular party scenes. It is odorless and colorless, and has a slightly bitter taste. Each “hit” often comes on absorbent paper, which is cut into small squares. These represent a single dose. It can also come in the form of tablets or micro dots, saturated sugar cubes, or the classical, liquid.

Side effects from taking LSD are the following.​
  • Physical. Dilated pupils, increased body temperature, increased heart rate and blood pressure, excessive sweating, loss of appetite, insomnia and trouble sleeping, dry mouth, blurred vision, chills and goosebumps, and tremors​
  • Mental. Visual and auditory distortions (hallucinations), huge shifts in mood, impaired judgement and focus​

LSD as a potential therapeutic treatment

Belonging to the group of classical hallucinogens, together with psilocybin and DMT, it binds to the serotonin receptors in the brain, causing the person ingesting it to momentarily feel better, happier, and more relaxed. Consequentially, this helps reduce anxiety, stress, and depression, with research extending to PSTP and even opioid addiction treatment. It’s why many people have begun microdosing LSD.

Unfortunately, most current research comes from small-scale trials — so there isn’t much available. Until anything changes, it will be difficult to explicitly push for the drug’s use in treatments for various mental health disorders.

However, LSDs history does trace back to the 1950s-1970s. During those years, the drug showed potential treating behavioral and personality changes. This includes mental health issues, too, such as anxiety, depression and addiction.

For patients with cancer, previous subjects claim LSD helps with pain and depression.

Unfortunately, many of these studies don’t meet today’s contemporary standards. It’s why many restrictions against LSD still exists, and why it has yet to gain support as an alternative treatment option.

So, can you overdose on LSD?

The question of whether or not you can overdose on LSD is fair. After all, there’s a stigma around the safety of many drugs — especially as a psychedelic treatment.

As a recreational drug, LSD seems not to form an addiction as most other substances do, with those taking it on the regular even building up tolerance.

LSD is a hallucinogen, but it exhibits very low physiological toxicity. Even at high doses, there is no evidence of organic damage or neuropsychological deficits from using LSD. For that reason, LSD is one of the safest psychoactive recreational substances.

Due to its low toxicity levels, overdosing on LSD seems to be incredibly hard, but not impossible. Taking an extremely large dose may lead to a severe reaction, which may carry the description of an overdose. A typical dose of LSD is between 50 micrograms to 150 micrograms. So, if someone takes 10 times the typical dose, experiencing harsh symptoms is quite possible.

These unpleasant symptoms include panic and aggression, suicidal or homicidal thoughts, severe depression, hypertension, increased heartbeat, loss of appetite, extreme sweating and flushing, nausea, diarrhea, insomnia, drowsiness, dry mouth, tremors, pins and needles sensation, hyperactive reflexes, and a mild fever.

More severe overdose symptoms include reactions like seizures, excessive vomiting, irregular heartbeat, intracranial hemorrhage, as well as respiratory arrest. The latter can lead to death.

Potential of having a bad trip

Don’t confuse overdosing with having a bad trip. A bad trip is a negative psychological reaction to a drug which causes anxiety and panic, as well as the feeling of helplessness and inability to control the situation. This often causes a ton of distress, paranoia, and fear, repelling the person from taking the drug again.

The good thing about a bad trip is that it typically ends in the same amount of time as a good trip does. It just leaves a negative taste in your mouth. Although it can happen to anyone, it’s more likely to occur in people with a pre-existing mental health condition, as they’re more liable to experience fear, anxiety, paranoia, and depression.

Overall, LSD is a classical hallucinogen with a very low toxicity level and little to no dependency characteristics. So, while it’s highly unlikely that you can overdose on LSD, it isn’t impossible. Like any drug, taking extreme doses of will be too hard for the body to process.

 
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Some ways of taking psychedelics are safer than others*

by Lester Black | The Stranger | 25 Sep 2019

In the summer of 1972, someone at a dinner party in San Francisco made a terrible error. They mixed their cocaine with their LSD and accidentally served lines of powdered acid, two apiece, to seven of their friends.

A drop of acid can send someone into an eight-hour psychedelic trip. Snorting milligrams of the chemical's powdered form is unthinkable. These people had just inadvertently consumed a massive dose. Within five minutes, they were vomiting. After 10 minutes, five of the people were comatose, according to a case report in the Western Journal of Medicine. These people appeared to be on their way to sudden death.

But no one died. Within 12 hours, every single patient was conscious. After a year of follow-up exams, there were "no apparent psychologic or physical ill effects" in any of the eight individuals, according to the case report.

There's a high probability that you will come across psychedelics at least once during your higher education. Every drug has its milieu, its natural social environment. Just like meth wallows in misery and trailer parks, and cocaine mingles with mistakes and nightclubs, psychedelics (with their mind-expanding quality) fit naturally at universities where young people are regularly encouraged to challenge their usual way of thinking. So what lesson should you take from the story of the San Francisco dinner party?

To begin with, our government's classification of psychedelics as the most dangerous type of drug on earth makes no sense. Though what happened to the dinner party guests is scary, it also might be the record for most LSD ever consumed by a human. There are no known fatal human overdoses on LSD, which has led multiple scientists to determine LSD is not toxic. The theoretical lethal oral dose to humans, based on intravenously shooting mice with LSD, is somewhere around 20 milligrams, according to erowid.org, an internet hive mind for psychedelic information.

Teri Krebs, a neuroscientist at the University of Norway, has said psychedelics in their pure form are as risky as riding a bike or playing soccer.

"It is generally acknowledged that psychedelics do not elicit addiction or compulsive use and that there is little evidence for an association between psychedelic use and birth defects, chromosome damage, lasting mental illness, or toxic effects to the brain or other body organs," Krebs wrote in a letter published in the Lancet.

But the story of this dinner party also illustrates a profound irony of psychedelic drugs like acid, mushrooms, or mescaline: They may not be harming your organs like a cigarette or vodka does, but the very essence of large doses of these drugs is madness. Many of the hallmarks of a "successful" psychedelic trip—temporary paralysis, severe visual distortions, extreme confusion—seem a lot like temporary bouts of insanity.

In fact, when researchers in the early 1900s started discovering and synthesizing these drugs, they first called them psychotomimetic, which literally means mimicking psychosis. It wasn't until 1956 that the term psychedelic, or "soul revealing," was first coined.

That renaming coincided with a massive amount of research into psychedelics, with doctors administering LSD to more than 40,000 patients from 1950 to 1965 and producing convincing evidence that psychedelics could be an effective treatment for a wide range of disorders from alcoholism to depression. That research was stunted by the American prohibition of psychedelics in 1970, but research is now restarting. Johns Hopkins University announced this year that it is launching an entire center dedicated to psychedelic research.

So how do you ensure that your trip on psychedelic drugs is revealing of your soul and not corrupting of your mental stability? Here are four tips to keep in mind if you decide you want to take these fascinating drugs.

First, consider your medical history. People with a history of mental illness are at a greater risk of developing adverse effects from psychedelics (and also from pot, by the way), and many of these drugs can create harmful interactions with antidepressants and heart medications. Anyone on prescription medicines should be wary of taking these drugs without medical supervision.

Second, consider the drug's source and purity. LSD isn't toxic by itself, but an adulterated version could easily be dangerous. Psychedelics like MDMA are particularly prone to adulteration with dangerous additives like meth or even bath salts. The best way to safely consume psychedelics is by having them tested by nonprofit testing services like drugsdata.org or by buying an at-home drug testing kit.

Third, consider the dose of the drug. Microdosing, which involves taking a fraction of the dose that is required for a full psychedelic trip, is becoming increasingly popular because it offers a way to lightly experience the effects of psychedelics. Even if you want to feel the full weight of a mind-bending trip, it is probably a good idea to start slow by first microdosing and seeing how you respond.

Finally, consider where and when you are taking these drugs. The psychedelic experience, more than any other type of drug, is integrally tied to the context in which you take the substance. Psychiatrists specializing in psychedelics call this contextual information your set (or your mind-set when you take the drug) and your setting (the place and environment where you take the drug). For your first time, don't do it at a music festival where you're surrounded by crowds of people. Try doing it in a park with a few trusted friends, or a very comfy room in your house. Ideally, one of your friends will not get high and can help you if you start freaking out.

It's no accident that ancient uses of psychedelics, like the thousand-year-old indigenous use of the hallucinogenic substance ayahuasca, always occurred in tightly controlled religious settings where individuals were intentional with their mood before entering the trip, outside stimulus was limited, and there was an expert ready to guide them through the experience. Taking large doses of these drugs when you're in a hostile mood or in an unruly environment—say, Pike Place Market on a Sunday—is only asking for a bad trip.

And that "bad trip" might be the biggest danger from psychedelics. A powerful dose of psychedelic mushrooms probably won't kill you, but that doesn't make jumping out of a window or running into traffic while on mushrooms any less dangerous. (And eating the wrong kind of mushrooms can kill you, so don't go off into the woods just picking and eating anything that looks right.)

Psychedelics are powerful drugs that demand respect. Use them intentionally, and your understanding of reality, of the earth, of your connection to other human beings may be forever changed for the better. But disrespect them, and you're asking for a problem. So make sure you know what you are taking, have friends to guide you through the experience, and remember to never mix your cocaine with your LSD.

*From the article here :

 
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Risky sex and the recreational use of MDMA

by Georgette Monserrat | Psychedelic Science Review | 21 Aug 2020

MDMA is associated with feelings of positivity but does it also increase risky sex behavior?

When used recreationally, MDMA elicits prosocial feelings such as empathy, closeness, and an increase of positive word use. A 2009 study suggests at least one mechanism to explain why this happens: researchers found that 15 volunteers taking MDMA experienced a significant and positive correlation between increased oxytocin levels in the blood and the positive prosocial feelings described above. Oxytocin is also known as the “love hormone” and is released naturally in various situations, including post-coitus.

There is abundant research showing an association between sensation seeking, impulsive decision making, and sexual risk-taking. Regarding MDMA, what feelings does it alter? And what is MDMA’s association with sexual activity? In psychedelic research, it’s important to look at the factors surrounding risky sex, including impulsivity and sexual behaviors in the context of MDMA.

MDMA and impulsivity

A study by Morgan, published in Neuropsychopharmacology in 1998, looked into the association between MDMA and impulsivity. Researchers recruited undergraduate and graduate student volunteers through poster advertising and vetted the subjects through interviews. The 44 participants were divided into the following three groups:​
  • Non-Drug control group – 16 people who reported never using illicit drugs.​
  • MDMA group – 16 recreational users of MDMA who had used it at least 20 times.​
  • Poly-Drug control group – 12 people with drug histories and characteristics similar to MDMA users but who reported never taking MDMA.​
Study participants completed various tests including:​
  • Self Reporting Mood (Likert) scale — Used a 6 point rating from “not at all” to “extremely” on the categories of happy, depressed, joyful, pleased, fun, frustrated, anxious, and angry​
  • Personality Impulsiveness, Venturesomeness, Empathy (IVE) test — Impulsiveness & Empathy has a 19 point rating scale and Venturesomeness has a 16 point rating scale. The higher the score, the more they displayed that characteristic.​
  • Tower of London (TOL) test — This test assesses executive functioning. Participants had two different arrangements of balls and had to match the order of the second group to the first one in a set amount of moves.​
  • Matching Familiar Figures (MFF20) Test — A behavioural measure of impulsivity. Participants are given a stimulus figure and then are shown 6 different options of which they must pick the one that matches exactly to what they were shown.​
The data indicated no significant differences in empathy scores or TOL test scores across groups. However, in the TOL test, the participants in the Non-Drug group took significantly longer thinking before answering compared to participants in the other two groups. This demonstrates that participants in both drug groups were more impulsive when answering the TOL test (although it didn’t affect their test scores).

In the MFF20 test, the MDMA users committed significantly more errors than the Non-Drug and Poly-Drug groups. This test also illustrates that the MDMA group carelessly answered without thinking and reaffirms that the MDMA group is more impulsive given that they committed more errors than the other two groups.

Additionally, the results of self-reports and behavioral measures indicated that MDMA users had an increase in impulsivity and venturesomeness compared to Non-Drug users. The data also showed that MDMA users exhibited an impulsive characteristic trait, with heavier MDMA users exhibiting even higher levels of impulsivity.

There are limitations to the Morgan study including a small sample size of participants and relying on self-reporting.

Sexual behaviors while using MDMA

A qualitative study conducted by McElrath in 2005 examined MDMA and the sexual behaviors displayed while on it. This test consisted of 98 face-to-face interviews with current and former MDMA users.

McElrath used several recruitment strategies to attract participants across Northern Ireland. These included:​
  • Placing posters in music shops and health centers.​
  • Advertising in a music magazine.​
  • Contacting diverse local organizations including STD (sexually transmitted disease) clinics, drug counseling centers, university unions, and LGBTQ programs.​
  • Volunteer Referral Program: participants would refer other participants to the study.​
  • Recruiter Referral program: recruiters would bring in participants for a small stipend.​
  • The interviewers also reached out to their own contacts.​
Of the total participants, 69% were male between 17-45 years old and the rest were female. Additionally, 16% of them identified as gay or bisexual.

The table below shows the breakdown of the drug use history of study participants. Note that 84% of participants consumed beer, lager, ale, or stout on a weekly basis and 32% used Cannabis on a daily basis.

McElrath-2005.jpg


McElrath’s qualitative research showed some interesting results: MDMA users had an increase in openness regarding sexual exploration which was defined as bisexuality or group sex. A 28 year old MDMA user expressed his feelings about sex on MDMA as, “You want to creatively indulge yourself in new forms of sex.”

Additionally, the 18-25-year-old MDMA users were more likely to engage in risky sex. Although “risky sex” is subjective, it was defined as having sex with multiple partners or sex without a condom.

Regarding overall arousal, there were mixed results: some MDMA users saw an increase while others had a decrease in sex drive. Those affected the most by the inability to ejaculate were male MDMA users of 25 years of age or younger. Some respondents (both male and female) reported not being aroused at all, but MDMA did elicit feelings of emotional intimacy, love, trust, and sensuality without sexuality. A young 22-year-old woman stated, “You feel loved up . . . I would have very little sexual encounters when I’m on E. In fact, none, because I’m more interested in the emotional aspects.”

It wasn’t just females who expressed feeling this way on MDMA. A 28-year-old male also had a similar perspective on sex with MDMA, “It wasn’t like the horn you get with speed, it was a lovey-lovey kind of thing.”

The limitations of this study are the small sample size, the data having been collected in the late 1990’s, and the subjectivity of “risky sex.” The study was also a purely qualitative and based on people’s subjective experiences. Furthermore, it is difficult to decipher how much of people’s experiences are due purely to MDMA as respondents also engaged with a variety of other drugs and alcohol on a monthly, weekly, and even daily basis. In addition, the study lacked data on what drugs were combined with MDMA during the experiences the participants shared in their interviews.

Conclusions

Overall, the data indicates that MDMA elicits positive and negative feelings from emotional intimacy and closeness to increased impulsivity and increased sexual risk with young adults. However, “sexual risk” is subjective across ages and cultures, especially with more non-traditional relationships, like polyamory, on the rise. Additionally, MDMA affects people differently with some having an increased sex drive while it is decreased for others.

More research is required to examine how MDMA specifically affects today’s population across races, gender identification, relationship styles, and neurodiversity.

 
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Free psychedelic help is just a call or text away

by Wesley Thoricatha | Sep 24, 2021

If you were to poll every psychedelic user in the United States and ask them if there was ever a time they were having a challenging trip and needed someone to talk to, or if they ever had an intense psychedelic experience that they had trouble integrating afterwards, my guess is that it would be well over 50%, perhaps even 75% or higher.

There are a lot of ways that people can find help in these situations, including trip sitters, psychedelic-friendly therapists, having a close friend you can call, or in-person offerings at festivals like Zendo tents, but none of these supports are available instantaneously, free, and agnostic to location and social circles.

Enter Fireside Project. Launched on April 14th of 2021, they provide free, confidential, peer-to-peer emotional support by phone and text message. Their Psychedelic Peer Support Line is a service people can call or text for immediate psychedelic support, whether they are in the throes of a difficult trip, supporting a friend having a difficult trip, having a hard time with the ripples of an intense prior journey, or just need someone to talk to. The line is staffed by volunteer psychedelic peer support specialists who are trained in providing a safe space and a helping hand to the psychonaut in need.

I sat down recently over Zoom with co-founders Hanifa Nayo Wahington and Joshua White to discuss the intention behind Fireside Project and how such a novel and important endeavor has fared since going out into the world.

Thanks so much for speaking with us Hanifa and Josh. Fireside Project was a long time in the making, and it finally launched this year. I’m curious, how has the launch been?

Hanifa: It’s been a huge learning experience. It’s been really phenomenal to launch a service that’s so unique and is driven by peer support that’s really helping people. To think on the very first shift of the support line, we were on shift to receive those first calls and texts, it was a really special feeling to feel that we are switching on to help all these people who need support and connection. The people who call us went from having no place to go to having a crew of volunteers ready to support and witness and be with them in this way. It feels really special to be part of something like that and know that we are helping people.

As founders of a startup project like this, we are wearing lots of different hats all the time on the backend. It can be stressful, but it’s a wonderful invitation to seek that balance.

Josh: I would say it has been a profoundly beautiful and extremely challenging experience. The current number of calls is around 800, which is a pretty large number, and when you think about what each of those calls meant, I think the impact is off the charts. We’re also very excited to be collaborating on a study with UC San Francisco and Dr. Rachel Yehuda at Mount Sinai’s Icahn School of Medicine that explores our risk reduction potential.

Following every conversation we send out post-call surveys to ask about our callers’ experience with us. About 70% of people say we helped them reduce their psychological distress. Around 50% say that they would have been physically or psychologically harmed but for their conversation. Around 30% said they would have gone to the ER or called 911 if they didn’t reach out to Fireside Project. Those are pretty staggering numbers, and they highlight for me the yin yang of our mission- to help people reduce risk and fulfil potential of their psychedelic experiences.

When you create a safe container for people, that reduces their risk. And, having that safe container provides people with the opportunity to turn towards their experience and see it for what it is, which is an unparalleled opportunity to learn about themselves and to fall in love with every part of themselves.

That’s beautiful and leads me to my next question. You mentioned harm reduction, and I know your volunteers go through a lot of training before taking calls, but how much are they taught to just hold space for people, versus helping them to lean into their experience, versus guiding that experience? Where do you fall on that whole spectrum of harm reduction, space holding, trip sitting, and guiding?

Hanifa: An overwhelming 92% of the folks who have responded to our surveys said that they felt cared for and witnessed, and I think that speaks really strongly to what our volunteers are doing and providing on the line.

Our training is really focused on peer support. While some of our volunteers do have other credentials, we are very clear that we do not provide medical support or therapy, we provide emotional peer support. Our training heavily leans on removing the ego, not being a guide, allowing space for the person to go through what their experiencing, to be encouraging, to normalize, to witness, all the while assessing if there is harm or risk, and to know the scope of services that we provide on the support line, or where they need to be transferred to a supervisor or emergency services or other services they may need.

We always encourage our trainees to hang their credentials at the door, and people really do that. We are looking for people who are excellent listeners and can speak really clearly and reflect back, because so much of the time people are really wanting to be heard. When you are reflecting back what you hear, the callers are learning things and able to reflect on what’s going on within them.

Josh: I think you expressed it perfectly, Hanifa. We are not guides. We are peers who are offering the benefit of our own lived experiences as a way of helping callers learn from the experiences they are going through. We have no agenda whatsoever other than to meet people where they are.

I also just want to say that we are not a substitute for calling 911 or for seeking medical care. If someone truly is in immediate danger, our job is to call emergency services, or if we don’t know their location, to encourage them to call emergency services. We’re also not a suicide hotline. If someone is intending to end their life by suicide, or has a plan or the means to do so, we are not a resource for them.

Everything you’ve shared resonates perfectly with my own experience in peer support. It’s critical to understand the distinction between peer support and other things.

I have to ask, the psychedelic space can be… strange… sometimes. With such high call volumes are you running into people with more serious mental issues, or folks that just take too much all the time, or who abuse your service?


Josh: We’ve been very fortunate to have almost no one use the line inappropriately, which is pretty amazing after 800 calls. People seem to really respect what we are trying to do, and reach out to us with an open heart and with so much gratitude.

One of the most common reactions that people have beyond just gratitude when they reach out to us, is incredulousness that something this beautiful could possibly exist. If you actually think about what this is, a service where you can call to process a psychedelic experience and speak to a stranger who is deeply passionate about supporting you on your journey, it’s a mind-boggling idea, and we get so much gratitude and almost shock that such a thing exists.

Hanifa: Early on there were a lot of people calling in and just saying “Is this real? I can really call this number?” And we’re like “Yep, so save this number in your phone in case you need us.”

That’s beautiful, and it echoes my own experience as an integration coach and being coached by others. The power of this disembodied benevolent helper that exists over the phone, who is not tied to your social circles, there’s no in-person complications, the connection is very clean and helpful. Being able to connect with someone who’s sole purpose is to simply be present and reflect with you, is just like you were saying Josh, such a profound thing to experience when you need it.

Josh: In the psychedelic space and in other spaces, I’m a big believer in this idea of abundance, that people should have multiple options and find which option works for them. And I think that’s true in the psychedelic support arena as well. I think there are people for whom a psychiatrist having an experience on the couch is the perfect experience for them. There may be others for whom maybe a guide or shaman in the Amazon is perfect. There are people for whom speaking to their friends is the perfect opportunity. We see ourselves as one of many options that are available to people.

Diversity is resilience!

Hanifa: Absolutely, and with that I would just say also that we hold this work really highly and always moving towards more liberation and more equity. We try to put those words into action. Sometimes people don’t have the resources to afford an integration coach or a therapist, and I think over half of our calls have been people wanting help integrating a previous experience. Everyone should have access to that kind of service. We are not a replacement for clinicians or psychotherapists or other professionals, but we are part of the net to make sure nobody falls through. We need to ensure access, especially as this psychedelic industry grows and continues to bloom and explode right now.

Indeed. I’ve seen in your materials that Fireside is “culturally sensitive.” What does that mean and look like in practice?

Hanifa: In the future there will be an opportunity for integration calls for people who are from marginalized communities, black, indigenous, veterans, trans, etc. If someone wants to have integration calls with others from that community, we want to provide that. There’s a depth of safety and expression and understanding that folks can have with people who have shared identities, so we want to be able to offer that side of integration support, starting with those I mentioned and growing to support other communities as well in the future.

We also understand that doing inner work is super important when we talk about removing our egos, or looking at and investigating where some of our cultural biases lie. We try to create a culture of belonging, and invite our volunteers and our staff to be engaged in this process of inner work as a vital part of our service. Although it’s not a magic wand that makes anyone 100% attuned to all sorts of cultural identities, it’s a step in the right direction, and it’s a core part of how we operate.

We are very grateful to Josh and Hanifa for taking the time to speak with us. Check out Fireside Project on the web and download their app, and if you find yourself needing psychedelic support, call or text 62-FIRESIDE, or 623-473-7433. Currently, they are open Thursday to Sunday, from 3:00 p.m. to 3:00 a.m. PST and Monday from 3:00p.m. to 7:00 p.m. PST. Starting on October 10, 2021, the line will be open every day from 3:00 p.m. to 3:00 a.m. PST.

*From the article here :
 
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Rapid, mobile test kits for MDMA, LSD, and Psilocybin

by David Carpenter | LUCID NEWS | 25 Aug 2021

n a world’s first, German startup Miraculix has launched a simple and affordable assortment of at-home testing kits for assessing the potency of various psychoactive drugs. Called QTests, they provide rapid analysis mobile kits designed to measure concentrations of MDMA, LSD, and psilocybin.

While currently a host of drug testing “reagent” products are available on the market to provide qualitative data on desired substances — typically used to reveal the presence of misrepresented substances or potentially harmful adulterants — Miraculix’s kit is the first to offer quantitative rapid results within 10 to 30 minutes. It’s a significant innovation, considering many of the substances people desire to test are illegal and, of course, are not subject to standards and guidelines that adhere to consistent dosing. It’s a pervasive problem. Active ingredients in psychedelic compounds vary wildly, which makes the accurate gauging of potency both costly and time-consuming.

Results of Miraculix’s Qtests have proven to be remarkably reliable, close to analysis done by lab-level high-performance liquid chromatography (HPLC) processes, which are considered the industry standard for chemical analysis in research, manufacturing, and medical applications. Miraculix states that results are not far off HPLC testing, coming within a 10 percent deviation range.

Dr. Felix Blei, microbiologist and CEO of Miraculix, came to the idea for potency kits following extensive research dedicated to psilocybin-containing mushrooms. While earning his PhD in microbiology at Germany’s Hans Knöll Institute, he published a number of studies on the biochemistry of psilocybin production in mushrooms. His research with Psilocybe mushrooms also showed him the substantial difference in potency levels between what might appear to be the same type of mushroom. Significant variations in psilocybin amounts, says Blei, are seen not just from species to species but from batch to batch in the same species grown in similar conditions.

Following his doctoral thesis, he set to work designing an innovative rapid test method for determining the concentration of psilocybin in mushrooms that would be simple and mobile. His invention involves employing a color complex — similar to test strips used to balance pool water chemicals — to assess potency using an accompanied evaluation scale.

After teaming up with colleagues Roxana Preuß and Frank Junger (currently chief strategy officer and chief content officer at Miraculix, respectively), the trio recognized their unique business opportunity. Riding the wave of public interest in psychotropic drugs — reinforced by research institutions like Johns Hopkins and Imperial College London studying psilocybin therapy treatments — the three entrepreneurs felt their Qtests would be a hit in places that had passed laws decriminalizing psychedelic plants, such as Denver and Oakland.

In 2021, the partners embarked on a crowdfunding campaign to test the waters. Their Start Next page reads: “Imagine you walk into a bar and read on the menu: ‘Alcohol.’ What effect will a glass of alcohol have on you? Without any information about the content of the alcohol, everything from a slight buzz to a coma is possible. However, this is exactly the situation that currently exists worldwide for psychedelic substances. We want to change this and provide a scientifically validated product in an uncontrolled and unsafe environment to increase awareness of concentration and composition and to avoid life-threatening situations.”

That month-long crowdfunding effort netted them just under $19,000 US — but more importantly demonstrated a demand for their kits. It also brought them enough cash, says Blei, to purchase a fume hood, the basis for their laboratory in Jena, Germany. While the team has since received many investor inquiries, they have not accepted any of the lucrative offers. “We intend to build up a family business with our company that exists sustainably and in the long term,” says Miraculix’s compliance officer, Junger. “We are not interested in quick money from investors with an exit strategy, but are looking for strategic partners who are interested in long-term cooperation.”

Now they’re presently off and running attracting supporters, including a partnership with the Beckley Foundation, established in 1998 by longtime psychedelic advocate Lady Amanda Feilding, whose organization is dedicated to cutting-edge scientific research in the field of psychedelics and a commitment to harm reduction and global drug reform. Miraculix will also work with Mimosa Therapeutics, an organization co-founded by Feilding in 2020, whose mission, according to the company website, is to “help people access the best, healthiest version of themselves through the careful and intentional use of entheogens.”

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“We share the same values and goals, so we’re excited to have found a valuable partner in this area,” says Junger. “They have provided support during the development of our testing kits and will be involved in their distribution in Europe. As a result of our partnership, within Europe our QTests will feature the branding of both Miraculix and the Beckley Foundation.”

Final adjustments are currently being made to a smartphone app that will provide more precise evaluation via color scale. “The basic principle of the smartphone app is to be a support for the user in evaluation and make it more accurate,” says Junger. “A photo of the sample should be taken after the staining is completed and the app will determine the correct value of the agent. This will then make the app a cost effective and mobile small spectral analysis.”

Kits are currently only available in the U.S. and Europe through Miraculix’s website and are relatively inexpensive — $17.50 US for psilocybin/LSD tests kits and $29 US for MDMA kits. A psilocybin QTest requires crushing 150mg of dried mushroom material and mixing well ; cutting half of an LSD blotter; and evenly scraping off 50mg from an MDMA pill.

*From the article here :
 
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Gabapentin helped my chronic pain – but it's also killing people*

by Abi Palmer | Vice | 1 Apr 2022

At the end of my first week using gabapentin, I awoke butt naked, face down, in a diamanté choker. The night before, I’d been celebrating a friend’s birthday in the secret lounge above a wood-panelled strip club in east London. The party was full of ladies holding apples and wrapped in live snakes. “It feels like a party one of the Kennedys would have been photographed at,” I texted my boyfriend.

While a lot was unusual about the evening, strangest of all was the fact I had been in attendance. For the entire year before, I’d barely been able to function, crashing into out-of-body experience and paralysis with so much pain and fatigue that I had to drop out of university to attend a physical rehabilitation programme. The entire act of attending a party, and casually falling asleep afterwards, was alien to me.

I was prescribed gabapentin in 2013, as an inpatient at a sleep clinic. My consultant observed that I was waking 17 times an hour and diagnosed neuropathic pain, a side effect of my many other musculoskeletal conditions. Apparently the hallucinations and paralysis I was experiencing are common side effects of extreme sleep deprivation. The consultant told me that the medication was usually used to treat epilepsy and that I was being offered an off-label usage, emphasising that it might not work – and if it did, we wouldn’t know why.

Within weeks of taking gabapentin, my hallucinations and paralysis had settled down. A strange side effect was that I stopped having to stretch my legs excessively before bed. Previously, I’d required between one to three hours of physiotherapy to ease the cramping.

Beyond partying, by the end of 2013 my newfound energy allowed me to return to university for two more years. But I also learned that gabapentin was not a drug to be messed with. The first time I missed a dose, I woke at 4AM, sweating profusely, hallucinating little spiders running over my skin. To avoid withdrawal, I made sure I always had several additional months’ worth of prescription in my cupboard. During uni, when I found my fatigue increasing, I wondered if it might be the old restless legs playing up again. A doctor gave the OK for me to increase my gabapentin dosage to 900mg from 600mg. After all, I’d initially been told it was harmless.

Shayla Love’s 2019 VICE article about the gabapentinoid scandal sent ripples of shock through the sick and disabled community. “GABAPENTIN IS A PLACEBO AND IT’S DANGEROUS,” one of my friends posted on Facebook. “Be careful out there.”

The article details the manner in which gabapentinoids – anticonvulsant medications such as pregabalin and gabapentin – had been aggressively marketed as an off-label treatment for multiple hard-to-treat and poorly researched conditions, including chronic pain, anxiety and phantom limb syndrome. In most cases, there was little clinical evidence to suggest that the drugs provided any medical advantage. In some trials, they were less effective than placebo. Worse still, they had been connected to higher risk of death, suicidality and opioid misuse (gabapentinoids proved popular among heroin users, due to their ability to increase highs and make the lows more manageable).

Meanwhile, deaths in the UK attributed to gabapentinoids had increased dramatically – particularly among prison populations – jumping from tens to hundreds in the six years between 2012 and 2018. Just a few months before I was aware of any potential harm, they had been urgently upgraded to a controlled class 3 substance in the UK, meaning tighter prescription regulations. NHS guidance stated in bold: “It is not helpful or appropriate for anyone to stockpile these medications.”

In the wake of this news, I found myself questioning my use of gabapentin. Was my initial energy due to finally sleeping through the night, or was it simply the drug’s euphoric side effects? It was possible, but my late-night googling also suggested that gabapentinoids might have a positive impact on my particular brand of nerve pain, and that alternative treatment options were limited. It seemed to have helped – it had changed my life – and I didn’t know what else to do.

The medical community was also reacting to the drug’s updated profile. A new GP approached my prescription with an unexpected hostility. “If you want to keep on taking this medication, we’re not the surgery for you,” she said. When I explained the basis for my gabapentin use, she rolled her eyes. “It’s a prison drug. For all I know, you could be selling your medication to prisons.”

Rather than address the issue I was there to discuss, I ended up spending the best part of my appointment attempting to persuade her that I was a responsible patient, followed by two panicked weeks where I was unsure whether my repeat prescriptions would continue. Eventually, I was able to return to the surgery and discuss my situation with a more empathetic doctor, who honoured my prescription immediately and helped me consider a longer-term pain management strategy.

The gabapentinoid scandal is fuelled by a history of chronic pain patients being underserved. A 2017 New England Journal of Medicine article suggests that the increased prescription of gabapentinoids is a direct response to the opioid epidemic, with practitioners looking for a fast and effective alternative solution to chronic pain conditions, which can be complex and need time to manage. Chronic pain patients are often reminded that there’s no magic pill to completely cure a chronic pain condition, but it doesn’t feel like the medical system has caught up with this fact, or really addressed how it might change its procedures.

Recently, new NICE guidelines were issued to propose that doctors offer absolutely no pain relief medication to patients with chronic pain, instead advising treatments such as exercise, CBT and acupuncture. The guidance focuses on the risk of addiction, even with medications such as paracetamol and aspirin. Whilst these guidelines primarily focus on chronic pain without an “underlying condition,” it’s worth acknowledging how long it takes for pain to be taken seriously by a medical professional, how little funding or research there is into chronic pain, and how ill-equipped medical services are to deal with ongoing conditions.

Navigating pain is becoming an increasingly traumatic minefield, with doctors “correcting” their colleagues’ prescription choices in ways that punish the patient. In the US, 70 percent of respondents to a survey by Pain News Network reported that doctors had reduced or simply cut off their prescriptions, with reports of no withdrawal plan being offered. In response to the UK’s new NICE guidelines, a statement issued by the Faculty of Pain Medicine lists the risk of “the potential withdrawal of useful medications from patients by GPs” as one of their primary concerns.

Within a decade, gabapentinoid users like myself have had to adjust from having cupboards overflowing with too much medication, to being treated with suspicion and threat. No symptoms are improved by this experience of panic, stress and stigma.

The constant fear of having our bodies policed by medical professionals under constantly changing guidelines leads to so much mistrust in the patient/doctor relationship that we are more likely to end up making risky or unsafe decisions for ourselves with little oversight. Although gabapentinoids require a prescription, patients who are frantic and at risk of withdrawal are more likely to turn to fake and illegal versions, which are easily accessed online.

For my part, I’m well aware that gabapentin is far from a perfect drug. My brain is often very foggy, and it’s unclear if this is due to my strange body or the well-charted side effects of the medication. I am uncomfortable with my dependency and terrified of the consequences of stopping. The GP who threatened to turn me away from her surgery did not have a positive impact on my gabapentin usage, but requesting my prescription each month now provokes a spiral of anxiety, guilt and shame. I also still don’t really understand my alternative options.

Instead of the substantial medical research and funding we deserve, we are faced with a reality where every medical interaction we have is at the mercy of the crimes that came before us: a marketing scandal, overprescription, pills in lieu of adequate trauma therapy, all the way back to the still-too-common accusation that pain is a symptom of hysteria.

If medical practitioners want to help their chronic patients, and avoid becoming part of the next wave of scandal and repercussions, it is important to attempt to remove their biases: to offer patients a space where they are able to speak honestly about their present needs and experiences, time to review medication, ask questions and explore alternatives. In the long run, better funding for research and long-term treatment options is essential, but right now, the best way for doctors to support their chronically ill patients is through collaboration and dialogue: to offer them trust, and seek to earn it.

*From the article here :
 
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Harm Reduction in Psychedelic Research

by Abigail Calder, MSc | Psychedelic Scvience Review | 16 Jul 2021

Psychedelic science operates with an abundance of caution.

Psychedelics are not tame substances. Their therapeutic benefits are becoming better known, but they are also perfectly capable of mayhem. This leaves sober-minded people with a dilemma: what do we do with drugs famously capable of sending people to both heaven and hell?

If you’re a scientist, you come up with a long list of safety precautions to keep hell at bay. Most of the scientific knowledge we have about psychedelics comes from clinical trials, perhaps the safest possible setting in which to take them. As something of an insider, I hope I can help people appreciate the depth of the precautions we take in research, as well as what that means for interpreting study results and implementing psychedelic therapy in different settings. As with rock climbing, new cars, and trampoline parks, a lot of thought goes into safety behind the scenes.

First, a basic question: what are safety precautions trying to prevent? In essence, three things. The first and easiest is a dangerous physical reaction to the drug, which with psychedelics is exceedingly rare; one influential researcher called LSD and psilocybinfreakishly safe” when it comes to physical toxicity. The second is an acute negative reaction – a “bad trip” – especially one that is either so strong or so prolonged that it is not likely to turn beneficial. The third is the most dire: a sustained negative reaction, at worst a prolonged psychological crisis. Though also incredibly rare, the fact that this is theoretically possible means we take it seriously.

Not everyone should take psychedelics

Safety begins with the belief that some people, at some points in their lives, should not take psychedelics. This is obviously not a radical idea; most people have at least heard that those with schizophrenia should not tempt hallucinogenic fate. But researchers also typically exclude participants with any history of psychotic episodes, bipolar disorder, or personality disorders, as well as anyone with a close relative suffering from schizophrenia (it has a strong genetic component). In studies with healthy volunteers, any psychological disorder at all may be disqualifying, as is the intake of psychoactive medications.

Beyond a psychiatric history, some studies require participants to pass a general medical screening, which particularly looks for abnormalities in the cardiovascular system (psychedelics modestly elevate heart rate and blood pressure). Pregnant women are always out, and frequent psychedelic fliers usually are. And though less common, researchers may also look for certain personality traits in their participants. In general, the ideal study participant is emotionally stable and not averse to novelty; the kind of person who won’t scream at the guy who cuts them off in traffic on their way to a new sushi restaurant. A few studies have even screened out people who score high in neuroticism, a core personality trait that describes someone’s predisposition to experience negative emotions and may predispose people to unpleasant trips.

Participants aren’t the only ones to get this extreme vetting. The professionals who are responsible for safety, whether they be therapists, guides, or unassuming grad students, must have particular characteristics as well. Participants in studies are always supervised by trained professionals, often a pair of psychologists, who are not only knowledgeable about psychedelics and altered states but also highly empathetic and able to create a trusting atmosphere with a participant in a relatively short period of time. Though they often have formal training, their interpersonal abilities and knowledge of the psychedelic state are widely considered more important than a degree.

Preparing person, space, and substance

Before taking any drugs, participants in clinical trials undergo extensive preparation for the psychedelic experience. The aforementioned trained guides take time to get to know the participants and build trust, and to educate them on what they might experience in a psychedelic session. They also advise people on the possibility of difficult experiences and how to handle them. This preparation can take up many hours spread out over several weeks so that by the end of it, the participant has asked all of their questions and ideally feels absolutely safe with those supervising them.

At least some of these preliminary appointments take place in the psychedelic session room. Even in clinics, the sterile hospital look is switched out for a comfy, living room-like aesthetic. Couches, pillows, and serene decorations are common, as is soft lighting and the occasional mushroom statue. This is a private, safe place to give up control, and it greatly reduces the risk that unexpected events might intrude on the trip.

Last but not least, the drug itself is prepared beforehand: a moderate to high dose of a pure, top-quality substance, often from a government-sanctioned lab. This takes the risk of contaminants and inaccurate dosing out of the equation.

An ever-present guide

Before the session starts, many of the risk factors for negative reactions have already been greatly reduced. Once the trip begins, medical personnel are available in case of emergency and at least one guide is always present in the room while participants are under the influence. These guides are able to respond in case of distress and nip a potential bad trip in the bud, as well as stop participants from doing anything harmful (or embarrassing). The trusting relationship they have built greatly enhances their ability to do this.

In case participants start to feel distressed, guides are trained to radiate a sense of empathetic calm, not only with comforting words but also with their tone and body language. They are the anchor to reality, and their calm demeanor in crisis can communicate to participants that even a frightening experience is not really going to hurt them. Music is also almost universally used in psychedelic sessions, and it can be instrumental (sorry) in helping participants feel safe and calm. Even an escalating negative reaction can often be impeded with the right words or music, a comforting touch, and a reminder that the participant is safe and their experience is transient.

As a last resort, guides can administer an antidote (usually a benzodiazepine) to weaken or end the trip, although this is rarely necessary. Indeed, the fact that participants know they can get off the ride makes them less likely to want to. At the root of many bad trips is a fear of losing control, and the presence of an antidote gives people a sense of control even if they never use it.

Integration

The final cornerstone of psychedelic safety is integration or discussing and processing the experience together with the guides after it is over. Often, integration also means taking any perceived lessons from the experience and applying them to one’s life in hopes of improving well-being. Participants benefit from at least one integration session, but the integration period may be longer if needed and feasible.

Integration’s primary value as a safety measure is checking for persistent negative effects that might appear after a psychedelic experience, and if need be, preventing them from getting worse. Especially if the experience was challenging, therapists and guides consider it highly important to support participants afterwards and give them space to discuss these strange and potentially life-changing experiences. They specifically ask whether any negative effects have lingered, including persistent perceptual changes (e.g. flashbacks), dissociative symptoms, or signs of psychosis, and can make sure participants get the help they need for such symptoms.

Credible reports of negative effects after psychedelic use in recreational settings exist, although they are still relatively rare. But in studies with modern safety standards – so, in the past 25 years – none of these long-term reactions have been observed: a powerful testament to the effectiveness of safety procedures in psychedelic research.

What about other settings?

Clearly, scientists do a lot for safety. It may also be clear that many of their safeguards are hard to implement in other settings. Does this mean that other environments are more dangerous?

To answer this question, let’s review how scientists prevent adverse reactions in trials. Studies take place in a private, safe environment, with clean substances and moderate doses, screened participants, sufficient preparation, competent guides, and integration afterwards. Any setting which has this basic profile is probably about as safe as a clinical trial. Religious psychedelic use within many indigenous communities checks these boxes, as does regulated psychedelic therapy outside of research (e.g. in compassionate use exemptions). Other settings are riskier to the extent that they neglect these basic safeguards, with more neglect probably meaning higher risk.

This does not mean that people are guaranteed a horror trip in less controlled settings. It rather means that if one starts to build, there are fewer things that can stop or transform it, and it may be more likely to negatively affect the person after it’s over. The precise risk of a malignant bad trip is difficult to judge. On the one hand, psychedelics are still relatively safe and prolonged adverse reactions are not common. On the other, many recreational users report having had difficult experiences that at least temporarily exceeded their coping mechanisms or affected them negatively for some time afterwards.

People can consider this when evaluating retreats, clinics, and other settings in which they might plan on taking psychedelics. If guests are not well-screened, if the preparation is minimal, if the session monitors are not well-trained or numerous enough to handle a crisis, and if there is little follow-up after the experience, one cannot assume the same level of safety seen in studies. The acceptable level of risk is a personal decision, but it should be made with the best information.

Judging the risks of psychedelics is a balancing act between avoiding an unrealistic account of their dangers, yet taking rare adverse effects seriously. The clear success of clinical trials in ensuring participant safety shows that it is possible to reap the benefits of psychedelics while reducing the risk of severe adverse effects, especially prolonged ones, to nearly zero. Understanding how scientists manage this can improve people’s ability to judge the safety of different settings and contribute to a culture of safety around the use of these powerful substances.

Abigail is a doctoral candidate in medical neuroscience at the University of Fribourg, Switzerland. Her research concerns various effects of LSD on the brain in healthy people, including both acute drug effects and enduring neuroplastic changes.

*From the article here :
 
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MDMA and LSD drug testing kits that could save your life

Danielle Simone Brand | Double Blind | 10 April 2020

Everything you should know about 'the best MDMA and LSD test kits on the market.'

Drug testing, sometimes called drug checking, is an essential harm reduction tactic to ensure that a substance is truly what you think it is, and not adulterated by potentially toxic chemicals that could cause an unpleasant or fatal reaction.

The best thing about drug checking is that you don’t need a whole chemistry lab to do it! In fact, you can test your drugs in the privacy of your own home with a drug checking kit such as for MDMA or LSD. Indeed, drug checking is easy, requiring only a few reagents (liquid testers) to ascertain whether your substance is pure, or contains other elements.

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Alexander Shulgin

MDMA

MDMA first surfaced as a psychotherapeutic aid in the 1970s. Though analogs of the drug had been synthesized earlier, most sources credit chemist Alexander Shulgin for discovering the formula, along with psychotherapist Leo Zeff for helping bring its psychotherapeutic properties to light. Because of MDMA’s particular euphoric and empathic influence on the user, it showed promise in therapeutic settings for healing trauma and promoting personal and spiritual growth. In the 1970s and 1980s, early adopters caught word of the molecule’s recreational uses, and by 1985 MDMA was listed in the U.S. as a Schedule I drug.

Effects of MDMA

MDMA causes your serotonin neurons in the brain to release larger amounts of serotonin. It also causes the release of dopamine neurotransmitters, as well as oxytocin and prolactin hormones. This effect can lead to feelings of euphoria, greater willingness to communicate, decreased fear, increased connection to others, and feelings of love or empathy.

MDMA moreover decreases activity in the amygdala, which is where memories are stored. This effect, coupled with those listed above, is why MDMA has been so useful in treating PTSD, which the nonprofit MAPS is currently investigating. In fact, MDMA for PTSD has been placed on the FDA fast track to become an approved medication in psychedelic-assisted psychotherapy early this decade. MAPS is currently in the third and final phase of FDA-approved research.

On the physical side, MDMA may cause loss of appetite, shivering, feelings of restlessness, or even feelings of warmth. It’s important to note that MDMA should not be taken on a regular basis, as for some, there is a comedown, which entails the time it takes for your brain to replenish its serotonin.

How long does MDMA last?

The total duration of MDMA is about three to six hours, with an initial onset of 20 to 90 minutes.

What does MDMA look like?

MDMA often comes as a white or light brown crystalline powder, contained in a clear capsule. Sometimes it may come as light brown rocks. In other cases, especially if you’re taking ecstasy (which may contain other components beyond MDMA), it comes as a pressed pill, which may be a variety of colors and feature a design.

Why you should test your MDMA

According to Emanuel Sferios, founder of DanceSafe, MDMA prohibition has created 'the most adulterated market in history.' Over the last few decades, hundreds of drugs have been sold as ecstasy or molly that contain little to no MDMA. Of the numerous counterfeit drugs DanceSafe has tested, dangerous cathinones (a.k.a. “bath salts”) and meth surface frequently. While these MDMA counterfeits may yield psychoactive effects, they won’t likely feel as pleasurable or expected as those of MDMA. And, in the wrong doses, they could also be fatal.

Sferios was first introduced to MDMA as an informal therapy that helped him process difficult experiences from childhood. About a decade later, a friend brought MDMA back to his attention as a party drug—a use that resonated with Sferios, given its ability to boost energy, euphoria, and social connection. “I was blown away when I went to my first rave in Oakland—by how beautiful the culture was,” he tells DoubleBlind, citing the diverse demographics and peaceful vibe he found. By that time, MDMA had become the most sought-after rave drug and prohibition was well underway; the substance that Sferios had known to be both fun and therapeutic was being widely publicized as dangerous.

“No one is saying that MDMA use carries no risk,” Sferios says. Consumers of an unadulterated version of the drug can suffer adverse effects, and even die, if they take too large of a dose, or drink too much or too little water during the roll. But the risks grow when those who believe they’ve taken MDMA have actually taken meth, PMA, cathinones, or something else entirely. To be ultra-clear: It’s counterfeiting—which results from prohibition, and an unsupervised black market—that poses the biggest risk; in the right doses, and with a thoughtful set and setting, taking MDMA is a fun, transcendent, and even therapeutic experience for many people.

The MDMA-associated deaths in the 90s and the subsequent media villainization of the drug prompted Sferios to found DanceSafe in 1998. The organization’s mission is to educate consumers of club drugs and to encourage and facilitate testing for risky counterfeits. Altogether, DanceSafe’s four staff members and hundreds of volunteers practice a philosophy known as harm-reduction that’s gained traction in Europe but has yet to receive widespread credit in the U.S. The idea behind harm reduction is simple: to reduce the negative consequences associated with drug use.

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MDMA test kit

Of the two testing methods used by DanceSafe, one employs infrared spectroscopy, which can yield detailed information about a molecule. But testing by means of spectroscopy involves funding and staff hours to utilize the machine at festivals.

The other method is much more cost effective and can be done at home by anyone. DanceSafe offers testing kits for MDMA, LSD, and a number of other compounds, both online and at festivals. The point of the MDMA and LSD testing kits is to tell you whether the primary ingredient is what you intended to consume.

Testing is critical, says Sferios, because you can’t reliably identify MDMA or LSD by look, smell, or taste.

MDMA testing at a glance

- Common MDMA counterfeits: PMA and PMMA (two compounds producing similar effects to MDMA but with more toxicity), cathinones (aka “bath salts”), and methamphetamine

- Risks of consuming counterfeits include: hypertension, elevated temperature, difficulty breathing, and death

- Most counterfeits don’t contain any MDMA

- Roughly 80-90 percent of what’s sold today as MDMA is authentic; as recently as 2015, that figure was closer to 30 percent

- Fentanyl, the dangerous synthetic opioid, hasn’t cropped up on the MDMA market yet, though some observers think it could soon

- DanceSafe MDMA kits contain one free fentanyl test strip; additional fentanyl strips can be purchased separately*

- MDMA test kits include three reagents, or liquids that turn color in the presence of particular chemicals: Marquis, Simons, and Froehde

- Used together, these reagents can reliably determine whether MDMA is the main ingredient in a pill—though they can’t indicate absolute purity

- Follow all steps in the kit. Read the testing kit instructions in advance, and be sure you’re sober when you test.

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Albert Hofmann

LSD

LSD is a 'classic' psychedelic that was initially synthesized in 1938 by chemist Albert Hofmann, who was working for the Swiss company Sandoz Pharmaceuticals. Hofmann had intended for it to be used as a respiratory and circulatory stimulant, without having realized its psychoactive properties. It took him another six years to rediscover and appreciate its psychedelic qualities: First he accidentally ingested a little bit of LSD on April 16, 1943, and three days later intentionally tried it on April 19 and wrote a bicycle home, high on LSD. This day is now celebrated as the holiday Bicycle Day.

Effects of LSD

LSD binds to several 5-Hydroxytryptamine (5-HT) receptors in the brain, which causes an excess of serotonin in the synaptic cleft between neurons. LSD can alter perception, mood, and cognitive processes by acting on the serotonergic system. It also acts on the dopaminergic system, which affects processes like learning, reward systems, and motivation. The increased levels of dopamine and serotonin can make LSD feel energetic and provide an extroverted experience.

LSD can enhance the imagination and senses, stimulate thoughts, cause feelings of euphoria, universal connection, or on the flip side anxiety or paranoia, and can produce hallucinations. As a classic psychedelic, LSD in high enough doses may cause temporary ego dissolution that can result in mystical experiences and a sense of transcendence.

Prior to it being outlawed by the Nixon administration under the Controlled Substances Act, LSD was used as a powerful tool in psychotherapy. Today, researchers are returning to LSD as a tool for addiction treatment, as well as for anxiety, depression, or other conditions.

How long does LSD last?

The effects of LSD can last anywhere from eight to 12 hours, or in some cases even longer.

What does LSD look like?

Most often, LSD comes in the form of a liquid, or as a tab (upon which that liquid has been dispersed with a dropper), torn from a piece of perforated paper. In other cases, LSD may appear in the form of tablets, capsules, or gelatin squares.

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Testing LSD

The LSD market looks a little different from MDMA. Until recently, LSD counterfeits weren’t considered especially risky. But the influx of a class of drugs known as NBOMes about ten years ago changed that. Variants of NBOMe, which stands for N-benzyl methoxy, simultaneously thicken the blood and constrict vessels, potentially causing heart attacks, renal failure, or stroke. Fentanyl and analogs like carfentanyl also appear as counterfeits or adulterants in the LSD market today.

While Sferios notes that in recent years, the illicit markets have, to some degree, cleaned themselves up (with certain distributors now refusing to sell fentanyl or fentanyl analogs for instance), a staggering array of new, illicit compounds and research chemicals hit the market every year. Besides prohibition and growing demand, factors contributing to the illicit market today include the rise of the dark web and the cover of anonymity provided by cryptocurrencies.

When it comes to the intentions of illicit manufacturers and dealers, Rachel Clark, who works in communications and development with DanceSafe, gives these folks the benefit of the doubt. “The purpose [of selling counterfeit drugs] is not to kill people,” she tells DoubleBlind. "Instead, some manufacturers and dealers are likely unaware of the ins and outs of new molecules or research chemicals which, in some cases, mimic the effects of the better-known drugs, but carry more risks. Some may not even know the origins of what they’re selling.”

Testing LSD at a glance

- The last decade has seen a proliferation of drugs sold on blotter paper resembling LSD, but with high levels of toxicity

- NBOMes mimic the effects of LSD but carry significantly more risk; the analog known as 25i NBOMe is highly toxic

- Between 2013 and 2016, roughly one person a month died after ingesting an NBOMe sold as LSD; fortunately, the rate has since slowed

- Carfentanyl, an extremely potent fentanyl analogue, is—like LSD—active at the microgram level. Because it’s sometimes sold on blotter paper, confusion between the two drugs can arise.*

- The DO series of drugs, including DOB and DOC, are psychedelics, sometimes sold as LSD, that typically have longer lasting effects and are not well-documented for safety

- LSD test kits are simpler than those for MDMA: Ehrlich’s reagent turns purple in the presence of LSD or closely related drugs. According to Sferios, “If it turns purple it’s pretty much going to be LSD, or a prodrug of LSD like 1P-LSD or ALD-52.”

Drug testing and the law

Law enforcement and harm reduction efforts have a checkered relationship. For instance, about half of U.S. states have laws on the books criminalizing testing agents and paraphernalia. But when it comes to testing, these laws are rarely enforced. To Sferios’ knowledge, no one with DanceSafe—staff, volunteer, or festival-goer—has ever been arrested for participating in drug testing. In some cases, DanceSafe works under amnesty agreements with local law enforcement—which makes sense from a humane standpoint, considering the fact that fewer deaths and injuries occur when testing and other harm-reduction strategies are at play.

The psychedelics renaissance and drug testing

There are many reasons for the comeback of psychedelics. They’re a productivity hack in small doses and a socially-bonding tool made for dancing. They also help quench the yearning many of us have to understand the self in relation to the whole—to see past artifice and step into another way of being. Because of psychedelics’ potential therapeutic uses for PTSD in particular, Sferios theorizes that the current renaissance is a means of collective healing from 9/11—and today, in the midst of the Covid crisis, we may see even more relevance for the therapeutic uses of psychedelics.

But, as long as prohibition endures, the counterfeiting problem will remain. “The more successful the Drug War is at cracking down on real MDMA and LSD,” said Sferios, “the more motivation there’ll be for developing and selling counterfeits.”

 
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Preventing Sexual Abuse in Psychedelic Therapy

by Evan Lewis-Healey | PSYCHEDELIC SPOTLIGHT | 15 Oct 2021

Recent study interviews 23 underground psychedelic therapy practitioners about the biggest ethical issues and boundary challenges they face while sharing such an intimate space with clients.​

Clinical trials of psychedelic therapy are hugely promising in the battle against mental health issues. However, recent research has highlighted that there are a myriad of ethical issues associated with the therapeutic use of psychedelics.

One of the most focal, and potentially rife, issues identified in a study published in the Journal of Humanistic Psychology involves sexual abuse between psychedelic therapists and clients. The researchers of this paper hope to illuminate ways in which these cases can be prevented as psychedelic therapy moves into the mainstream.​

Vulnerability and power

Psychedelic therapy itself, whether that be MDMA-assisted or psilocybin-assisted, leads us into sketchy ethical territory. There is a huge imbalance of power between therapist and client during psychedelic sessions; patients already have existing mental health issues, which is coupled with the often incapacitating effects of a high dose of a psychedelic.

This has led to some psychedelic therapists exploiting their patients’ vulnerability. There have been reports of sexual abuse in psychedelic therapy as recently as 2018, in an FDA phase III trial of MDMA for PTSD.

These issues are not isolated to psychedelic therapy. Sexual abuse cases are shockingly high in traditional talk therapies (around 7-12 percent). But this begs the question: If cases are this high in traditional therapies, how high could it be if and when psychedelic therapies move to the mainstream? And how can these sexual abuse cases be prevented?​

Underground interviews

This is the question on the lips of the authors of the current paper. To try and answer this question, the researchers interviewed 23 underground psychedelic therapists. The authors and therapists explored how ethical issues may arise in psychedelic therapy, and ways in which they can be prevented.

When interviewed, some therapists highlighted that the lengthy sessions, coupled with the therapeutic use of touch can lead to a level of intimacy not seen in classic talk therapy. The authors write, “Many therapists felt that this intimacy is part of what is therapeutic about psychedelic work. However, they noted that it has also led to ethical boundary challenges, often by inadvertently encouraging romantic feelings in the client.”

This may also be doubly challenging during MDMA-assisted therapy. The effects of MDMA can include heightened empathy, sexual arousal, and increased intimacy, which may further blur the boundaries for a patient during the session. Again, this highlights the patient’s extreme vulnerability, which always needs to be at the forefront of a therapist’s mind.

One of the main preventative issues around psychedelic therapy was to do with consent. One of the therapists discussed their two-stage process of consent surrounding touch, “Ahead of time, before we even get into the experiential session, I ask, ‘Is it OK if I work with your body or touch you.’ If not, then I will not touch them. Even if they said yes, in the journey itself, I’ll ask them first, ‘Can I put my hand on your shoulder, your chest, your belly?’”

Other therapists highlighted the need to be supervised when conducting psychedelic therapy. Having two therapists present, one man and one woman, should form a gold standard practice in psychedelic therapy, and hopefully prevent as many sexual transgressions from occurring.​

Psychedelic Therapy moving forward

The emerging profession is, undoubtedly, a minefield.

The power imbalance between therapist and patient is already huge, and only gets bigger when psychedelic substances become involved. The authors of the paper highlight this by saying that psychedelic therapy is “rife with unique ethical challenges that require self-awareness and practical approaches that go beyond the training of a conventional psychologist.”

However, this research represents a step in the right direction. Hopefully organizations pick this research up, and form more stringent guidelines for psychedelic practitioners.

https://psychedelicspotlight.com/preventing-sexual-abuse-in-psychedelic-therapy/
 
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Addressing Abuse in Psychedelic Spaces
by Joe Moore | Psychedelics Today | 28 Oct 2021

Some commentary on recent events and long-standing issues in psychedelia.

The psychedelic world had a major shake-up in the past few weeks. A few popular teachers in the space had some pretty serious accusations leveled at them by Will Hall, who has previously been on our podcast here and here.

You can read Will’s article on Mad in America here. He had further things to say in this article on Medium.

I’ve been hearing rumors and firsthand accounts related to the accused for a few years now and have been working internally and with allies on the best approach for dealing with it all.

It’s not talked about a lot, but sex and psychedelics are closely linked (drugs and sex generally, for that matter). Think about the sexual liberation that boomed in the 1960s and is still seen in parts of the Burning Man and EDM culture today. Think about how powerful feelings of love and connection can be while on any number of mind-altering substances, and how easily they could morph into something more sexual.

Perhaps you’ve never experienced it, but regularly in psychedelic therapy sessions, sexual feelings do arise and can create challenging dynamics for both the client and therapist to navigate. What does someone in a fragile mind state, dealing with a maze of conflicting emotions and energies, do with an affectionate or sexual feeling they may suddenly have? What does the therapist do? How does either person know they can truly trust the other? This all leads to a big question many may not want to consider: Is it possible to totally divorce sexual feelings and ideas from psychedelic sessions?

I’d suggest that no, it isn’t possible. Psychedelics unleash all sorts of energies without any bias or filter, so why would sexual energy be exempt?

I believe that psychedelics can be transformative for mental health, religious practice, spirituality, physical healing, creativity, celebration, rites of passage, and even for the development of planet-saving technology — and this is an abbreviated list. Psychedelics are extremely powerful things that can serve as near miracle cures and beautiful spectacles, but unfortunately, they can also be used as weapons.

For a long time on the podcast (and in day-to-day life — sorry, friends), I’ve complained about how I’ve unintentionally taken on the role of the “Psychedelic Police.” Because of my many years in the psychedelic world and my perceived expertise, many folks have divulged negative or abusive stories about what they’ve experienced in underground (and occasionally aboveground) situations. I shouldn’t complain about this, since it’s an honor to be so trusted, and some stories may have helped me side-step traps Psychedelics Today could have fallen into.

It is frustrating though, and puts me in a tough spot.

Due entirely to the drug war, there are serious legal and financial consequences for bringing such things to light on behalf of someone else. What if the story isn’t entirely true? What if it is, but can’t be proven? What if proving it relies on multiple people admitting illegal activity and they’re not willing to do that? I could be hit with cease-and-desist letters, defamation lawsuits, or just be perpetually dragged into court for any number of things. Lawyers are expensive and what’s right doesn’t always win.

Without ruining my reputation and finances, and possibly destroying my best tool for bringing positive impact to the psychedelic space (this very website), I have little recourse. We have developed some ideas about the next best steps, but it is hard to know with certainty if we are doing the right thing. So I do what I can, which never feels like enough. I anonymize these stories and turn them into generic ethical warnings, encouraging people to do their research and be as safe as possible.

At the Horizons Conference in 2019, Dr. Carl Hart suggested that immediately ending the drug scheduling system would be an amazing first step in resolving a range of harmful consequences from the war on drugs. Others have proposed that a state-by-state or region-based decriminalization similar to what we’ve seen over the last few years in Oakland, Oregon, and Denver would be the ideal starting point (especially from the perspective of political expediency). Whichever side of the solution you land on, I think we can all agree that we need to fix our laws around controlled substances and plants.

Given that facilitators and guides work with substances that are federally illegal, there could be massive consequences for someone participating in underground work who is apprehended by law enforcement for any reason. For both the facilitator and the participant; consider the attention to detail needed to ensure you’re protected from liability, the knowledge and support systems needed to be able to handle serious medical cases, and the amount of apprehension and secrecy necessary to maintain anonymity for all involved.

Add in the complications of how differently an action can be perceived by different people in different mind states, and this almost creates an incentive structure to sweep things under the rug — a bypassing of anything perceived as a threat to the overall good. People who could force change can be, and often are banished from communities for asking the “wrong” questions.

Since so many people are forced to operate in an underground capacity, it makes sense that these problems exist. And they will continue to exist if we can’t have open and honest conversations about what we’re experiencing, and start working together to figure out how to answer so many of these complicated questions within the confines of the drug war.

How do we talk about sex and psychedelics?

What are the appropriate ways to deal with sexual energies and consent in situations where people consume mind-altering substances in situations with clear power dynamic differentials?

How do we report issues of abuse to local leaders and elders?

Will they fight for us?

Do they have any teeth?

What capacity do they have to investigate?

Does the victim have any legal ground?

Will law enforcement toss out reports due to drugs being involved?

What if other senior leaders become complicit in a cover-up surrounding their colleagues?

At what point should leaders step down and elevate new leaders?

Is restorative justice even possible if the victim or perpetrator doesn’t feel safe or supported enough to come to the table?

While some acts are inexcusable, we have to be honest with ourselves and understand that good people make mistakes; bad people can be anywhere; and while it’s easy to blame the individual person, bad policies and dysfunctional systems incentivize bad behavior and can scare good people into silence.

Ending the destructive and racist drug war in the US and internationally would improve safety and transparency in vulnerable spaces that often don’t have much of either. When the legal status of underground work is improved, frameworks for safety can be established, and abusers simply won’t be able to get away with bad behavior to the same degree they can today. When we can be more open, people will be safer, and practices can be improved more rapidly.

Ending the drug war is an enormous undertaking, and while there aren’t clear steps on how to accomplish such an incredible feat, many in this field are working tirelessly to do what they can.

See Drug Policy Alliance, Drug Science, and Transform Drug Policy for just a few examples.

The best thing I can do is to use my voice at Psychedelics Today; creating courses, podcasts, and articles that help normalize psychedelics as part of everyday, contemporary life; shed light on under-discussed topics; and give voices to people who aren’t well-known in the space.

I will continue to do my best to address these tough questions around abuse. I hope you’ll join me.

 
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Everyone should understand the potential heart risk of psychedelics

The Psychedelic Scientist | Dec 6 2019

An important part of building a healthy psychedelic community is being fully aware of the risks of psychedelics.

This includes both being educated about the risk of trauma and injury from challenging psychedelic experiences, but also the potential physiological harm they can do to us.

It appears that occasional large doses of psychedelics don’t do much harm to healthy individuals, as long as they are properly looked after to prevent really damaging traumatic experiences. But we don’t have any evidence yet that regular microdosing is safe.

There are reports of people microdosing for many months in succession, with no ill effects aside from tiredness. But there is always the chance that with longer term microdosing regimens, unwanted physiological side effects could start building up. Ingesting any substance over a long period, no matter how harmless they are in single doses, could cause significant changes in your body.

Here’s what we know so far about the potential risks of taking frequent doses of psychedelics…

MDMA and heart disease

Various studies have shown that there is a link between regular, high-dose MDMA use and heart defects. Although the conclusion of this research is that the occasional dose of MDMA will not harm you, it has potential implications for frequent, long-term psychedelic use – especially microdosing – and I’ll explain how.

MDMA’s harmful effects on the heart are due to its activation of the 5-HT2B receptor. This receptor is present all over the heart, and convincing evidence suggests that the long-term activation of this receptor leads to the formation of ‘valvular strands’, which can lead to Valvular Heart Disease (VHD) in extreme cases.

Classic psychedelics, including LSD and psilocybin, also activate this 5-HT2B receptor.

Again – cases of VHD are only found in people who use MDMA very frequently (several times a week) and at high doses. The question we want to answer is: do the classic psychedelics (LSD and psilocybin) activate the 5-HT2B receptors in our hearts as much as MDMA? And – is there a risk of VHD with long-term usage, like microdosing?

LSD, psilocybin, and the 5-HT2B receptor

LSD and psilocybin work by mimicking the effect of our natural neurotransmitter, serotonin. Therefore both these psychedelics activate a wide range of serotonin receptors, including the 5-HT2B receptor. The real question is, are these psychedelics activating the 5-HT2B receptor enough to cause damage to the heart?

Unfortunately, we don’t have a clear answer to that question yet. We know that LSD and psilocybin bind strongly to the 5-HT2B receptor, but we don’t know how comparable this is to the way that MDMA (and other cardiotoxic molecules) binds to 5-HT2B. So right now, there is no way of knowing for sure if there is any risk.

We can, however, make some educated speculation.

We can look at a previous study of a compound that definitely causes heart damage through the 5-HT2B receptor: fenfluramine. This was a weight-loss drug that was withdrawn in the 90s after a small percentage of people developed heart disease after using it.

Studies found that fenfluramine roughly doubled the risk of developing VHD after a 90-day treatment course, at a dose of around 30mg/day. Fenfluramine has an affinity (Ki) for the 5-HT2B receptor of around 30nM.

LSD has a similar affinity for the 5-HT2B receptor as fenfluramine, a Ki of around 30nM. However, when we take a dose of LSD, it is several hundred times less than a single dose of fenfluramine (100ug compared to 30mg). So it’s highly unlikely that a single dose of LSD, even if it’s a high dose, would have any immediate cardiotoxicity.

With microdosing, it’s a different story. A typical microdosing regimen involves taking the equivalent of around 3ug/day, several thousand times less than fenfluramine. However, the main reason that fenfluramine is cardiotoxic is because it is taken every day in a continuous regimen.

The comparison to fenfluramine isn’t great – it’s quite possible that a daily dose of fenfluramine affects the 5-HT2B receptor in a vastly more harmful way than intermittent microdoses.

Overall, it seems reasonable to assume that microdosing probably has nowhere near the heart risk associated with fenfluramine. At the same time, it’s also very possible that even very minor, but frequent activation of the 5-HT2B receptor could slightly increase our risk of heart disease.

Conclusions

It seems likely that single large dose psychedelic experiences, and short-term microdosing routines, are relatively safe for your body. Decades of anecdotal reports and epidemiological studies back this up.

What remains to be seen is whether long-term microdosing regimens (i.e. for many months or even years) have a potential to damage the heart. This is why it is sensible to microdose for no longer than 90 days, and spread out your microdosing regimens throughout the year. If you have a pre-existing heart condition, it is especially important to avoid extended periods of microdosing.

It’s important for the community to be aware of these potential risks. I often come under fire for “scaremongering” when I bring up this research. But the reality is that educating ourselves about the science, and showing that we have a firm understanding of psychedelic safety, gives us the best chance of defeating the authorities hell-bent on shutting down our movement.

 
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Psychedelic Medicine: Safety and ethical concerns

Brian T Anderson, Alicia L Danforth, Charles S Grob | The Lancet Psychiatry | October 2020

With the current surge of interest in the field of psychedelic research, a psychedelic renaissance in psychiatry depends primarily on the ability to establish safe and ethical settings for the use of these experimental medicines. However, few opportunities exist for learning the safe and effective administration of psychedelic therapies. When psychedelics were embraced by modern medicine in the 1950s and 1960s, enthusiasm and fervent portentousness overtook pragmatism before psychedelic

science could develop safe and consistent structures. A similar collective enthusiasm is palpable in psychedelic psychiatry—a field that does not yet have in place the means to manage the consequences of its much-anticipated success. We wish to draw attention to several issues that need to be thoroughly addressed to allow the field of psychedelic research to grow in a safe and sustainable manner.

With the FDA granting breakthrough therapy designations for both MDMA and psilocybin, and with growing interest from investors and health-care entrepreneurs, many investigators today are excited to examine how psychedelic therapies might address the unmet needs of patients with substance use disorders, treatment-resistant mood disorders, and trauma-related disorders, among others. Heifets and Malenka described the study of psychedelics as “disruptive psychopharmacology.” We agree These compounds have the potential to lead to substantial innovations in therapeutics and neuroscience, but believe they can also be disruptive for other reasons. Classic psychedelics, such as psilocybin and lysergide, and atypical psychedelics, such as MDMA, have been found to be relatively

well tolerated in early-phase clinical trials. However, psychedelics can have lingering effects that include increased suggestibility and affective instability, as well as altered ego structure, social behaviour, and philosophical worldview. Stated simply, psychedelics can induce a vulnerable state both during and after treatment sessions. Therefore, to assure the safe and responsible clinical administration of psychedelics, we need to develop and disseminate rigorous ethical and practice standards that are commensurate with the novelty and breadth of the effects that these compounds can have on individuals.

We do not anticipate that eliciting clinically significant effect sizes in primary endpoints will be the key challenge to implementing psychedelic therapy given the current clinical data, heightened expectations regarding the so-called transformative effects of these drugs, and the pervasive functional unblinding that is evident across most of these studies. Instead, the more pressing issues affecting the roll out of these therapies will arise from dynamics between providers and patients (eg, the challenges of co-creating truly informed consent, minimising conflicts of interest, and avoiding practising outside the provider’s scope of competency). Unfortunately, not only are disruptive responses evident in some people who ingest psychedelics, but occasionally these responses can be found in some individuals who have a strong desire to administer the drugs to others. Even though treatment providers who have personal experience of taking psychedelics might be better at anticipating the clinical needs of their patients than those who do not have personal experience, we advise caution when evaluating the judgment of research and clinical colleagues who have only begun to take psychedelics within the past couple of years. Despite the association between psychedelic use and ego dissolution, grandiosity can loom large with initial psychedelic experiences, leading even conservative individuals to become wildly enthusiastic about the potentials of psychedelics to heal and transform. Although this enthusiasm tends to wane over time, the risks of ego inflation and grandiosity can persist in susceptible personality types. Conversely, people who take psychedelics might aggrandise and fetishise the therapists who administer the drugs to them. There are well known baseline risks of parental or erotic transference in conventional psychotherapy.8 We suggest that the risks of problematic interpersonal dynamics are magnified when a patient’s therapist not only administers unconditional acceptance and validation, but also expedites access to experiences of transcendence or profound catharsis via a drug.

We have served as investigators and clinicians on three early-phase clinical trials of psilocybin-assisted or MDMA-assisted psychotherapy, one safety and tolerability study of MDMA in healthy volunteers, and several biomedical and ethnographic investigations of psychedelic use in community settings involving observations of hundreds of individuals consuming psychedelics. With increasing frequency over the years, we have received letters, emails, and phone calls from concerned individuals who are seeking help while recovering from challenging psychedelic experiences, feel harmed by unethical psychedelic providers, or are desperately seeking psychedelic therapy for themselves or a loved one. Psychedelic medicines carry a truly uncanny allure and risk–benefit profile, and regulatory risk evaluation mitigation strategies can have their shortcomings. Hence, our collective challenge as future psychedelic providers is to develop a system of rigorous peer-review and supervision that will allow professionals in the field to more safely navigate the possible, and at times unavoidable, ethically murky undercurrents that might emerge.

We hope to bring transparency to a collection of heuristics that are often whispered about in the background, which we now feel would be appropriate for psychiatry at large to consider publicly.

Researchers and health-care providers have an ethical duty to mitigate the risk of repeating errors in judgment that curtailed early progress in psychedelic science. We encourage investigators and clinicians to contemplate the responsibility that we all have for the conduct of individuals who we train to provide psychedelics, and to seek guidance from institutions that oversee the ethical practice of other health-care providers (eg, anesthesiologists and geriatricians) who work with especially vulnerable populations. For the sake of patient safety and wellbeing, let us fulfill our responsibility to develop and implement elevated standards of clinical training, quality assurance, and peer-review for these wondrously disruptive medicines.

file:///C:/Users/user/Downloads/Anderson_Danforth_Grob_2020_psychedelics_safety_ethics_preprint.pdf​
 
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