DEPRESSION | +80 articles

[mr peabody]

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.
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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

 

[mr peabody]

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

 

[mr peabody]

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

 

[mr peabody]

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 | High Times

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

hightimes.com

 

[mr peabody]

Using Psychedelics to treat Depression and Trauma​

 

[mr peabody]

Summary: A Phase 2 randomized clinical trial demonstrates that a single 25 mg dose of psilocybin, combined with psychotherapeutic support, provides rapid, statistically significant, and clinically meaningful reduction in symptoms of common, recurrent depression.

The study showed that an antidepressant effect was noticeable as early as day two, with 53% of the psilocybin group reaching remission at six weeks. While the treatment was generally well-tolerated, researchers noted long-term efficacy challenges and highlighted the ongoing methodological hurdle of patient blinding in psychedelic research.​

Source: Karolinska Institute

Depression is a public health problem that causes great suffering. SSRI drugs are the most common treatment, but many patients do not benefit from them. Their effect can also take several weeks to kick in and side effects are common.

Psilocybin, found in so-called magic mushrooms, has shown antidepressant effects in previous studies. However, most studies have focused on cancer-related or treatment-resistant depression. In the current phase 2 study, published in JAMA Network Open, the researchers investigated whether psilocybin can also alleviate common depression.

A total of 35 people aged 20 to 65 with moderate to severe recurrent depression took part. Participants were randomly assigned to receive either a single dose of 25 mg of psilocybin or an active placebo in the form of niacin, a vitamin that causes a noticeable physical reaction.

Both groups received psychotherapeutic support on five occasions: before, during and after treatment. On the day of dosing, participants were asked to lie down and focus inwardly whilst wearing an eye mask and listening to music via headphones.

The effect of the treatment was measured using the MADRS (Montgomery–Åsberg Depression Rating Scale). The measurements were taken by doctors who were blinded to the treatment on days 8, 15, 42 and 365 following dosing.

To be included in the study, participants were required to have a total score of at least 22 points. The primary outcome of the study was the change in depressive symptoms eight days after treatment. At this point, the MADRS score had decreased by an average of 9.7 points in the psilocybin group, compared with 2.4 points in the placebo group.

This represents a group difference of 7.3 points in favor of psilocybin. The difference was statistically significant and is considered clinically meaningful. The effect persisted even after 15 and 42 days.

Participants also completed a self-report version of the MADRS. Their own assessments showed an antidepressant effect as early as day two, which persisted for just over three months compared to the placebo group.

After six weeks, 53 per cent of participants in the psilocybin group were in remission, compared with six per cent in the placebo group. After one year, the same proportion of the psilocybin group remained in remission, but by then no confirmed difference between the groups was observed, as many of those who had received the placebo had also recovered.

”Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important.”, says the study’s lead author Hampus Yngwe, consultant psychiatrist and PhD student at the Department of Clinical Neuroscience, Karolinska Institutet. He continues:

”However, the long-term effects are uncertain. Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies.”

The treatment was generally well tolerated. Most side effects were mild or moderate and transient. However, two participants who received psilocybin reported severe and persistent anxiety that required medical attention.

“It is important to emphasise that the treatment is not risk-free and that some patients may need extra support,” says Johan Lundberg, professor at the Department of Clinical Neuroscience and the Centre for Psychiatry Research, Karolinska Institutet, who led the study.

Research into psychedelic treatments faces methodological challenges because the substances produce strong and easily recognisable experiences. If participants and researchers can tell whether psilocybin or placebo was given, it becomes harder to separate the effect of the treatment from that of expectations.

In the current study, almost all participants were able to guess which treatment they had received, which may have influenced the outcomes, the researchers suggest.

“We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” says Hampus Yngwe.

The next step in the research is to analyse data from the PET scans, as well as blood and cerebrospinal fluid samples collected before and after dosing.

”Research suggests that the interaction between parts of the brain is impaired in depression and that this may be linked to changes in the connections between nerve cells, known as synapses.

“In preclinical studies, psychedelics have been shown to stimulate synaptic growth. We therefore want to investigate whether psilocybin alters synaptic density in the brain”, concludes Hampus Yngwe.

The study was conducted in collaboration between Karolinska Institutet and the Brain Stimulation Clinic within Northern Stockholm Psychiatry, Stockholm Region.

Facts about the MADRS:

The MADRS (Montgomery–Åsberg Depression Rating Scale) is used to assess the severity of depressive symptoms. The scale ranges from 0 to 60 points, with higher scores indicating more severe depression:

* 0–12 points: no depression or very mild depression

* 13–19 points: mild depression

* 20–34 points: moderate depression

* 35–60 points: severe depression
​

Key Questions Answered

• Rapid and Lasting Impact: On day 8 post-dosing (the primary outcome target), the psilocybin group’s depression rating score dropped by an average of 9.7 points compared to just 2.4 points in the placebo group, a clinically meaningful difference that persisted through day 42.​
• High Remission Rates: At the six-week mark, 53% of participants who received the single psilocybin dose achieved full clinical remission, compared to only 6% of those in the active placebo group.​
• Uncertain One-Year Outlook: By day 365, the same 53% of the psilocybin group remained in remission, but no significant group difference remained because a large portion of the placebo group had naturally recovered over the year.​
• The Blinding Problem: Despite using niacin as an active physical placebo, almost all participants correctly guessed their assigned group, highlighting a methodological challenge where expectations might partially inflate treatment scores.​

Author: Press Office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute

Original Research: Open access.
“Acute and Late Effects of Psilocybin on Symptoms in Major Depression: a randomised clinical trial” by Hampus Yngwe, Pontus Plavén-Sigray, Carl Johan Ekman, Eva Henje, Anders Berglund, Mikael Tiger, Maria Beckman, and Johan

Single Psilocybin Dose Sparks Rapid Depression Remission - Neuroscience News

A single dose of psilocybin triggers rapid depression remission in 53% of patients.

neurosciencenews.com

 

[mr peabody]

Inflammation and Depression*​

by Luana Steffen | Intelligent Living

For several decades scientists have seen a distinct association between inflammation and depression. Various autoimmune conditions, including inflammatory bowel disease, have been steadily linked with higher rates of mood disorders, while chronic, low-grade inflammation has been linked with lower dopamine levels and motivation. However, there is still significant debate over what kind of causal mechanism could directly connect inflammation with depression.

Histamine

A new robust study conducted by an international team of scientists has discovered one possible missing link clarifying how inflammation leads to depression. Through a series of mouse experiments, the team found evidence that inflammation-induced histamine activity can inhibit the release of serotonin in the brain. Thus, the findings suggest histamine may play a significant role in triggering depression.

The scientists started by making a new kind of microelectrode that can be implanted in the hippocampus of mice to measure serotonin levels, a critical mood-regulating neurotransmitter, in real-time. Serotonin is often focused on as a therapeutic target for depression.

Next, the team injected the mice with a toxin that triggers inflammatory responses to investigate how inflammation impacts serotonin activity. Within only minutes, serotonin levels were seen plummeting in the animals’ hippocampus. Since the toxin used in the experiment cannot cross the blood-brain barrier, the researchers were confident that inflammation was responsible for the serotonin reduction.

Further investigations led to the researchers discovering that increased histamine levels in the brain, produced as part of the animals’ inflammatory response, caused the reduction in serotonin levels by “acting on inhibitory histamine H3 heteroreceptors on serotonin terminals.”

The next phase of the experiment involved administering the animals’ escitalopram, a common anti-depressant drug belonging to a family known as selective serotonin reuptake inhibitors (SSRIs). However, serotonin levels did not increase in the animals treated with the inflammatory toxin SSRI administration. Instead, the anti-depressant’s effect was blunted since it hindered the brain’s ability to clear histamine, interfering with the regulation of serotonin levels.

Finally, the researchers treated the animals with histamine-reducing drugs alongside the anti-depressant to confirm this potential mechanism. And sure enough, this combination of drugs saw serotonin levels increase in the inflammation-induced mice.

Parastoo Hashemi, the study’s lead author, said:
​

Our work shines a spotlight on histamine as a potential key player in depression. This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.​

People who have or know someone with allergies and hay fever are familiar with histamines. These molecules play a significant role in the body’s immune response to foreign pathogens and influence sleep cycles, sexual function, and blood pressure.

Standard anti-histamines that are available over-the-counter for allergies work by hindering the ability of histamine molecules to bind with specific histamine receptors. Therefore, it is essential to note that these common anti-histamines for allergies do not affect this newly discovered mechanism.

Instead, in this study, the scientists used drugs that completely stifle histamine levels across an entire body. Therefore, since histamine is vital for various bodily functions, it is not feasible to translate these findings to humans just yet.

In addition, this research, published in the journal JNeurosci, was only conducted on animals. That said, more work is needed to confirm whether the exact mechanism is at play in humans. Nevertheless, the team suggests that it is possible this inflammation-induced histamine mechanism could help shed light on some of the inconsistencies in SSRI anti-depressant effectiveness from patient to patient.

However, suppose it can be validated in humans, and a pharmacological target is identified. In that case, new depression treatments can be developed, including ones that boost the efficacy of currently available SSRI drugs by preventing histamine from disrupting serotonin levels.
​

Inflammation is a whole-body response and is therefore hugely complex. Depression is similarly complex, and the chemicals involved are affected in myriad ways by both genetic and environmental factors. Thus, we need to look at more complex models of depression behaviors in both mice and humans to get a fuller picture of both histamine and serotonin’s roles in depression.​

Gut microbiota

Unhealthy gut microbiota can lead to several conditions, including inflammation and depression. For example, a 2019 study found that two different gut bacteria are depleted in people with depression, regardless of anti-depressant treatments. They discovered this from the first population-level study on the link between gut bacteria and mental health, precisely quality of life and depression.

Therefore, what you eat is significant. A good diet full of fiber and varied fruits and vegetables is vital for a healthy gut microbiome. Aside from fighting depression, making the right food choices can also help control histamine levels and combat inflammation.

Foods to control histamine levels

A healthy diet comprises moderate histamine levels. However, some foods that are high in histamine can trigger inflammatory reactions and other negative symptoms.

Histamine-rich foods to avoid:​

• Alcohol and other fermented beverages;​
• Fermented foods and dairy products, like yogurt and sauerkraut;​
• Dried fruits;​
• Avocados;​
• Eggplant;​
• Spinach;​
• Processed or smoked meats;​
• Shellfish;​
• Aged cheese​

Foods that activate histamine release in the body:​

• Alcohol;​
• Bananas;​
• Tomatoes;​
• Wheat germ;​
• Beans;​
• Papaya;​
• Citrus fruits;​
• Nuts, specifically walnuts, cashews, and peanuts;​
• Food dyes and other additives.​

People who have histamine intolerance should incorporate low-histamine foods into their diet to help reduce negative symptoms. However, keep in mind that a histamine-free diet does not exist.​

Some of the best foods to eat that are low in histamine:​

• Fresh meat and freshly caught fish;​
• Non-citrus fruits;​
• Eggs;​
• Gluten-free grains, like rice and quinoa;​
• Dairy substitutes, such as almond milk and coconut milk;​
• Fresh vegetables except for spinach, avocados, tomatoes, and eggplant;​
• Cooking oils, like olive oil.​

Foods to fight inflammation

Aside from depression, inflammation can result in many harmful health conditions, like cancer, heart disease, and obesity. What you eat plays a big part – it can either reduce inflammation or cause it.

A minor inflammation is natural because it’s part of the body’s immune response necessary for healing. However, when it’s out of control, that’s when serious health issues occur. So, here are some tips and a list of the best things to eat that will keep your inflammation levels to a minimum.

First: Eliminate foods and beverages that cause inflammation, including high-sugar, processed, and fatty foods (like doughnuts, fried chicken, and soda, for example).

Second: Incorporate foods that curb inflammation. These include:​

• Oily fish- such as anchovies, herring, mackerel, salmon, sardines, and tuna.​
• Whole grains- Avoid refined white bread, rice, cereal, and pasta. Instead, consume whole grains.​
• Dark leafy greens- such as broccoli, brussels sprouts, kale, spinach, and swiss chard.​
• Avocados.​
• Nuts.​
• Peppers.​
• Tomatoes.​
• Beets.​
• Turmeric.​
• Garlic and onions.​
• Extra virgin olive oil.​
• Parsley.​
• Berries.​
• Green tea and Matcha.​
• Dark chocolate and cocoa.​

Some foods help relieve tension more than others, while the lack of some stress-fighting foods can make you feel worse (like anxiety, depression, and panic attacks).

Of course, occasional bouts of stress are usual. But chronic stress isn’t, and it can lead to severe health problems not only mentally but physically too (like heart disease). So, to help, here’s a list of some of the best things to eat that will keep your stress levels to a minimum.

Green Leafy Vegetables: Spinach and other leafy vegetables contain a vitamin called folate (also known as folic acid or Vitamin B9) that reduces the risk of depression symptoms.

Sweet Potatoes: Sweet potatoes are a great source of whole, nutrient-rich carbs, vitamin C, and potassium, helping lower stress hormone cortisol levels. Chronic stress can lead to cortisol dysfunction, resulting in pain, inflammation, and other adverse effects.

Artichokes: Artichokes are high in magnesium, potassium, vitamins C, and vitamin K, all of which are essential for a healthy stress response. On top of that, they’re especially rich in prebiotics, a type of fiber that feeds the good bacteria in your gut.

Artichokes contain a concentrated amount of prebiotics like fructooligosaccharides (FOSs), which have been shown to reduce stress levels in animal studies. Another study demonstrated that people who consumed five or more grams of prebiotics daily experienced improved depression and anxiety symptoms.

Broccoli: Eating broccoli or other cruciferous vegetables can reduce your risk of mental health disorders as well as certain cancers and heart disease. Broccoli can be considered a superfood with concentrated nutrients, including stress-fighting magnesium, folate, and vitamin C.

Another excellent thing broccoli provides is a high amount of sulforaphane – a sulfur compound with neuroprotective properties. In addition, it may offer anti-depressant and calming effects – and vitamin B6, which is linked to a lower risk of depression and anxiety in women if taken in higher amounts. One cup (184 grams) of the vegetable (cooked) has more than 20% of the daily value for vitamin B6.

Blueberries: Blueberries are high in flavonoid antioxidants, which provide powerful neuroprotective and anti-inflammatory effects. Eating flavonoid-rich foods may protect against depression and improve your mood.

Organ Meats: The heart, liver, and kidneys of animals are an excellent source of B vitamins – especially B6, B12, folate, and riboflavin. These vitamins are essential for stress control because they produce neurotransmitters like serotonin and dopamine that regulate mood.

Turkey Breast: Turkey breast contains the amino acid tryptophan, which helps produce serotonin – the chemical that regulates feelings of well-being, happiness, and hunger. Other foods high in tryptophan include beans, lentils, nuts, seeds, oats, tofu, fish, and eggs.

Fatty Fish: Fatty fish like herring, mackerel, salmon, and sardines are high in mood-enhancing omega-3 fats and vitamin D. Omega-3s are so essential for brain health that low omega-3 intake may cause increased anxiety and depression. Similarly, low levels of Vitamin D can result in an increased risk of anxiety and depression.

Dark Chocolate– small indulgence of dark chocolate (70% cocoa or more) may have the power to regulate your stress levels because it can reduce stress hormones like cortisol.

Chamomile Tea– The medicinal herb Chamomile has been used as a natural stress reducer since ancient times. It can be consumed to promote restful sleep and reduce depression and anxiety symptoms.

Psychedelics

In 2019, Johns Hopkins researchers surveyed the anti-depressant qualities of DMT – a short-acting psychedelic. They reported that it resulted in extraordinarily positive improvements in self-reported depression and anxiety when given in a ceremonial group setting.

Another study, conducted last year, revealed preliminary evidence that psychedelic drugs can improve mental health by forcing individuals to confront their issues and become more accepting of distressing experiences. The research adds to a growing body of work that suggests using psilocybin substances can result in long-term improvements in depressive symptoms.

According to the study’s author Richard Zeifman, a Ph.D. student at Ryerson University, psychedelic therapy is promising as a novel treatment for a variety of mental health conditions, including:​

• Anguish, associated with a life-threatening illness.​
• Major depressive disorder.​
• Substance use disorders.​

Zeifman added:
​

Our results provide further support for the negative mental health effects associated with avoidance. This can be summed up with a saying that is often used in the context of psychedelic therapy, that ‘The only way out is through.’​

Besides confronting your problems, other simple ways to avoid depression include:​

• Reducing alcohol and drug use.​
• Quitting nicotine.​
• Exercising regularly.​
• Cutting back on social media.​
• Staying away from toxic people.​
• Reducing stress.​
• Minimizing your daily chores.​
• Getting plenty of rest.​

*From the article here :

Links To Depression And How To Prevent And Reduce It

Here are many factors that cause depression and what foods you can eat to help control it, lower histamine levels, and fight inflammation.

www.intelligentliving.co

 

[mr peabody]

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PSYCHEDELICS MAY EASE CANCER PATIENT'S DEPRESSION, ANXIETY

by Manish Agrawal | Washington Post | 2nd April 2022

Throughout my medical training and more than 20 years as a practicing oncologist, the emphasis in cancer treatment has always been on treating the tumor. But I also know that my patients’ suffering extends far beyond the physical. Over time, the deep, emotional distress that turns their lives upside down has gone from a whisper of concern to a deafening, unavoidable blast.

Those of us who treat cancer patients cannot deny the painful emotions they and their families experience. Facing that reality includes looking for practical, effective ways of easing the pain. The trouble is the tools to address the emotional dimensions of cancer have been scant.

That began to change a few years ago when evidence emerged indicating that psychedelics could reduce death-anxiety that many cancer patients experience. In the United States, more than 90 clinical trials are exploring whether one of these substances — psilocybin, a natural hallucinogenic found in certain mushrooms — can give patients the emotional relief they desperately seek.

Along with my work as an oncology clinician, I’m the principal investigator for one of those trials. Our trial is suggesting that these drugs, which were banned decades ago, might have a meaningful, positive effect in treating major depression, anxiety other mood issues.
‘Acid Test’: The case for using psychedelics to treat PTSD, depression

Dramatic changes

One patient with metastatic cancer, who has suffered from severe emotional distress because of her difficult diagnosis and treatment, decided to participate last year in the clinical trial my colleagues and I were conducting. She found that shortly after a single psilocybin therapy session her life and perspective changed dramatically.
Her session had been quite challenging in contrast to the typical mystical experience some have recounted; she faced her death directly, which she found to be painful. Then, while at her lake house a day after her psilocybin session, as the light was fading into darkness and the chirping of crickets rose to a crescendo, she felt a blanket of peace envelop her, and she arrived at an insight: All these crickets would inevitably soon die and a new crop of them will take their place. It reminded her that, when she was born, she was replacing others who had died, and, with her death, others will come after her. All this was a part of the natural cycle.

This feeling of being part of something greater than herself, of seeing how she fit into the complex puzzle of nature, helped her place her fast-approaching mortality in a larger context and with that the heavy weight of anxiety about her death lifted.

In the past, I might have said to her, “Dying is natural; it’s part of the human experience,” but without this experience, it would not have landed well. She had to feel this in her whole person, not just as an intellectual or philosophical exercise. By her own account, it was an experience that she had never had before and that lasted for many weeks and months more. She could only attribute her dramatic change only to her psilocybin treatment.

Another trial participant recalled during her psilocybin session a scene in nature where she saw trees that had died and were filled with living organisms and nutrients that allowed younger trees to feed and grow. It left her feeling that, even after her death, she would leave to her children a legacy that provides them with emotional and spiritual support.
​

Promising evidence

Results from the clinical trials my colleagues and I conducted have not yet been published, so it is too soon to make any definitive conclusions about the use of psilocybin for treatment of depression. But the pre-publication evidence is promising: half of all the 30 participants no longer had clinical depression eight weeks after a single dose of psilocybin and accompanying therapy, and 80 percent of the people studied had their depression scores drop by at least 50 percent. (The trial measured depression with the Montgomery-Asberg Depression Rating Scale, or MADRS.)

These clinically significant results are consistent with a growing number of other studies on psychedelics’ effect on illnesses, such as depression and post-traumatic stress disorder. One small study from Imperial College London, reported in the New England Journal of Medicine last year, suggested that psilocybin could ease symptoms of major depressive disorder (or MDD) at least as effectively as a conventional selective serotonin reuptake inhibitor antidepressant — but with potentially fewer side effects. Another study, conducted at Johns Hopkins Bayview Medical Center, indicated that psilocybin treatments provided relief from MDD among cancer patients and others. And a study published last year concluded that the psychedelic drug MDMA “represents a potential breakthrough treatment” for PTSD.
Ecstasy could be ‘breakthrough’ therapy for soldiers, others suffering from PTSD

The promise of psychedelic therapy is significant for not only patients but also clinicians like me who have exhausted our arsenal to help those crushed by the emotional burden of cancer.

Intense psychological agony

Oncologists are well-equipped to fight the physical threats of cancer with powerful, yet sometimes-imperfect tools including chemotherapy, radiation and surgery, but they often feel helpless when it comes to treating the intense psychological agony many patients experience.

Many of the approved therapies to treat my cancer patients’ mental health don’t help them. Not surprisingly, research has shown a high degree of depression and burnout among oncologists as well, some of which stems from watching patients suffer and not being able to help.

Clinical trials studying psilocybin and MDMA are now picking up where others left off before 1970, when the federal government passed the Controlled Substances Act that banned the use of and even research into psychedelics. They’re finding that, for some people, even a single dose of psilocybin in a supportive environment — accompanied by therapy — may be more impactful and have longer lasting effects than current protocols: talk therapy combined with existing antidepressant drugs.

Like many of my colleagues, I was initially skeptical about embracing psychedelics, which many see as easily abused recreational drugs. But the growing evidence from rigorous research has caused many physicians, like me, to reassess. In the trials at our center, we provide treatment within a highly controlled, safe environment. The format is the opposite of a traditional “take two of these and call me in the morning” form of care.

Trial participants are screened based on a set of inclusionary and exclusionary criteria and meet for hours before their session with our well-trained therapists. And a team closely monitors the administration of the treatment, sitting with each patient until the effects of the drug completely wear off. There are then several meetings after the session to help integrate the psilocybin session, so the insights and experience gained continue to have benefit.

The research is also helping to diminish concerns many have about the potential for the abuse of psychedelics. While abuse is always possible, developing standards of care and rigorous training criteria help assure that trial participants and future patients are getting safe and qualified care.

One of the messages I share with patients is that the deep distress and the dark feelings they experience after being diagnosed with cancer are normal and deserve as much attention as the physical effects of their cancer. Patients should not have to go somewhere outside the cancer treatment center to get that help.

If further research into psychedelic therapy is validated and approved by the Food and Drug Administration, I think cancer centers would do well to offer it as part of an in-house continuum of cancer care. Besides chemotherapy and radiation, oncologists must work to address the psychological issues their patients face.

I have never witnessed the sort of dramatic response to any medical intervention as I have with some patients through psychedelic-assisted therapy. It is not a magic bullet or cure for a cancer patient’s suffering — and it won’t change their prognosis or life expectancy. But it could be a spark that begins their healing journey, helping them come to terms with their most difficult fears.

Manish Agrawal is an oncologist for Maryland Oncology Hematology at the Aquilino Cancer Center in Rockville, Md., where he is medical director. In 2021, he helped launch Sunstone Therapies, whose mission is to address the emotional effects of cancer diagnoses.

https://webcache.googleusercontent.com/search?q=cache:EW0-9oL4MBoJ:https://www.washingtonpost.com/health/2022/04/02/cancer-psychedelics-psilocybin-anxiety-depression/+&cd=2&hl=en&ct=clnk&gl=us

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[mr peabody]

Compassionate Use – Psychedelic Therapy for those who can’t wait

“Obviously, bureaucracy is not a human being. People have compassion. Bureaucracies don’t always have compassion.' -- Spencer Hawkswell

Psychedelic Review - December 29, 2020 - by Abigail E. Calder, MSc

For the moment, psychedelic-assisted therapy takes place primarily in clinical trials. Legal, widely accessible treatment is at least several years away, assuming these trials continue to find positive results. But for some of the most desperate patients, it is already here in the form of compassionate use. ​

What is compassionate use? ​

Compassionate use, also known as expanded access, allows severely ill patients to try an experimental treatment if conventional therapies fail them.1 Drug approval policies are slow, and there are good reasons for not rushing medicines to market prematurely. But while some patients can afford to wait, for others, it is now or never. Compassionate use acknowledges desperate patients’ suffering and allows them to legally access promising medicines that have not yet been fully approved. Certain countries currently allow compassionate use of LSD, MDMA, and psilocybin, with some doctors calling for these programs to expand as soon as possible.​

“Mind-dissolving” therapy with LSD​

One country in the world allows legal LSD-assisted psychotherapy: LSD’s original birthplace. In Switzerland, LSD therapy has been quietly available to a small number of patients since 2015. Of course, there are limitations: patients must live in Switzerland, and they must attempt approved treatments first. Apart from that, psychiatrists use their professional judgment—and current science—to decide which patients will benefit most from LSD-assisted therapy.

The evidence in favor of LSD’s safety and efficacy is strongest for depression, alcohol abuse, and especially anxiety associated with life-threatening diseases. The small sample sizes of many studies on LSD suggest restraint when interpreting the results. However, LSD’s effects closely resemble those of psilocybin, which modern scientists have researched more heavily than LSD itself. This leads some psychiatrists to generalize promising results from psilocybin studies to LSD, although research should still investigate possible differences in efficacy between the two.

Switzerland is not only unique for offering LSD-assisted therapy; it also has its own treatment philosophy. In most clinical research today, patients receive one large dose of a psychedelic drug sandwiched between several drug-free therapy sessions. Switzerland, on the other hand, largely integrates them into psycholytic therapy. “Psycholytic” means “mind-dissolving,” referring to the theory that psychedelics dissolve the mind’s defenses to the benefit of the therapeutic process. Rather than one large dose, psycholytic therapy uses multiple, often smaller doses embedded in conventional psychotherapy, starting at 30µg for LSD. According to Swiss psychiatrists, this allows patients to contact important issues in their lives quickly and have deeply spiritual experiences whose benefits extend beyond the therapy itself.​

MDMA therapy for PTSD​

Of all the substances lifted by the rising tide of the current psychedelic renaissance, MDMA could gain approval first. Its ability to ease the processing of traumatic memories makes it particularly promising for treating post-traumatic stress disorder (PTSD). In one of several Phase 2 trials, 83% of patients no longer fulfilled clinical criteria for PTSD after receiving MDMA-assisted therapy, compared to 25% of patients who received non-pharmacological therapy. Another study found that 67.8% of patients were still cured one year after treatment – and many had previously had PTSD for over a decade.

Impressive data like this has convinced regulatory bodies in multiple countries to allow MDMA-assisted psychotherapy in special cases. Switzerland permits it according to the same regulations as for LSD, and Israel has also allowed 50 patients to receive MDMA treatment for PTSD outside of clinical trials. The United States, too, now has an expanded access program directed by MAPS. Researchers at MAPS hope this is just the beginning: they are aiming for widely available MDMA-assisted psychotherapy by 2023.​

Psilocybin therapy for end-of-life distress​

Like MDMA, psilocybin-assisted therapy has strong data behind it which has begun to justify expanded access. Although psilocybin may be useful for a broad spectrum of mental health issues, one particularly well-established application is treating distress in patients with life-threatening diseases. In a landmark 2016 study of cancer patients with depression and anxiety, 80% of participants experienced clinically significant improvements that lasted for at least six months after psilocybin treatment.<span>10</span> Over half of them no longer had depression or anxiety at all. Further studies have supported and expanded upon these findings.

Based on these impressive data and the urgency inherent in treating terminal patients, Canada has begun allowing compassionate use of psilocybin therapy. While initial permissions were limited to four terminal cancer patients, they will likely not be the last. And because someone must be competent to administer psilocybin therapy, Canada has granted 17 healthcare professionals access to psilocybin for use in their training. According to those therapists, patients should be led into psychedelic experiences by those familiar with the terrain.​

Doctors appeal for more access​

While compassionate use of psychedelic therapy has been granted for a few patients in a few countries, some doctors are not satisfied with the pace of government approval. They argue that for patients with life-threatening diseases, the clock is running out, and indeed runs out for more people every day. To them, “life-threatening” does not only mean terminal illness: it also includes diseases with an elevated risk of suicide, like depression and PTSD. Their argument is simple: especially for treatment-resistant patients, the expected benefits far outweigh the risks, including the risks of doing nothing.

A recent policy paper, co-signed by several prominent doctors and scientists, focuses on the debilitating chronic pain condition of cluster headaches. Cluster headaches affect millions of people worldwide and rank among the worst pain known to humankind — right up there with childbirth and kidney stones. Nicknamed “suicide headaches” by patients, they can be excruciating enough to cause PTSD. They also share commonalities with other chronic conditions eligible for compassionate use: they increase the risk of suicide, current treatments aren’t always effective, and preliminary studies suggest that psychedelic drugs can help.

According to the signatories of the policy paper, this combination of patient need and promising safety and efficacy data should justify access to psilocybin therapy. To the chagrin of many patients and their doctors, it is not legally available outside of clinical trials, even for compassionate use.

Psychedelic therapy, once a strange and obscure research topic, may now have enough good data behind it to justify a small place in the medical system. Compassionate use is where experimental treatments begin migrating from research labs to the real world. For many, treatment with unapproved drugs could potentially hurt more than help. But for some, doing nothing is far worse. As one Canadian patient said after receiving psilocybin therapy, “The acknowledgment of the pain and anxiety that I have been suffering with means a lot… [Psilocybin] changed everything for me.”

Compassionate Use - Psychedelic Therapy for Those Who Can’t Wait

“Obviously, bureaucracy is not a human being. People have compassion. Bureaucracies don’t always have compassion.

psychedelicreview.com

 

[mr peabody]

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New psychedelic-like drugs could treat depression without making you trip

Neuroscience News - Date: May 13, 2026 - UC Davis

Summary: UC Davis researchers created brand-new psychedelic-like compounds by shining UV light on amino acid-based molecules. These compounds activated key serotonin receptors tied to brain plasticity and mental health benefits, but surprisingly did not cause hallucination-like behavior in animal tests. Scientists say the discovery could lead to future treatments for depression, PTSD, and addiction without the intense psychedelic experience.

Researchers discovered a new class of psychedelic-inspired molecules that may boost brain healing without causing hallucinations. The unexpected finding could pave the way for safer treatments for depression, PTSD, and addiction.

Researchers at UC Davis have developed a light driven technique that converts amino acids, the molecules that make up proteins, into compounds that behave similarly to psychedelics in the brain. These newly created molecules activate serotonin 5-HT2A receptors, which are associated with brain cell growth and are considered promising targets for treating conditions such as depression, PTSD, and substance-use disorder. Unlike traditional psychedelics, however, the compounds did not produce key hallucinogenic-like behaviors in animal testing.

The findings were published in the Journal of the American Chemical Society.

"The question that we were trying to answer was, 'Is there whole new class of drugs in this field that hasn't been discovered?" said study author Joseph Beckett, a Ph.D. student working with Professor Mark Mascal, UC Davis Department of Chemistry, and an affiliate of the UC Davis Institute for Psychedelics and Neurotherapeutics (IPN). "The answer in the end was, 'Yes.'"

The work could lead to a more efficient and environmentally friendly approach for discovering serotonin-targeting drugs that provide some of the therapeutic effects linked to psychedelics without dramatically altering perception.

"In medicinal chemistry, it's very typical to take an existing scaffold and make modifications that just tweak the pharmacology a little bit one way or another," said study author Trey Brasher, also a Ph.D. student in the Mascal Lab and an affiliate of IPN. "But especially in the psychedelic field, completely new scaffolds are incredibly rare. And this is the discovery of a brand-new therapeutic scaffold."

Building new psychedelic-like molecules with UV light

To create the compounds, the researchers combined several amino acids with tryptamine, a naturally occurring metabolite derived from the essential amino acid tryptophan. The team then exposed the resulting molecules to ultraviolet light, triggering chemical changes that produced entirely new compounds with potential medical applications.

Using computer modeling, the scientists evaluated how strongly 100 of the new compounds interacted with the brain's 5-HT2A serotonin receptor.

From that group, five compounds were selected for more detailed laboratory testing. Their activity levels ranged from 61% to 93%. The strongest performer acted as a full agonist, meaning it could trigger the maximum biological response possible from the 5-HT2A receptor system.

Researchers named this compound D5.

A surprising result in mouse experiments

Because D5 fully activated the same receptor targeted by psychedelics, the scientists expected it to produce head twitch responses in mice, a widely used indicator of hallucinogenic-like effects.

That did not happen.

Even though D5 strongly activated the receptor, the mice did not display the expected psychedelic-like behavior.

"Laboratory and computational studies showed that these molecules can partially or fully activate serotonin signaling pathways linked to both brain plasticity and hallucinations, while experiments in mice demonstrated suppression of psychedelic-like responses rather than their induction," Beckett and Brasher said.

Why didn't the compound cause hallucinations?

The research team now plans to investigate whether other serotonin receptors may be reducing or blocking the hallucinogenic-like effects produced by D5.

"We determined that the scaffold itself possesses a range of activity," Brasher said. "But now it's about elucidating that activity and understanding why D5 and similar molecules are non-hallucinogenic when they're full agonists."

New psychedelic-like drugs could treat depression without making you trip

UC Davis researchers created brand-new psychedelic-like compounds by shining UV light on amino acid-based molecules. These compounds activated key serotonin receptors tied to brain plasticity and mental health benefits, but surprisingly did not cause hallucination-like behavior in animal tests...

www.sciencedaily.com