DEPRESSION | +80 articles

[mr peabody]

Microdosing LSD for Treatment-Resistant Depression

by Sherry Amatenstein LCSW | Third Age

For years Rachel found herself battling a recurrent and noxious depression. She tried Zoloft but it had little effect. Nor did regular psychotherapy. In 2010 the then 45-year-old, a life coach, yoga devotee, and single mother began contemplating hallucinogens. She’d tried an LSD tab decades before at a music festival and found the 20-hour experience “intense but scary.”

However, her research into the efficacy of microdosing LSD (between 1 and 10 micrograms, below one/tenth of a regular dose) under controlled conditions convinced her to try this unorthodox “treatment.”

“The idea is to produce subtle changes in cognitive function without having to enter that world of hallucinogens where I experienced the walls collapsing in on me. Swallowing a few drops I put on a mint didn’t seem too risky. Yes, this was crude and unscientific but the protocol is very new.”

For five years Rachel microdosed LSD every three days. Afterward she typically did yoga or meditated. “I wasn’t taking it and going to a party or kite-surfing afterward! And I always waited to dose until my daughter left for school.” She finished, “It’s not like drinking alcohol or smoking pot. LSD made me very lucid and very sharp.”

The lucidity helped her combat the “emotionally cancerous mental loops in my head and find more joy.” Three years after stopping she still feels clarity and joy. But, she cautions, “Everyone has to make her own decisions about giving LSD a try.”

Ayelet Waldman’s 2017 article How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life is an eye-and-mind-opening look at this controversial drug as a tool to achieve emotional well-being. And Michael Pollan’s just-released How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence is not just a story of personal experimentation, but also a deep dive into the revolution occurring in the scientific and academic communities about psychedelics as healing agents.

However, caveat emptor. What is billed as the first comprehensive study about the potential effects of LSD microdosing is in the early stages.

In the meantime, Dr. Gladys Frankel, a NYC-based clinical psychologist who has been on the faculty of Weill Cornell College of Medicine, is among the many mental health practitioners urging caution. She says flatly, “Microdosing is a horrible idea. I have had patients who have been fried after one dose. A patient would look at a door and see the wood grain flowing, moving all of the time, years later! For people who have a vulnerability to schizophrenia, this can potentiate it.”

Julie Barron LPC offers an invaluable perspective on this issue. Founder of the Michigan Psychedelic Society, Barron, who has a Masters in Transpersonal Counseling Psychology explains, “When I was much younger I was very interested in psychedelics and studied at Naropa University where I was taught how to do therapy while in an altered state of consciousness.” Years later, she was in the midst of a depression for which she was both in talk therapy and on a cocktail of drugs – sleeping meds, pills for anxiety and depression. This regimen was having a detrimental effect on her life. So she began to microdose. “It had and has a huge positive impact. I was able to stop the pharmaceuticals.”

Clients come to her for advice on microdosing. “I can’t supply the drug but I’ll do therapy with them and share education and safety advice. Over all, I’m the feedback person. They’ll report, ‘I tried this, and such was my experience. What should I try next?’” says Julie. “I am very clear, it’s a personalized process. There is no one size fits all microdose strategy.” Indeed, sometimes Julie microdoses every day for weeks on end. Other times her protocol is every other day; sometimes once a month.

“Someone who hasn’t tried psychedelics can’t really help others. We are not a society that understands this from normal experience. I help people learn how to integrate microdosing into everyday life,” Julie says.

https://thirdage.com/considering-mic...ad-this-first/​

 

[mr peabody]

Ibogaine rescued me from overwhelming anxiety and depression

by Holly Stein | Reset.me | 12 Mar 2015

For the last 12 years I’ve battled with general anxiety and depression and have taken an insane variety of anti-anxiety and anti-depressant pharmaceuticals (all of which either didn’t help, made me better but disconnected, or left me feeling worse than before). I’ve been through hundreds of hours of therapy and spent countless hours reading self-help books using different approaches and methods.

I had ups and downs over the years, and after a steady improvement I weaned off anti-depressant and anti-anxiety medication with the support of my psychiatrist in January of 2012.

In July 2013, I had my first panic attack since I was 18, and after that my anxiety escalated tremendously. It felt like everything started to make me panic, and I started to slowly lose my confidence and ability to function. From suffering and feeling massive anxiety throughout my whole wedding day, to panicking on chair lifts snowboarding and developing anxiety on airplanes and boats, I started to lose the ability to do things I enjoyed. Worse yet, “everyday” normal things started to fall apart — from getting in elevators (as a wedding planner I ride in elevators all of the time), not being able to be a passenger in a car, being scared of getting sick after eating, and much more. I felt like the walls were closing in on me. I was physically and mentally sick with anxiety all of the time.

I’ve had multiple weddings where I’ve sat outside an elevator for 10 minutes trying to “will” myself to get in, only to end up carrying my emergency kits up and down many flights of stairs. Nothing helped, and the anxiety led me to an onslaught of severe depression and dependency on my husband. I felt like the only thing I was good at was faking it. There was rarely a day that went by that I didn’t crawl into a ball in my bedroom and sob uncontrollably from depression. But as soon as I was in front of other people, at work, I could lock it up and put on the best fake smile around, which only made me feel worse.

I developed an extreme identity of self-loathing and was unable to control my emotions. I took every comment personally and blamed myself for everything that happened. About once a week someone would tell me to “eat a cheeseburger” or that I was too skinny, and while I would laugh it off, it left me feeling crushed and insecure.

I knew things were starting to unravel pretty badly when I started having suicidal thoughts. It got so bad that I had to ask my husband to get the gun out of the house because I really didn’t know what I was capable of when I was in those dark moments. However, rationally and logically, I knew everything. I knew to be positive, and to not say the word “can’t” and all of the most important tools to change these horrific mental habits, but I somehow lacked the ability to convert them into usable feelings and thoughts.

Researching and learning that psychedelics have an unbelievable success rate in curing anxiety, depression, PTSD and other mental struggles when used in the correct setting, I discovered the medicine, iboga, which is the bark of a root from Africa that has been used medicinally for hundreds, if not thousands of years. I then found a retreat overseas and researched and talked to them for months before booking a psycho-spiritual session with them in 2015.

Iboga is a very spiritual medicine, and from the moment I booked the trip in November, 2014, I knew I made the right decision. And then, from the moment I arrived, I could feel the medicine was working on me. During my stay I did two sessions with iboga, which we call “journeys.” They last about 10 hours each. The results were nothing short of life-saving. From the two journeys I had, I experienced visions that showed me where all of my anxiety, depression, insecurity, and self-loathing stemmed from when I was 9 years old. It showed me that I was beautiful, that I loved myself, and that I had everything I needed to overcome all of my struggles and fears, and that I could do it. It let me take all of the knowledge that I had and finally convert it into usable emotions and thoughts. Iboga is not a magic plant that solves all of your problems, but rather a tool that gives you the insight to conquer your demons. It was by far the toughest week I have ever gone through, but it was the most rewarding, life-changing weeks of my life and I would do it over a million times.

So many of us battle these demons of self-loathing, insecurity, anxiety, and depression, and we bury them deep inside as not to show weakness. I know, I was the best at it. Many people reading this will probably think, “No way — she always seemed so happy.” If anyone reading this wants to hear more about my experience and journey or learn more about iboga, or wants someone to talk to, please, please, please message me. I would love nothing more than to share my experience with you or lend an ear, with absolutely no judgment. If I can inspire just one person to keep going amongst their struggles, or inspire one person to try iboga, or inspire just one person to know they are not alone, that is more than I could ever ask for. Also, for those not suffering, please try to keep in mind that everyone is on their own path in life, doing the best they can, so be kind, and do your best to reserve judgment. What you see on the surface may not be the whole story. One kind comment can give someone the encouragement to keep going, while one hurtful comment can spiral someone’s entire day into depression. It’s happened to me a lot.

Lastly, I want to thank my husband, for all of the support and love he provided me through what was the darkest year of my life, which I know caused him tremendous pain at times as well. I also want to thank the providers at the retreat. You guys literally saved my life, and I will be forever grateful. I consider you all a part of my family, and you will all be forever in my heart. You guys know more about me than some of my closest friends, and I know I will never be able to repay you for what you’ve done for me. Know that I will be thinking of you often.

So, while 2014 was the worst year of my life, I can finally see that you can’t appreciate the good without the bad. I feel as if I’ve been to mental hell and back, and know that 2015 will bring (and already has), strength, love, inner-beauty, and the ability to conquer all challenges that come my way.

For the first time in my life I can say that I am genuinely happy, and it feels incredible! I have finally found the meaning of life.​

 

[mr peabody]

Tiny amounts of LSD for depression

by Olga Khazan | The Atlantic | 14 Jan 2017

Throughout Ayelet Waldman’s entire life, she’s been “held hostage by the vagaries of mood,” as she explains in her new book, A Really Good Day. She is a bestselling author, mom of four, and devoted wife, but her mental illness threatened it all. On good days, she was funny, productive, and kind. But on bad ones, she would catastrophize and snap at her family. So profound was her self-loathing at times that, planted on a couples’ therapist’s couch, she couldn’t bring herself to say that her husband, the novelist Michael Chabon, loves her.

A clear diagnosis (was it bipolar II or extreme PMS?), effective treatment (Effexor or Adderall?), and even the fleeting tranquility of a “good day” were all elusive. So Waldman did what few middle-aged American moms—though perhaps quite a few moms living in Berkeley, California—would think to do: Drop acid.

She procured a small, cobalt-blue bottle of diluted LSD from a friend of a friend. It was meant for “microdosing”—taking a fraction of a typical dose every few days, not enough to hallucinate or get high. Instead, the mind opens up just a crack and allows the bleak thoughts to escape for a while. (“Not so much an acid trip as an acid errand,” she says.)

Waldman begins taking two drops every three days. As the title suggests, over the month her supply lasts, she enjoys several unfrazzled, hyper-aware, “really good” days.

As a relatively drug-averse former attorney, Waldman offers a different perspective from the young tech entrepreneurs who have copped to microdosing to enhance their creativity and output. Her newbie status distinguishes her book, as does the unique way she weaves in digressions about drug policy and the criminal-justice system.

I spoke with Waldman recently about her experience; an edited transcript of our conversation follows.

Olga Khazan: What would you say was the biggest advantage for you of the microdosing, from your mood to your work?

Ayelet Waldman: I think for me personally the most important thing was that it kind of jump-started me out of a pretty significant depression.

Let's say an incident happens, someone says something that hurts your feelings, you see a tweet, whatever it is, some kind of stimulus, there's sort of this four-part process. You see this, there's the incident, you have an emotional reaction, a feeling, then you have a thought about that feeling, then you have a kind of impulse, and you act on the impulse, right?

What has always happened to me is those four separate responses were all sort of clumped together. So I would see something on Twitter, and I would respond right away. There was no time at which I thought, oh you're having a feeling about this, this is making me angry. Is it really making you angry or is it making you sad? Is it making you scared? And then, here's the impulse to act. Is that the right way to really be acting? I would do these things that I would regret, which would, for me, end up catalyzing kind of a depression.

For some reason the LSD microdose sort of slowed me down. I'm sort of trying to figure out 100 different ways to say this other than “mindfulness,” because I find the whole concept sort of aggravating. But I do think it came down to that. I felt happier or at least not as profoundly depressed almost immediately the very first day I took it. God, here I am twisting myself into a knot to not say “mindfulness,” but that really is what it is.

Khazan: You tried a lot of different pills in the past, antidepressants and other drugs. Those are all newer things and they have lots of scientists working on them, testing them, and trying to market them. Why do you think this old psychedelic worked better than all those different drugs?

Waldman: First of all, this is a one-month experiment, and there's no guarantee that it would have continued to work, and there's also no research that what I was experiencing wasn't, as I say in the book, "the mother of all placebo effects."

But let's say that it was, let's say that what I experienced taking the microdose was an actual, real effect and not all in my head. I took SSRIs, I took Wellbutrin, I took some of the ADHD drugs, but only very briefly. But they didn’t work to enhance neuroplasticity in the same way that LSD does. My theory is that it has something to do with the neuroplastic effects.

And the range of side effects of all these newer meds is really robust. LSD just doesn't have that many side effects. I mean except the most obvious one, which is if you take too much you start tripping your balls off.

Khazan: One thing I loved about this is you explore other issues in drug policy throughout the book. I was wondering if you could give a couple-sentence layman's-terms summary of why people can't just microdose with LSD. Why is it illegal to acquire even in really small amounts?

Waldman: Very simply, LSD is in Schedule 1. Schedule 1 is a drug that's considered to have no medical use and significant harm. Heroin is on Schedule I, LSD is on Schedule I, marijuana is on Schedule I. You say to yourself that doesn't make any sense. No medical use and significant harm? How is marijuana in the same place on the schedule as heroin? But therein lies the incoherence of American drug laws.

When LSD was invented in the 1930s, it was invented as a medicine, but in the 1960s it basically became a party drug. In the 1960s, the drug was criminalized, and the reason it was criminalized has everything to do with what was going on politically and socially in the country. So when Timothy Leary stands up in front of the massive crowd at the Human Be In at San Francisco and says "Turn On, Tune In, and Drop Out" to a group of basically all young people—and all white young people—that's very important.

They start taking LSD, and more importantly they start protesting the war, and their parents—nice, middle-class, white parents—freak out, and it becomes a scapegoat for this moment of social upheaval and it's thus criminalized. It's interesting because the criminalization of LSD is not like the criminalization of marijuana, the criminalization of cocaine, the criminalization of opium. Those drugs were specifically tied to different minority groups. Marijuana criminalization was a way to attack Mexican Americans, and cocaine was really a way to attack African-Americans.

LSD came from a different place. The idea that your kid would take a drug and start to trip just scared the shit out of everybody, so it became criminalized. And as soon as something is placed on Schedule I, all research grinds to a halt.

Khazan: How are the health risks of microdosing different from regular dosing?

Waldman: When I went into this, I assumed I was going to find all of these terrible things about the health risks of LSD, but if you took a microdose, maybe you could ameliorate those risks.

It turns out actually that there has never been a recorded incident of a fatal overdose of LSD. If I tried to think about what the health risks might be, it's not so much physical, it's not like MDMA, which causes a range of physical side effects. The danger, such as it is, is most closely related to something that was once called LSD psychosis. If you have a hallucinatory experience in an uncomfortable setting, it can be terrifying. The anxiety and the fear of that unpleasant experience can have emotional repercussions, particularly if you're someone with a mental illness.

So that's what I was worried about. Could it trigger some kind of anxiety in me that would be worse than the profound despair I find myself in now?

But the anxiety response is to the hallucination itself and to the feelings engendered by the hallucination, and microdosing isn't hallucinatory at all. And even though I'd read that a million times, I didn’t believe it until I took it. I mean you're taking LSD, aren't the walls gonna breathe?

The only thing that I noticed was it was easier for me to see the beauty in my natural world. I live in Northern California, it's ridiculously beautiful. You walk out my door and there's jasmine everywhere, the smell is overwhelming. And 99.999 percent of the time, I don't even notice. When I was microdosing I would stop and say, "wow, that is a beautiful redwood tree."

And again, here I am, back in that horrible mindfulness place where I have to use that word.

Khazan: Sometimes it's the only one that fits. Have you listened to the Reply All podcast episode where they microdose and have kind of a bad time?

Waldman: Yeah, I have.

Khazan: What did you think of that, how do you think your experience was different?

Waldman: First of all, here's a little tip: Don't take double the microdose and do something like drive a car on a really tiresome road trip. That seems like a mistake.

First of all, we don't know that what they took was LSD, because they didn’t test it. They also took too much. They were trying to keep it a secret from their colleagues, and that maybe enhanced their own anxiety.

The microdose is a little activating. If you've ever taken Adderall or Ritalin, I think for me it was not dissimilar to that, but much less intense. So I think if you're someone who doesn't normally experience those feelings of activation, then that might be disconcerting and unpleasant.

But, you know, no drug is for everyone.

Khazan: Given your history as a public defender working on drug cases, while you were doing this did you ever get paranoid and think "I'm gonna get arrested!"

Waldman: I decided that I didn’t want to stop but when my bottle ran out, because I was feeling so much better and I cannot understate how depressed I was. It was the closest I've ever come to being suicidal. I would Google the effects of suicide on younger children and older children, because I have both.

But I do think I would have destroyed my marriage as a kind of suicide because it's so important to me, and because I love my husband so much, and my marriage is such a source of comfort and strength. I think destroying the thing that made me feel the most safe in the world was how I would have effectively committed suicide.

But I woke up and took the dose, and 90 minutes later, the fog lifted. I hadn't felt like that for months and months and months.

So at the end of 30 days, I was like fuck that, I am not going back to that pit. I'm going to go buy drugs.

So I found a person, a number, and I texted the number, and the individual who I called “Lucy” texted me back, and I was all set to go buy drugs. I think I wanted five doses or ten doses, which I thought would carry me for a year.

Khazan: And they were like, “can you buy 60 doses?”

Waldman: "Yeah, I can't separate it, could you take 60?" And that pumping up the figure is just what happened to every one of my clients [when I was a defense lawyer]. That like, "I wanna buy a little methamphetamine” ... “oh here take a lot!” That's what you do when you wanna get someone into a mandatory minimum jail sentence.

So I was in my very lovely neighborhood in Berkeley, outside a Lululemon, when I decided that the mighty forces of the DEA had been marshaled to bring down this middle class, middle-aged mom of four.

I ran home and sat in bed and readied myself for incarceration. I was like, “Alright, you'll be able to read, there's lots to read. You're a lawyer, you can help people, there are a lot of people in jail who need legal help. You can't practice law, but you can surely be like a jailhouse lawyer." I was sitting there figuring out how I was going to turn my period of incarceration into an altruistic enterprise.

I'm constitutionally incapable of buying illegal drugs. I've just never bought any illegal drugs. Anything I've ever taken has just been given to me.

Khazan: The kind of shady nature of this, I think, does discourage people from trying it because it's not fun to try to acquire.

Waldman: It's so shady. It's true. The big thing I say to my kids, every time I say goodbye to them is "use a condom, test your molly." Because I really believe that one of the most problematic side effects of criminalization is no one knows what they're taking and especially now when it's so much cheaper and easier for criminal enterprises to create these “alphabetamines,” some of which are incredibly dangerous. Synthetic cannabinoids are just a nightmare. I live in fear that one of my kids is gonna decide they're gonna take molly one night and end up ingesting one of those.

Khazan: Are you still worried about getting into legal trouble, having published this book?

Waldman: I was quite confident that nothing was going to happen. I think it's grandiose to imagine that I am a high priority of Jeff Sessions. That said, we have just elected a president whose attorney general is so retrograde, such a dinosaur in his thinking about the drug war, that anything is possible.

A consensus had formed before this election that the war on drugs was costly and ineffective. And simultaneously with electing Donald Trump and bringing in Jeff Sessions, we also legalized marijuana in a bunch of states. So it's a really schizophrenic moment in history. So yeah, I think it's possible.

Khazan: I noticed that a couple times in the book when you talked about your experiment with people, the reactions were sort of mixed. You almost felt like people were judging you a little bit. Now that it's a little more public and there's a book about it, are people still judging you or have they become more accepting?

Waldman: There are certainly people who will judge. Some people say, “Oh that Ayelet Waldman, being confrontational again, being outrageous again," as if that were my goal. The response from people who have dealt with issues like depression has been overwhelming and wonderful. Because even if they have no interest in doing something like this, they know that other people who suffer from depression, from anxiety, from bipolar disorder, they know what it's like to be desperately searching for a way to feel better.

You know my parents, my straight-up parents, were so wonderful and supportive and nonjudgmental. And judgment is built into the Waldman DNA even more assertively than mental illness. And they were really wonderful.

Khazan: I read that you're not saying when this took place, but to the extent that you're able to share, have the effects lasted? How long did they last?

Waldman: It's kind of interesting, the effects of the drugs have not lasted. LSD does not hang around in your system like that, but the effects of the end of the depression have lasted. I have not cycled into as low as a mood since I don't attribute that as much to LSD as to the insight brought about by that one-month experiment.

Even when my mood has dropped since then, I've had a much clearer image in my mind of what not being depressed is like, so that's one thing. It's allowed me since then to be somewhat less reactive and somewhat less impulsive. I still feel as impulsive, but for some reason since then, and with a tremendous amount of work using all these other therapeutic modalities that are boring and annoying but can be effective if you use them, I have been able to put the brakes on more inappropriate behaviors.

I still make tons of mistakes. I'll yell at my husband, but we don't have the same kind of fights really, it doesn't build to the same kind of place, or if it does I know how to repair without going to a place of suicidal ideation. I'm in this therapy now that's called dialectical behavioral therapy, and for some reason since this experience I've been more adept at the tools, and I've been more able to force myself to do them.

That being said, if it were legal, I would still be doing it, no doubt.

A Tiny Dose of This Drug Made Her Happier and Better at Her Job

Instead of an “acid trip,” she took an “acid errand.”

www.theatlantic.com

 

[mr peabody]

Is ketamine the first rapid-acting antidepressant medication?

by Cameron Schallenberg | OPEN | 29 July 2016

Ketamine has been used for over half a century as an anaesthetic, but interest has been steadily growing in its ability to rapidly decrease depressive symptoms. This interest has culminated in many studies attempting to elucidate its antidepressant mechanism, and in turn, these studies have contributed to our understanding of depressive disorders. Ketamine was first synthesised in 1962 as a dissociative anaesthetic, inducing a state of conscious sedation in which patients are awake, but cognitively dissociated from their pain. In 1970, the FDA approved ketamine as an anaesthetic, but throughout the 1970s ‘special K’, as it was known on the street, was gaining popularity as a recreational drug. The drug became notorious for its ability in high doses to lead users down a ‘K-hole’ – or a state of complete bodily dissociation. In 1999, the FDA scheduled the drug in the United Stated, banning non-medical use. While ketamine’s use and abuse was being argued over by policy makers, a team of scientists began to investigate ketamine as an antidepressant. Following this first human trial of ketamine as an antidepressant, the drug quickly garnered interest in the field of mental health, where since the publication of the fourth edition of the “Diagnostic and Statistical Manual of Mental Disorders” in 1994, depression was considered as a unitary concept and psychiatric disorder.

Depression and the pharmacological response

Major depressive disorder (MDD) is the most prevalent mental disorder, affecting roughly 16% of the world’s population at some point in their lives. The dominant pharmacological hypothesis came about by trying to understand why certain monoaminergic-targeted medications seemed to alleviate depressive symptoms over time. The monoamine hypothesis of depression describes the disorder as the dysregulation of a group of monoaminergic neurotransmitters in the brain, specifically, the transport of dopamine, adrenaline, noradrenaline and serotonin into and out of synapses. First-line treatment of depression involves selective norepinephrine or serotonin reuptake inhibitors. These drugs inhibit the transport of key neurotransmitters out of the synapse between neurons. Unfortunately, less than half of those who suffer from MDD respond to monoamine-targeted medication, and for those who do, it takes at least two weeks and often longer for any symptom relief to become clinically noticeable. Some studies have also linked SSRI treatment to an increased risk of suicide attempts and completed suicides. There is clearly a need for a more rapid and efficacious treatment of this debilitating disorder.

Ketamine as an antidepressant

Ketamine is rare in that it is a psychoactive substance that is classified in the U.S. in Schedule III under the Controlled Substances Act and available to be prescribed by physicians, making research accessible; however, the drug’s status as a non-patentable substance has proven to be a hurdle to funding research. Nevertheless, research into ketamine as an antidepressant has been ongoing since 2000 and resulted in over 1500 studies. Studies have found that single intravenous infusions of ketamine at doses ranging from 0.1-0.5 mg/kg over 40 minutes show robust efficacy in short-term relief of MDD symptoms. Symptoms decrease within 40-60 minutes and during the first 24 hours suicidality is also rapidly decreased. Interestingly, reduced suicidality was found to be a specific effect of ketamine, as it was also found in patients who did not respond to the antidepressant effects of the drug. The promise for ketamine lies in its rapid-acting antidepressant and antisuicidal effects, as few current treatments achieve clinical significance in such a short time frame. Remission of depressive symptoms, on the other hand, only lasts between five and eight days, but can be extended to months through administration of repeated infusions. This technique is somewhat controversial as the effects of repeated exposure to sub-anaesthetic doses of ketamine are yet to be known. Some patients who receive these sub-anaesthetic doses of ketamine report mild side-effects including headaches, dizziness and nausea, as well as dissociative effects and mild psychotomimetic experiences; however, these effects are transient and rarely outlast the time in which the drug is pharmacologically active (about 4 hours).

*From the article here :

Ketamine could be the first rapid-acting antidepressant medication

Ketamine has been used for over half a century as an anaesthetic, but interest has been steadily growing in its ability to rapidly decrease depressive symptoms. This interest has culminated in many studies attempting to elucidate its antidepressant mechanism, and in turn, these studies have...

www.stichtingopen.nl

 

[mr peabody]

As someone who has had severe clinical depression off and on for decades and tried psilocybin once, I can verify that it works, and works very well. It's positive, it promotes joy and imagination, and I feel much more in touch with my feelings. I stopped taking my antidepressant that was making me feel even more detached. I felt the medication I'd been taking was pushing me in the wrong direction. After taking psilocybin, I never took that medication again.

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I've suffered from depression for many years, yet all available medication has come with severe side effects. Psilocybin has worked for me, and it has no long-lasting adverse effects!

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After decades of suffering from debilitating depression myself, I am now cured following a controlled experience with a psychedelic substance. These substances get to the core of the issues rather than sedate. Handled with care they offer medicinal effects that can not be matched by contemporary pharmaceutical products.

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Being a veteran and someone who had a tough childhood I found myself very depressed and suicidal. Even after I began to sort my life out, gave up alcohol and got myself fit again, I still had a pain in my heart that left me feeling like ending my life. I stumbled across information on how psychedelics had helped others with these feelings, and after much research I decided to try mushrooms. To make a long story short, after the first journey, I can with hand on heart say that it took me to a place of love that removed these negative feelings and the pain. These feelings have never returned.

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I have suffered from depression plus alcoholism with two deep bouts which led to many weeks of work. Through the ceremonial use of magic mushrooms I was able to recover from both, without the use for any antidepressants or CBT. Psychedelics work!

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I have experienced the healing benefits of psilocybin first hand. Dealing with depression has been a life-long struggle for me, and since taking psilocybin, I have experienced a significant change in my way of thinking and behaving. Microdosing especially helps me to break habits and rusty old patterns.

https://psychedelicsociety.org.uk/pe...ession-anxiety​

 

[mr peabody]

New clues in the psychedelic treatment of depression

The Psychedelic Scientist | 10 May 2018

Depression, despite affecting millions worldwide, is still a condition we don't fully understand.

In fact, we understand it so poorly that typical pharmaceutical treatments indiscriminately target whole neurochemical systems, resulting in unstable effectiveness and a host of side-effects.

Up to 44% of people suffering from depression have not found relief from typical antidepressant therapies. Even patients who find some form of relief from the usual prescribed antidepressants need frequent doses, sometimes causing unpleasant side-effects, and these drugs often lose their effectiveness after several years of treatment.

But where pharmaceuticals are failing, psychedelics could be a new hope.

Recent large studies using psychedelics such as psilocybin have shown that a single moderate dose of these substances can significantly reduce depression scores in patients with treatment-resistant depression. The antidepressant effect of psychedelics also last much longer than typical treatments, with reduced depression scores maintained for several months after treatment.

A big part of the reason that psychedelics appear to be so effective at treating depression is due to their ability to induce a mystical experience. Participants who describe a highly spiritual or personally meaningful experience with psilocybin were more likely to have reductions in depression scores, according to one study, and the strength of the mystical experience has also been directly linked to psychedelics' anti-addiction effects.

It appears that there's something special about having a transcendental encounter during treatment. Linking this powerful effect of psychedelics to their mechanisms of action in the brain is helping scientists start to piece together the way that depression works, and potentially the best ways of treating it.

A recent review from Dr Robin Carhart-Harris and Professor David Nutt presents a new, all-encompassing model of depression that explains how both typical antidepressants and psychedelic therapies could help treat depression in different way.

Their bipartite model of serotonin signalling proposes that depression can be most effectively treated through two receptor systems - the 5-HT1A and the 5-HT2A receptors.

The author's theory is that the 5-HT1A system of the brain is generally in charge of regulating anxiety during normal consciousness. This is the receptor system that typical SSRI medications work through, reducing levels of anxiety directly. This is the system that deals with passive coping.

However, when people start to experience abnormally high levels of stress (such as in cases of severe depression), the brain's 5-HT2A system takes over, and starts to change the receptivity of the brain. In other words, it makes the brain more flexible to change, and makes us more sensitive to the environment.

This is the system that deals with active coping. It's the receptor system that psychedelics activate, and this explains a lot about their effects.

The activation of the 5-HT2A system can backfire if we're in a dangerous or stressful environment. While suffering the stress-inducing effects of severe depression, activation of the 5-HT2A system can amplify our anxiety and make things worse. This explains why people can have traumatic psychedelic experiences if they're not in the right setting, or receiving the proper guidance.

Activation of 5-HT2A receptors can also produce significant changes in people's cognition, helping them address serious problems in their life in a unique form of self-therapy. This has been observed in participants of clinical trials into the effectiveness of psychedelic therapy, who report the most significant benefits after experiencing major personality changes.

The theory is that the brain has two mechanisms in reacting to depression. Firstly, the brain's 5-HT1A system tries to address feelings of anxiety. When this becomes too much, and the brain faces too much stress, the 5-HT2A system takes over, and tries to change the way the brain responds to the world in a more dramatic way.

Therefore, the ideal therapy for depression could be a combination of 5-HT1A activation (to help people cope with anxiety as a first defence), followed by 5-HT2A activation (to help people adapt and heal).

It's important to know that this is still just a theory. The authors acknowledge that this is an oversimplification of one of the most complicated neurotransmitter systems in the brain, and that the evidence isn't yet complete. But this is arguably the most coherent model of depression that has been put forward so far.

We're living in a special time, science is starting to provide us with evidence that an holistic approach to mental health is within our grasp. We're starting to understand the power of mystical and transformative personal experiences, and scientific advancements will help us marry the worlds of transpersonal psychology and modern psychiatry.

Psychedelics could be the catalyst for a theory of depression that treats patients as minds rather than objects; as people rather than malfunctioning machines.

Here's to a humane, holistic, psychedelic future.

https://thepsychedelicscientist.com/...ion/#more-1271​

 

[mr peabody]

Low-dose Ketamine benefits cognitive function in Treatment Resistant Depression

Psychiatry Advisor | 21 Aug 2018

A low dose of ketamine infusion can provide a rapid and sustained antidepressant effect in patients with treatment-resistant depression, according to a study published in the Journal of Affective Disorders. In addition, a subanesthetic dose of ketamine was shown to improve functional impairment traditionally associated with treatment-resistant depression.

This randomized, double-blind, placebo-controlled study included 71 adults aged 21 to 65, diagnosed with major depressive disorder according to the DMS-IV, and who additionally met criteria of treatment-resistant depression. Patients with major comorbidities or a history of alcohol or drug abuse were excluded. Participants were randomly assigned into a group receiving ketamine 0.5 mg/kg, ketamine 0.2 mg/kg, or normal saline placebo infusions. The Hamilton Depression Rating Scale was used to assess the participants’ depressive symptoms at baseline and at different time points following infusion; cognitive function was evaluated by testing the participants’ working memory and go/no-go tasks at baseline, day 3, and day 14 post treatment.

Study results showed that depressive symptoms improved across different time periods among patients with treatment-resistant depression receiving either ketamine infusion (0.5 or 0.2 mg/kg) or placebo. Paired t tests were used to stratify results by treatment group and treatment response, and they revealed that correct responses in the go/no-go task significantly increased from baseline to day 14 in the 0.5 mg/kg ketamine infusion group. After adjusting for age, gender, and education, a significant association was also observed between depressive symptoms and changes in cognitive function at day 3 in the 0.5 mg/kg infusion group.

A limitation of the study was the add-on design, in which normal medications taken by the participants were not discontinued during the ketamine treatment and evaluation; therefore, the findings are more appropriately explained as an add-on effect of low-dose ketamine infusion. The study was also limited by testing only working memory and go/no-go tasks in assessing cognitive function; it did not test episodic and autobiographical memory. Furthermore, researchers did not arrange post-ketamine infusion assessments for Day 2 to avoid a potential learning effect attributed to the cognitive tasks.

The study findings indicated that a single low dose of ketamine infusion did not impair cognitive function of patients with treatment-resistant disorder; rather, patients in the 0.5 mg/kg ketamine infusion group demonstrated specific cognitive improvement measured by the go/no-go task. Although this study showed that ketamine had beneficial effects on cognitive function in relation to its antidepressant effect, further studies are needed to understand the effects of repeated ketamine infusions on cognitive function.

Low-Dose Ketamine Benefits Cognitive Function in Treatment-Resistant Depression - Psychiatry Advisor

Ketamine also had beneficial effects on cognitive function in relation to its antidepressant effect.

www.psychiatryadvisor.com

 

[mr peabody]

Fast-acting psychedelic 5-MeO-DMT associated with improvement in depression*

Neuroscience News | March 18, 2019

5-MeO-DMT, a fast-acting synthetic psychedelic, shows promise for treating depression and anxiety. 80% of test subjects reported improvements in their symptoms associated with depression and anxiety after taking the drug. - Johns Hopkins University

Johns Hopkins researchers have discovered that use of the synthetic psychedelic 5-methocy-N,-N-dimethyltryptamine (5-MeO-DMT) appears to be associated with unintended improvements in self-reported depression and anxiety when given in a ceremonial group setting. 5-MeO-DMT is a psychedelic that is found in the venom of Bufo Alvarius toads, in a variety of plants species, and can be produced synthetically.

In a survey of 362 adults, approximately 80 percent of respondents reported improvements in anxiety and depression after use. These improvements were related to more intense acute mystical effects during the 5-MeO-DMT experience, as well as increases in rating of the personal meaning and spiritual significance of the experience. Improvements were also related to stronger beliefs that the experience contributed to enduring well-being and life satisfaction. These results were published in The American Journal of Drug and Alcohol Abuse.

One of the unique properties of 5-MeO-DMT is the fast action and short duration of the psychedelic effects when compared to other psychedelics. "Research has shown that psychedelics given alongside psychotherapy help people with depression and anxiety. However, psychedelic sessions usually require 7 to 8 hours per session because psychedelics typically have a long duration of action," says Alan K. Davis, Ph.D., a postdoctoral research fellow in the Behavioral Research Unit, at the Johns Hopkins University School of Medicine. "Because 5-MeO-DMT is short-acting and lasts approximately 30-90 minutes, it could be much easier to use as an adjunct to therapy because current therapies usually involve a 60 to 90-minute session."

The unique properties of 5-MeO-DMT are the fast action and short duration of psychedelic effects
as compared to other psychedelics.

Last year, Davis published a study in Frontiers in Psychology that found that 5-MeO-DMT administered in a psychospiritual retreat setting produced comparable ratings of mystical experience as a high-dose psilocybin session in the laboratory setting. Another study by Davis that came out last year in The Journal of Psychopharmacology showed that 5-MeO-DMT had a safe profile of use and low risk for health and legal consequences.

"It is important to examine the short- and long-term effects of 5-MeO-DMT, which may enhance mood in general or maybe particularly mood enhancing for those individuals experiencing clinically significant negative mood," says Davis. "Regardless, this research is in its infancy and further investigation is warranted in healthy volunteers."

The authors on this paper were Alan K. Davis, Sara So and Roland R. Griffiths of Johns Hopkins, Rafael Lancelotta of the University of Wyoming and Joseph P. Barsuglia of New School Research.

*From the article here :
https://neurosciencenews.com/psyched...ews+Updates%29​

 

[mr peabody]

Could psilocybin treat depression without the trip?

by Jon Kelvey | LUCID | 15 Jun 2021​

• New research on mice suggests that the "trip is not necessary for the acute antidepressant effect."​
• "Preventing or minimizing the psychedelic experience would reduce fears about the triggering of latent psychotic responses, but it's not yet clear if the antidepressant effects will last as long without the psychedelic experience," says Natalie Hesselgrave.​

A growing body of early evidence suggests the psychedelic psilocybin could be a powerful and effective treatment for people suffering from treatment-resistant depression. But psilocybin treatment requires a deep commitment on the part of both patients and physicians, as the drug engenders hours of sometimes intense distortions of perception, time, and self. The psychedelic experience, in other words. A trip.

It has long been assumed by researchers that the antidepressant effects of psilocybin are tightly connected to the psychedelic experience, and are likely a direct result of that experience, but the causal relationship between the two remains poorly understood. However, according to the authors of a new paper, preclinical research conducted in mice suggests it might be possible to disentangle the antidepressant and psychedelic effects of psilocybin. If the results hold up in further studies, the authors suggest that it could make a potentially life-changing treatment available to many more people.

A team at the University of Maryland conducted the study using chronically stressed male mice as an animal model of depression, with the mice no longer responding normally to pleasurable stimuli. It’s believed the hallucinatory, psychedelic effects of psilocybin depend on the activation of a subtype of serotonin receptor in the brain, the 5-HT2A receptor, so the researchers pretreated mice with the 5-HT2A antagonist ketanserin to block psilocybin from activating the receptors. They then gave the mice a single injection of psilocybin.

Despite blocking the psychedelic effects of psilocybin, the researcher’s found the treated mice regained their responsiveness to pleasurable stimuli, a behavioral sign that psilocybin helped alleviate symptoms of depression. The treated mice also developed stronger neural connections in a part of the brain known as the hippocampus, similar to the strengthened connection seen in this region with the use of more traditional antidepressants. These strengthened neural connections, the researchers note in a paper published in April in the Proceedings of the National Academy of Sciences, are a potential mechanism of action for psilocybin’s antidepressant effects.

“The tentative conclusion of our study is that the trip is not necessary for the acute antidepressant effect,” says University of Maryland School of Medicine Ph.D. student and lead author of the study, Natalie Hesselgrave. “Of course, our results were obtained with mice and depression is a uniquely human condition.” It’s also not yet clear if the antidepressant effects will last as long without the psychedelic experience, she says.

Ketanserin has been used in human clinical trials to mitigate the psychedelic effects of psilocybin in people without depression, Hesselgrave notes, and so it could provide a safe way to extend her work in human subjects with depression. If confirmed to be effective, a non-psychedelic psilocybin treatment for depression could make a potentially life-changing treatment available to many more people. “One of the biggest potential patient populations that could benefit are those with a personal or family history of bipolar or psychotic disorders,” Hesselgrave says. “Preventing or minimizing the psychedelic experience would reduce fears about the triggering of latent psychotic responses.”

A recent study on psilocybin published in the New England Journal of Medicine, for instance, excluded 891 of the 1,000 applicants based on their personal or family history of mental illness, according to Hesselgrave.

The ability to prescribe psilocybin without psychedelic effects could also improve health equity, Hesselgrave said. "Typically, a psilocybin session requires a full day in the clinic and the assistance of one or two facilitators," she says, "which represents a significant cost barrier to wider participation.”

Could Psilocybin Treat Depression without the Trip? - Lucid News

New research on mice suggests that the “trip is not necessary for the acute antidepressant effect.”

www.lucid.news

 

[mr peabody]

Albert Hofmann

Mounting evidence that psilocybin can effectively treat depression

by Mark Travers | Psychology Today | 26 Apr 2019

Depression rates are shockingly high. The condition is estimated to affect 10-15 percent of the global adult population and has been ranked as the fourth highest contributor to the global disease burden by the World Health Organization.

To make matters worse, approximately 30 percent of people who suffer from major depression are classified as "treatment-resistant," meaning that they respond poorly to the different types of antidepressant medications currently available.

Put these facts together and you have a public health crisis. This has prompted many scientists to look for out of the box treatments for depression. One treatment that has shown promise in recent studies is psilocybin, the active chemical compound in hallucinogenic mushrooms. A new study published in the journal Acta Psychiatrica Scandinavica adds more credibility to the claim.

In the study, researchers in the United Kingdom recruited 20 patients suffering from treatment-resistant depression. Patients were first asked to complete a depression screener and a personality test measuring the Big-5 personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness). Then, over the following weeks, participants were given two doses of psilocybin (10 mg and 25 mg doses, respectively). Finally, after a few more weeks, patients filled out the same depression screener and personality test they did at baseline.

The goal was to see if and how the psilocybin treatment reduced depressive symptoms and altered personality. Indeed, they found promising improvements on both counts. Depression, as measured by the 16-item Quick Inventory of Depressive Symptoms, showed directional reductions from the baseline measurement to the follow-up. Moreover, psilocybin treatment appeared to have a marked effect on personality. Neuroticism significantly decreased from baseline to follow-up, while extraversion, conscientiousness, and openness significantly increased.

What's especially intriguing about these results is that the antidepressant effects produced by psilocybin appear to function in an altogether different manner than mainstream antidepressants, such as SSRIs and MAOIs. Whereas mainstream treatments have been shown to improve the personality dimensions of neuroticism and conscientiousness, the increases in extraversion and openness appear to be exclusive to psilocybin treatment.

Reiterating this point, the authors write, "Where changes in neuroticism and conscientiousness are consistent with what has been observed previously among patients responding to antidepressant treatment, the pronounced increases in extraversion and openness might constitute an effect more specific to therapy with a psychedelic."

While the exact way in which psilocybin works to alleviate depressive symptoms and alter personality is still unknown, the researchers speculate the construct of "insightfulness" may play a role. They write, "Of the acute experience factors that are most related to personality change, greater insightfulness during the 25 mg experience was found to be correlated with decreased neuroticism as well as increased extraversion."

Taking all of this together, the question might not be whether psilocybin should be a last-resort or fringe treatment for depression, but rather, one of the first lines of defense instead.

The Magic of Mushrooms

There is mounting evidence that psilocybin can effectively treat depression.

www.psychologytoday.com

 

[mr peabody]

Psychedelics repair brain cells "shriveled" by depression

by Alex Matthews-King | The Independent | 12 June, 2018

Psychedelic drugs have been shown to stimulate the growth of new branches and connections between brain cells which could help address conditions like depression.

University of California researchers have found that psychedelics can rewire the brain, and trigger the growth of new neuronal branches between brain cells, long after the drugs' effects have worn off. Dr David Olson, one of the study's authors and lead researcher, notes that in depressed persons, neurites in the prefrontal cortex of the brain tend to shrivel. Psychedelics act as a counter to this.

Researchers in California have demonstrated these substances, banned as illicit drugs in many countries, are capable of rewiring parts of the brain in a way that lasts well beyond the drugs' effects. This means psychedelics could be the "next generation" of treatments for mental health disorders which could be safer and more effective than existing options, say the study's authors from the University of California.

In previous studies by the same team, a single dose of DMT, the key ingredient in ayahuasca medicinal brews of Amazonian tribes, has been shown to help rats overcome a fear of electric shock meant to emulate post-traumatic stress disorder (PTSD).

Now they have shown this dose increases the number of branch-like dendrites sprouting from nerve cells in the rat's brain.

These dendrites end at synapses where their electrical impulses are passed on to other nerve cells and underpin all brain activity. But they can atrophy and draw back in people with mental health conditions.

“One of the hallmarks of depression is that the neurites in the prefrontal cortex – a key brain region that regulates emotion, mood, and anxiety – tend to shrivel up,” says Dr David Olson, who lead the research team.

These brain changes also appear in cases of anxiety, addiction and post-traumatic stress disorder, and stimulating them to reconnect could help to address these conditions.

The research, published in the journal Cell Reports, looked at drugs in several classes including tryptamines, DMT and magic mushrooms; amphetamines, including MDMA, and ergolines like LSD. In tests on human brain cells in the lab, flies and rats, it found these substances consistently boosted brain connections.

Dr Olson compared the effects to ketamine, another illicit drug which represents one of the most important new treatments for depression in a generation, and found many psychedelics have equal or greater effects.

A ketamine nasal spray is being fast-tracked through clinical trials after it was shown to rapidly relieve major depression and suicidal thoughts in people who cannot be helped by other treatments. However its use has to be weighed against its potential for abuse, and its ability to cause a form of drug-induced psychosis.

“The rapid effects of ketamine on mood and plasticity are truly astounding,” said Dr Olson. “The big question we were trying to answer was whether or not other compounds are capable of doing what ketamine does.”

“People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis."

The fact that these drugs seem to mimic the groundbreaking benefits of ketamine opens up an array of new treatment options, which may be less open to abuse, if they can make it to clinical trials.

Dr Olson said: “Ketamine is no longer our only option. Our work demonstrates that there are a number of distinct chemical scaffolds capable of promoting plasticity like ketamine, providing additional opportunities for medicinal chemists to develop safer and more effective alternatives.”

The news that yet more banned substances could help tackle serious and debilitating disease comes as the UK Home Office is embroiled in a row over medicinal cannabis in treating epilepsy.

After months seizure-free, 12-year-old Billy Caldwell had a seizure last night after airport customs officials confiscated his prescription from Canada.

Billy had previously had the UK’s only NHS medical cannabis prescription, for an oil which banished seizures that used to strike 100 times a day, but the Home Office intervened to block his GP from prescribing it.

https://www.independent.co.uk/news/...y-lsd-dmt-amphetamines-ketamine-a8395511.html​

 

[mr peabody]

Ketamine a life-saver for some with hard-to-treat depression

CTV News | 31 Jan 2018

William Jamieson is only 23, but hes already spent almost one-third of his life battling severe depression.

Once a top student and athlete with a large group of friends, the young Ottawa man fell into a depression at age 16 that he couldnt shake.

"It got pretty bleak," he says. "In terms of energy, I just couldn't get out of bed. I couldn't eat. I didn't have the energy to eat. I was wasting away."

"I kind of kept myself in the dark. That goes to how you see the world," he adds.

He tried at least 10 medications and received electric shock therapy -- but nothing worked.

Watching his son sink further into his depression left William’s father Charles desperate to help.

"There was nothing more they (the doctors) could do, and as a parent, that is not what you want to hear, because the depths of William's depression were as dark and black as you can imagine," Charles says.

Fearing for his son’s life, the elder Jamieson went online. I typed into Google: breakthrough depression treatments, and ketamine came up, he says.

Ketamine has been used as an anesthetic and painkiller for decades. But in recent years, its been explored as a treatment for depression.

Researchers say the drug can lift depression and suicidal thoughts in patients with even one treatment.

Doctors at the Royal Ottawa Mental Health Center have been using intravenous ketamine on patients with treatment-resistant depression and say they are seeing promising results.

Ketamine isnt approved by U.S. regulators to treat depression, but hundreds of private health clinics have been offering it off-label. Jamieson now travels from his home in Ottawa to New York City every six weeks for Ketamine infusion therapy from anesthesiologist Dr. Glen Brooks.

"The darkness began to lift two days after the first treatment. It feels like there is a loosening of the fist that is inside of your head," William says.

His father Charles grows emotional thinking about that weekend.

I say, 'Will, how are you feeling?' He says, Dad, it is gone. The depression is gone. The colors are brighter." I will never forget those words. "The colors are brighter. The fog is gone," he says.

Dr. Brooks has used Ketamine for 35 years to treat neuropathic pain. After reading research on using of Ketamine for depression, he began to offer the drug to patients with long histories of post-traumatic stress disorder and other mood disorders, charging up to $400 per infusion.

Many of his patients have tried multiple medications and electroshock therapy and have not responded. "This is generally more of a last stop than a first stop," he explains.

He says the improvements are often rapid and dramatic. "What patients report is a sense of calmness and wellbeing that comes over them," he explains.

Dr. Brooks believes that for suicidal patients, ketamine saves lives every day. "I don't think anything is as effective as Ketamine has been," he says.

In Canada, many psychiatrists are excited to better understand how ketamine works in the brain, but others are urging patience until more is known about the drug’s possible side-effects, including elevated blood pressure, blurred vision, and bladder inflammation.

"We don't know who is more prone to the side effects or indeed, the long-term consequences of the side effects," says Dr. Sidney Kennedy, the Arthur Sommer Rotenberg Chair in Suicide and Depression Studies at St. Michael’s Hospital in Toronto.

But Dr. Brooks says patients should be able to access a drug that could save their lives.

"In my experience of treating over 1,500 patients, I see no reason for any patient to wait, especially if they are critically ill with their mood disorder," he says.

Charles Jamieson thinks Ketamine should be more widely available in medically supervised settings. Until it is, he will pay for his son to get the drug in the U.S.

"I got my son back, and I know he will have the life that he wants to make. He's had an opportunity he wouldn't have had. Without Ketamine, it would have been a terrible... a different story," says Jamieson.

https://www.ctvnews.ca/health/the-fo...sion-1.3784490​

 

[mr peabody]

The magic of my mushrooms: A depressive’s journey to microdosing

by Dana Saxon | The Establishment

Since 1978, psilocybin—the active ingredient in psychedelic mushrooms—has been illegal in the United States. According to the U.S. Dept. of Justice archive:

“Psilocybin is a Schedule I substance under the Controlled Substances Act. Schedule I drugs, which have a high potential for abuse and serve no legitimate medical purpose in the United States.”

Today, the State is actively withholding psilocybin treatment that could change the lives of those suffering with depression, a treatment that has already helped droves of people like me who never thought they’d shake their psychological shadows.

David Nutt, the director of the neuropsychopharmacology unit at Imperial College London, is a pioneering researcher who studies the use of psychedelics to treat mental illness.

Nutt summarized the findings of one of his studies around chronic depression:

“We treated people who’d been suffering for 30 years, and they’re getting better with a single dose. That tells us this drug is doing something profound.”

Robin Carhart-Harris, a research fellow at the same London institute, echoes the staggering impact of psilocybin on the patients’ psyches. After one week, all 12 participants reported an improvement in their depression and 2/3 of the people were depression-free. By three months, about 58% showed improvement — 5 were in remission while 5 relapsed. “The efficacy of the treatment is impressive,” says Carhard-Harris.

Additional studies at NYU and Johns Hopkins that centered around depression and cancer   found that a single dose of the medication can lead to an immediate reduction in depression that can last up to 8 months. Dr. Stephen Ross, at NYU Langone Medical Center, called this depression treatment “unprecedented,” insisting that “we don’t have anything like it.”

Although these revolutionary medical studies provide convincing evidence that psilocybin can be an effective treatment for depression, NYU and Johns Hopkins researchers emphasized the “danger” and illegality of psychedelic mushrooms, cautioning, “…the drug was given in tightly controlled conditions in the presence of two clinically trained monitors… [The researchers] do not recommend use of the compound outside of such a research or patient care setting.”

Also, both studies stressed that their research was for terminally ill cancer patients, not average sad people, like me.

15 years ago, I was diagnosed with depression. As a depressed person, I understood my condition was physical, and not something I could sleep away. So, after sharing my detailed descriptions of worry and grief with a soft-spoken and apparently concerned doctor, I received the permission I needed for my only option to heal—a prescription for Prozac.

When it comes to health care in the U.S., we’re not given many opportunities to think outside the box. For physical and emotional pain alike, prescription drugs are widely accepted as the primary solution for people seeking relief — you're diagnosed, placed in a box, and given the “right pills.”

At the time, I was in law school in Philadelphia. Not only did I hate school and my accidental career path, my father was recently diagnosed with colon cancer, and I felt every part of life slipping from my control. Therapy helped, and the drugs numbed the symptoms of depression.

After law school, having rejected the law and earning most of my income under the table as a private teacher for children, I was uninsured for more than a year. Even after I found more stable jobs, I never quite found my bearings, bouncing from coast to coast, and confronting periodic reminders that my depression was still very much untreated.

Although I was coping, I occasionally searched online for any kind of solution to the overbearing pain that haunted me on my worst days. Honestly, sometimes even the research itself was too much to bear. So in truth, I didn’t try too often.

When it comes to healthcare in the U.S., you are diagnosed, placed in a box, and given the ‘right' pills. And even finding a therapist was no guarantee for treatment. After one decent session with a doctor I liked, my insurance company refused to pay for treatment. More than a year later, after a tolerable session with a doctor who was both arrogant and racist, she refused to treat me because “we wouldn’t be a fit."

I began coping with my symptoms of depression and rejection.

In New York City, about five years after the initial diagnosis, I found a doctor who offered a “trial session,” which was a common routine. I’d pay out of pocket; he’d listen for an hour, then recommend a treatment over the course of some months. My insurance company would consider his opinion, then decide if the whole thing was appropriate.

Like my earlier attempts to heal within the system, I committed to it.

I spilled my guts and tears on his couch. I told him about being diagnosed with depression years earlier, my father’s death, growing anxiety, insecurity and loneliness — the works. He talked at a normal volume, in non-condescending tones. Although I didn’t think he could relate to my grief, I liked the way he listened.

“Finally, I’ll get this thing under control,” I thought. “He’ll help.”

We planned to start treatment in a week. He only needed to mail a confirmation, which arrived just a few days later. I wasn’t surprised until a check fell out — with my signature on it.

The doctor’s handwritten note explained that my insurance would only cover a small portion of my therapy. And since I was not super rich, he knew it wouldn’t be possible for us to continue. He kindly returned my non-refundable fee for the trial session, explaining, “I feel terrible about this and can’t justify taking your money. I hope you find the help you need.”

I was sad, frustrated, helpless, and now pitied. I cried fiercely over that letter. He was the last therapist I would ever see.

Since then, I’ve forged my own path to recovery, involving plenty of self-discovery, and a fair share of scientific research. In the process, I’ve become aware of the box in which I’ve been trying to heal, one that was designed by cold-hearted, American insurance providers and pharmaceutical companies that make commercials with happy white women on beaches.

Now? I’m growing psychedelic mushrooms in my living room.

Since I migrated from the U.S. to The Netherlands several years ago, I can legally purchase a grow kit for magic mushrooms at a lovely, pro-woman and pro-healing herbal shop that’s a short walking distance from my apartment. I explained to the shop’s owner that I read about the benefits of taking magic mushrooms in microdoses to treat symptoms of depression, so I wanted to try them for the first time.

“Oh, yes, absolutely!” She exclaimed. “I know several people who use mushrooms this way. They can give you a spiritual experience in larger doses, and a healing experience in smaller doses.”

It’s what I hoped to confirm; my online research included piles of papers and personal accounts from people hailing from all parts of the world, all treating their depression with psychedelic mushrooms.

I took my first mushroom kit home and quietly hoped for relief — from depression and the limitations of American health care.

I started my homegrown treatment with a full trip, eating about 4 grams of mushrooms. That night I recorded an emotional conversation with myself. I worked through some of the sore spots and identified a source of generational trauma, including a connection with my father and previous generations, all of whom dealt with a depression that reaches back to slavery and unfulfilled promises of freedom.

I questioned my self-doubt. I cried over unaddressed pain. And I laughed at the absurdity of the situation. By the next morning, I felt like I had been through months of therapy.

From there, I turned the mushrooms into pills, creating microdoses of 0.2 grams. I started by taking a microdose every 2–3 days. Now, after several months of consistent doses, I’m down to an average of one microdose per week.

I started my homegrown treatment with a full trip. By the next morning, I felt like I had been through months of therapy.

In addition to increased focus and energy, the mushrooms have brought me levity and gratitude. Unlike Prozac, which felt like placing a blanket over my problems, the mushrooms have lifted away a burdening weight. I can’t say all problems are solved by swallowing a mushroom microdose, but they provide me the needed perspective and clarity to perceive (internal) barriers and negative thoughts, and then address them.

At some point, I expect I’ll no longer need a dose every week or every month, or even at all. But for now, as long as I experience the benefits of the treatment, I’ll continue microdosing.

And, in the meantime, I’ll participate in the growing movement to legalize psychedelic mushrooms in the U.S., because other treatment-seekers deserve relief from their depression, a mental illness that affects 6.7% of the U.S. population age 18 and older.

The magic of these mushrooms shouldn’t be kept under lock and key, but warm on a windowsill.

https://theestablishment.co/the-magi...g-1675a7cf15a4​

 

[mr peabody]

Are magic mushrooms the answer to depression?

by Josh Jacobs | The Guardian | 10 Jun 2019

New trials have shown the drug psilocybin to be highly effective in treating depression, with Oakland the latest US city to in effect decriminalise it last week. Some researchers say it could become ‘indefensible’ to ignore the evidence – but how would it work as a reliable treatment?

Lying on a bed in London’s Hammersmith hospital ingesting capsules of psilocybin, the active ingredient of magic mushrooms, Michael had little idea what would happen next. The 56-year-old part-time website developer from County Durham in northern England had battled depression for 30 years and had tried talking therapies and many types of antidepressant with no success. His mother’s death from cancer, followed by a friend’s suicide, had left him at one of his lowest points yet. Searching online to see if mushrooms sprouting in his yard were the hallucinogenic variety, he had come across a pioneering medical trial at Imperial College London.

Listening to music and surrounded by candles and flowers in the decorated clinical room, Michael anxiously waited for the drug to kick in. After 50 minutes, he saw bright lights leading into the distance and embarked on a five-hour journey into his own mind, where he would re-live a range of childhood memories and confront his grief. For the next three months, his depressive symptoms waned. He felt upbeat and accepting, enjoying pastimes he had come to feel apathetic about, such as walking through the Yorkshire countryside and taking photographs of nature.

“I became a different person,” says Michael. “I couldn’t wait to get dressed, to get into the outside world, to see people. I was supremely confident – more like I was when I was younger, before the depression started and got to its worst.”

The trial, finished in 2016, was the first modern study to target treatment-resistant depression with psilocybin, a psychedelic drug naturally occurring in around 200 species of mushroom. To varying degrees, Michael and all 18 other participants saw their symptoms reduce a week after two treatments, including a high, 25mg dose. Five weeks later, nine out of 19 patients found that their depression was still significantly reduced (by 50% or more) – results that largely held steady for three months. They had suffered from depression for an average of 18 years and all had tried other treatments. In January this year, the trial launched its second stage: an ambitious effort to test psilocybin on a larger group and with more scientific rigour (including a control group, which Michael’s study lacked), comparing the drug’s performance with escitalopram, a common antidepressant. The team has now treated about a third of the 60 patients and say that early results are promising for psilocybin.

Imperial’s current work is among a string of new studies that a group of professors, campaigners and investors hope will lead to psilocybin’s medical approval as a transformative treatment. Others soon to begin include an 80-person study run by Usona Institute, a Wisconsin-based medical non-profit, and a trial at King’s College London, as well as a 216-person trial that is already under way around the US, Europe and Canada, managed by the London-based life sciences company Compass Pathways. Robin Carhart-Harris, head of Imperial’s Centre for Psychedelic Research and a Compass scientific adviser, believes psilocybin could be a licensed medicine within five years, or potentially even sooner. “By about that point,” he says, “it would be like an irresistible force, and indefensible to ignore the weight of the evidence.”

Psilocybin mushrooms have been part of religious rituals for thousands of years. The Aztecs of Mexico referred to the mushroom as teonanácatl, or “God’s flesh”, in homage to its believed sacred power. In 1957, Albert Hoffman, a Swiss chemist working for the pharmaceutical company Sandoz, isolated psilocybin from the mushroom. Fifteen years earlier, he had accidentally ingested LSD, left work feeling dizzy, and experienced its psychedelic effects when he got home. During the 1960s, Sandoz sold psilocybin and LSD for research in medical trials, but the substances were soon outlawed after they became associated with the 60s counterculture.

Psilocybin remains in the most restricted category today under the UN Convention on Psychotropic Substances, the US 1970 Controlled Substances Act and the 1971 UK Misuse of Drugs Act, among others. David Nutt, a professor of neuropsychoparmacology at Imperial, who is overseeing the current trials, disputes the evidence for this, saying that heavily restricting the drug (and other psychedelics) has hindered research and propelled “lies” about its risks and medical potential. For him, the decision is “one of the most atrocious examples of the censorship of science and medicine in the history of the world”.

If successful, the new wave of research may continue to change psilocybin’s reputation after decades of prohibition. Carhart-Harris believes the drug offers a better and more comprehensive treatment than current antidepressants, and that it could well be a powerful new therapy for a host of other mental illnesses, including anxiety and food disorders. A 2016 Johns Hopkins University study of 51 patients with life-threatening cancer showed high doses of psilocybin significantly reduced end-of-life depression and anxiety for six months in 80% of cases, and helped patients accept death; a New York University study that year showed similar results. Current trials are looking further at psilocybin’s potential for reducing smoking addiction and alcohol dependency, after initial pilots yielded powerful results. (Johns Hopkins researchers showed in a small study, for example, that 80% of heavy smokers had not smoked for a least a week, six months after psilocybin treatment.)

Carhart-Harris thinks part of the reason the drug has been effective in treating depression in trials so far is that it can help people see their lives more clearly. When watching patients tripping, he often feels as if they see a truer version of reality than the sober therapists guiding them: “It is almost like being in the presence of someone particularly wise, in terms of what comes out of their mouth.” It is unclear how much of the depression alleviation comes from the psychiatric support surrounding the treatment. Either way, several patients have sourced top-ups independently since the first trial, as their depression has returned.

Much about the neuroscience of psychedelics remains unknown, but fMRI scans of patients’ brains after taking psilocybin showed reduced blood flow and resting activity in the amygdala, which is often overactive in depression and anxiety. They also show looser connections between brain networks, which then reintegrate in what the Imperial team suggests is part of the brain “resetting” itself on psilocybin. This may explain why the drug drives some patients to rethink entrenched beliefs and break compulsive thought patterns and behaviours. Imperial researchers believe that psilocybin operates differently from most current treatments. If common antidepressants dull emotions to help people cope, they theorise, psilocybin works on our serotonin system to heighten emotional responses and encourage people to actively confront their depression, which can prompt enduring shifts in mind-set.

For 48-year-old university design technician Kirk Rutter, this is why psilocybin seems to work – and why he hopes it will become medically available. He sees the drug not as a silver bullet but as a medicine that shows patients deep truths and requires them to apply teachings of this kind. Some other treatments, such as cognitive behavioural therapy, also seek to reshape thinking patterns, often in conjunction with antidepressants, but for many the current options fail to work. More than 300 million people suffer from depression globally, according to the World Health Organization, but researchers say that many of the most serious cases do not respond to antidepressants.

Rutter was in this group, having tried counseling and two prescription medicines in the five years before the Imperial trial, as his depression worsened following his mother’s death. After psilocybin, he began to break cycles of catastrophic thinking and had the confidence to make profound life changes, such as selling his house and moving away from abusive neighbours, reorganising his finances and traveling for enjoyment after years of not leaving the country. He says of psilocybin: “It removes any barriers and allows you to process what you need to in an almost seductive way. You are inevitably and irresistibly drawn into it.” One week after the treatment, he noticed a feeling of optimism come back to his life. “Hell,” he thought, “I haven’t had this for a long time.”

Even psilocybin’s fiercest proponents agree that it will take more evidence of its effectiveness on larger groups in controlled settings, and investigation into potential adverse effects, before it can be unleashed as a medicine. Current trials exclude people with a family history of psychosis for fear that the drug could trigger latent schizophrenia. And there are questions about psilocybin’s impact. Some patients say they hardly experienced the psychedelic effects, while others such as Michael had strong reactions to lower doses but less to higher ones. James Rucker, who worked on the first Imperial study and now directs psilocybin trials at King’s College London, remains agnostic about the drug as a reliable treatment.

“It’s an illusion that we know so much about psilocybin,” says Ekaterina Malievskaia, co-founder of Compass, which hopes to sell the drug as part of an approved treatment. “We really don’t. We know it can cause profound personal experiences; it can also cause all sorts of complications.”

But Malievskaia hopes that the Compass trials will provide the evidence needed to get the drug medically approved for treatment-resistant depression. She founded the company with her husband, George Goldsmith, three years ago, after her son’s severe depression and OCD got progressively worse while he was being treated with traditional antidepressants in a top US hospital. He later recovered with the help of psilocybin therapy, and the company says it has now attracted around £28m in funding, including from the venture capitalist Peter Thiel, and has applied to patent a process to make psilocybin at scale. Some former Compass associates fear the company seeks to monopolise the psilocybin market and control medical access, criticisms that were aired last year by the US business website Quartz, although Malievskaia denies this.

There are already signs that authorities may be beginning to shift. In October, US regulators gave Compass’s treatment breakthrough therapy status, a designation given to new medicines that might improve treatments for serious conditions, which means authorities will expedite their review of evidence. That decision was followed this May with Denver’s vote to in effect decriminalise magic mushrooms, making it the first US city to do so, followed last week by a similar measure for several psychedelic plants in Oakland, California. Activists are pushing for a state-wide vote in Oregon next year on whether to legalise psilocybin for medical use. Meanwhile, Compass hopes to request marketing authorisation for the drug within three years, if its trials are successful. It is proceeding slowly, though, having treated around six people since trials began in January, and Malievskaia says the process could take a decade until approval. She aims to accelerate progress, with new treatment sites recently opened at Columbia University, as well as in New Orleans and the Netherlands, among others.

Licensing is not the only obstacle to the drug becoming a common medicine. Taken over multiple hours in clinical settings with expert guides, psilocybin therapy does not come cheap. The new Imperial treatments cost more than £2,000 each, including doctors and therapists, and many patients could need multiple treatments each year for continued benefits. Malievskaia would not comment on how much Compass would plan to charge, but says she wants to maximise how many people can access the drug. Carhart-Harris says psilocybin therapy would be significantly more expensive than antidepressants and potentially more than counselling. “There is a cold reality as to why selective serotonin reuptake inhibitors [antidepressants] dominate mental healthcare and that is that they are cheap,” he says.

The scientific, legal and commercial challenges may take years to be settled. But for many of the patients who have already been treated, and for some of the therapists guiding them, there is little doubt: it is only a matter of time before psilocybin and similar psychedelics reshape how we treat suffering – and understand our minds.

Forty-year-old operations manager Melissa Elwin is among them. After an unpleasant first treatment, in which she felt trapped, during her second psychedelic trip inside Hammersmith Hospital, she felt as though she had left her body and was seeing her problems objectively. Psilocybin helped her confront her depression, fueled by a difficult relationship and fraught breakup, and anxiety she had had since childhood. Under the drug, she started to find a resilience that has since helped her face her father’s death from dementia and a protracted legal battle with her ex-partner. Her descriptions of the trip are similar to the awe and unity Hoffman at times experienced on psychedelics while testing them: he saw in them a powerful ability to put our self and troubles in perspective.

“I was literally everywhere during my trip,” says Elwin. “In the most amazing nature scenes, like the orb of light twinkling through trees, in the ocean, in waterfalls. I had no recollection of time and I just wanted it to last for ever. For so long, I felt my depression was part of me, there was nothing I could do to change it. The antidepressants only made me feel drowsy and stopped me caring about things. This made me completely break my mental shackles. I returned to work and I was euphoric. I felt: 'I can do this, I can change my situation.' ”

'They broke my mental shackles': could magic mushrooms be the answer to depression?

New trials have shown the drug psilocybin to be highly effective in treating depression, with Oakland the latest US city to in effect decriminalise it last week. Some researchers say it could become ‘indefensible’ to ignore the evidence – but how would it work as a reliable treatment?

www.theguardian.com

 

[mr peabody]

What's it like to treat severe depression with ketamine?

Everyone's depression is different, but Ted, a 40-year-old resident of Portland, Oregon, describes his as "a continuous dark veil — a foul, dark, awful perspective that informs every moment of your whole life." He tried to treat it with antidepressants, therapy, visits to psychiatrists, the whole nine, but although the antidepressants kept him functional, they by no means offered relief. He was getting desperate, so when his sister — an obstetrician who works in New York — mentioned the National Institute of Health was conducting experimental studies using Ketamine to treat depression, he gave them a call.

The use of Ketamine to treat depression is still fairly novel. A general aesthetic, ketamine can knock someone out without slowing down their heart rate, which is handy in combat situations where breathing tubes aren't readily available. It also has a psychedelic effect when taken in large doses. The illegal use of Ketamine took off in the 70s and 80s, and the Center for Substance Abuse Research estimates it is even more popular today, although its production and distribution is more tightly restricted.

Studies have shown that extremely low doses of Ketamine can also reverse the effects of the most severe depression — depression like Teds that once seemed untreatable. The response rate is unbelievable, Dr. Enrique Abreu, who runs the Portland Ketamine Clinic, and whom Ted sees about once every three weeks, told the Washington Post. "This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kinds of numbers."

Although Ketamine holds up well in clinical trials, without further study it is impossible to know if there are long-term risks associated with its use. It is also incredibly under-regulated; doctors have yet to standardize dosage level, and there is no protocol for frequency of treatment or follow-up care. But to Ted, the short-term effects are well worth whatever comes down the line — for him, one Ketamine infusion is enough to immediately quell suicidal thoughts. It works right away, which is enough to convince people suffering from depression that there is a possibility their quality of life will improve.

Teds certainly has. He calls Ketamine infusions the single most profound thing he has ever done, and he told Science of Us exactly how they work.

How would you describe your depression?

I had situations where I just wasnt getting out of bed, I was completely dysfunctional, and it was shredding my relationship my wife. Id get hypercritical of myself and my surroundings. It would get so bad sometimes that I could walk down the street and be offended just by someone walking toward me — that is how sour and bitter Id get. Id go through elaborate games to get myself to do things. Pride was a strong motivator for me because even though the feeling of doing anything was awful, my sense of self-incrimination was so strong that Id have to do it. Often times I would use obligations to people or animals to motivate myself; you just try and work with what you've got. You are pressing along, essentially deluding yourself to try to avoid the next crisis.

Say you are rummaging through your happy-memory closet — if you are depressed enough, that door is slammed. You have the option to open it, because we are human beings and we are responsible for our own thoughts, but its excruciatingly difficult. It would be like asking me, a 40-year-old dude who’s six feet tall, to dunk a basketball: not going to happen.

How did you treat it initially?

I was prescribed Wellbutrin, a pretty common antidepressant, when I was seeing a therapist through New York University in my late 20s. Later I saw another therapist in San Francisco, and he tried me on a number of different SSRIs in the Prozac vein. Those were not very effective, so I went back on Wellbutrin again. Many psychiatrists stack medications, and in my early 30s I was also given atypical antipsychotics.

Did the antidepressants help?

The indicator that an antidepressant is working is often what is missing rather than a feeling that is there. What I found to be most noticeable is that some of the antidepressants would lift that veil a little bit. It would be gray instead of pitch black, and instead of the weave being so tight that you can’t even see through it, it would be more of a fishnet.

What is the veil like after a Ketamine infusion?

It completely goes away.

Before your first infusion, did you believe that was possible?

I am such a skeptic. I went in thinking, Im going to watch this fail. You think you've seen depression? I'll show you depression. I had completely steeled myself for disappointment. But a lot of this was motivated by desperation — I was willing to try almost anything at that point, and it sounded a lot more appealing than electroconvulsive therapy.

What are the infusions like?

The infusion space is like a surgical ward, but its more relaxed. The machinery doesnt look that complex. I wear an insulin pump, so I am very familiar with devices like this — it's a standard IV. It looks like a computer attached to a plunger on a king-size syringe. Before the first infusion I was bracing myself for the possibility of being nauseous, but that was probably just my anxiety talking.

The first thing I notice is that my vision starts to shift out of focus. With Ketamine, you know you're in the zone when you get an outside perspective, like you are watching your own brain. It almost has a lucid-dreaming effect to it because you have a very rational passenger that's always onboard and always assessing what is going on. It is such a foreign experience, and it is not really comfortable because you are not in the drivers seat, which can be a little intimidating. But a lot of what you're doing is processing thoughts in that moment. I have these classic moments of epiphany like, "Oh my God, this is brilliant! I need to write this down," but I am sure if I read it when I came to it would make no sense. Honestly, if you asked me what I was thinking about, I couldn't really tell you.

There’s a certain paralytic effect to it, but its completely mental; you can't necessarily stand up and walk around, but it doesn’t immobilize you. There's a texture to it — a smushiness — and a physical feeling almost like stretchiness, like you are a Gumby made out of memory foam.

I know I am starting to come to when things slowly begin to sink back into focus. My rational mind says, "I have been noticing all these things," and when it begins to verbalize them, I know it is taking over again. I would never get behind the wheel of a car, but I am able to get up and walk right out of there. I am usually a little foggy for the rest of the evening, but it is impossible not to notice that I feel better.

How do you feel afterward?

For me, what I notice most is the silence. There's a mental quiet — none of the continuous self-assessment, being completely certain of failure, being so certain that I'm not to going enjoy something I've been looking forward to for the last four months. It’s a much more peaceful place to be. It doesn't make me feel happy; it just makes me feel not bad. It brings me back to homeostasis — to where I imagine the rest of the world lives. It gives me the ability to experience the world as it is, rather than as a tarnished toilet bowl.

After my first infusion, when I realized it had worked, I felt so relieved. I'd been fighting a war against my own brain for so long, and finally the tables were even. And all the work I'd put into overcoming those little day-to-day struggles — all the coping skills Id learned — was no longer being continually undercut.

How long does that feeling usually last?

Its not so great the next day; there is a little bit of a hangover. Some of it may be unique to my brain chemistry, but the day after an infusion, especially in the morning, I feel mentally sluggish. I always wait at least 24 hours to judge the success of an infusion. By the end of the following day, I'm usually like, Oh, okay.

This medication has a set half-life, so I guess its out of my system within 48 hours, but it has lasting effects. It resets my brain and keeps it that way for different lengths of time. Im guaranteed 3 weeks out of it, but depending on the time of year or what is going on in my life I can sometimes get it to last as long as 6 weeks. I think the longest I went was a little over 2 months between infusions. The hardest part for me to understand is: Why is it still working? I don't know. Sure, Ketamine affects neurotransmitters — research they've done at Yale has shown that after someone uses Ketamine there are increases in the length of dendrites between the neurons in your brain — but once it's out of your system there's no way it’s affecting them directly anymore, it just works. And to me, it doesn't really matter why.

How do you know when you need a re-up?

It is very clear to me and has to do with that silence that I was talking about. At around the three-week mark I start to get little pop-throughs of that nasty, self-critical voice. As soon as I start to hear that voice cranking up again, I know the infusion has run its course.

As you do successively more infusions, do they tend to last longer?

Possibly. I do think that the infusions maybe last a little longer the more Ive done them, but what I do notice is that the bottom doesn’t fall out as far and as fast. When I first started doing them, after 3 weeks, my typical time frame, I'd start to see the gloss come off, and by the end of that week it was covered in poop. And now the gloss wears off over a couple of weeks. We don't really know what the long-term effects are, but I know other patients of Dr. Abreus are experiencing similar things. But every brain is different and everyone’s tolerance is different.

Did it take a while to get the dose right?

Dr. Abreu uses the NIH-recommended dose, which is half a milligram per kilo, as a good starting point because you are never going to overshoot with that dose. In my case we ended up finding that I was not as responsive, so it took a little bit of fine-tuning. There’s definitely a Goldilocks effect: If the dose is too low my brain is constantly grasping for reality, and I try to push off the intoxication that is creeping in because I want to remain in control. If it is too high, you can become so disoriented that things stop making sense. There seems to be a sweet spot, and I have found that if you are in that Goldilocks zone the effects of the infusion last much longer.

Of course, this dose is a tiny fraction of what people use in a black-market context; its like 0.01. And not only is it a fractional dose, but its being administered gradually over 45 minutes to an hour, whereas people who abuse it send it straight to their brain in less than a minute.

Right, I was going to ask about that: There is a certain stigma associated with Ketamine...

I am very protective of it, and I bet you can sense this, but I am completely unapologetic about using it. When I told my older relatives, my parents generation, that I was using Ketamine, they were all ears. I told them, more or less: You may have heard some strange things about this, but like any medication, if taken out of context and given to a bunch of people when there's heavy music on the dance floor, it can make some bad impressions.

Can you see Ketamine becoming more popular as a drug to treat depression?

I know there is a lot of work being done right now to develop some analogs to Ketamine that have the same effects on neurotransmitters and receptors without the bizarre mental effects. I know this because in conjunction with the infusions Ive tried oral Ketamine doses and lozenges, but haven't noticed that any of it works. I am convinced that the dissociative portion of the infusion is essential to what is going on. There is something about the infusion process that relates to how successful it is.

I think Ketamine as a drug has so much potential, but it is so old and so cheap and so generic that its patients and care providers — and not the drug companies — who are going to drive demand. But if hospitals start to administer Ketamine on intake, if they can quickly assess people who are depressive and suicidal, I think it could really save some lives.

https://www.thecut.com/2016/03/what-...enic-drug.html​

 

[mr peabody]

Psilocybin offers hope for those suffering with depression*

The Economist | Jun 8 2019

"My childhood was similar to those of many immigrants: my parents were under a lot of stress, and there was violence and alcoholism in the family,” says Carlos Plazola. “When I was under stress, I reacted with fear and anxiety. I always regretted my responses, but I couldn’t override them. After a mushroom journey, I found new ways to respond that included compassion and empathy.” That is why Mr Plazola joined Decriminalise Nature Oakland, a group which this week persuaded the council of the Californian city in effect to tolerate the consumption of magic mushrooms and other psychoactive plants and fungi. Last month Denver voted to do the same, but just for magic mushrooms. A campaign in Oregon wants to legalise their use by registered therapists. A Republican state senator in Iowa, Jeff Shipley, has filed a bill to allow the use of psilocybin and other hallucinogens for medical purposes.

After half a century, psychedelic drugs are inching in from the cold. Magic mushrooms, whose active ingredient is psilocybin, are in the vanguard.

Attitudes towards the drug may be moving back towards those prevalent in the 1950s and early 1960s, when psychedelics elicited interest rather than horror among ordinary Americans. The name “magic mushrooms” was coined, improbably, by a headline writer in stodgy old Life magazine. The magazine’s owner, Henry Luce, who had been taking LSD with his wife, had commissioned a banker friend to write about taking part in the secret mushroom ceremonies that had persisted in Latin America for centuries after the drug was suppressed by the Spanish invaders.

The therapeutic potential of psychedelics was discussed by scientists and enthusiasts. Bill W., co-founder of Alcoholics Anonymous, said he got sober with the help of a hallucinogen—the seeds of Belladonna, or deadly nightshade. Over 1,000 research papers, involving 40,000 volunteers, are reckoned to have been published in the period looking into their potential for treating a wide range of mental ills. But the research effort was scuppered by the moral panic sparked by Timothy Leary, founder of the Harvard Psilocybin Project, who, to the horror of parents and politicians, urged America’s young to “turn on, tune in and drop out”.

Magic mushrooms were banned in America in 1970, and are listed as Schedule 1 drugs by the UN, an assessment meaning that the potential for abuse outweighs their medicinal potential. Though barred in most of the world, psilocybin is legally available in a few places, such as Jamaica and the Netherlands, which has led to a small but flourishing psychedelic-tourism business.

But things are changing, for a few reasons. That the widespread decriminalisation of marijuana in America did not bring the social and moral collapse some detractors predicted has opened minds to the possibility of doing the same for other drugs. Psychedelics have enjoyed a vogue in Silicon Valley. Steve Jobs said taking LSD was “a profound experience, one of the most important things in my life.” And consuming tiny doses of psychedelics to enhance productivity is fashionable these days. Influential pundits such as Sam Harris discuss their potential.

All this has helped rehabilitate psychedelics. But the main reason for the revival of interest is probably the determination of a group of scientists. A few of the older ones first worked on the drugs in America in the earlier wave of research; they have been joined by a younger, transatlantic band. Earlier this year, Imperial College in London opened the world’s first Centre for Psychedelic Research.

The scientists’ findings are reaching a wider public through, for instance, the journalism of Michael Pollan, who last year published “How to Change Your Mind”, a book about the history and use of psychedelic drugs. In the words of Del Jolly of the victorious decriminalisation campaign in Denver: “There’s so much information out there. Healthy normals are beginning to understand the potential of these things.”

There are plenty of psychedelics researchers could work on, but the focus is on psilocybin. That is partly because nobody has heard of it, so, unlike LSD, it does not raise hackles. It is also relatively easy to synthesise. Since 2006, when the results of the first of the new wave of studies was published, there have been a dozen papers showing that it may be a useful treatment for obsessive-compulsive disorder, tobacco addiction, alcoholism, depression and the anxiety that so often afflicts people when they are approaching death.

Legal lows

Research has gone slowly because of the drug’s illegality. Getting funding can be difficult. David Nichols, a former professor of medicinal chemistry and pharmacology at Purdue University, Indiana, who first worked on psilocybin in 1969, founded the Heffter Institute because he knew that governments would be loth to fork out for research into illegal drugs. Backed by philanthropists, it has paid for a lot of research.

The paperwork is horrendous. It took Peter Hendricks at the University of Alabama at Birmingham, who is conducting trials on the impact of psilocybin on cocaine addiction, six or seven years to overcome the bureaucratic hurdles. Because so little psilocybin is produced, getting hold of it is tricky and expensive. According to David Nutt, professor of neuropsychopharmacology at Imperial, and a former adviser to the British government (famously sacked for saying that horse-riding accidents did more damage than ecstasy), each dose of psilocybin used in Imperial’s trials has cost around $1,900.

The trials are mostly small—only a couple involve more than 50 patients—and some have no placebo comparison. But the results are encouraging. A study at Imperial followed 12 patients with treatment-resistant depression. Nine were classed as seriously and three as moderately depressed; three months after taking a dose of psilocybin, one was seriously and six were moderately depressed, while five were no longer depressed. A study at Johns Hopkins University (JHU) of 51 patients with late-stage cancer suffering from depression and anxiety found that four-fifths had statistically significant improvements in their mood after six months; another at the same university into tobacco addiction found that six months after a dose of psilocybin 80% of volunteers had not had a cigarette for a week. The JHU study covered just 15 patients, who also benefited from a lot of psychological support. But the rates for the various drugs on the market is 25-35%. For cognitive behavioural therapy, it is 17%.

How the drug works is a bit of a mystery. It induces perceptions and sensations that commonly include a sense of oneness with the universe and of the revelation of a great, spiritual truth. A third of the 36 patients in a trial carried out at JHU rated its effects as the most profound spiritual experience of their lives; a further third said it was in the top five. That aspect seems to be essential to its efficacy: several studies have shown that the more profoundly mystical the experience, the greater the therapeutic effect.

Magnetic resonance imaging gives some clues to what is going on. Psychedelics seem to act in part through the default mode network (DMN), an interconnected group of bits of the brain that switch on when people remember the past, imagine the future or ruminate on themselves, and which is overactive in depressed people. When people take psychedelics, the DMN switches off; at the same time, other bits of the brain communicate with each other more than they normally do, perhaps forging new neural pathways that override old, destructive patterns of thinking. So it may be that these drugs tackle mental problems on a higher level than existing medicines and can thus act across a wide range of disorders. Matthew Johnson, of JHU, likens their effects to “a reboot of the system—it’s like pressing control-alt-delete”.

A study at JHU highlights another interesting parallel: that what is happening in the brain resembles what happens to those who meditate intensely. “It may be that what you get from psychedelics is a crash course in the effects that you could get from a long-held meditation practice,” says Dr Johnson. “My expectation would be that the self-control and cognitive benefits from meditation couldn’t come from a crash course. But in terms of the enhanced sense of self, this may be a helicopter ride to the top of the mountain, while those on the meditation path are hiking up.”

Researchers are excited. Depression and addiction are huge problems: 300m people worldwide suffer from depression, according to the WHO; 8m people die from tobacco addiction every year; and America is suffering from an opioid epidemic. Existing medicine for addiction, such as methadone for heroin, or nicotine substitutes for tobacco, is not very effective. And as Dr Nutt points out, no serious advances have been made in drugs for depression for 30 years. A variant of ketamine, a widely abused controlled drug, has recently been licensed for use in America in the most serious cases of depression, but its effect lasts only about a week. Psilocybin’s seems to persist for at least six months.

America’s Food and Drug Administration has given “breakthrough” status to psilocybin trials being conducted by a British company, Compass, whose seed investors include Peter Thiel, a tech billionaire. Compass is undertaking the first large-scale trial of the safety, efficacy and appropriate dosage of psilocybin for treatment-resistant depression. “Breakthrough” status means that “the drug may demonstrate substantial improvement over existing therapies”, and the FDA is keen to “expedite” its licensing. Compass is seeking a patent for a particular molecular form of psilocybin and the process to manufacture it. The drug’s current illegality will not be a problem if the FDA approves it. “If the science holds,” says Ekaterina Malievskaia, one of Compass’s co-founders, “there are no political and ideological hurdles.”

Compass’s patent application is raising a few eyebrows in the field. Some researchers feel that psilocybin is a spiritual gift which people have enjoyed for millennia and nobody should try to own. Usona, a non-profit founded by Bill Linton, CEO and founder of Promega, a biotech company, and Malynn Utzinger, a doctor, is also starting a trial—for “major” depression, a broader category than “treatment-resistant” depression. It is funded by philanthropy and is not seeking a patent: “We feel the work we’re doing is so transformational that we’re best serving the world by not attempting to monopolise treatment through patents,” says Mr Linton.

But there are also questions about whether Compass will be able to make money. Synthesised psilocybin will certainly be needed, for although magic-mushroom cultivation is widespread, whether decriminalised or not, sick people will need to be given controlled quantities in a safe, cheerful environment, not a handful of Psilocybe mushrooms.

Even so, as Mr Linton points out, “This molecule has been synthesised many times since 1958 when Albert Hoffmann, the chemist who discovered LSD, first did so. There are many synthetic routes to reach the final product, and it is highly unlikely that anyone could obtain a blocking patent.” Compass, however, might gain a commercial edge if its particular molecular form gets FDA approval and a patent.

There is a long way to go yet. Few drugs make it through the FDA process, and even if everything goes swimmingly, psilocybin will not be on the market for four or five years. Some of the drug’s proponents worry that decriminalisation could jeopardise its progress by reigniting the moral panic of half a century ago. Mr. Pollan, generally an enthusiast, cautions against “premature decisions about psychedelics before the researchers have finished their work.”

Although psilocybin seems safe compared with other mood-altering drugs (see chart), messing with your mind is inherently risky. “People will get hurt,” says Brad Burge of MAPS. “That’s inevitable. People will drive when on magic mushrooms. That can lead to a pushback.” But nobody in the field wants to prolong a situation in which, in the words of Cindy Sovine, who worked on the decriminalisation campaign in Denver, “people are going to jail and losing their children” for personal use of a drug that can bring pleasure and enlightenment.

In the current climate, progress towards a more liberal regime, whether through the medical or the legal route, is likely to continue. After all, as Max Planck, a great physicist, put it: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die.”​

 

[mr peabody]

Psychedelics as a life-changing treatment for depression

Scientist Robin Carhart-Harris wants to use psychedelic drugs to treat psychiatric disorders, and early results are promising. But can he convince big pharma and the public of their potential?

For half a century, researchers interested in psychedelic drugs have inhabited the fringes of neuroscience. In the UK, Carhart-Harris is responsible for making this field of study respectable again. He has spent much of the past decade investigating the ways certain compounds give rise to uncommon conscious states. He thinks LSD, psilocybin and DMT are powerful tools for accessing the brain. He also believes that psychedelics could potentially be used for treating mental illness. Current treatments for depression, anxiety and addiction can be life-saving, but they also have limits. About a third of people treated for depression never fully recover.

In 2006, a study by Francisco Moreno at the University of Arizona, Tucson, found that psilocybin reduced the symptoms of obsessive-compulsive disorder in nine patients. Then, in 2011, another study found that the same alkaloid significantly eased the anxiety of people dying of cancer. Each year, there are progressively more clinical trials with psychedelics. In 2016, three investigated the therapeutic action of psilocybin; another looked at ayahuasca.

A few years ago, Carhart-Harris undertook a study to see if psilocybin could be used to treat depression. He enlisted 20 people who had tried at least two courses of medication, so called treatment-resistant depressives. On average they had lived with the disorder for 17 years. On dosing day, each patient arrived at Imperial at 9am. After answering a questionnaire, they were led to a room that had been decorated to look more like a bedroom than a clinic, with drapes, flowers, music playing and electric lights that flickered like candles. After swallowing the psilocybin capsule, the patients were invited to stretch out on a bed. Two psychiatrists stayed in the room – Carhart-Harris believes that a soothing environment and psychological support before, during and after dosage is essential. People on psychedelics are psychically vulnerable; anxiety and paranoia are not uncommon.

When the results came in, they showed that the depression had reduced in all of the patients. (The results reflect the experiences of 19 people; one dropped out.) Three weeks after dosage, nine were in remission; after five weeks, all but one felt less depressed. For some of the participants, the treatment was life changing. “Before, I was like a beetle on its back, now I am on my feet again,” reported one. Another went out for dinner with his wife for the first time in six years, feeling “like a couple of teenagers”.

By studying LSD, Carhart-Harris has found that psychedelics do something unusual to the default-mode network. In a 2016 study published in the Proceedings of the National Academy of Sciences journal, he injected 20 healthy volunteers with either 75 micrograms of LSD or saline, a placebo, on two separate occasions. As the drugs kicked in, volunteers reported a “sense of eerie dread” as their anchorage in the world shifted. “Usually, depending on how it goes, there’s a bit of a kick back, there’s some anxiety.” They then had two fMRI scans followed by a magnetoencephalography (MEG) scan – if the various scans pointed to the same mechanisms the results would be stronger. Afterwards, volunteers responded to a questionnaire so that scan data could be correlated with experience. Statements included “sounds influenced things I saw” and “edges appeared warped”.

In the brains of the volunteers, as the visual network became more connected, the blood flow in the default-mode network receded, indicating that it had lost its force. For the participants, this correlated with a change in the way they processed the world. The monkey mind had gone quiet.

In society we talk approvingly of “well-rounded” individuals and “getting ourselves together.” But a little chaos can be a good thing. In certain psychiatric disorders, the brain becomes entrenched in pattern. Someone with depression might have relentlessly negative thoughts about themselves; people with obessive-compulsive disorder get trapped in repetitive action.

Carhart-Harris believes that psychedelics work like a reset button. He likes the analogy of shaking a snow globe. Under LSD, as the default-mode network disbanded, other segregated parts of the volunteers’ brains began communicating in an unpredictable way – a state of increased entropy. Psychedelics seem to break down entrenched ways of thinking by dismantling the patterns of activity on which they rest.

For instance, the most-prescribed class of antidepressants, selective serotonin reuptake inhibitors (SSRIs), raise levels of serotonin in the brain by blocking its natural reabsorption. When we are anxious or stressed, parts of the brain become overactive. Serotonin, a neurotransmitter, binds to receptors in the brain that are prevalent in regions involved in stress and emotion, the 5-HT1A receptors. Once bound to the receptor, serotonin initiates a signal that decreases the activity of the neurons. By keeping the 5-HT1A receptors doused in serotonin for longer than normal, SSRIs calm the stress circuitry. But they also blunt emotion more generally.

Psychedelics work on the brain rather differently. Though they also temper serotonin, they target the 5-HT2A receptors, concentrated in the cortex. Humans have vastly more cortex than other species, and the 2A receptors are dense in regions with human-specific traits such as introspection, reflection, mental time travel and the self itself.

Carhart-Harris thinks that when psychedelics disrupt the level of connectedness in the cortex they create space for insight and catharsis. For patients, the process can be difficult. “You need to be able to say to people: this could be tough, it could at times be the worst experience of your life and you may see your worst fears staring at you in the face.” But he believes that the process can be freeing. “I think it’s possible to know your defences and know your insecurities and through knowing them not be at the mercy of their force.”

In July 2017, Carhart-Harris gave a talk at a conference called Breaking Convention, which bills itself as “the largest psychedelic conference in the known Universe.” Held at the University of Greenwich, the program listed 150 speakers from across the psychedelics spectrum. In the question-and-answer session, Carhart-Harris’s hand shot up. “Have you plotted the correlation between the affinity of psychedelics for the 5-HT7 receptor and the drug’s potency?” Ray said that he had not. “I think that you should, it’s important.” People fidgeted: this was not a hostile crowd.

Afterwards, Carhart-Harris left the conference and stopped in a local cafe for lunch. He was quiet, almost ruminative. “How can you present such poor science? I think that people should be allowed to speculate. But the people who contribute to the mainstream perception that this research is pseudo-scientific undermine the field.”

The episode had tapped into something deeper. Research with drugs that are strictly controlled by the law is not straightforward. In the UK, LSD is a class A, schedule 1 drug. Heroin, which causes more harm to individuals and society than LSD, and is addictive, is in the slightly less prohibitive schedule 2 because it is a diamorphine, which can be used for medication. For a lab to stock LSD it must acquire a licence from the Home Office and meet certain criteria, such as having a fridge that is bolted to the wall. All this is demoralising. It took Carhart-Harris three years to execute the psilocybin-depression pilot.

Funding is also an issue. Big pharmaceutical firms are generally not inclined to back research into drugs that are illegal and un-patentable. Carhart-Harris’s studies have been largely financed by grants, donations and crowdfunding. In 2016, he applied to the Wellcome Trust, the largest charitable supporter of science in the UK. When he was shortlisted, he thought he stood a chance. He had meticulously designed the two trials he was hoping to carry out if he got the $1.5 million-plus grant. But one of the judges on the panel took issue with his suggestion that “well-being” should be a primary outcome. Carhart-Harris had the impression that the judge considered it flowery. He didn’t get the grant.

Of all the psychedelic drugs, Carhart-Harris believes that psilocybin is probably the closest to becoming legal. It has fewer stigmas attached to it, and in the brain, LSD is active for far longer, making it less practical in the clinic, while DMT is probably too powerful. The fact that psilocybin occurs naturally in mushrooms also helps. It could be marketed as a natural alternative to antidepressants. He believes that, one day, psychedelic therapy will be available on the NHS, just like SSRIs and cognitive behavioural therapy are today.

This spring, he plans to do another psilocybin study, this time directly pitching psychedelics against SSRIs. Fifty people living with depression will receive either daily doses of escitalopram, an antidepressant, or a single 25mg shot of psilocybin, plus therapy. The contest is unequal, in one sense, because those taking escitalopram will have a regular reminder that they are taking medication. “Maybe psilocybin will work at least as well, that’s my prediction,” Carhart-Harris says. “But imagine that psilocybin is more effective? That’s really quite…” he tails off. “That would be something.”

http://www.wired.co.uk/article/psychedelics-lsd-depression-anxiety-addiction​

 

[mr peabody]

Ketamine is changing the course of treatment for Major Depressive Disorder

Psychiatry Advisor | August 9, 2019

Currently, there is an unmet need for the development of rapid-acting antidepressants aimed at treatment-resistant patients with either major depressive disorder (MDD) or bipolar disorder. A review of existing treatment options, as well as future possibilities, was published in Psychiatry and Clinical Neurosciences.

Approximately 320 million people worldwide are affected by MDD, with a noted >18% increase in MDD incidence between 2005 and 2015. Currently available antidepressants present several treatment limitations, including long-time lags and low response rates.

“There exists an unmet medical need for rapidly acting novel antidepressants that are also effective in treatment-resistant patients, and patients with suicide ideation,” wrote Kenji Hashimoto, PhD, of the Division of Clinical Neuroscience at Chiba University Center for Forensic Mental Health in Chiba, Japan.

Could ketamine be the answer?

Recent research has revealed the “robust” antidepressant and antisuicidal effects of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist in patients with treatment-resistant MDD or bipolar disorder.

“The discovery of the robust antidepressant actions of ketamine is regarded as the greatest advancement in mood disorder research in the past 60 years,” Dr Hashimoto noted.

In 2000, researchers at Yale University first reported the rapidly acting antidepressant effects of ketamine in patients with MDD. This double-blinded, placebo-controlled trial was followed by subsequent studies that were able to replicate the antidepressant actions in this patient population. A 2013 study found that, as compared with midazolam-treated patients, ketamine-treated patients “showed greater improvement in depressive symptoms.” Similar research also indicated that ketamine therapies lowered suicidal ideation.

Ketamine Changes Course of Major Depressive Disorder Treatment - Psychiatry Advisor

Researchers found data that showed ketamine is effective for treatment-resistant major depressive disorder, but the way that it is administered and biomarkers for response need further testing.

www.psychiatryadvisor.com

 

[mr peabody]

'Microdosing lifted me out of my depression'

Little research exists on the effects of tiny doses of psychedelics, but devotees of the practice report remarkable benefits.

Erica Avey, 27, microdosed on LSD for 8 months, using an analogue that was legal in Germany. "I started microdosing because I was in a really depressed stage of my life. It was for mental health reasons, mood balancing, mood management. It was hard for me to leave my apartment and do normal things as a human being," she said.

Depression or sadness are very common reasons for starting; Avey was unusual only in that she could be open about it. Her workplace knew and thought it was fine. "As long as I wasn't out of control or permanently high at work they were quite OK."

She took about 15 micrograms. "That was a good amount for me. Some people take as little as six," she said. She adopted a popular protocol, one day on, three days off.

It worked for her. "It definitely had the effect I wanted", she said. "It lifted me out of a pretty deep depression. I am still trying to wrap my head around what it has done to me in the long-term. I think it has changed me." She had been "pretty negative," she said, "mindlessly going through social media, plagued with obsessive thoughts."

"I am able to be more mindful of my emotions. If I am feeling sad, that is OK. I don't obsess anymore. I don't dwell on it. I don't get worked up about it."

She and others spoke of becoming more aware of the need to be active, cut down on alcohol and eat healthily. She talked of heightened energy and heightened awareness. In the beginning she felt more productive and creative, but later that became more of a problem.

"I was able to get all my work done, but around 2 to 3pm I would hit this wall of really needing to go out for a walk, a need to be moving," she said. Although it lifted her depression, she felt more anxiety. "There were one or two experiences when I did feel a bit overwhelmed. If people experience high levels of anxiety, I don't think this is for them."

Microdosing, for her, is a transformative psychological experience and she is not the only one who feels it is in danger of being misused in Silicon Valley. "To think of people using this just to write code faster does seem a bit superficial. But it might be good for them. They might re-evaluate their lives in ways."

It's not the answer to everything. She left her job and moved on. In a blog, Avey wrote: "There is no magic pill. Microdosing is not a good-time-guaranteed, or quick fix. Our minds are in conversation with our environments. We create and are created by our contexts. And in many cases, we don't need drugs, just a new environment."

Alex, 35, (not his real name) is a paramedic in the NHS and can tell nobody that he microdoses. Severely depressed, he turned down his GP's offer of antidepressants which he had 'tried before without success,' he said. He did a lot of reading and researching online before experimenting with microdoses of LSD.

"What struck me was that there was no discernible difference at first," he said. "I'd never tried LSD recreationally, so I had no idea what to expect. I stared at a blank wall every now and then just to make sure I didn't see any hallucinations, but there was nothing. Weirdly, it's not until the next day, in retrospect where you look back, that you realise you handled things, or reacted to things differently. It's so subtle it's easy to miss. But it definitely worked."

"I continued taking it for approximately three months. Sometimes I'd take a dose before work (around 9 mcg dose). I found that whilst it improved my concentration, I didn't want to become dependent on it for that purpose. Once I was out of that black hole cycle, I stopped taking it. But I will take it again if I need to."

Adam, 30, (not his real name) lives in Germany and has been microdosing on magic mushrooms for five months, on and off. He also follows the one day on, three days off protocol. He says he is stereotypical of those who microdose: "Someone who's been struggling with more or less intense depression all my life." Before he started, he was 'stuck in a rut,' he said. "I lost all interest in my everyday activities. I had no sense of pride or joy." He was drinking too much red wine after work to calm down.

"Microdosing," he says, "doesn't make me feel better. It forces me to reflect on things. It helped me to reshape my daily habits." He got back into exercise, running on the days he microdosed, going to the gym the day after. He ate and slept better.

"There are downsides. I can get a little anxious on dosing days, he said. "He talks of underestimating challenges, having to confront things and not duck them, whether thoughts or encounters with strangers. On microdosing days," he said, "he is exhausted and in bed by 10pm. The second day brings an afterglow," he said, "which is more pleasant."

He doesn't believe microdosing should be used to try to boost your career. "I am not a big fan of people promulgating microdosing to a bunch of CEOs to increase their work," he said.

https://www.theguardian.com/science/...-for-your-mind​

 

[mr peabody]

The complete guide to ketamine therapy for depression, from someone who’s tried it

by Allegra Ringo | allure | Oct 30 2019

Ketamine is an anesthetic that's used off-label for depression, but does it work?

When I entered the ketamine clinic for the first time, I started crying almost immediately. This was for two reasons: First and foremost, I was scared. After watching a documentary that introduced me to the subject and reading several accounts of ketamine infusion therapy, I knew a fair amount about the process. But the experience sounded strange, disorienting, and mysterious. Despite having done my research, I still didn’t feel like I had a good idea of exactly what it would feel like.

I was also crying simply from sadness. I’d been trying for almost 10 years to manage my depression with medications and therapy but felt worse than ever. The many medications I’d been prescribed over the years would work for a little while, then inevitably stop being effective, sending me into a progressive spiral that would worsen every time. I felt like I'd tried everything, but that wasn’t quite true. I hadn’t tried ketamine.

Ketamine has been used as an anesthetic since the1960s. In the 1990s and 2000s, researchers began looking into trying it off-label as an antidepressant. Fairly recently, it has come into use for people with treatment-resistant depression, as well as people with other diagnoses, like bipolar disorder and post-traumatic stress disorder (PTSD). (It’s also used for treating pain.) Ketamine clinics have opened in select states throughout the U.S., including California, where I live.

Ketamine is available in a couple of different forms: It can be administered through an IV or ingested via a nasal spray called esketamine. Esketamine is approved by the FDA for the treatment of treatment-resistant depression. IV ketamine is not, and thus treating depression with ketamine is an off-label use. Ketamine lozenges are also available to some patients.

I was about to give IV ketamine a try, and although I was terrified, the unknown was preferential to continuing on the same path I was used to because it came with a massive potential benefit: finally finding relief from my depression.

What ketamine can do for depression

Ketamine has been shown to be effective in treating symptoms of depression and can be especially helpful for treatment-resistant depression (TRD), which is generally defined as “inadequate response to at least one antidepressant trial of adequate doses and duration,” according to a study published by Harvard Medical School. If you’ve tried multiple antidepressant medications (possibly in combination with other treatments) without success, you might have treatment-resistant depression.

In several studies at Yale, more than half of the participants who were given ketamine infusions showed a significant decrease in symptoms associated with depression after only 24 hours. These results are significant for two primary reasons: One, these participants were people who had experienced no “meaningful improvement” on other antidepressants. Two, the alleviation of depression symptoms after just 24 hours is extremely fast compared to other antidepressants, which can take weeks to kick in. To a severely depressed person who might be experiencing suicidal ideation, a fast-acting treatment could make all the difference in the world.

John Krystal, the Robert L. McNeil Professor of Translational Research and chair of the Yale department of psychiatry, believes that ketamine is a promising treatment for depression for several reasons. First, it can be effective for people whose depression symptoms have not responded to other treatments. Second, as noted above, the effects are rapid. “People who are severely depressed, suicidal, and might otherwise need hospitalization may get better as quickly as 24 hours after their first dose,” says Krystal.

A third reason is that ongoing ketamine therapy can protect a patient against a return of depression symptoms. “The reason that this is so important is that even after trying many different treatments, as many as 30 percent of patients will remain significantly depressed,” Krystal tells me.

How it works

Robert C. Meisner is the medical director of the McLean Ketamine Service in the psychiatric neurotherapeutics program at McLean Hospital, the major psychiatric hospital for Harvard Medical School. In an article for Harvard, he writes that experts aren’t exactly sure how ketamine works to combat depression, but that one likely target is N-methyl-D-aspartate (NMDA) receptors in the brain. “By binding to these receptors, ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons,” Meisner writes. Then it activates connections in another receptor, called the AMPA receptor.

“Together, the initial blockade of NMDA receptors and activation of AMPA receptors lead to the release of other molecules that help neurons communicate with each other along new pathways,” writes Meisner. This process likely affects mood, thought patterns, and cognition.

Ketamine may also reduce symptoms of depression in other ways, such as reducing signals involved in inflammation. Meisner and other experts theorize that ketamine likely works in several different ways at the same time.

Potential risks of ketamine therapy

I asked Meisner about the risks of ketamine therapy, including whether ketamine can be addictive. “All of us who specialize in this area remain concerned about the potential for physiologic and psychological dependence,” he tells me. At his clinic, for example, a previous history of substance use usually means a patient will not be treated with ketamine (though there are some rare exceptions).

“It’s important to understand that even though you may suffer from treatment-resistant depression, ketamine may not be the wisest choice,” he says.

That said, Meisner and his colleagues have not seen a high volume of patients who show signs of ketamine addiction. “To the best of my knowledge, we have received only one consultation request over the phone in which the caller was seeking treatment with ketamine for reasons consistent with addiction,” he tells Allure. “Moreover, to the best of my knowledge, not a single one of our patients has gone on to develop physiologic or psychologic dependence to ketamine after completing our protocol.”

However, experts remain alert about any potential for abuse. Currently, there is an epidemic of oral ketamine abuse in parts of Asia. Ketamine as a street drug is quite a different experience from ketamine as a treatment for depression (and street drugs carry the risk of being cut with other substances), but epidemics like this are always cause for concern.

In addition, there are some basic physiological changes that happen when ketamine is administered, such as a rise in blood pressure. For many patients, this isn’t a problem, but if you have some preexisting conditions, it may pose a health risk. That’s why it’s so important to find a ketamine clinic that prioritizes safety.

The financial cost

Ketamine therapy isn’t cheap. When I was determining where to go for my ketamine infusions, I asked about pricing at several clinics. The range I found in the Los Angeles area was $450 per infusion (the lowest price I could find) to $750 per infusion. Anecdotally, the highest price I’ve heard of is $1,000 per infusion. The clinic I ultimately went with charged $750 for the first two infusions and $600 for all subsequent infusions.

In other U.S. states, the price varies, but it’s never exactly an inexpensive option. (A map of “active clinics in good standing” from the website Ketamine Clinics Directory lists the price of ketamine infusions at clinics across the U.S. The lowest price listed is $250 per infusion, at a clinic in New Jersey.) Many clinics recommend six initial infusions, though of course, they can’t make you do any more than you want to.

The other big question associated with cost is whether health insurance will cover it. All of the clinics I spoke to in Los Angeles billed out of network, meaning that my insurance company might end up covering some of it, but either way, I would have to front the cost. (After many months, I am still waiting to hear back from my insurance company about whether I will be reimbursed for any of my treatments.)

If you have health insurance, you’re at the mercy of your insurance company to determine whether they’ll cover any of your ketamine therapy. To be fair, this is true of most medical procedures that are still considered experimental. I haven’t found a clinic that is an in-network provider for any health insurance plans, although that doesn’t mean they don’t exist. If you don’t have health insurance, of course, you’ll be paying the cost yourself. This can add up to many thousands of dollars, depending on the number of infusions you receive. On the bright side, some ketamine clinics offer payment plans.

If you are able to find an academic center in your area, the pricing may be different. At this time, it’s difficult to find any comprehensive list of prices throughout the U.S., so it’s important to call around and ask for pricing information when you’re doing your research.

What it feels like

This remains the most difficult part of the ketamine process to describe. Even after seven sessions, I never got very good at describing what it feels like to undergo a ketamine infusion.

I spoke to a writer, who I’ll call Rebecca for the purposes of anonymity, who was prescribed esketamine after suffering from treatment-resistant depression for many years. She described her first two experiences of esketamine (which were a higher dose than her subsequent doses) thusly: “There was a physical sensation of heaviness but at the same time I felt separated from my body. Or it might be more accurate to say, separated from my consciousness. I was able to view certain things more objectively. Things that were upsetting suddenly seemed less important.”

This description rang true for me. If you’ve ever done a hallucinogen, like LSD or mushrooms, this probably all sounds familiar to you. Ketamine felt similar to other hallucinogens but way more intense, and for me, it lacked any feeling of euphoria, though I did find myself laughing during several of the treatments.

Now, let's talk results

Like almost anything, the effects of ketamine therapy vary greatly from person to person. Studies show that ketamine is associated with a rapid reduction in depression symptoms, including suicidal ideation. Overall, ketamine is promising in terms of its general effectiveness, as well as its fast-acting properties.

However, that doesn’t mean it will be effective for every individual. Like any treatment for depression, there is, unfortunately, no way to test whether it will be effective for a given person. When intravenous ketamine does work, patients usually respond to it within one to three treatments. If a patient doesn’t respond at all to those initial treatments, further infusions are not likely to be effective.

In addition, most experts agree that ketamine works best as part of a larger treatment plan, which usually involves talk therapy and sometimes ongoing use of antidepressant medication. Meisner says "it’s important to remember that ketamine is not a magic bullet."

In my case, the first two treatments did not feel effective to me, although I experienced mild euphoria for short periods after each of them. After my third infusion, though, I began to feel significantly better. Many of my symptoms subsided, I felt “lighter,” and I laughed a lot more.

Between my third and sixth infusions, and for about a week afterward, I continued to feel relief from my previous symptoms. Unfortunately, that relief faded quickly. My symptoms returned about a week after I finished my sixth infusion. Ketamine’s effects are known to be relatively short-term; the staff at my ketamine clinic told me that most of their patients feel relief for about three months after completing six infusions. I was one of the people who experienced its effectiveness for a very short time. After trying a seventh infusion, I was prescribed ketamine lozenges, which are supposed to prolong the effects of the ketamine infusions. I do find the lozenges effective, though for very short periods. For me, their effects last about a day.

However, I spoke to other people who reported success with ketamine therapy. Rebecca, who takes esketamine for depression, has experienced a significant reduction in her symptoms.

Her first two doses were eight sprays each, taken under the doctor’s supervision, followed by a “maintenance dose” of two sprays a week, taken at home. Rebecca told me that she experienced immediate positive effects, that it boosted her energy levels and took the edge off her depressive symptoms. Before the ketamine treatment, her depression was causing her debilitating levels of “brain fog,” negatively affecting her memory and cognition. She feels that the esketamine, which she continues to take at home, is helping with that. She says that after about a month and a half of treatment, she’s cautiously optimistic.

How to seek out ketamine therapy

If you’ve been diagnosed with major depressive disorder (MDD), bipolar, or PTSD (or some other diagnoses, in some cases), and other treatments haven’t helped you, you might be a good candidate for ketamine therapy. However, it’s important to get an opinion from your psychiatrist first as to whether ketamine is a good option for you. “They may not be especially familiar with these emerging treatments, but they should understand your response to first-line antidepressants and be able to offer an opinion regarding the likelihood that further trials with more established medications will yield different results,” says Meisner.

Start by researching ketamine clinics in your area. Again, this map is a handy place to start, though it’s not comprehensive, and the quality of each clinic is not guaranteed. If you don’t feel up to doing this research, this is a great project to ask a non-depressed loved one to do for you. The person doing the research should determine a reasonable distance from where you live and call any ketamine clinics in that area. They should ask about price, insurance options, payment plans, and how many initial sessions the clinic recommends.

Many clinics recommend six infusions within a two- or three-week period, so if you do go ahead with treatment, be sure to schedule them when you can spare that time. My infusions lasted 55 minutes each, plus 15 to 20 minutes of recovery time afterward — you need some time before you are steady enough to walk again. You also can’t drive yourself home after an infusion, and you will feel fuzzy and possibly sleepy in the hours afterward, so schedule accordingly. Also worth noting: My clinic instructed me to fast for four hours before each infusion.

What to look for in a ketamine clinic

Additionally, many ketamine clinics will ask to be put in contact with a therapist, psychiatrist, or general practitioner who can confirm your diagnosis, so have that information ready. Meisner also stresses the importance of finding a ketamine clinic that’s evidence-based and data-driven, and that puts safety first. He has a few key recommendations for anyone considering ketamine treatment:

- Seek out a specialist who is “not only willing — but enthusiastically supports — close collaboration with your outpatient psychiatrist.” Collaboration of this kind can be time-consuming and is often not reimbursed but is extremely important with “emerging treatments” like ketamine.

- Find a specialist who is willing to be transparent about the uncertainties of ketamine treatment. “This is not a sub-field in which arrogance — of any kind — is a marker for competence,” says Meisner. “If you sense someone is overpromising, they probably are.”

- Be relentless about ensuring that the clinic has appropriate safety measures in place. “Don't be afraid to ask what specialists are on sight, and why they are qualified for a psychiatric use of a medication typically categorized as an anesthetic,” says Meisner. "For example: Are both a psychiatrist and an anesthesiologist present? What sort of training does staff have that qualifies them to administer ketamine? And crucially, what kind of monitoring is in place during treatment?"

In all honesty, I wanted ketamine to cure my depression instantly and forever. Deep down, though, I think I knew it couldn’t do that. Ketamine isn’t for everyone, and it isn’t a magic bullet. But it taught me that my brain, as hopelessly entrenched in sadness as it sometimes seems, has the potential to change, and that it’s possible for me to feel better. For those of us who have spent a long time suffering and who have been unable to find an effective treatment, ketamine therapy offers a ray of hope. For some of us, that hope can be life-saving.

Here’s What Happened When I Went on Ketamine for My Depression

I wanted it to be a magic bullet, but it wasn't that simple.

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