DEPRESSION | +80 articles

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Psilocybin treatment for Major Depression effective for up to a year for most patients

Johns Hopkins Medicine | Neuroscience News | 15 Feb 2022

The antidepressant effect of psilocybin-assisted therapy, in combination with psychotherapy, appears to provide up to a year of symptom relief for some patients with major depressive disorder.

Previous studies by Johns Hopkins Medicine researchers showed that psychedelic treatment with psilocybin relieved major depressive disorder symptoms in adults for up to a month. Now, in a follow-up study of those participants, the researchers report that the substantial antidepressant effects of psilocybin-assisted therapy, given with supportive psychotherapy, may last at least a year for some patients.

A report on the new study was published on Feb. 15, 2022 in the Journal of Psychopharmacology.

“Our findings add to evidence that, under carefully controlled conditions, this is a promising therapeutic approach that can lead to significant and durable improvements in depression,” says Natalie Gukasyan, M.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

She cautions, however, that “the results we see are in a research setting and require quite a lot of preparation and structured support from trained clinicians and therapists, and people should not attempt to try it on their own.”

Over the last 20 years, there has been a growing renaissance of research with classic psychedelics — the pharmacological class of compounds that include psilocybin, an ingredient found in so-called magic mushrooms.

According to the National Institute on Drug Abuse, psilocybin can produce perceptual changes, altering a person’s awareness of their surroundings and of their thoughts and feelings. Treatment with psilocybin has shown promise in research settings for treating a range of mental health disorders and addictions.

For this study, the researchers recruited 27 participants with a long-term history of depression, most of whom had been experiencing depressive symptoms for approximately two years before recruitment. The average age of participants was 40, 19 were women, and 25 identified as white, one as African American and one as Asian. Eighty-eight percent of the participants had previously been treated with standard antidepressant medications, and 58% reported using antidepressants in their current depressive episodes.

After screening, participants were randomized into one of two groups in which they received the intervention either immediately, or after an eight-week waiting period. At the time of treatment, all participants were provided with six to eight hours of preparatory meetings with two treatment facilitators.

Following preparation, participants received two doses of psilocybin, given approximately two weeks apart between August 2017 and April 2019 at the Behavioral Biology Research Center at Johns Hopkins Bayview Medical Center. Participants returned for follow-up one day and one week after each session, and then at one, three, six and 12 months following the second session; 24 participants completed both psilocybin sessions and all follow-up assessment visits.

The researchers reported that psilocybin treatment in both groups produced large decreases in depression, and that depression severity remained low one, three, six and 12 months after treatment. Depressive symptoms were measured before and after treatment using the GRID-Hamilton Depression Rating Scale, a standard depression assessment tool, in which a score of 24 or more indicates severe depression, 17–23 moderate depression, 8–16 mild depression and 7 or less no depression.

For most participants, scores for the overall treatment decreased from 22.8 at pretreatment to 8.7 at one week, 8.9 at four weeks, 9.3 at three months, 7 at six months and 7.7 at 12 months after treatment.

Participants had stable rates of response to the treatment and remission of symptoms throughout the follow-up period, with 75% response and 58% remission at 12 months.

“Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression,” says Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research.

“Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments.”

The researchers emphasize that further research is needed to explore the possibility that the efficacy of psilocybin treatment may be substantially longer than 12 months. Johns Hopkins is one of the sites of a national multisite randomized, placebo-controlled trial of psilocybin for major depressive disorder.

About this psychopharmacology research news
Author: Marisol Martinez
Source: Johns Hopkins Medicine
Contact: Marisol Martinez – Johns Hopkins Medicine

Psilocybin Treatment for Major Depression Effective for up to a Year for Most Patients - Neuroscience News

The antidepressant effect of psilocybin-assisted therapy, in combination with psychotherapy, appears to provide up to a year of symptom relief for some patients with major depressive disorder.

neurosciencenews.com

 

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New promise for psychedelics and depression

by Kurt Hackbarth | Freethink | 2 Apr 2022

New research shifts old paradigms as we seek better treatments for depression.

New research on psychedelics and depression is causing the medical community to take a fresh look at age-old medicines — and government policy may soon follow. Like the movement kicked off by Timothy Leary in the 1960s, today’s experiments with “microdosing” psychedelic drugs began as a grassroots effort challenging taboos, both cultural and legal. This time around, however, in the midst of a spiraling opioid epidemic, an overdependence on pharmaceuticals, and widespread dissatisfaction with the human and financial costs of the war on drugs, there is evidence that the government may in fact be listening.

Psychedelics, then and now

Although microdosing for depression is relatively new, use of psychedelics for transcendental experience or medical benefit has a long lineage. Psilocybin was a fundamental part of many ritual ceremonies in pre-Columbian Mesoamerica, where the mushrooms that provided it were known as teonanácatl, literally the “God mushroom.” Similarly, ayahuasca is so important to the identity of Amazonian peoples that the government of Peru made the ritual part of its National Cultural Heritage in 2008.

In the United States, the use of psychedelics has a more controversial history. The synthesis of LSD in 1938 set off three decades of research into the substance, culminating in the countercultural experimentation of the 1960s. In 1970, with Vietnam protests still raging in the streets, the Nixon administration moved to criminalize psychedelics through the Controlled Substances Act.

From then on, psychedelics would be categorized as Schedule 1 drugs, with “no currently accepted medical use.” Federal dollars dried up, and official research came to a generation-long standstill.

Outside of sanctioned laboratories, however, experimentation continued. In addition to being generally non-addictive, these substances can provide a perspective that many have likened to a spiritual awakening. Decades of anecdotal testimony claim that, far from constituting a form of escapism, these experiences can be positively, and permanently, life changing.

Used in smaller amounts, however, the effect is much more subtle. “I can get stuck in ruminative, negative thoughts, and microdosing streamlines them so I can stay more in the moment,” says Michelle Janikian, journalist and author of Your Psilocybin Mushroom Companion, a book that dives deeply into the various ways of using psilocybin, including the connection between psychedelics and depression.

As an adolescent, Janikian was misdiagnosed with bipolar disorder and prescribed a raft of pharmaceuticals from Lamictal to lithium, with side effects including nausea, apathy, and constant fatigue.

“Because these drugs numbed my emotions at such a young age, I wasn’t really learning how to process and handle them,” she adds.

Microdosing mushrooms for depression, she says, allows her to fully experience emotions in a healthy way.

New research on psychedelics and depression

The grassroots resurgence of interest in microdosing psychedelics for depression has caused the medical community to take notice of the drugs. In fact, psychedelics — in larger doses — are now being trialed for use in treating major depression in the terminally ill.

Recently, NYU commissioned a study to test the effectiveness of using psychedelics to treat depression among patients with terminal illnesses — a cohort that has been difficult to treat in the past. Participants in the study were given either psilocybin or a placebo, asked to state their intention, then lie down on a couch in comfortable, living room-like surroundings. Equipped with headphones playing soothing music and an eye mask to blot out distracting stimulation, they were accompanied throughout by a guide.
​

“I thought the first 10 or 20 people were plants — that they must be faking it.” - Dr. Stephen Ross ​

According to Dr. Stephen Ross, professor of psychiatry and the study’s director, just one psilocybin treatment was enough for cancer patients to experience dramatic reductions in anxiety and depression, effects that lasted for at least six months.

“I thought the first 10 or 20 people were plants — that they must be faking it,” Ross told journalist Michael Pollan. “They were saying things like ‘I understand love is the most powerful force on the planet,’ or ‘I had an encounter with my cancer, this black cloud of smoke.’ People who had been palpably scared of death — they lost their fear. The fact that a drug given once can have such an effect for so long is an unprecedented finding. We have never had anything like it in the psychiatric field.”

But how do they work?

The chemical wall that stops 95% of pharmaceuticals dead in their tracks is known as the “blood-brain barrier.” While this necessary defensive system protects us, it creates a significant difficulty for those attempting to treat diseases of a neurological nature, such as depression, brain tumors, and Alzheimer’s.

But many psychedelics are able to cross that no-man’s land, either by being lipid-soluble (which is how psilocybin works) or by increasing the permeability of the barrier itself (which is the case for MDMA, the active ingredient in ecstasy).

Although there are significant differences in the chemistry and effects of different psychedelics, there are some traits that they have in common. These substances appear to quiet areas in the brain that have to do with our sense of self, such as the default mode network (DMN) or the amygdala, thus fostering a greater feeling of connectedness. Meanwhile, they stimulate areas such as the limbic system, which governs our emotions, and the prefrontal cortex, the brain’s executive processing center. In short, they seem to quiet the areas that get us “stuck in ourselves” — and thus, perhaps, susceptible to depression.

Through various mechanisms, psychedelics also tend to stimulate the production of serotonin, which is thought to improve mood. Depending on the substance, other chemicals such as oxytocin and prolactin, regulating love and bonding, or dopamine, promoting pleasure, can also be stimulated. The immediate “high” of the drugs can last anywhere from the very short (ayahuasca) to the very long (LSD); although in small studies, the effects on disorders such as depression and PTSD can be remarkably long-lasting. In contrast to the interaction of psychedelics and depression, the effects of current methods of mental health treatment — such as antidepressants and therapy — often tend to fall off once halted.
​

Just one psilocybin treatment was enough for cancer patients to experience dramatic reductions in anxiety and depression, effects that lasted for at least six months.​

Psychedelics — even when microdosing for depression — do come with dangers. Although not physically addictive, there is a potential for psychological addiction, especially for those suffering from personality disorders. A small percentage of users have reported suffering from hallucinogen persisting perception disorder, a condition where visual phenomena, such as “snow” and color distortions, persist after the experience. As a stimulant, MDMA can increase the risk of heart disease. And because the substances are illegal, there is the risk that black market dealers may lace them with addictive and seriously dangerous drugs, such as fentanyl, ketamine, or meth. All the more reason, then, to proceed with caution.

Moving toward wider acceptance

Although researchers are exploring the interplay between psychedelics and depression, the substances are still classified as Schedule 1, meaning that they are not available for legal purchase, even at your local cannabis dispensary. Experts also caution against picking magic mushrooms in the wild, as more people are harmed every year from poisonous mushrooms than from bad trips.

The wave of marijuana legalization across the U.S. may be ushering in a new social paradigm, in which ancient medicines and taboo substances are being given a fresh look — and for good reason. According to the National Center for Biotechnology Information (NCBI), between 10 and 30% of people who suffer from major depression do not experience improvement when they use currently available medications. Although more research needs to be done, the implications for psychedelics and depression, especially when it comes to relieving the suffering of people with such “treatment-resistant depression,” are hard to overstate.

Beyond relieving depression, though, the side benefits of microdosing psychedelics may also be worthy of further scientific exploration. As Janikian puts it, “Psychedelics help us get in touch with what really matters. They’re a way to show yourself appreciation and gratitude. People call it an emotional reset — you feel a greater appreciation for the world after seeing it from a different point of view.”

New promise for psychedelics and depression

New findings on psychedelics and depression show the benefits of microdosing, and could present more effective treatment options.

www.freethink.com

 

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LSD-analogs that may treat depression without the trip*

by Jon Kelvey | LUCID | 10 Apr 2022

Researchers at the Shanghai Institute of Biochemistry and Cell Biology may have created LSD analogs that can treat depression without the trippy hallucinations — in mice anyway.

Their paper in the journal Science is the latest piece of evidence suggesting it could be possible to provide many of the therapeutic effects of traditional psychedelic experiences, but without the potential risks and costly monitoring required for lengthy trips. If proven safe and effective in humans, such “no-trip psychedelics” could potentially deliver relief from depression and other mental health conditions to millions more people than could traditional psychedelics.

“We are evaluating the compounds for their drug-like properties in other preclinical experiments,” Jianjun Cheng, one of the study authors, wrote in an email. “Our goal is to identify a preclinical drug candidate.”

But it’s not yet clear if Jianjun and his colleagues’ findings in mice will translate to primates or humans, or if his team’s explanation for the compounds’ effects — that they bind to different parts of brain receptors than do drugs like LSD — will prove true in future replication studies.

Furthermore, given the progress of for-profit companies like Compass Pathways, and non-profit organizations like the Multidisciplinary Association for Psychedelic Studies (MAPS), in conducting clinical trials of traditional psychedelic therapies such as psilocybin and MDMA — not to mention psilocybin mushroom legalization in Oregon — it’s likely “no-trip” psychedelics will take a back seat to full trip psychedelics for the time being. But work like that of Jianjun’s team nevertheless opens the door of possibilities a bit wider for psychedelic therapies, and could help scientists better understand how all psychedelic compounds actually work in the brain, trip or no trip involved.

Scientists have long theorized that many psychedelics work their magic by binding to and activating the 5-HT2A receptor in the brain, a complex of proteins normally activated by the neurotransmitter serotonin and triggering a cascade of subsequent signaling within a neuron. Substances like psilocybin, DMT, and portions of the more complex LSD molecule all closely resemble serotonin, allowing them to fit into and activate the 5-HT2A receptor like an accidentally matching puzzle piece. Compounds that activate a receptor are known as agonists.

But while serotonin and LSD both bind to a site known as the “orthosteric binding pocket” on the 5-HT2A receptor, Jianjun, and his team may have discovered a different area on the receptor where compounds can bind.

“They found through some of their structural biology studies this idea of the ‘extended binding pocket,’” said Ryan Gumpper, a structural biologist and post-doctoral researcher at the University of North Carolina who is familiar with the paper, but not involved in the research. “Then they designed some new drugs that targeted that [extended binding pocket] and they’re saying they are non-psychedelic. That’s the main takeaway of the paper.”

The research team created multiple compounds similar to LSD, including two they call IHCH-7079 and IHCH-7806. In tests with mice, IHCH-7079 and IHCH-7806 failed to elicit head twitching behavior that scientists have established as a sign of psychedelic effects in the rodents. But the new compounds also reduced mouse behaviors associated with depression. The researchers hypothesized that the binding of the compounds at the extended binding pocket, along with related changes in signaling after activating the receptor, is what allowed the therapeutic effects to be split from the traditional psychedelic effects.

The kind of functionally altered compound-to-receptor binding that Jianjun and his colleagues show in the paper is sometimes called biased agonism, meaning the compound binds to a receptor, but in a way that triggers a different than typical response through only partially activating the receptor or altering subsequent signaling. In opioid painkiller research, for instance, scientists have found that certain biased agonist opioid drugs may trigger pain relief when binding to opioid receptors, but present less risk of respiratory depression and overdose.

IHCH-7079 and IHCH-7806 may well be biased agonists of the 5-HT2A receptor, but Gumpper said he is uncertain about the way the models in Jianjun’s paper explain how the compounds are acting.

A structural biologist with a background in using X-rays to uncover the molecular structure of viruses, Gumpper joined the Bryan Roth lab at the University of North Carolina in 2020 specifically because of work the lab published in 2017 elucidating the structure of LSD bound to another serotonin receptor, the 5-HT2B receptor (one of the Roth lab researchers on that 2017 project, Sheng Weng, is the principal investigator on the new paper in Science).

But when Gumpper looked at Jianjun’s paper, something seemed off with the researchers’ models of psilocin, LSD, serotonin, the 5-HT2A receptor, and a well-known non-psychedelic LSD analog called lisuride.

X-ray crystallography is a technique for mapping the density of molecules by shining X-ray light on them to create something like a pattern of light and shadow called an electron density map. The “ball and stick” models of molecules familiar to anyone who has taken a chemistry class, Gumpper said, are derived from these maps.

When he looks at the maps and the models Jianjun’s team used in the paper, Gumpper isn’t sure they match each other very well.

“If somebody tries to use those for other drug discovery purposes, like some sort of computational pipeline, they could just go down the wrong path,” he said. “Just from my perspective as a structural biologist.”

Asked about Gumpper’s criticism, Jianjun stood by his team’s electron density maps.

“The resolutions were not perfect, but good enough to support our models,” he wrote in an email.

Another structural biologist, Stanford’s Georgios Skiniotis, argued that the maps and models used by Jianjun’s team were fine, but that the necessarily incomplete nature of X-ray crystallography still led him to withhold judgment about the paper’s structural explanation for the effects of IHCH-7806 and IHCH-7806 pending further research.

“Any [molecular] structure is not an absolute truth,” Skiniotis said. “Any structure is just a snapshot.”

Looking at the model of psilocin bound to the 5-HT2A receptor in the paper, in particular, he said the structure looks to him as if the “snapshot” Jianjun’s team took caught psilocin in the act of migrating toward the usual orthosteric binding site, rather than binding to an extended binding pocket. "It’s possible for example," Skiniotis added, "that a fatty acid present as part of the experimental conditions could have gotten in the way of the psilocin, preventing it from reaching the usual orthosteric binding site."

Ultimately, he said, he’s not sure about the existence of an extended binding pocket, or that IHCH-7079 and IHCH-7806 work their effects through binding there, but “that doesn’t mean it doesn’t exist.” It may just take future studies attempting to replicate the findings to determine if the structures modeled by Jianjun’s team do indeed determine the mechanism through which IHCH-7079 and IHCH-7806 are acting.

Ambiguity around how psychedelic compounds actually work in the brain is, after all, the default, with neuroscience only now coming close to determining how classical psychedelic compounds like LSD work their magic. In the same way, the effectiveness of IHCH-7079 and IHCH-7806 at relieving signs of depression (in mice) doesn’t depend on an accurate understanding of their molecular structures.

And, Gumpper pointed out, It’s certainly not necessary to understand the details of how a drug works before taking it through a successful clinical trial.

“As long as you’ve already proven safety and some sort of efficacy in mouse models or rat models — or other non-primate human models — you can take it into clinical trials without necessarily having to know exactly the potential mechanism because it’d be therapeutically useful,” he said.

A number of companies are developing compounds they also hope will provide the psychiatric benefits of psychedelics — rapid alleviation of depression, post-traumatic stress disorder, or help with addictions — but without the trip. Delix therapeutics, founded by University of California Davis Professor of chemistry David Olson, is pursuing dozens of novel no-trip psychedelic compounds the company hopes will promote neural healing, for instance. And Better Life Pharma is pursuing a non-psychedelic LSD analog long used to treat cluster headaches, 2-bromo-LSD, for treating depression.

In academia, the Roth lab where Gumpper works has been pursuing just such a drug with funding from the US Department of Defense (Skiniotis’s lab at Stanford is also involved in the work, although to a lesser degree than the Roth lab). It’s possible, he said, that no-trip psychedelics could be entering clinical trials within five years.

But that doesn’t mean that work on underlying mechanisms shouldn’t continue or isn’t ongoing. The Roth lab, for instance, has been working on the underlying mechanisms of both traditional and new, no-trip psychedelics since before the Department of Defense grant.

“I think the ultimate question would be, what makes each of those compounds hallucinogenic versus something that’s not?” Gumpper said. “Something like psilocybin is similar to serotonin, and so what makes those big differences?”

*From the article here :

Researchers May Have Created LSD-Analogs that Treat Depression Without the Trip - Lucid News

If proven safe and effective in humans, such “no-trip psychedelics” could potentially deliver relief from depression and other mental health conditions to millions more people than could traditional psychedelics.

www.lucid.news

 

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Can I use mushrooms to treat my depression if I can’t afford therapy?

by Rachel Clark | LUCID | 27 Jan 2022

I want to treat my depression but I can’t afford therapy. I’ve heard mushrooms are super helpful. Is there a special way to do them that focuses on treating depression?

This is a hot-button question right now! Researchers around the world are working feverishly to determine what, exactly, is the cause of psilocin’s antidepressant effects. Is it the mystical experience? The serotonin agonism? The neurogenesis? Is there an entourage effect? So much to consider!

For some people, just the act of consuming mushrooms is helpful for their depression. This might be due to a reduction of blood flow to the default mode network, a neural network that’s responsible for biographical thinking/rumination. Others find more benefit when the experience itself holds some kind of meaning.

As far as I know, current research seems to suggest that more mystical experiences lend themselves to higher reductions in depressive symptoms. You can’t ask the mushrooms for a mystical experience, though – that’s the beauty of it! Part of taking psychedelics is relinquishing control over the outcome of your day. You have to be willing to be uncomfortable, a practice which is therapeutic in and of itself.

Additionally, I personally find mushrooms particularly useful for learning to work with yourself, not against yourself. When you’re in such a vulnerable and suggestible mind-state, you are put in a position where you are forced to try different things to see what works for you. To me, this is an invaluable opportunity to rewire existing rigid behaviors and experiment with self care. It may be helpful to keep this at the front of your mind during the trip. Working with yourself is a powerful intention-setting tool.

Arguably the most therapeutically important part of a psychedelic experience is the integration: the practice of intentionally bringing new lessons into your daily life. There are an increasing number of resources available on integration. Off the top of my head I suggest Trip App, which is designed for people who can’t access therapy, and a workbook for psychedelic integration entitled Beyond the Narrow Life that I haven’t read and can’t vouch for outside of having seen someone else vouch for it. It might be worth checking out so that you can proceed with a little more structure.

You can also find integration circles like those hosted by your local Psychedelic Society chapter, or The Ancestor Project (BIPOC only). There are specialized integration circles for OCD, autism, and a variety of other mental health conditions.

Otherwise, you might just want to play around with different modes of consumption. There are so many ways in which psychedelics can produce experiences that have antidepressant effects, either directly or indirectly! Alone, with friends, inside, outside, sunny, rainy, light, dark, painful, euphoric, talkative, quiet, lemon tek, orange juice, straight shrooms, mushroom chocolates, capsules, 4-AcO-DMT, microdoses, macrodoses… it’s all very experimental. No two psychedelic experiences are identical. There’s so much to learn about yourself!

If my friends and I are in a “cuddle puddle” and snuggling together while doing drugs, what steps should we take to make sure that everyone is safe if we fall asleep? I don’t want someone to get hurt at my party while everyone else is napping.

Whenever you’re hosting a party where drugs are involved, I suggest keeping a whiteboard or sheet of paper where everyone writes down the time and dose of any substances they consume. This provides an easy and effective way of tracking what went wrong if someone gets sick, and allows you to check interactions and comedown times.

I’d say that one of the biggest risks in a sleepy cuddle puddle is the consumption of depressants like alcohol, benzos (benzodiazepines), or opioids. If someone is super drunk, slurring, or otherwise not lucid, it is not a good idea for everyone to fall asleep until that person’s state has been evaluated and responded to.

For example, someone who is extremely drunk should be a) placed in the recovery position to prevent choking if they vomit, and b) monitored for alcohol poisoning. Verbally check in with the group every 30-60 minutes to see if anyone feels sick or is clearly very intoxicated.

Note that it is particularly dangerous to combine multiple depressants (e.g. Xanax with alcohol. Anyone who has ingested this combination should be monitored by the group to make sure their breathing and heart rate do not slow too much. You might want to look into snagging a pulse oximeter to aid in this. Ideally, have a group discussion about what people are planning on taking before everyone doses. You may want to have one or two people designated to stay up for a while and keep tabs on everyone after they’ve fallen asleep.

If everyone’s rolling, being in a hot pile of humans increases the risk of overheating. Overheating is arguably the biggest danger of MDMA, as it may cause serious physical effects (like seizures or coma) and/or exaggerate MDMA’s neurotoxicity. Cuddle puddles don’t generally get you as hot as dancing in a packed warehouse – in a cuddle puddle you’re not very likely to overheat to the point of seizing.

If someone has taken a large dose, is wearing warm clothes (like a onesie), or is visibly sweating, however, they should probably not be covered in 99-degree bodies. I advise staying as cool as possible while rolling to reduce the risks of MDMA toxicity from hyperthermia.

Is it safe to mix psychedelics or ketamine with prescription pain relievers like vicodin or muscle relaxers?

As far as I’m aware, classical psychedelics (LSD, mushrooms, DMT, mescaline) don’t generally have significant interactions with opioids. These kinds of questions are tricky, though, because when you’re looking at combinations you really need to be looking at the specific drugs. Take DMT, for example. Mixing DMT with an MAOI will prolong the experience, a desirable effect for many people. Mixing 5-MeO-DMT with an MAOI, however, can cause lethal toxicity according to a mixture of anecdotal reports and scientific literature.

This is also applicable to tramadol, which is technically a “pain reliever” but also possesses a myriad of other pharmacological properties. Tramadol has more interactions than most other drugs I can think of. In addition to being an opioid agonist, it’s also an SNRI (serotonin-norepinephrine reuptake inhibitor), has activity at multiple acetylcholine receptors, and does a whole bunch of additional granular stuff. There are lots of anecdotal reports of people having seizures or experiencing serotonin syndrome from mixing tramadol and LSD.

The same applies to ketamine: which drug are you trying to mix it with? How much of each drug are you intending to consume? Ketamine doesn’t depress your breathing or heart rate like opioids do, and it’s commonly co-administered with opioids during surgery. I hesitate to suggest that this combination can be tried at home, though, because accidentally enhancing an opioid’s sedative effects through some obscure mechanism can be life-threatening.

Even if your heart rate and breathing aren’t significantly depressed, losing consciousness and choking on vomit remains a risk. Interactions can be very difficult to trace from start to finish. Do you know which liver enzymes break down the drugs you’re using? Do you know whether there’s a substrate/inhibitor interaction? Do you know whether the metabolites interact? Are you on any OTC (over-the-counter) medications? Everything adds up.

In summary, you need to look at the individual drugs in question to determine the risks of mixing them. If you really want to mix opioids and ketamine, do it with supervision and make sure that you start very low and go very slow. You’ll also need to pay particular attention to any additional interactions that may come from OTC or psychiatric medications.

As for psychedelics, interactions with opioids depend on the pharmacology of the specific substances you’re using, but will likely be less of a concern than with ketamine – with the major exception of tramadol, and possibly other substances. And as for “muscle relaxants,” this phrase encompasses a wide variety of drugs that is too large a topic for me to address without more specificity.

Can I Use Mushrooms to Treat My Depression if I Can’t Afford Therapy? - Lucid News

This month Auntie discusses how to use mushrooms for depression if you can’t afford therapy, how to stay safe when napping in a cuddle puddle after taking substances, and if it’s safe to mix psychedelics or ketamine with prescription pain relievers.

www.lucid.news

 

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Depression and grief wrecked a man's life—until he took psilocybin*

by Aristos Georgiou | Newsweek | 26 Dec 2021

We are in a psychedelic renaissance, in which long-stigmatized drugs such as psilocybin—the psychoactive compound in magic mushrooms—and MDMA are being assessed in clinical trials and showing promise for the treatment of a host of mental health problems, ranging from depression to PTSD.

Last month, mental health care company Compass Pathways announced the results of a Phase IIb study—the largest psilocybin therapy trial ever conducted—that found the drug appears to be effective as a therapy for treatment-resistant depression.

Five years earlier in 2016, researchers at Imperial College London completed a small study that was the first trial to assess psilocybin as a treatment for this condition.

Imperial's pioneering study formed the basis for the U.S. Food and Drug Administration's designation of psilocybin as a "breakthrough therapy"—an action intended to expedite the development and review of drugs designed to treat serious or life-threatening conditions—and much of the subsequent research on this issue.

Among the participants in the 2016 study, published in The Lancet Psychiatry, was Kirk Rutter.

Five years later, Rutter, now 51, spoke to Newsweek about his experiences of the trial and its impact on his mental health. The conversation below has been edited for length and clarity.

How was your mental health in 2016?

I was suffering from very bad depression that was basically kicked off by the death of my mother. She was ill for some time. It was a terminal illness. My mother told me she had started to come to terms with dying and felt it might be some relief from the pain she was experiencing. And so I thought, foolishly, that I was quite prepared and it wouldn't impact me in a normal way, because I'd already done some grieving through dealing with her illness and supporting my dad, who was a full-time carer for her. I really thought that it would take some of the sting out of the grief.

But when it finally came, it was the opposite—it was like being hit by a truck. I got stuck in the grief. At the same time, I was living with really terrible neighbors who were above me. They would fight, they were alcoholics, they would smash things up. I had this oppressive presence and noise above me all the time. So, I didn't really have any peace at home. And then I'd go to work and, well—work is work. Then around a year after the anniversary of my mother's death, I ended both the relationship with my partner and a friendship. That was another big loss. I found it very difficult to be positive.

The treatment-resistant depression trial involves people who are depressed and have tried a few treatments that haven't worked. I tried some antidepressants and didn't really like the way they made me feel. I knew anyway that it wouldn't cure anything or sort anything out, it was just chemically altering how you felt. Deep down I didn't have a lot of faith in it because I knew it wasn't really working on the problem itself. And then I did a year of talk therapy. I think it helped in some ways, but I was still feeling kind of terrible. I was still being hit by the grief. And then the opportunity came to do the psilocybin trial.

So, I had a telephone screening with Imperial. They checked my notes to make sure I had had treatment and accepted me into the trial based on the screening. That was where the journey started.

Had you tried psychedelics before?

I was new to psilocybin and had never tried psychedelics before.

What was your view of psychedelic substances at the time?

I was worried about it. I remember walking through Camden [an area of London] and seeing the magic mushrooms there when they used to be on sale. I would think, 'Dangerous, stay away from that,' because of all the stuff that was in the media. You know, the kind of bulls*** stories about people jumping out of windows and stuff like that. So, I didn't have a positive view of it, really.

How many times did you receive the psilocybin during the trial?

Twice. There was a 10 milligram session, which was fairly psychedelic, and then there was a 25 milligram session, which was the more potent dose.

Before that there was a telephone screening, then a meeting in person that lasted about two or three hours. We talked about everything—what I could expect, what the issues would be, what could potentially come up, etcetera. I was very nervous. During the sessions I had a therapist either side of me and it was all underpinned by music.

The 10 milligram session was quite pleasant. It was nice, being relaxed and listening to the music. You're in a hospital, so I felt safe eventually, even though I was very anxious about it. It came on quite slow. I started seeing almost like an orange glow, just kind of flickering slowly and then it would get more and more intense. And then it was like going down a psychedelic tunnel on a toboggan. Nothing major really came up in the first session, although I was really blown away by hearing Indian instruments like the sitar. It just sounded absolutely amazing. So, that was that.

And then a week later, it was the 25 milligram dose. I was very nervous about that because I'd had the 10 milligram and that was quite potent. I thought, 'This is gonna blow my socks off.' But even with the 10 milligrams I thought this could be really dialled up—I knew that the colors are quite muted, for example, so, I was looking forward to it in a way.

In the end, it was very potent. It really penetrated me emotionally in a way that the 10 milligram dose didn't. The music kind of seeps into you, it gets into your pores. So, particularly sad music was quite moving, for example. And then I reflected a lot on situations with my mother and I started to see that the way I was hanging on to the grief … I was afraid to let go. I had a realization that you can let go of the grief and it doesn't mean you're letting go of the person. And that you can still have that connection without the grief poisoning you and keeping you in that place. Previously, I was worried that detaching from the grief or letting it go would almost be a betrayal or something like that. So, that was a good insight.

There were a few other things as well. I realized that I needed to make a connection with one or two people. I did that and it worked out quite well. I also told [the therapist] about these thoughts I had that go round and round. This rumination that was almost like a fixed record—this negative playlist. And that was broken.

It was quite a startling experience. It knocked me out of that hole and allowed me to start picking things up again. I needed to make some infrastructure changes though. As I said, my neighbors were kind of toxic, alcoholic criminals. So I realized I needed to get out of that situation. Mentally, I wasn't in a place where I could have done that beforehand. After the trial, I sold my flat and I bought a house because I didn't want to live underneath anyone. That was one big change that really was very helpful. I also moved in a more creative direction work-wise, which was very good.

I just think, generally, I started taking care of things I needed to. I still have the grief—not as bad as I did, it's still there—but I'm not feeling it all the time. So for me, it was really beneficial. It was overall a positive experience.

So would you say you experienced lasting changes from those two doses?

Yes, very much so. You have these insights and awareness of stuff. I think psychedelics are the difference between knowing something and then really absorbing it and feeling it.

What's your view on growing interest in psychedelic therapy?

I think it should be available. The efficacy of it looks good. It's been used for thousands of years. It's a very humane intervention.

*From the article here :

Depression and grief wrecked a man's life—until he took magic mushroom ingredient

Five years after participating in the first trial that used psilocybin as a therapy for treatment-resistant depression, Kirk Rutter tells Newsweek: "It really penetrated me emotionally."

www.newsweek.com

 

[mr peabody]

Psilocybin causes ‘significant reduction’ in symptoms of depression*

COMPASS Pathways' psilocybin study shows a significant improvement in treatment-resistant depression symptoms.

by Benjamin Adams | High Times | 24 May 2022

At the American Psychiatric Association (APA) 2022 Annual Meeting that began on May 21 in New Orleans, Louisiana, COMPASS Pathways unveiled the “largest randomized, controlled, double-blind study of psilocybin therapy ever completed,” according to a May 24 press release, and the data shows “significant” improvements to treatment-resistant depression (TRD) symptoms.

Participants were given a single dose of investigational COMP360 psilocybin, in doses of 25 mg or 10 mg, compared to 1 mg in patients with TRD. For the study, 233 patients with TRD received either 1 mg, 10 mg, or 25 mg COMP360 psilocybin, along with psychological support from therapists. Symptoms of depression were calculated using the Montgomery-Åsberg depression rating scale (MADRS).

The MADRS system has been used in the world of psychiatry since 1979 and measures apparent sadness (despondency, gloom), reported sadness, inner tension (discomfort, turmoil, dread), reduced sleep, reduced appetite, and concentration difficulty, typically in a ten-item questionnaire.

The people who received a 25 mg dose of COMP360 psilocybin with psychological support experienced a “highly statistically significant reduction in symptoms of depression after three weeks.” The difference between the group that received 25 mg and the group that received 1 mg was -6.6 on the MADRS depression scale at week three.

The effects also lasted very long—for three months, in some cases. The findings show that psilocybin provides “a rapid and durable response for up to 12 weeks.”

Twice the number of patients who received 25 mg (20 percent) had a “sustained response” at week 12, versus those who received 1 mg (10 percent). Tolerability and adverse effects were both reported mostly favorably, despite some reports commonly seen in people with TRD such as self-injury, but it was typically over a month after treatment.

“Treatment-resistant depression is one of the biggest challenges we face in psychiatry, and chances of success decreases with each treatment that a patient tries,” said David J Hellerstein MD, a Principal Investigator on the trial and Professor of Clinical Psychiatry at the Columbia University Irving Medical Center. “It’s rare to see such positive outcomes of clinical trials in this disease area, which is why these results are so significant. I hope this represents a major step in finding new options for people living with treatment-resistant depression.”

Columbia University’s Department of Psychiatry said last year that its study is the “largest to date using psilocybin to treat depression in people who aren’t helped by existing therapies.” Tough challenges require thinking outside the box, in this case, with the active alkaloids from psilocybin mushrooms. Even Canadian Senator Larry Campbell admitted that he takes microdoses of psilocybin for the treatment of depression.

“Our mission is all about developing mental health innovations through scientific evidence, which is why we’re so honored to present the largest study of its kind at the APA,” said Dr. Guy Goodwin, Chief Medical Officer, COMPASS Pathways. “In this study, a significant number of patients experienced improvement in their symptoms of depression after just a single dose of 25 mg psilocybin with psychological support, with effects lasting for up to three months of the study. We now need to continue our research to understand if this can be replicated in even larger trials.”

COMPASS is based in London, with offices in New York City and San Francisco, with clinical studies in North America and Europe.

There’s a divide in beliefs surrounding serotonin reuptake inhibitors (SSRIs). While some say SSRIs are a life-saver, others say they instead create an unnatural imbalance of neurotransmitters. Only a doctor can give you the final answer to that, and it’s assumed that people with TRD have already ruled out SSRI drugs like Prozac, Paxil, Zoloft, and Celexa.

The study cites data showing that over 320 million people globally suffer with major depressive disorder (MDD). About a third of these patients—a whopping 100 million people—aren’t helped by existing therapies and therefore have TRD.

And the most sobering data point? As many as 30% of them attempt suicide at least once during their lifetime.

In any case, psilocybin presents an entirely new mechanism for controlling treatment-resistant depression. The APA will also hold an online experience June 7-10 in case you missed the May event in New Orleans.

*From the article here :

Psilocybin Causes ‘Significant Reduction’ in Symptoms of Depression, Largest of its Kind Study Shows

COMPASS Pathways psilocybin study shows a significant improvement in treatment-resistant depression symptoms.

hightimes.com