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    Bluelighter mr peabody's Avatar
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    ‘Ketamine saved my life’

    Ketamine has undergone promising clinical trials in Australia and America to treat depression using IV drips with micro-doses of Ketamine.

    An anesthetic drug, Ketamine is now increasingly being used as a revolutionary — and sometimes life-saving — medication for those struggling with treatment-resistant depression, who are chronically suicidal or experience frequent psychotic episodes. After turning to every other treatment on the market, including over 40 sessions of electroshock therapy, one member of New Zealand’s trials, Jemima Lomax-Sawyers, associates Ketamine with saving her life:

    “I am so much more stable than I was a year ago. Stable to the point that I am able to make decisions about my wellness that I would not have been able to make in the past…Things feel lighter inside my head. I have more energy, I can concentrate better.”

    That is why Sawyers and others like her are extremely concerned that New Zealand’s only Ketamine Clinic would no longer be accepting new patients, and that current patients may be taken off its lists once new treatment plans are agreed upon with the country’s Ministry of Health.

    “For many of us, ketamine was our last chance, our only chance for living a life out of hospital, or even for living full stop,” says Sawyers. “Ketamine gave me some hope back: the glimmer that I might actually be able to live life without the constant worry of relapse, hospitalisation, then having to pick myself up and put all the pieces back together again and again and again.”

    http://dancingastronaut.com/2018/02/...ne-saved-life/

    -----

    I've been depressed for years and tried every medication possible. Nothing helped me. So I decided to give Ketamine a try. The Ketamine infusions relieved my depression and after several weeks, I am feeling much more optimistic and hopeful.

    -John A.

    My depression caused physical pain and other dreadful symptoms for years and years. Many of my symptoms disappeared with my first treatment of ketamine, and while I still get depressions I can live an active life and my mood chart is consistently happy for months on end. I had literally tried everything and this really works.

    James J.

    I was in an extreme state of deep depression and I needed help. I believe that first infusion saved my life. I've now had 4 infusions. The compound prescription has been filling in the gaps, with no unpleasant side effects.

    Liz P.

    I was in search of a solution for my treatment resistant depression and figured I'd give ketamine infusions a shot. I feel more positive, relaxed and overall better after the five infusions I received. I would highly recommend Ketamine infusion therapy to anyone.

    J.M.

    I received the ketamine infusions after 20 years of severe depression. We were skeptical at first, but boy did it help. My depression seemed like it was almost gone after just one session and got better with each session for the 5 total sessions. After the infusions, I was placed on the nasal Ketamine spray, and that has continued the amazing benefits I received with the infusions. It's been 2 months and I'm doing great.

    Dan M.


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    Magic mushrooms: Treating depression without dulling emotions

    Two new studies confirm the hypothesis that the psychoactive compound found in "magic mushrooms" may be a useful treatment for depression, avoiding some of the side effects of conventional antidepressants.

    At Medical News Today, we have reported on a range of studies that pointed to psilocybin — the psychoactive substance in "magic mushrooms" — as a potential remedy for depression.

    Two such studies showed that the psychoactive compound can reduce feelings of anxiety and depression in people with advanced cancer, while another small trial suggested that the compound could succeed where previous depression treatment has failed.

    Treating depression can be challenging not only because some depression types are treatment-resistant, but also because existing therapies have a range of unwanted side effects.

    One such adverse effect frequently reported by people living with depression is the "emotional blunting," indifference, or apathy that comes with taking antidepressants.

    A new study — which was carried out by researchers at Imperial College London (ICL) in the United Kingdom — suggests that magic mushrooms could treat depression while avoiding these side effects.

    The new research consists of two studies, both of which were led by Leor Roseman, a member of the Psychedelic Research Group at ICL.

    Participants felt 'emotionally reconnected'

    In the first study, published in the journal Neuropharmacology, 20 people diagnosed with moderate to severe depression participated in two dosing sessions with psilocybin.

    Using functional MRI (fMRI), the team scanned the brains of the participants while they looked at pictures of emotive expressions. The scans were taken before and after each drug intervention.

    In order to assess the impact of the treatment on depression, the subjects were all provided with psychological support before, during, and after the intervention.

    After the treatment, the participants reported feeling better, "emotionally re-connected, and accepting."

    The fMRI scans revealed a stronger brain response to emotive faces. Specifically, the scientists saw more activity in the brain's amygdala, an emotion-processing area associated with depression. The study authors explain:

    "Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions."

    Roseman comments on the new findings, saying they "are important as they reveal biological changes after psilocybin therapy and, more specifically, they suggest that increased emotional processing is crucial for the treatment to work."

    But the authors also caution that more research is needed to establish firmly whether the positive effects were due to the psychoactive compound itself, the psychological counseling, or the interruption of the antidepressant treatment the subjects had been on before the study.

    "Having a healthy control group in future studies should be helpful in answering some of these questions," Roseman admits.

    'Mystical experience' improves efficacy

    The second paper, published in the journal Frontiers in Pharmacology, examined whether or not the quality of the psychedelic experience was linked with the success of the treatment.

    Roseman and colleagues gave questionnaires to another group of 20 volunteers who underwent two treatment sessions with psilocybin.

    The researchers looked at the so-called feeling of oceanic boundlessness, which is a "mystical-type experience" involving feelings of unity and a lack of boundaries between the self and the universe.

    The study revealed that the more strongly the participants felt this experience, the better was their mental health in the long-term.

    Depressive symptoms subsided, and the mental benefits lasted for weeks after the treatment in participants who reported a strong mystical experience.

    "Future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model," conclude the authors.

    The researchers say they plan on carrying out larger trials with a healthy control group in which the effects of psilocybin could be compared with an existing antidepressant.

    "We also want to investigate how the amygdala responds a longer time after treatment," Roseman adds, "which will inform us about longer-term effects — compared to the first study, which was only looked at 1 day after the therapy."

    Additionally, in light of the findings of their second study, the group recommends that future trials with psychedelics should aim to enhance the "mystical" aspect of the experience.

    https://www.medicalnewstoday.com/articles/amp/320636



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    Are psychedelics the answer to depression?

    Roland Griffiths was trying to meditate – but he couldn’t do it. If he sat there for a few minutes, it felt like hours were stretching out before him, like a long, slow torture. So he quit.

    The young scientist, who was rapidly rising through the ranks of academic psychology, would not meditate again for 20 years, but when he returned to mindfulness, he became part of unlocking something crucial. Professor Griffiths was going to make a breakthrough — just not for himself, but for all of us.

    * * *

    I came to Roland Griffiths’ door towards the end of a 40,000-mile journey, from Sydney to Sao Paulo to San Francisco. I set out on this trek to interview the world’s leading experts on what causes depression and anxiety, and what really solves them, because I had been downcast and acutely anxious for much of my life, and the solutions I'd been offered up to then hadn’t taken me very far.

    Everywhere I went for my book "Lost Connections: Uncovering The Real Causes of Depression – and the Unexpected Solutions," I heard people talking excitedly about the new research into psychedelics that was slowly creaking open. Until the mid-60s, many reputable scientists had set up clinical trials where they gave these drugs to people suffering from depression, alcoholism, and other problems. There were some quite striking early findings – and then, in a cultural panic, the research was slammed shut by the Nixon administration.

    And then came Roland Griffiths.

    * * *

    Griffiths was a young grad student when he walked away from his attempts at meditation, pissed off. Years later, he is a Professor of Psychology at Johns Hopkins University School of Medicine in Maryland, one of the best academic institutions in the world. He rose, he says, by being “a certifiable workaholic.” He was succeeding on all the measures of success in his world – but he felt like there was a hole in his life. It was, he told me “as though in some respects I was going through the motions of being a scientist and having a career in science.”

    He found himself thinking back across the decades, to his aborted stab at mindfulness. He began looking to see if there was any scientific evidence for the benefits of mindfulness – but he quickly saw that in his academic world, it was almost heresy to talk about the deep inner self. This was not regarded as real science.

    He went to an ashram – and found that this time, he could meditate after all. “This inner world started to open up, and I started to open up,” he said. The people he was meeting who had been meditating for years seemed to have a spiritual dimension to their lives that really benefited them in all sorts of ways. They appeared calmer, and happier, and less anxious.

    So Roland started asking himself some basic questions. What happens when a person meditates? If you meditate for long enough, most people say they start to experience a spiritual change. Why did meditation make people feel they were being changed in a way that was mystical? He stumbled across the psychedelics studies from the 1960s, and it seemed to him that the way people described feeling when they took psychedelics was very similar to the way people described when they were in a state of deep meditation. He began to wonder if they were, in some strange sense, two different ways of approaching the same insight. Could investigating one unlock the secrets of the other?

    So he did something bold. He applied to conduct the first clinical trial on a psychedelic since the ban a whole generation before. He wanted to give psilocybin to “respectable” citizens who had never used it before, to see if they would have a mystical experience — and to discover what the longer-term consequences, if any, would be.

    “I have to say, frankly, that I was a skeptic,” he told me one afternoon. When he got the permission to proceed, people were startled. They assumed it was because the regulators thought Roland, with such a solid reputation, could only find that these drugs were harmful.

    So dozens of ordinary professional people were recruited in Maryland. We want you, the advertisements said, to do something unusual.

    * * *

    Mark didn’t know what to expect as he walked into Roland’s lab. It was decorated to look like a living room in an ordinary home, with a sofa, soothing pictures on the wall, and a carpet. He was a straight-laced forty-nine-year-old financial consultant who had never taken a psychedelic before; he hadn’t even smoked cannabis.

    He responded because he had become divorced from his wife a few years earlier and become depressed. He'd been taking an antidepressant for four months, but it was just making him feel sluggish. Now he was worried about himself. He felt he kept everybody at arm’s length, and never really connected to them.

    This had begun when Mark was 10 years old and his father had developed a heart problem — a defect in one of his valves. One day he started experiencing terrible pain, and as Mark watched him get into the ambulance, he knew he would never see his father again. In the years that followed, Mark’s mother was so lost in her own grief she couldn’t discuss the death with the boy, and nobody else did, either. “I think I just stuffed it all. I think I just went into denial mode,” Mark told me. It was the beginning of a pattern for him — of hiding, in order to protect himself.

    As he lay on the sofa in the pretend lounge, his anxiety flared. This was the first of 3 sessions in which he was given psilocybin. He lay down on the sofa, and when he was comfortable, he was handed a small psilocybin pill to swallow. He looked at some images of landscapes in a book with his guide, Dr. Bill Richards, and then Bill placed a blindfold over Mark’s eyes and put some headphones on him, playing gentle music. And within forty-five minutes, Mark started to feel something different. “I could feel my mind getting looser,” he said to me.

    The scientists had explained to him in the long preparation process that calling these drugs “hallucinogens” is a bit of a mistake. A true hallucination involves seeing something that isn’t there and thinking it’s as real as the device on which you’re reading this article, a physical object in the world. It’s more accurate, they said, to call them “psychedelics,” which in Greek means mind-manifesting. What these drugs do is draw things out of your subconscious and bring them into your conscious mind. So you don’t hallucinate. Rather, you see things in the same way you see them in a dream, except you are conscious; and at any given moment, you will be able to talk to your guide, and know he is physically present, and know that the things you are seeing as a result of the drug are not physically there.

    “There’s no visual experience of the walls turning or anything like that,” Mark told me. “It’s totally dark. And all you hear is this music as a means of grounding you—and then it’s just internal visualization . . . I would say it is like dreaming awake,” except he could remember it all afterward, vividly, “as vividly as anything in my life.”

    * * *

    As he lay back on the sofa, Mark felt he was paddling in a great cool lake. He started wandering up and down, and he could see there were different coves around him, and that there would be inlets from those coves. He sensed intuitively — as you do in a dream—that this lake symbolized all of humankind. All of us empty out into this lake, he thought — all our feelings, all our longings, all our thoughts.

    He decided he was going to explore one of these coves. He hopped from rock to rock, all the way up the stream, and he felt something was calling him to keep going deeper. He then reached a sixty-foot waterfall and stood before it in awe. He realized that he could swim up it, and he thought that when he got to the top of the waterfall, he would be wherever he wanted to go in life, and “the answer would be there for me.”

    He told Bill, his guide, what was happening. “Drink it in,” Bill said.

    When Mark reached the top of the waterfall he saw a little fawn in the water, drinking from the stream. It looked at Mark and said “There’s some unfinished business here for you to take care of,” from your childhood. “This is something that you need to take care of if you want to continue to evolve and grow.”

    Now, at the top of this waterfall, Mark felt for the first time in his life that it was safe to approach the grief he had hidden away since he was ten years old. He followed the fawn farther down the river and he found an amphitheater. And there, waiting for Mark, was his dad, as he had been that last time Mark saw him.

    Mark’s father explained that he was going to tell him some things he had wanted to be able to say to him for a long time. First of all, he wanted Mark to know that he was fine. “That he had to leave,” Mark recalls, “and he felt bad about it, but he said ‘Mark—you are perfect just the way you are, and you have everything you need.’”

    Mark cried when he heard that, in a way he had never cried for his father before. His father held him, and he said: “Mark, don’t hide. Go seek.”

    Then, later, Mark met another a smiling guide – a man who had come to help him through this journey, he said. He reached inside him, and he began to pull out a great slew of concrete walls. The guide said: “Mark, we need to talk to this part of you.” The guide said to the walls: “You have done an amazing job for Mark.. You have protected him. You've created these beautiful walls for Mark, these trenches, this scaffolding which has protected Mark for many years, and got him to this place. We need to make sure you’re okay with taking these walls down so you can experience what’s next.”

    “And it was done with such love,” Mark told me. “No judgment.’” And the frightened parts of Mark consented to let his walls come down. And as he did, Mark realized that close by, he could see people he had loved, who had died—his father, and his aunt—applauding him.

    Mark knew then—“this whole journey, everything I had experienced, this whole push, was to say—life is for living. Go out and live. Go out and explore, and enjoy, and just take it all in.” He had an intense sense of the beauty of being alive, of being human—“the magnificence of it, the wisdom of it, it was just overwhelming.”

    And then he began to feel the drug wearing off, and it was “like you were back in your own ego,” as he puts it. He had arrived at Johns Hopkins at nine o’clock, and he left at five thirty. When his girlfriend, Jean picked him up, she asked him how it had gone, and he had no idea what to say.

    * * *

    In the months that followed, Mark found he was able to talk about his father in a way he never had before. He felt strongly that “the more open I am, and the more revealing I am, the more I’m going to get from anything.” He felt his anxiety had, to a significant degree, been replaced with a sense of wonder. “I felt I was able to be a little bit more human with people,” and he even started to go to ballroom dancing with his girlfriend, something he would have had to be dragged to kicking and screaming before.

    * * *

    Part of the job for Roland — the skeptical scientist who was running this experiment — was to interview everyone who had been given psilocybin, two months after the experience. These people would come in, one by one, and their answer was almost always the same. Routinely, they would say it was “one of the most meaningful experiences of my life” and compare it to the birth of a child, or the death of a parent. Mark was typical. “It struck me as kind of wildly implausible at first,” Roland said to me. “My immediate thought was — what kind of life experience did these people have before the experiment? But they were high-functioning, mostly professional-level people.”

    Some 80 percent of people like Mark still said, two months later, that it was one of the five most important things that had ever happened to them.

    This was the first of many striking results they found when they gave psylocibin to patients. They tried administering it to long-term smokers who had tried everything to quit. Incredibly, 80% of them quit, and remained non-smokers a year later. As a comparison point: the next most successful tool for quitting smoking, nicotine patches, works for 17% of people. This has opened up an array of studies currently looking at whether it can help with other forms of addiction.

    Roland’s work played a key role in re-opening the gates of psychedelic research across the world. I also traveled to interview the scientists who have done this work in Los Angeles, New York, London, Sao Paulo, and Oslo. They've all made startling discoveries. For example, a team working at University College London gave psilocybin to people who had severe depression and hadn’t been helped with any other form of treatment. It was only a small preliminary study without a control group, so we shouldn’t overstate it, but they found that nearly 50 percent of patients saw their depression go away entirely for the three-month period of the trial.

    So what, I wanted to know, is happening here?

    * * *

    Whatever is happening, all the scientists involved warned that people should not lightly decide to try these experiences. If meditation is the beginners’ ski-slope, Dr Bill Richards told me, psychedelics are the Olympic slopes. They should only be tried in carefully monitored circumstances, where you can be monitored by people with deep experience.

    * * *

    I learned that within all this research, there are two smaller findings – ones that I think begin to tell us what is really going on here. They show us the power of these substances – and their limitations. At first glance, they will seem a little strange.

    Here’s the first one. When you take a psychedelic, most people will have a spiritual experience – you get a sense that your ego-walls have been lowered, and you are deeply connected to the people around you, to our whole species, to the natural world, to existence. But it turns out the intensity of the spiritual experience varies from person to person. For some people, it will be incredibly intense, and some people have no spiritual experience at all. At Johns Hopkins, the team discovered that many positive effects correlate very closely with the intensity of the spiritual experience.

    * * *

    Here’s a second strange finding. Dr. Robin Carhart-Harris was one of the scientists who ran the experiment giving psilocybin to severely depressed people in London. As we sat for hours discussing it in a cafe in Notting Hill, he described something they noticed as the experiment went on. The psychedelics had a remarkable effect in the first 3 months or so: most people felt radically more connected, and so they felt radically better. But he described one patient in particular who seemed to represent a wider trend.

    After this extraordinary experience, she went back to her life. She was a receptionist, in a quite degrading job, in a horrible little English town. She’d had this awakening—that materialism doesn’t matter, that we’re all equal, that our status distinctions are pointless. And now she was back in a world that teaches us, all the time, that materialism is the most important thing, that we’re not equal, and that you’d better bloody respect status distinctions.

    It was a return to the cold bath of disconnection. And slowly she became depressed again.

    * * *

    I spent a long time thinking about this. It was only when I spoke with Dr. Andrew Weil, who did some of the 1960s research in this field, that I saw what it really meant. Nobody claims that psychedelics work in the way we were told, in a flurry of hype, that antidepressants did in the 1990s: they don’t change your brain chemistry and therefore “fix” you. No.

    What they do is give you—when the experience goes well—a remarkable sense of connection, for a very short period. “The value of the experience,” said Andrew, is "to show you the possibility” — what it can be like, to be connected in a deep way... Then, he says, “it’s up to you to find other ways to maintain the experience. Its value," he said, "is not as a drug experience, but as a learning experience. And you need to keep practicing the lesson, one way or another."

    On their own, psychedelics are not the solution. The psychedelic experience is like a moment when we see, on a compass, the direction we need to travel in, to sail beyond our epidemics of depression, anxiety, and addiction. It’s not the ship that will take us there alone. But it is pointing us to where we need to go – back to a sense of deep connection, to each other, to meaning, and to the natural world.

    * * *

    I explained in a TED talk that the opposite of addiction is connection. The fact psychedelics can give you a taste of deep connection helps us to understand why they helped to break one of the fiercest addictions we know, to nicotine, in 80 percent of cases, and why they are now being studies with other forms of addiction.

    * * *

    These are the lessons that Mark, who had such vivid insights as part of the Johns Hopkins study, took from the experience. He asked, after the experiment was over: “Roland, what the hell do I do with this now? . . . I need something in my life to ground this.” And Roland — who had once been so lost in workaholism that he hadn’t been able to meditate for more than a few minutes — now knew the answer. He introduced Mark to a center that studies the deep techniques of meditation.

    By the time I found my way to Roland and Mark, I was gathering evidence for seven new and different kinds of anti-depressant (which should be offered alongside the existing ones). Psychedelics — and the wider reorientation in values they can produce — are one of them.

    Mark knows he can’t live entirely in the space he found using psilocybin, and he wouldn’t want to—but he has found a way to integrate its insights into everyday life. “I didn’t want to lose this sense of what I had taken in,” he told me.

    The last time Roland, he said he never expected to be the guy recommending meditation and psychedelics, and Mark never expected to be eagerly receiving those recommendations. To both of them, it seemed like an improbable turn in their life stories, but they were moved by the sheer profundity of what they’d seen. The wired young scientist who couldn’t stare at a candle-flame in meditation for two minutes was gone – replaced by a prophet of reconnection.

    https://www.salon.com/2018/04/22/are...and-addiction/



    Ann and Sasha Shulgin


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    New clues in the psychedelic treatment of depression

    Depression, despite affecting millions worldwide, is still a condition that 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.

    Psilocybin Mushrooms and Depression

    Recent large studies, using psychedelics such as psilocybin mushrooms, 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 psychedelics seem 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 there is 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 psychedelic icons 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.

    Psychedelics and Stress

    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 authors’ 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.”

    This is the receptor system that psychedelics activate – and it 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 also suffering the stress-inducing effects of depression, the 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.

    However, activation of 5-HT2A receptors can also produce the most 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 overall theory, state the authors, 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).

    But this is still just a theory. The authors acknowledge 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.

    So what does this mean for our use of psychedelics?

    Although this ‘bipartite’ theory of depression highlights how typical antidepressants may work, it also shows that the most important treatment of depression lies through the 5-HT2A receptor system. And psychedelics activate this receptor system with inscrutable precision.

    The review also highlights the immense importance of environment and context during a psychedelic experience. Because psychedelics increase cognitive flexibility, and make us more sensitive to external stimuli, their therapeutic benefit relies heavily on the way in which they’re administered.

    So before people dive in and take a big dose of psilocybin to self-treat their depression, they should consider why they’re doing so, and whether they’re doing it in an optimal environment. People should never take psychedelics in vulnerable situations, unfamiliar locations, or without sober people they trust to guide and look after them.

    Ideally, psychedelic therapy will always be administered by professionals. However, until an accessible and affordable framework for psychedelic therapy is created, people should educate themselves about responsible use. There are plenty of resources available to help people learn about safe and effective psychedelic journeying; including an extensive microdosing course for those not ready to jump in at the deep end of psychedelic healing.

    The Future of Psychedelics

    We are living in a special time. Science is starting to provide us with evidence that a holistic approach to mental health is within our grasp. We are 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://thethirdwave.co/new-clues-ps...nt-depression/





    Antidepressant use leads to worse long term outcomes, study finds


    Results from a 30-year prospective study demonstrated worse outcomes for people who took antidepressants, even after controlling for gender, education level, marriage, baseline severity, other affective disorders, suicidality, and family history of depression.

    A new study has found that those who took antidepressants were more likely to have worse depression symptoms after 30 years. This finding was independent of illness severity as well as a large number of other potential confounding factors.

    The authors published their findings online this month in the journal Psychotherapy and Psychosomatics. The study followed 591 Swiss adults from the age of 20/21 until they were 49/50 years old. Antidepressant use at some point in the study was associated with worse depression symptoms at the end of the study.

    “These findings are in line with a growing body of evidence from several naturalistic observational studies suggesting that (long-term) antidepressant use may produce a poor long-term outcome in people with depression,” Hengartner writes.

    The evidence that antidepressants worsen long-term outcomes comes mostly from research that charts real-world outcomes. For instance, a 1-year study in a community sample found that only 5% enjoyed a “sustained remission,” a much lower remission rate than is typically found in studies of unmedicated depressed patients. Similarly, in the large STAR*D trial, only 108 of the 4041 patients who entered the study remitted and then stayed well during the one-year followup. All of the others either never remitted, relapsed, or dropped out of the study. Another study in real-world patients published last year found that antidepressant use was associated with worse outcomes after 9 years.

    The prevailing theory on why antidepressants might make depression worse is receptor sensitization—the idea that long-term use modifies the ways that neuroreceptors work, causing the medication to become ineffective, and potentially making people vulnerable to worsening depression.

    This new contribution to the literature presents the results of 591 adults in a community sample. The participants were assessed by trained psychologists and psychiatrists. Assessments began in 1979 when participants were all 20-21 years old, and assessments were conducted again in 1981, 1986, 1988, 1993, 1999, and finally in 2008 (when they were 49-50 years old). At each assessment, the primary outcome was the severity of depressive symptoms within the previous year. Also at each assessment, participants reported whether they had been prescribed antidepressants within the previous year.

    In order to create their predictive model, the authors tested whether being prescribed antidepressants at one assessment increased the likelihood of more severe depressive symptoms at the next time point. The authors divided the participants into several groups: no depressive symptoms; few depressive symptoms that did not last for more than 2 weeks; “subthreshold” depression that did not quite reach diagnostic criteria; and major depression as defined by meeting criteria as specified in the Diagnostic and Statistical Manual (DSM).

    Averaged across time-points, 6% of those with few depressive symptoms were taking antidepressants; 7% of those with “subthreshold” symptoms were taking antidepressants, and 22% of those with major depression were taking antidepressants.

    After controlling for numerous factors—including gender, education level, marital status, any affective disorder at baseline, suicidality at baseline, family history of depression, subjective distress, childhood adversity, and low parental income—the researchers found that antidepressant use was associated with an 81% increased likelihood of depression severity increase. For example, this means that people who had “subthreshold” depression but took an antidepressant were 81% more likely to worsen to major depressive disorder than those who had “subthreshold” symptoms but did not take an antidepressant.

    Because the researchers in the current study could not randomize people to antidepressants or a control group, this limits causal conclusions. There is always the possibility that some other factor accounted for the poor long-term effect that the researchers found, e.g. some trait shared by people who sought medication that led to worse outcomes. However, when the researchers controlled for all the usual risk factors—such as depression severity, subjective distress, baseline symptoms, demographic traits (e.g. gender, education level) and even childhood adversity—they still found that antidepressant use was associated with a worse long-term outcome.

    https://www.madinamerica.com/2018/04...s-study-finds/
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    The depression drug researchers are calling "the most important discovery in half a century'


    - Ketamine is emerging as a potential new drug for depression — the first of its kind in 35 years.

    - Johnson & Johnson plans to file for FDA approval of a nasal spray formula called esketamine this year.

    - On Saturday, they presented new research suggesting the drug worked well alongside a traditional antidepressant for a month.

    - Like any drug, however, it also had some unpleasant side effects.

    - Other companies are also going after ketamine-inspired antidepressants.

    Ketamine, which has been called "the most important discovery in half a century," just got a step closer to becoming the first new depression drug in 35 years.

    Johnson & Johnson, one of the pharmaceutical companies pursuing the drug's fast-acting antidepressant qualities, presented some promising new research on Saturday that could raise the drug's profile as a potential treatment for the condition.

    It's a dramatic departure for a compound that most people know either as a surgical anesthetic or a party drug. And it's a seemingly welcome one, according to physicians and psychiatrists who say they've grown tired of giving patients the same mediocre drugs for the past four decades.

    Johnson & Johnson isn't the only drugmaker that's hot on the ketamine trail. Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine, and San Francisco drugmaker VistaGen is studying a similar ketamine-inspired drug.

    J&J's version of ketamine is a nasal spray made with a compound called esketamine, the chemical mirror image of ketamine. In its latest clinical trial, the company's neuroscience partner, Janssen Research, wanted to show that the spray was safe, well tolerated, and superior to both a placebo and a traditional antidepressant.

    To do it, the researchers had 236 adults with treatment resistant depression — known as one of the hardest forms to treat — take a traditional antidepressant for four weeks alongside a nasal spray. Only half of them got a spray with J&J's drug in it; the other half got a placebo.

    Their results were promising: The people who got the real spray saw significantly better improvements in their depressive symptoms than those who got the placebo, over the course of 28 days. More importantly, it is also the first time a novel treatment has come out on top even when compared to a traditional antidepressant drug.

    The findings come roughly a month after J&J published the results of a small, preliminary version of this study which suggested that over the course of a single day, the spray and traditional antidepressant combo was better than a placebo and traditional antidepressant combo. That study, however, suggested the results diminished over the course of four weeks, while the longer and larger study suggests they might not.

    The emerging science on ketamine

    Depression is one of the world's leading causes of death. Current treatments for depression, which take roughly five weeks to begin to take effect, may not work well in up to 80% of the people who get them.

    Most existing antidepressants, from Abilify to Zoloft, work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in mood. The result is more free-floating serotonin and, in some people, relief from a dark curtain of depressive symptoms.

    Like serotonin receptors, those for NMDA play an important role in our mood and help keep our emotions in check. But NMDA receptors also keep our brain's synapses — the delicate branches that serve as the ecosystem for our thoughts — flexible and resilient.

    Potentially because of depression's damaging effects on these brain switches, it appears to cause our synaptic branches to shrivel up and in some cases even to die. Scientists think existing antidepressants send help to those branches indirectly over time by way of serotonin. Ketamine, by contrast, delivers its aid directly to the source, plugging up NMDA receptors like a cork in a bottle, and nipping depressive symptoms within hours.

    A 2012 study published in the journal Science analyzed ketamine's rapid ability to reduce depressive symptoms in people who'd failed to respond to other drugs. The authors called ketamine "the most important discovery in half a century." Five years later, researchers concluded in a study in the American Journal of Psychiatry that the drug's antidepressant effects appeared to last at least a month.

    Still, like any drug, ketamine has a range of unpleasant side effects, the most troublesome of which appears to be its tendency to produce what are known as dissociative, or "out of body," experiences.

    Experts worry those effects could lead patients to either react negatively to the experience and not want to repeat it, or react positively and want to repeatedly use, potentially leading to a drug-use disorder.

    In J&J's most recent study, patients reported other side effects as well, including dizziness, headache, blurred vision, and nausea.
    The biggest unanswered question: long-term effects

    Besides its immediate side-effects, some researchers approach ketamine with hopeful caution for another reason.

    Without a good number of long term studies on ketamine for depression, it's tough to know what the drug's effects might look like over the course of several months or years. Its beneficial effects, for example, could wear off; other negative side effects could emerge as well.

    Allergan and VistaGen are currently doing long term studies of their new drug candidates, which act on the same pathway as ketamine but appear to have substantially fewer side effects; results from those trials are expected in the next two years.

    J&J is also pursuing more research on its nasal spray ketamine formula, some of which will include longer trials. Company representatives told Business Insider that in addition to the research they've presented so far, they also have plans to study the nasal spray formula in teens with major depression who are at imminent risk for suicide.

    The company is expecting to file for approval of their drug with the US Food and Drug Administration later this year.

    http://www.businessinsider.com/depre...r=US&IR=T&IR=T
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    My experience with ketamine therapy for depression

    Part 1 of Foreigner's (BL) great report from 2013 (chapters 1-5)

    I’ll be using this thread to talk about my use of low-dose ketamine as a mental health aid, specifically for chronic depression that has never been really cured with conventional treatment.

    My inspiration comes partly from Jamshyd’s Ketamine Regimen, but I did not attach my report to his thread because there are going to be some divergences in opinion, plus I just have a lot to say and I’d like to be thorough.

    I originally was not going to write a report on this but in reflecting upon my own struggle with trying to get more precise information about how to carry out this regimen, I believe my input would help someone out there who might have already been considering this approach but is going through a similar challenge. Also, I feel there is just not enough first-person reporting on this regimen to coincide with the research findings, and it's a gap I would like to contribute to filling.

    Most importantly, this regimen appears to have worked for me, and I believe that seed of truth deserves to shine somewhere.

    Disclaimer

    Although I am trained in the scientific method, this work was not carried out in a professional setting. Please keep in mind that this regimen remains controversial. Although NMDA antagonists offer a wealth of promise for the future treatment of depression and other mental health issues, most sources admit that ketamine is a rather raw and unrefined approach for this purpose, and is being employed until better alternatives can be developed. You should therefore not be considering this regimen unless the conventional approaches have all failed.

    Another warning I must give – probably more important than the above – is that this regimen is for those who embody the utmost self-discipline. Ketamine’s euphoric and transcendent properties make it a substance easily abused. Even in a low-dose regimen, the temptation to do “just a little more this dose” can be ever present. Each brief period of euphoria makes you feel as though you are close to a supreme truth, if only you could do just a little more to figure it out. Do not chase this feeling, it is a transient, false lure. If you can avoid the pitfalls by always sticking to the allotted dose, this regimen could very well work for you. For those who lack the discipline, I believe a clinical setting where someone else controls the allotment would be more ideal.

    Side effects

    Ketamine is not without its side effects, and this is not a perfect therapy, even for someone like me who is in a state of finely tuned health. (For more details, see the section on "negative effects" below.)

    Because I am an eastern medicine practitioner, I am able to pick up on subtle signs of physiological changes more readily than the more obvious western diagnostic signs. From day one there were impacts to the kidneys and urinary system. Urine was darker no matter how much I hydrated, and there was usually floating matter in the urine. There was minor kidney colic as well as spasm of the kidney meridian down the inside of the legs. My kidneys were in a constant state of trying to purge, including at night time when I was awoken repeatedly to urinate. I had minor lower back pain (also a kidney sign).

    Liver and gallbladder both took a hit too. The constant bitter taste in my mouth, red and dry eyes, and systemic sluggishness due to processing metabolites, were not major, but still noteworthy.

    I’m prone to insomnia and ketamine made it much worse. My sleeping schedule was basically in chaos for most of the time and I slept at all random hours on the 24 hour clock. But then, this happens to me when I take most drugs, even cannabis. If you are prone to insomnia I strongly urge you to approach this regimen with caution, but with that said, this might actually help your sleep for all I know.

    Though the evidence remains inconclusive, there is the uncharted risk of Olney’s lesions in the brain. This is admittedly due to higher doses of ketamine and regular abuse. I personally believe that the risk is unfounded but it’s one that prospective users of this regimen should know about. Interestingly, Jamshyd mentioned that using gabapentin in combination with this therapy helped him a great deal. This link states that, "In medical settings, NMDA receptor antagonists are used as anaesthetics, so GABA-A receptor positive allosteric modulators are used to effectively prevent any neurotoxicity caused by them." This could suggest that any potential toxicity of ketamine could be at least partially mitigated by gabapentin, though I did not use it so I cannot comment.

    The science

    The empirical evidence behind ketamine being an effective diffuser of depressive and suicidal states has already been explored relatively thoroughly in Jamshyd’s thread. I will however add these summary links for further reading:

    http://www.sciencedaily.com/releases...0819141913.htm
    http://www.sciencedaily.com/releases...1004141747.htm

    In most of the clinical research they administered single larger doses, which usually resulted in temporary depression relief for up to 7-10 days. The regimen I am using, modelled after Jamshyd’s, is based on the hypothesis that ultra low, frequent dosing could have a more cumulative nootropic effect on the NMDA system and therefore could result in longer lasting relief, as well as actual regeneration of synaptic tissue.

    A slow release transdermal patch would work great for ketamine. I came across reports of some hospitals using these for post-operative pain in gynecological procedures, but it was formulated to work locally and not pass the blood brain barrier. Since the pharmaceutical industry is hard at work making non-psychedelic NMDA medications, don’t expect a ketamine patch for depression to happen anytime soon.

    Why I chose to do this

    A combination of reasons really. One reason is that I anecdotally noticed being in a better mood after a brief stint of recreational ketamine use almost 10 years ago, and that already got me thinking about it. The main reason though is that my unusual metabolism means I process most oral pharmaceuticals irregularly from the established norms. I either suffer rarer side effects or I have no effects at all. SSRIs have proven to be of limited value to me. Ketamine’s rapid action means I would have to endure side effects for less time if the medicine ends up working, and its injectable form means I can bypass the limitations of the digestive route.

    Additionally, I’ve long since had the perception that trauma after trauma in my life has caused unfavourable neurological and personality changes, combined with past heavy drug abuse with MDMA, and these are all aspects which talk therapy and conventional pharmaceuticals have never seemed to help me recover from. Eventually there comes a time when you've talked until the cows came home and you still feel unfulfilled; and sometimes, it really is just a neurochemical imbalance and there is nothing outwardly the matter anymore. I would describe myself this way.

    For a very long time there has been that missing link - something in my mind that feels blocked, unable to be overcome or bypassed. It's not necessarily about logic, but it has felt like a deficit. Now the science about PTSD is more clear on this, but effective reparative alternatives are either still under development or simply not being offered. If there is any remote chance that low-dose ketamine could act as a regenerative nootropic to years of traumatic down-regulation, it’s a chance I’m willing to take.

    Last but not least, I needed a medicine that has a psychoactive component in order to connect psychospiritually to the process, which is the opposite of the emotionally deadening effects that conventional anti-depressants sometimes induce. Without this necessary quality, no therapy can work for me. I’m of the opinion that modern medicine should not be trying so hard to demonize “euphoria” as an unwanted side effect of medication, as bliss can be a useful healing tool in the right context.

    Preparation advice

    I only acquired 1g of pure ketamine, more than enough to last for one cycle of this regimen. Though I am not prone to addiction, the choice to not purchase more was a precautionary measure to prevent abuse. I advise anyone doing this procedure to do the same. Even if you decide to do a second cycle of treatment, just acquire the additional amount at that time, and not in advance.

    I recommend titrating your solution so that you are only administering 0.5cc per dose because I found regular injections of bacteriostatic solution (plus the ketamine itself) to be dehydrating and imbalancing to the electrolytes of my body.

    I timed this regimen during a period when I would be off work and free of the usual daily obligations. I let my closest and most supportive friends know what I was about to do, both because I planned to still spend time with them while there was ketamine in my system, and because I wanted them to observe me for positive or negative personality changes. (Hey, sometimes it’s possible to go off the deep end and not realize it!) I also made sure the fridge was stocked so that going outside was optional, and had a good playlist of tunes at the ready in case silence became a burden.

    Basically, try to make life as materially easy on yourself as you can. During this period of neuroplasticity, you don’t want to be bogged down with run of the mill minutiae. Treat this as therapy and build your healing container accordingly.

    In my case I decided that a healthy balance between social time and alone time were necessary. Exposure to the outside world allowed me to alter my approaches and reactions to many different situations, at will, thanks to the enhanced novelty effect. (More on this later.) Being with friends helped me to expand the pallet of venues and events that I could practice new ways of being in. Then, being alone allowed time for deep reflection, inner processing, and connecting with whatever was surfacing. Even at low doses, I would not recommend isolating oneself as dissociatives can be illusory.

    I do believe that ketamine in of itself relieves the symptoms of depression, but perhaps more crucially than that, it offers the opportunity for you to explore the root of it. You can just sit there and do nothing while the biochemistry does some of the work for you, or you can go a bit further and delve into your own psyche. The choice is yours.

    Continued here:

    http://www.bluelight.org/vb/threads/669468-Experience-with-ketamine-therapy-for-depression



    Last edited by mr peabody; 30-09-2018 at 23:43.
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    Ayahuasca may ease severe depression

    “Leon” is a young Brazilian man who has long struggled with depression. He keeps an anonymous blog, in Portuguese, where he describes the challenge of living with a mental illness that affects some 300 million people worldwide, according to the World Health Organization.

    Leon is among the roughly 30 percent of those patients with treatment-resistant depression. Available antidepressant drugs like selective serotonin reuptake inhibitors do not alleviate his depressed mood, fatigue, anxiety, low self-esteem and suicidal thoughts.

    A new study may offer hope for Leon and others like him.

    Our team of Brazilian scientists has conducted the first randomized, placebo-controlled clinical trial of ayahuasca – a psychedelic drink made of Amazonian plants. The results, recently published in the journal Psychological Medicine, suggest that ayahuasca can work for hard-to-treat depression.

    The ‘vine of the spirits’

    Ayahuasca, a word from the indigenous Quechua language, means “the vine of the spirits.” People in the Amazonian region of Brazil, Peru, Colombia, and Ecuador have for centuries used ayahuasca for therapeutic and spiritual purposes.

    The medicinal beverage’s properties come from two plants. Banisteriopsis caapi, a vine that twists its way up to the treetops and across river banks of the Amazon basin, is boiled together with Psychotria viridis, a shrub whose leaves contain the psychoactive molecule DMT.

    Starting in the 1930s, Brazilian religions were founded around the use of ayahuasca as a sacrament. By the 1980s, the ayahuasca ritual had spread to cities across Brazil and the world.

    Ayahuasca first became legal for religious use in Brazil in 1987, after the country’s federal drug agency concluded that “religious group members” had seen “remarkable” benefits from taking it. Some people who drink ayahuasca describe feeling at peace with themselves, God and the universe.

    For our study, which took place at Brazil’s Federal University of Rio Grande do Norte, researchers recruited 218 patients with depression. Twenty-nine of them were selected to participate because they had treatment-resistant depression and no history of psychotic disorders like schizophrenia, which ayahuasca use may aggravate.

    These 29 people were randomly assigned to undergo a single treatment session, in which they were given either ayahuasca or a placebo substance to drink. The placebo was a brownish liquid, bitter and sour to the taste, made of water, yeast, citric acid, and caramel colorant. Zinc sulfate mimicked two well-known side effects of ayahuasca, nausea, and vomiting.

    The sessions took place in a hospital, though we designed the space like a quiet and comfortable living room.

    The acute effects of ayahuasca – which include dream-like visions, vomiting and intense introspection – last for about four hours. During this period, participants listened to two curated playlists, one featuring instrumental music and another with songs sung in Portuguese.

    Patients were monitored by two team members, who provided assistance to those experiencing anxiety during this intense emotional and physical experience.

    One day after the treatment session, we observed significant improvements in 50 percent of all patients, including reduced anxiety and improved mood.

    A week later, 64 percent of the patients who had received the Amazonian psychedelic still felt that their depression had eased. Just 27 percent of those in the placebo group showed such effects.

    Building on past evidence

    Our findings support a 2015 Brazilian clinical trial on the potential of ayahuasca as an antidepressant.

    That study, led by Dr. Jaime Hallak of the University of Sao Paulo, likewise found that a single ayahuasca session had a fast-onset antidepressant effect. All 17 participants reported that depression symptoms diminished in the first hours after ayahuasca ingestion. The effect lasted 21 days.

    This study received significant attention from scientists. Its promising conclusions were limited, however, because there was no control group of patients who received a placebo drug.

    In clinical trials for depression, up to 45 percent of patients who take a placebo may report significant benefits. The placebo effect for depression is so strong that some scientists have questioned whether antidepressants really work.

    Dr. Hallak and other researchers from the 2015 University of Sao Paulo study were part of our follow-up clinical trial.

    Religion turned science

    These two studies, while preliminary, contribute to a growing body of evidence that psychedelic drugs like ayahuasca, LSD, and mushrooms can help people with difficult-to-treat depression.

    But because these substances are illegal in many countries, including the United States, their therapeutic value has been difficult to test. Even in Brazil, using ayahuasca as an antidepressant remains a fringe, informal enterprise.

    Leon, the Brazilian blogger, discovered the drug doing internet research. “Desperate” to find solutions for his intractable condition, Leon decided to take part in a ceremony at a Santo Daime church in Rio de Janeiro, one of several Brazilian religions that use ayahuasca as a sacrament.

    The church does not track its membership, but the Uniao do Vegetal, a similar faith, has approximately 19,000 members worldwide.

    These religious organizations are among many groups across the Americas that harvest indigenous traditions around natural psychedelics. They believe psychoactive plants like ayahuasca, peyote or psilocybin open people’s minds to metaphysical realms and deeply meaningful experiences.

    This spiritual knowledge is now being translated into the language of science, as researchers in Brazil, the United States, Canada and beyond begin rigorous medical evaluations of these substances.

    The healing power of the psychedelic experience

    Leon’s blog provides an excellent description of his ayahuasca experience.

    At times, he conjured visions – dream-like scenarios that offered rare insight into the relationships in his life. At other times, Leon experienced “a feeling of ecstasy and a deep sensation of a manifesting inner spirituality.”

    We believe that these effects are critical to why ayahuasca works.

    Participants in our study responded to the Hallucinogen Rating Scale, which helps translate these ineffable experiences into numbers. Participants who took ayahuasca scored significantly higher on that questionnaire than those who drank a placebo.

    Those who described the most abundant visual, auditory and physical effects during their ayahuasca trip had the most prominent depression reduction benefits seven days later.

    Ayahuasca is not a panacea. Such experiences may prove too physically and emotionally challenging for some people to use it regularly as treatment. We have also observed regular ayahuasca users who still suffer from depression.

    But, as our study demonstrates, this Amazonian sacred plant has the potential to be used safely and effectively to treat even the hardest to treat depression.

    https://brazilian.report/2018/06/29/...ca-depression/

    Last edited by mr peabody; 02-10-2018 at 11:03.
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    Turning off default mode

    Normal consciousness relies, at least in part, on the brain’s Default Mode Network (DMN), according to neuroscientist Robin Carhart-Harris, head of psychedelic research in the brain sciences division of the Imperial College of London medical school. The DMN is a network of interacting brain regions that acts as a cognitive transit hub, integrating and assimilating information. As the name implies, it’s the usual system of organization for your mind. Carhart-Harris says the DMN “gives coherence to cognition” by connecting different regions of the brain, and is considered the “orchestrator of the self.”

    Carhart-Harris and his colleagues found what seems to be an important function of the DMN inadvertently. While studying brain networks, they got curious about what changes might occur when people are under the effects of psychedelics. In studies analyzing the effects of psilocybin on brain wave oscillation and blood flow, they found that when the DMN was inactive, an alternate network of consciousness seemed to arise.

    When some study subjects tested psilocybin, they reported a strong sense of interconnectedness, as well as spiritual, magical, and supernatural feelings.

    In the alternate mode, brains produced a different world that offered other sensations and realizations than in everyday life. In this mode, the self wasn’t the protagonist of the narrative. Meanwhile, scans of blood flow and brain wave oscillations showed new, unusual—but orderly and synchronous—connections forming between cortical regions, as if the brain was reorganizing its network. This led Carhart-Harris to posit that the DMN generates the feeling we each have that we’re individuals, a feeling that manifests very strongly as reality. And that means we can temporarily switch off, or mute, this part of the brain.

    Living in a society means living within certain limits, for our own safety and that of others. We need the ego to draw lines, protecting us from people who may take advantage of too much kindness or too open a spirit. But muting the ego can be a good thing. Switching off the default mode changes the connections between cortical regions and activates new modes, new sensations and thoughts, allowing us to “lose the inhibiting influence on one’s own narrative, which leads to insights that are kept from consciousness,” Carhart-Harris says.

    Experiencing this state of uninhibited consciousness can lead to lasting changes, even after the psilocybin wears off. For someone who is severely depressed, changing brain activity with psilocybin may be able to jolt them out of a cognitive rut, wherein their default mode repeats negative thoughts and feelings in a damaging loop, Carhart-Harris explains. And in someone who is psychologically healthy, the additional perspective provided by a peek at the alternate consciousness can also improve overall well-being.

    As Shelby Hartman wrote in Quartz last January, the data from three trials of psilocybin in 36 healthy volunteers showed that brief drug-induced mystical experiences changed people over time, leading them to report better moods, heightened altruism and forgiveness, more closeness with others, and a sense of connection six months later.

    https://qz.com/1196408/scientists-st...s-an-illusion/

    -----

    Can psychedelics target overly rigid brain networks?

    Dr. Carhart-Harris and his team have discovered that psychedelic drugs, such as psilocybin, may have the ability to temporarily disrupt these patterns, and when combined with a controlled psychotherapeutic experience, may produce changes in perception and behavior that persist long after the drug has worn off.

    Through use of fMRI (functional magnetic resonance imaging) and MEG (magnetoencephalography) scanning, Dr. Carhart-Harris and his colleagues have been able to study the stability of functional brain networks, such as the normally competitive relationship between the default mode network and the task-positive network. Studies suggest that psilocybin disrupts this normal competitive pattern.

    The task positive network is a problem solving, externally focused network comprised of the salience network (which determines what needs to be dealt with in the environment) and executive network (which determines what to do with this information). The structures involved with these networks, represented by the dorsolateral prefrontal cortex, lateral parietal cortex, and subgenual anterior cingular cortex, lie laterally in the brain.

    Along the midline, the default mode networkis more inwardly directed and is activated when we are introspective, engaged in theory of mind (ostensibly, empathy), or navigating complex social interactions. These midline structures consist of the mediotemporal lobe, the posterior cingulate cortex, the ventromedial prefrontal cortex, and the dorsomedial prefrontal cortex.

    It is important to understand that these two networks normally work in opposition to one another, so that when one is turned up, the other is turned down, like two sides of a seesaw. In a non-depressed brain, the ability to shift between these networks should be relatively easy.

    For example, when one is “lost in one’s work,” the dominance of the task positive network over the default mode network is evident. Conversely, when one is engaged in inward-focused activity, such as meditation or reminiscing, there is little external work being done.

    However, in the context of depression it appears that the introspective capacity of the default mode network becomes “stuck” in a ruminative mode, and that this rigidity prevents the task positive network from working normally. I translate this to patients with depression by explaining that this is why they can spend all day thinking negatively about themselves but cannot shift focus and respond to all those emails that have been piling up. This hijacking of the default mode network by rumination has been called “pathological introspection” and this rigidity of network activity in depression has been referred to as “overstability.”

    Dissolving the ego doesn’t happen once and for all. The default mode network will resume its duties, and it can be hard to stay in touch with alternative states of consciousness. The epiphanies some people experience on drugs, then, offer a touchstone to which we can return when the brain’s default mode is on.

    https://www.psychcongress.com/blog/c...brain-networks
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    New clues in the psychedelic treatment of depression


    Depression, despite affecting millions worldwide, is still a condition that 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 authors’ 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
    Last edited by mr peabody; 01-10-2018 at 11:20.
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    Two things psychedelics do for people with depression

    In 2016, researchers approached the European Medicines Agency seeking approval to use psilocybin in the treatment of anxiety and depression in patients with life-changing diagnoses. “Existential distress” is not an official DSM diagnosis, the regulators pointed out, so the national health services won’t cover it. But there’s a signal here that psilocybin could be useful in treating depression, so why don’t you do a big, multi-site trial for that?

    The EMA was responding not only to the Hopkins and NYU data but also to the small “feasibility study” of the potential of using psilocybin to treat depression that Robin Carhart-Harris had directed in David Nutt’s lab at Imperial College. In the study, the initial results of which appeared in Lancet Psychiatry in 2016, researchers gave psilocybin to six men and six women suffering from “treatment-resistant depression”—meaning they had already tried at least two treatments without success. There was no control group, so everyone knew he or she was getting psilocybin.

    After a week, all of the volunteers showed improvement in their symptoms, and two-thirds of them were depression-free, in some cases for the first time in years. Seven of the twelve volunteers still showed substantial benefit after three months. The study was expanded to include a total of twenty volunteers; after six months, six remained in remission, while the others had relapsed to one degree or another, suggesting the treatment might need to be repeated. The study was modest in scale and not randomized, but it demonstrated that psilocybin was well tolerated in this population, with no adverse events, and most of the subjects had seen benefits that were marked and rapid.*

    The EMA was sufficiently impressed with the data to suggest a much larger trial for treatment-resistant depression, which afflicts more than 800,000 people in Europe. (This is out of a total of some 40 million Europeans with depressive disorders, according to the World Health Organization.) Rosalind Watts was a young clinical psychologist working for the National Health Service when she read an article about psychedelic therapy in the New Yorker.

    The idea that you might actually be able to cure mental illness rather than just manage its symptoms inspired her to write to Robin Carhart-Harris, who hired her to help out with the depression study, the lab’s first foray into clinical research. Watts guided several sessions and then conducted qualitative interviews with all of the volunteers six months after their treatments, hoping to understand exactly how the psychedelic session had affected them.

    Watts’s interviews uncovered two “master” themes. The first was that the volunteers depicted their depression foremost as a state of “disconnection,” whether from other people, their earlier selves, their senses and feelings, their core beliefs and spiritual values, or nature. Several referred to living in “a mental prison,” others to being “stuck” in endless circles of rumination they likened to mental “grid-lock.” I was reminded of Carhart-Harris’ hypothesis that depression might be the result of an overactive default mode network—the site in the brain where rumination appears to take place. The Imperial depressives also felt disconnected from their senses. “I would look at orchids,” one told Watts, “and intellectually understand that there was beauty, but not experience it.”

    For most of the volunteers, the psilocybin experience had sprung them from their mental jails, if only temporarily. One woman in the study told me that the month following her session was the first time she had been free from depression since 1991. Others described similar experiences:

    “It was like a holiday away from the prison of my brain. I felt free, carefree, re-energized.”

    “It was like the light switch being turned on in a dark house.”


    “You’re not immersed in thought patterns; the concrete coat has come off.”

    “It was like when you defrag the hard drive on your computer . . . I thought, ‘My brain is being defragged, how brilliant is that!’”

    For many of the volunteers, these changes in the experience of their own minds persisted:

    “My mind works differently. I ruminate much less, and my thoughts feel ordered, contextualized.”

    Several reported reconnecting to their senses:

    “A veil dropped from my eyes, things were suddenly clear, glowing, bright. I looked at plants and felt their beauty. I can still look at my orchids and feel that: that is one thing that has really lasted.”

    Some reconnected to themselves: “I had an experience of tenderness toward myself. At its most basic, I feel like I used to before the depression.” Others reconnected to other people:

    “I was talking to strangers. I had these full long conversations with everybody I came into contact with.”

    “I would look at people on the street and think, ‘How interesting we are’—I felt connected to them all.”


    And to nature:

    “Before, I enjoyed nature; now I feel part of it. Before I was looking at it as a thing, like TV or painting. You’re part of it, there’s no separation or distinction, you are it.”

    “I was everybody, unity, one life with 6 billion faces. I was the one asking for love and giving love, I was swimming in the sea, and the sea was me.”


    The second master theme was a new access to difficult emotions, emotions that depression often blunts or closes down completely. Watts hypothesizes that the depressed patient’s incessant rumination constricts his or her emotional repertoire. In other cases, the depressive keeps emotions at bay because it is too painful to experience them.

    This is especially true in cases of childhood trauma. Watts put me in touch with a thirty-nine-year-old man in the study, a music journalist named Ian Rouiller, who, along with his older sister, had been abused by his father as a child. As adults, the siblings brought charges against their father that put him in jail for several years, but this hadn’t relieved the depression that has trailed Ian for most of his life.

    “I can remember the moment when the horrible cloud first came over me. It was in the family room of a pub called the Fighting Cocks in St. Albans. I was ten.” Antidepressants helped for a while, but “putting the plaster over the wound doesn’t heal anything.” On psilocybin, he was able for the first time to confront his lifelong pain — and his father.

    “Normally, when Dad comes up in my head, I just push the thought away. But this time I went the other way.” His guide had told him he should “go in and through” any frightening material that arose during his journey.

    “So this time I looked him in the eye. That was a really big thing for me, to literally face the demon. And there he was. But he was a horse! A military horse standing on its hind legs, dressed in a military outfit with a helmet, and holding a gun. It was terrifying, and I wanted to push the image aside, but I didn’t. In and through: Instead, I looked the horse in the eyes—and promptly started to laugh, it was so ridiculous."

    “That’s when what had been a difficult trip really turned. Now I had every sort of emotion, positive, negative, it didn’t matter. I thought about the Syrian refugees in Calais and started crying for them, and I saw that every emotion is as valid as any other. You don’t cherry-pick happiness and enjoyment, the so-called good emotions; it was okay to have negative thoughts. That’s life. For me, trying to resist emotions just amplified them. Once I was in this state, it was beautiful—a feeling of deep contentment. I had this overwhelming feeling—it wasn’t even a thought—that everything and everyone needs to be approached with love, including myself.”

    Ian enjoyed several months of relief from his depression as well as a new perspective on his life—something no antidepressant had ever given him. “Like Google Earth, I had zoomed out,” he told Watts in his six-month interview. For several weeks after his session, “I was absolutely connected to myself, to every living thing, to the universe.” Eventually, Ian’s overview effect faded, however, and he ended up back on Zoloft.

    “The sheen and shine that life and existence had regained immediately after the trial and for several weeks after gradually faded,” he wrote one year later. “The insights I gained during the trial have never left and will never leave me. But they now feel more like ideas,” he says.

    He says he’s doing better than before and has been able to hold down a job, but his depression has returned. He told me he wishes he could have another psilocybin session at Imperial. Because that’s currently not an option, he’ll sometimes meditate and listen to the playlist from his session. “That really does help put me back in that place."

    More than half of the Imperial volunteers saw the clouds of their depression eventually return, so it seems likely that psychedelic therapy for depression, should it prove useful and be approved, will not be a onetime intervention. But even the temporary respite the voluneers regarded as precious, because it reminded them there was another way to be that was worth working to recapture. Like electroconvulsive therapy for depression, which it in some ways resembles, psychedelic therapy is a shock to the system—a “reboot” or “defragging”—that may need to be repeated every so often. (Assuming the treatment works as well when repeated.) But the potential of the therapy has regulators and researchers and much of the mental health community feeling hopeful.

    “I believe this could revolutionize mental health care,” Watts told me. Her conviction is shared by every other psychedelic researcher I interviewed.

    https://tonic.vice.com/en_us/article...ith-depression
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    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 that 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 caf? 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 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/psych...iety-addiction
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    Ayahuasca tea helps patients rapidly overcome severe depression
    *

    An article published this week in Psychological Medicine shows ayahuasca providing rapid and sustained anti-depressant effects for people with severe Treatment-Resistant Depression.

    The paper was published by researcher and Kahpi.net teacher Dr Julio de Araujo, whose team at the Brain Institute in Natal, Brazil have been investigating the effects of ayahuasca on depression since 2014. The study included 29 patients with Treatment-Resistant Depression given a single dose of ayahuasca or a placebo. Those who received the ayahuasca scored significantly lower on both depression scales used for rating their states, and these effects were sustained for one week.

    The results of the study appear promising and timely. Depression is, without a doubt, one of the most severe global epidemics of the modern age. The World Health Organizations Depression and Other Common Disorders (2017) report provides an estimate that over 300 million people worldwide suffer from it, and according to a paper published by the Columbia University Mailman School of Public Health, this number is on the rise.

    Today, pretty much wherever in the world you live, you are likely to have at least one family member or friend who is depressed.

    With varying degrees of success, many cases of clinical depression can be treated with regular psychotherapy, antidepressants, and lifestyle changes such as physical activity, regulation of sleep and nutrition, stress reduction, and social support. A combination of all of the above is often effective, but not everyone has access, time, or energy to dedicate to a full-on treatment regime. And few depressed patients are in any shape to achieve that.

    And then, there are cases of depression so severe that pharmaceutical and psychological therapy are powerless to help. In this stage, the disorder is referred to as Treatment-Resistant Depression, and it is alarmingly frequent. It is estimated that around 30% of patients with Major Depressive Disorder fall in this category.

    There have been positive findings with a compound called ketamine, that is more in the grey zone between psychedelics and medication. This substance is often used for starting and maintaining anesthesia, but also holds a special place in many an underground ravers party drawer due to its trance-like sedative effects.

    Ketamine trials have so far shown excellent results, especially in eliminating suicidal ideation. A few peer-reviewed, double-blind, randomized, placebo-controlled studies have found rapid antidepressant effects in ketamine therapy. One trial reported 35% of patients maintained the effect after one week. Another study found this percentage to be lower, at 13%.

    Ayahuasca, however, is illegal in some forms and places, and is a highly intense undertaking in terms of its effects. This traditional shamanic brew has been gaining attention in the past decades as a spiritually transformational tool. Could it be used to help with an affliction such as depression? Some have compared a single ayahuasca experience to ten years of therapy.

    Psychedelics such as ayahuasca are becoming increasingly recognized as tools for combating many different mental health disorders. Psychedelic therapists suggest ayahuasca can help the individual access and change deep, unconscious patterns of thought and behavior.

    Depression, obsession, eating disorders--all are exacerbated by the tyranny of the ego and the fixed narratives it constructs about our relationship to the world,
    writes Michael Pollan in his latest book How to Change Your Mind. By temporarily overturning that tyranny and throwing our minds into an unusually plastic state, psychedelics, with the help of a good therapist, give us an opportunity to propose a new, more constructive story about the self and its relationship with the world--one that just might stick.

    The anecdotal reports and psychological studies on the benefits of ayahuasca and psychedelics are accompanied by fascinating neuroscientific studies.

    A recent model of brain functioning proposed by Dr. Robin Carhart-Harris and Professor David Nutt, who are among the biggest names in psychedelic research, suggests there is an important biochemical basis to ayahuasca therapy.

    Selective serotonin reuptake inhibitors (SSRIs), the most common medication used for treating depression, function by blocking the reuptake of serotonin, the neurotransmitter associated with feelings of well-being and happiness. This means that more of it stays in the space between neural synapses, and is available to bind to the receiving cell synapses, rather than be reabsorbed by the neuron endings. This process is thought, according to traditional models, to work by blocking two brain receptors in particular: the 5-HT1A and the 5-HT2A receptors.

    Carhart-Harris and Nutt argue that the inhibition of 5-HT2A receptors, which are the brain areas precisely targeted by psychedelics such as psilocybin and ayahuasca, could be more important than previously thought. They suggest blocking 5-HT2A receptors enables a process they refer to as active coping to help the brain actively addresses the source of stress. The brain does this by enhancing its plasticity or adaptive capacity. At the same time, 5-HT1A receptor blocking, which is supposedly done efficiently by SSRIs, corresponds to what they call passive coping or the elevation of the brains tolerance to stress.

    If these scientists are correct in their suggestion, psychedelics might have a very important role to play in overcoming depression and other common mental health disorders.

    This is a discovery we are on the brink of confirming. After a few promising, yet not completely controlled studies published by a group of researchers spearheaded by Osorio and Sanches in 2015 and 2016, we now finally have, with last weeks Psychological Medicine article, a fully fleshed out, double-blind, randomized, placebo-controlled ayahuasca trial. And the results are more than encouraging.

    Interestingly, compared to the previous studies conducted with the psychedelic compound ketamine, the authors of the recent ayahuasca study noticed a difference in immediate and later effects. Ketamine produced responses from between 37% and 70% of patients on day one, decreasing to between 7% and 35% on day 7. In this ayahuasca trial, 50% of patients responded positively on day 1, and this number increased to 64% by day 7.

    As usual in conducting medical trials, these effects need to be replicated on a larger number of participants throughout different societies in order to be validated. However, this study can be considered to be the strongest scientific demonstration to date of ayahuascas potential to heal.

    *From the article here: https://kahpi.net/ayahuasca-tea-rapi...re-depression/
    Last edited by mr peabody; 02-10-2018 at 11:08.
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    Psychedelics and depression*

    Psychedelics are substances that induce a "non-ordinary" state of consciousness. In use for thousands of years (at least), the medical potential for potent mind-altering substances has come in and out of vogue.

    Mescaline was isolated in 1897 and used in experiments as a truth serum and for treatments of psychiatric disorders just after the second world war. LSD was made freely available to scientists by the pharmaceutical company, Sandoz, and widely used in medical research in the 1950s and 60s, with tens of thousands of patients (and researchers) giving it a try for conditions such as schizophrenia and alcohol dependence. LSD was also used in psychotherapy to "assist" patients in recovering from their neuroses, for severe pain patients. Albert Hofmann published the synthesis of psilocybin in 1959 and it too was studied for a variety of conditions. Surprisingly, little concern was raised about the safety of psychedelics in these early papers.

    In today's psychiatry, psychedelics are considered possibly dangerous kindlers of ongoing psychotic disorders, particularly for people with personal or family histories of schizophrenia and bipolar disorder, and should be avoided. It would be malpractice (not to mention illegal) for a doctor to administer LSD to a schizophrenic patient today. However, the lack of success of almost any therapy, medicine or otherwise, for treatment resistant depression and some addiction disorders has led researchers to consider studying psychedelics again, starting with ketamine.

    All of these agents seem to act on a particular serotonin receptor, 5HT-2A, and ketamine additionally is an antagonist at the NMDA receptor. Activation of this serotonin receptor seems to influence "existential concepts of self, including moral values, self-identity, and purpose." It brightens the mood and makes people feel motivated to change. Interestingly, modern studies of ketamine for depression focus on low dose (typically 0.5mg/kg over 40 minutes in an IV, whereas 1-4.5mg/kg are typically used for anesthesia), and that the psychedelic properties of ketamine are minimized at this dose. However, some studies showed that the amount of dissociation symptoms measured during the infusion correlated with a longer antidepressant effect. All ketamine studies tend to be rather small, and some show no correlation between psychedelic and antidepressant effects.

    The other psychedelic with some promising modern research is psilocybin, derived from mushrooms. It too has a number of small studies for alcohol and tobacco addiction, end of life anxiety and depression, obsessive compulsive disorder, and treatment resistant depression. Scientists in London used fMRI to look for brain mechanisms in their study of psilocybin and depression. 19 patients were given psilocybin, and all 19 had their depression scores drop significantly (in fact, on average, depression scores were cut in half) a week after the dose. 47% still met the criteria for treatment response 5 weeks after the dose.

    The fMRIs were interesting too, showing decreased blood flow in the amygdala (the "fear" center of the brain) in correlation with antidepressant effects. fMRI can measure overall "connectivity" of the brain, or how much communication is going on between the different parts. Increased connectivity of some parts of the prefrontal cortex and parietal lobe predicted treatment response at 5 weeks, as did decreased connectivity between the parahippocampal and prefrontal cortices.

    In all these modern studies, carefully done in controlled conditions with medical and psychological support, psychedelics seem to immediately reduce depressive symptoms and promote positive change. The side effects of ketamine include vital sign changes, and some folks who take ketamine and psilocybin experience distressing hallucinations and dislike feelings of dissociation (others seem to like this feeling). Given that the only other end-of-line treatment that works very quickly for depression and, especially, acute suicidality, is electroshock therapy, the risks and benefits of psychedelics in this context is a different (currently experimental) conversation than for standard outpatient treatment. It seems likely, unless larger studies take a surprising turn, that ketamine, especially, is going to be used more in general practice, particularly in closely monitored settings such as locked inpatient psychiatric units and emergency rooms. This is not the optimism of a 1950s researcher who likes to dabble in LSD with his patients...this is science.

    *From the article here: https://www.psychologytoday.com/us/b...and-depression
    Last edited by mr peabody; 19-10-2018 at 10:15.
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    Can psychedelics save you from depression?


    Recent large studies, using the psychedelics psilocybin and ayahuasca, have shown that a single moderate dose of these substances can significantly reduce depression scores. The antidepressant effect of psychedelics also seems to last for much longer than typical treatments, with reduced depression scores maintained for several months after treatment.

    Scientists believe that the reason psychedelics have such a profound antidepressive effect is because of the unique way they work in the brain. Psychedelics appear to deactivate a control network in the brain called the Default Mode Network (DMN), which is normally responsible for self-reflection and maintaining a sense of self. The DMN is found to be overactive in depressed patients, perhaps linked to the repetitive and obsessive negative thoughts sufferers experience. Therefore, psychedelics, by taking control away from the DMN, may be allowing sufferers of depression to break free from negative, spiraling thoughts.

    Hundreds of millions of people suffer from depression worldwide, and up to 44% of these people have not found relief from typical antidepressant therapies. This ‘treatment-resistant’ form of depression is especially devastating, as patients can suffer for many years without hope of recovery.

    Even patients who find relief from the usual prescribed antidepressants need frequent doses, causing unpleasant side-effects, and these drugs often lose their effectiveness after several years of treatment. What we really need, argue many psychiatrists and mental health professionals, is a paradigm shift in the way we treat depression. It’s looking very likely that psychedelics could trigger this change.

    The Default Mode Network

    Much of the recent research into depression has focused on the Default Mode Network (DMN). This is a system in the brain that is a core aspect of our consciousness and sense of self. When you are remembering the past, daydreaming, or thinking about yourself or others, the DMN is active. The DMN is found to be overactive in patients with major depression, perhaps causing an increase in the intensity of negative thoughts.

    Some promising research has shown that psychedelics may possess antidepressant properties, through their interaction with the DMN. Several pilot studies from the group of Professor David Nutt in London have led the charge. One of these studies used psilocybin-assisted therapy to treat 12 people suffering from treatment-resistant depression, and other studies investigated the potential antidepressant effects that psychedelics might have in the brain.

    Pilot study of psilocybin treatment for depression

    The psilocybin study, led by Dr. Robin Carhart-Harris, set out to treat sufferers of depression with psychedelic therapy. 12 patients with severe depression were given 2 doses of psilocybin 7 days apart. The first session was a moderate dose of psilocybin (10mg) and the second session was a high dose of psilocybin (25mg).

    The patient’s depressive symptoms were measured before, one week after, and three months after the trial using an approved scoring system. All of the patients showed improved depression scores after a week, and seven patients retained this improvement after three months.

    Impressively, five of the patients went from a score of ‘severe depression’ to a score of ‘no depression’ immediately following the psilocybin therapy. After three months, five of the patients (who started with either severe or moderate depression) were scored as having no depression.

    Psilocybin caused a significant decrease in depression scores in 12 patients lasting at least three months.

    Although this was a small study, it remains a promising step forward into establishing psilocybin as a potential treatment for depression, when used as a therapeutic tool in the correct setting. The fact that this treatment could effectively reduce depression scores (sometimes to zero!) and keep depression at bay for at least three months in most patients, is really encouraging. Compared to typical antidepressant therapy programs, these early results look very impressive.

    How could psilocybin have such a dramatic effect on people’s depression?

    An earlier study by Dr. Carhart-Harris looked at the changes within the brain caused by psilocybin, in ordinary non-depressed people. The researchers found that psilocybin disrupts the DMN, a part of the brain that ties together our normal consciousness. By disrupting the DMN, psilocybin releases consciousness from its stringent control mechanisms, allowing consciousness to break free of this control. Psychedelics enable depressed people to move outside of their recurrent negative thoughts.

    Others from Professor Nutt’s group in London wanted to expand on these results and performed the first ever brain imaging study using LSD.

    Prof Nutt’s group took extensive images of people’s brain activity after a moderate dose of LSD (75ug). One of the most interesting findings concerned the DMN; Nutt’s group discovered that LSD reduced the activity of the DMN in a way similar to psilocybin, and the more the DMN was disrupted, the more their participants experienced ‘ego dissolution’, meaning patients lost their sense of self and became less focused on their typical worries of everyday life.

    Although these are early studies – and we don’t know anything for certain yet – it looks like two classic psychedelics – LSD and psilocybin – could catalyze a paradigm shift in psychiatry.

    We’ve been treating depression as a simple chemical imbalance that we can treat with frequent pharmacological intervention, but it has not worked as planned. Depression is a disorder in the complex, high-level parts of consciousness such as the DMN. We need a treatment that changes the way people think. Psychedelics, by disrupting the DMN and opening up consciousness to new ways of thinking, could be that treatment.

    Recent findings with ayahuasca

    The most recent comprehensive study on psychedelics as a treatment for depression focusses on the ancient psychedelic brew ayahuasca. There have been anecdotal reports of ayahuasca experiences curing people of their depression, with the psychedelic trance being described as being like hundreds of therapy sessions condensed into a matter of hours.

    This is the first randomised, placebo-controlled clinical study of the anti depressive effects of ayahuasca. 29 patients with severe depression were given either ayahuasca or a placebo, and then analysed for changes in their depression scores. 1 day immediately following the sessions, the ayahuasca group scored significantly lower on depression tests compared to the placebo group. After seven days, the placebo group had returned to a normal depression level, while the ayahuasca group were still on a much lower depression score.

    It’s important to emphasise that this study was conducted in a therapeutic, supportive environment. If ayahuasca does indeed possess antidepressant effects, it almost certainly needs to be consumed in a prepared, responsible and therapeutic environment.

    The Bipartite Model of Depression

    The mounting evidence of psychedelics’ effectiveness at treating depression has led some scientists to develop a new theory of depression. Know as the ‘bipartite’ model, it suggests that while antidepressants work through serotonin 1A receptors (known as a ‘coping’ mechanism), psychedelics work through serotonin 2A receptors (known as an ‘adaptive’ mechanism). This theory explains how antidepressants are effective at treating symptoms in many people – yet, why psychedelics could be required to produce lasting changes in perception and mood.

    https://thethirdwave.co/psychedelics-depression/
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    Do magic mushrooms work better than prozac?

    When her best friend announced she planned to fly to the Amazon to cure her lifelong anxiety with ayahuasca, Rosalind Watts begged her not to go. As a psychologist, she knew that conventional psychiatric medications are by no means a panacea. But the idea of her friend disappearing into the jungle to swallow a psychedelic concoction under the supervision of indigenous shamans didn’t just terrify her: It threatened to demolish the bedrock of assumptions that underpinned her career.

    “I remember putting the phone down and just being really, really worried about her,” says Watts, 36, speaking on her houseboat on a London canal. Then a by-the-book talk therapist working for Britain’s National Health Service, Watts is now one of the pioneers in a new generation of clinicians, neuroscientists and psychiatrists fomenting a revolution in mental health care. Their goal: To create safe settings where people trapped in depression, trauma and addiction can gain legal access to the healing power of psychedelic drugs.

    Watts is the clinical lead for a year-and-a-half-long study to test whether psilocybin could be more effective than a standard anti-depressant. It could be a landmark in her comrades’ broader struggle to transform mainstream psychiatry, which has developed an arsenal of pills to numb the symptoms of mental disorders, but needs new tools to tackle their causes.

    “The thing about psychedelics is what they get you hooked on is your deep, true self,” Watts says, surrounded by research papers spread amid potted wisteria, honeysuckle and geraniums on the roof of her houseboat — her open-air office when the sun shines.

    “People are so caught in the prisons of their minds, and there’s just something so beautiful about this because it can really just take people into their heart.”

    Watts’ curiosity about psychedelics was piqued 5 years ago when her friend, Carys Vaughan, returned from Peru unscathed. While there are plenty of reports of spiritual seekers suffering soul-searing damage at badly run ayahuasca retreats, Vaughan stepped off the plane clear-eyed and radiant. Freed from anxiety, Vaughan quit her sales job to work for a charity, fell in love and had 2 children — blessings she attributes to the visceral, priority-shifting experience of the plant medicine.

    As Watts watched her friend’s life change, her relief was tempered by perplexity: Nothing in her training could explain such a dramatic shift.

    Growing up in the quiet town of Stamford, Lincolnshire, Watts had once imagined a future as a barrister. Her mother and older sister were psychologists, but the law seemed a way to be both sensible and different. Watts had planned to start legal training after graduating with a degree in English literature.

    She realized she was on the wrong path while working in a prosecutor’s office that was charging a suspect who had turned to heroin to blot out childhood memories of being raped by her father and brothers. When Watts asked the prosecutor what sort of life the defendant could look forward to in jail, he snapped that if she wanted to ask such questions, she would be better off as a psychologist, not a lawyer.

    Watts went on to assist with group therapy in a prison before studying psychology at University College London and joining a team working with families in gritty inner-city neighborhoods. It was only when her daughter was born that she found the time to start reckoning with Vaughan’s transformation, spending long nights of her maternity leave devouring literature on psychedelics.

    Her big break came when she was taken on as a volunteer “guide” on a pilot study at Imperial College London on the impact of synthetic psilocybin on long-term depression, led by the neuroscientist Robin Carhart-Harris. Convinced that she would only be able to provide the best possible support if she underwent a high-dose psychedelic session herself, Watts booked a place on a legal psilocybin retreat in the Netherlands. The experience left her in no doubt as to the substance’s potential as a catalyst for profound inner work. As the study unfolded, Watts’ job was to sit with participants as they rode the psychic roller coaster unleashed by the drug and conduct follow-up interviews. She was fascinated by the sense of cosmic connectedness — with people, nature or themselves — that stayed with many of the subjects long after their trips.

    Hearing about these experiences reminded Watts of poems she had studied by Gerard Manley Hopkins: “As Kingfishers Catch Fire,” on bliss, and “No Worst, There Is None,” on suicidal despair. Her epiphany only deepened her conviction that reconciling the worlds of art, science, clinical research and sacred ceremony was her new calling.

    “She’s very much a connector; she brings people together,” says Michelle Baker Jones, a therapist who worked alongside Watts as a guide. “She brings a warmth into the team. She’s very open to people, and I think that’s really key in this type of work.”

    The study showed that most of the 20 participants had obtained at least 5 weeks of relief from their symptoms, and some were still depression-free at 6 months. Despite the hurdles to working with psilocybin, Watts is now working full-time to prepare for the more ambitious study pitting the drug against a commonly prescribed anti-depressant called escitalopram, which belongs to the same family as Prozac.

    Even within the psychedelic science community there are skeptics. Katherine MacLean, a research scientist who worked on a psilocybin trial at Johns Hopkins, says the substance is only likely to help lift entrenched depression if people undertake the painstaking work of changing the way they live once the afterglow has faded. She also questions how safe it is to give the drug to very depressed patients. “I don’t think the clinical model anyone is working with right now is going to somehow miraculously cure depression,” MacLean says. “Unless you’re really willing to make those core changes, then psilocybin is not going to change your life for you.”

    Watts is mindful of such concerns. In August, she and Baker Jones co-founded a monthly Psychedelic Integration Group to help people process ego-shattering trips and translate their insights into action. Her ultimate goal is to open a clinic to offer psychedelic-assisted therapy to anybody who needs it — assuming drug laws relax. “You could imagine a futuristic, incredible health center where we’re really exploring consciousness,” Watts says, no longer the rigid clinician she once was. “Because it’s still the great mystery.”

    ---

    ^^
    Absolutely a viable source. I have been microdosing for 6 months now. And my thought process has made such significant changes that it has allowed me to mentally move away from my old, negative, depressed thinking. I've dropped down to 15 mg Prozac and my head and heart are finally connecting, I feel a part of this world and love being present and engaging with my friends and community. I've suffered from PTSD, depression and then drug addiction to cope. This is the first time in my life that I have ever felt like I belong here on this earth. So I will continue on this path and look forward to my life ahead.

    -Donna Scott-Newman

    https://www.ozy.com/rising-stars/do-...find-out/87165
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    San Luis Obispo


    Psilocybin could provide new avenue for antidepressant research


    Psilocybin may offer a possible new avenue for antidepressant research, according to a new study published in The Lancet Psychiatry today.

    The small feasibility trial, which involved 12 people with treatment-resistant depression, found that psilocybin was safe and well-tolerated and that, when given alongside supportive therapy, helped reduce symptoms of depression in about half of the participants at 3 months post-treatment. The authors warn that strong conclusions cannot be made about the therapeutic benefits of psilocybin but the findings show that more research in this field is now needed.

    "This is the first time that psilocybin has been investigated as a potential treatment for major depression," says lead author Dr Robin Carhart-Harris, Imperial College London, UK. "Treatment-resistant depression is common, disabling and extremely difficult to treat. New treatments are urgently needed, and our study shows that psilocybin is a promising area of future research. The results are encouraging and we now need larger trials to understand whether the effects we saw in this study translate into long-term benefits, and to study how psilocybin compares to other current treatments."

    Depression is a major public health burden, affecting millions of people worldwide and costing the US alone over $200 billion per year. The most common treatments for depression are cognitive behaviour therapy (CBT) and antidepressants. However, 1 in 5 patients with depression do not respond to any intervention, and many relapse.

    "Previous animal and human brain imaging studies have suggested that psilocybin may have effects similar to other antidepressant treatments," says Professor David Nutt. "Psilocybin targets the serotonin receptors in the brain, just as most antidepressants do, but it has a very different chemical structure to currently available antidepressants and acts faster than traditional antidepressants."

    The trial involved 12 patients with moderate to severe depression. The patients were classified as having treatment-resistant depression, having previously had two unsuccessful courses of antidepressants. Most had also received some form of psychotherapy. Patients were not included if they had a current or previous psychotic disorder, an immediate family member with a psychotic disorder, history of suicide or mania or current drug or alcohol dependence.

    Patients attended two treatment days -- a low dose of psilocybin 10mg oral capsules, and a higher dose of 25mg a week later. Patients took the capsules while lying down on a ward bed, in a special room with low lighting and music, and two psychiatrists sat either side of the bed. The psychiatrists were present to provide support and check in on patients throughout the process by asking how they were feeling. Patients had an MRI scan the day after the therapeutic dose. They were followed up one day after the first dose, and then at 1, 2, 3, and 5 weeks and 3 months after the second dose.

    The psychedelic effects of psilocybin were detectable 30 to 60 minutes after taking the capsules. The psychedelic effect peaked at 2-3 hours, and patients were discharged 6 hours later. No serious side effects were reported, and expected side effects included transient anxiety before or as the psilocybin effects began, some experienced confusion (9), transient nausea (4) and transient headache (4). Two patients reported mild and transient paranoia.

    At 1 week post-treatment, all patients showed some improvement. 8 of the 12 patients achieved temporary remission. By 3 months, 7 patients continued to show an improvement in symptoms and 5 of these were still in remission. 5 patients showed some degree of relapse.

    The patients knew they were receiving psilocybin. The authors stress that most of the study participants were self-referred, meaning they actively sought treatment, and may have expected some effect. All patients had agreement from their GP to take part in the trial. They add that patients were carefully screened and given psychological support before, during and after the intervention, and that the study took place in a positive environment. Further research is now needed to tease out the relative influence of these factors on symptoms of depression, and look at how psilocybin compares to placebo and other current treatments.

    Writing in a linked Comment, Professor Philip Cowen, MRC Clinical Scientist, University of Oxford, Oxford, UK, says: "The key observation that might eventually justify the use of a drug like psilocybin in treatment-resistant depression is demonstration of sustained benefit in patients who previously have experienced years of symptoms despite conventional treatments, which makes longer-term outcomes particularly important. The data at 3 month follow-up (a comparatively short time in patients with extensive illness duration) are promising but not completely compelling, with about half the group showing significant depressive symptoms. Further follow-ups using detailed qualitative interviews with patients and family could be very helpful in enriching the assessment."

    https://www.sciencedaily.com/release...0517083044.htm
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    FDA Approves Landmark Psilocybin Trial for Treatment-Resistant Depression


    The US Food and Drug Administration (FDA) has granted approval to COMPASS Pathways’ planned clinical trial to test psilocybin therapy in patients with treatment-resistant depression.

    The phase 2b dose-ranging trial will involve 216 patients across 12-15 research sites in North America and Europe, beginning in the UK later this month. Federal regulatory agencies have already granted approval for the trial in the UK, Canada, and the Netherlands.

    Psilocybin therapy—a combination therapy of psychoactive medicine and the active agreement found in psychedelic mushrooms, plus psychological support—has been a frequent, if not controversial, investigative treatment for psychiatric conditions since the 1950s.

    Charles Raison, MD, a professor at the University of Wisconsin-Madison said in an interview with MD Magazine that the mushroom-based therapy was initially used fpr patients suffering from alcoholism or end-of-life anxiety. In the early 2000s, privately-funded investigators began to notice a consistent positive effect of the drug on patients’ mood.

    “It seems to have a long-term impact on people,” Raison said. “Even normal folks seem to feel better, and they take better care of themselves afterwards.”

    One study even suggested that patients’ personalities changed after being treated, Raison noted—more than a year after treatment, they were more expressive and less prone to depression. Another pair of randomized, controlled, crossover studies comparing a single psilocybin treatment versus placebo reported “amazing” results, Raison said.

    “One treatment just completely reduced depression and anxiety scores, from people being very clinical to reaching remission,” Raison said. “No other treatment, and 6 months later, 60-70% people are in remission from a single treatment.”

    COMPASS Pathways, a life sciences company founded in 2016, has focused its early efforts on late-stage clinical trial development for psilocybin in patients with treatment-resistant depression. They advocate for advances in neuroscience, psychotherapy, psychopharmacology, and technology.

    George Goldsmith, chairman and co-founder, expressed excitement for the beginning of the landmark trial.

    “Depression is the leading cause of ill-health and disability worldwide, and treatment-resistant depression affects more than 100 million people,” Goldsmith said in a statement. “It is a huge unmet need and the trial will teach us more about how this new approach might address it."

    https://www.mdmag.com/medical-news/f...ant-depression
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    I suffered severe depression since childhood until I tried psilocybin

    I've tried prescription antidepressants and therapy. I'm proactive and intelligent, I have never taken recreational drugs, and I try not to abuse alcohol. A good friend told me about psilocybin mushrooms and said they might help. Although deeply skeptical, I felt like it was worth a shot, so I took them in a safe, controlled environment. The difference has been enormous. It's like having the volume turned down on part of my brain that seizes onto negativity, waking up the next day and feeling optimistic about the future for the first time.

    -----

    I suffer from moderate to severe depression. I recently started taking a low dose of psilocybin, which has definitely helped my depression. Mushrooms are great because they are non-addictive, have no side effects, and I have a built in anti-abuse mechanism in the form of built up tolerance.

    It forces you to wait a couple of weeks before taking any more, and at a low dose that seems to be the right amount of time!

    -----

    Nothing helps quite so much as being fully rested, and taking the most minimal doses of psilocybin. I don’t particularly enjoy getting high, but a threshold dose, just enough to notice a slight peculiarity in the appearance of the world, shifts my mood tremendously. I find small, daily doses, for several weeks, seem much more effective than larger doses, less frequently. Low doses of psilocybin, once a day, for up to several weeks, leaves me in a fairly positive place for nearly a full quarter.

    -----

    I've had moderate to severe depression since 2007. I've tried therapy, all types of medicine, self medication, and everything else imaginable. Nothing has come close to helping me like psilocybin. I can 100% attest that psilocybin helps me with my depression for as long as 6 months after use.

    -----

    The benefits of psilocybin are amazing. Not only during trips, which can be life changing and eye opening experiences, but also in microdosing, to help me with the effects of depression and anxiety. Microdosing significantly helped me with many internal issues I was having.

    -----

    Being a veteran and someone who had a tough childhood I found myself very depressed and suicidal. Even when 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 help others with these feelings. After much research I decided to try mushrooms. to cut 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.

    -----

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

    -----

    Psilocybin is the only thing that's ever helped me. Self-medicating with psilocybin has saved my life twice, given me hope, and helped me see that I am connected, not isolated. Nothing medically prescribed by my GP has helped - just made it worse, numbed out and dumbed down, merely existing. I need this medicine in a legitimate clinical setting.

    -----

    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 my habits and rusty old thought patterns.


    ^^
    https://psychedelicsociety.org.uk/pe...ession-anxiety
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    Microdosing LSD for Treatment-Resistant Depression


    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/
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    Psilocybin could provide a new avenue for antidepressant research


    Psilocybin may offer a possible new avenue for antidepressant research, according to a new study published in The Lancet Psychiatry today.

    The small feasibility trial, which involved 12 people with treatment-resistant depression, found that psilocybin was safe and well-tolerated and that, when given alongside supportive therapy, helped reduce symptoms of depression in about half of the participants at 3 months post-treatment. The authors warn that strong conclusions cannot be made about the therapeutic benefits of psilocybin but the findings show that more research in this field is now needed.

    "This is the first time that psilocybin has been investigated as a potential treatment for major depression," says lead author Dr Robin Carhart-Harris, Imperial College London, UK. "Treatment-resistant depression is common, disabling and extremely difficult to treat. New treatments are urgently needed, and our study shows that psilocybin is a promising area of future research. The results are encouraging and we now need larger trials to understand whether the effects we saw in this study translate into long-term benefits, and to study how psilocybin compares to other current treatments."

    Depression is a major public health burden, affecting millions of people worldwide and costing the US alone over $200 billion per year. The most common treatments for depression are cognitive behaviour therapy (CBT) and antidepressants. However, 1 in 5 patients with depression do not respond to any intervention, and many relapse.

    "Previous animal and human brain imaging studies have suggested that psilocybin may have effects similar to other antidepressant treatments," says Professor David Nutt, senior author from Imperial College London "Psilocybin targets the serotonin receptors in the brain, just as most antidepressants do, but it has a very different chemical structure to currently available antidepressants and acts faster than traditional antidepressants."

    The trial involved 12 patients with moderate to severe depression. The patients were classified as having treatment-resistant depression, having previously had two unsuccessful courses of antidepressants. Most had also received some form of psychotherapy. Patients were not included if they had a current or previous psychotic disorder, an immediate family member with a psychotic disorder, history of suicide or mania or current drug or alcohol dependence.

    Patients attended two treatment days -- a low dose of psilocybin 10mg oral capsules, and a higher dose of 25mg a week later. Patients took the capsules while lying down on a ward bed, in a special room with low lighting and music, and two psychiatrists sat either side of the bed. The psychiatrists were present to provide support and check in on patients throughout the process by asking how they were feeling. Patients had an MRI scan the day after the therapeutic dose. They were followed up one day after the first dose, and then at 1, 2, 3, and 5 weeks and 3 months after the second dose.

    The psychedelic effects of psilocybin were detectable 30 to 60 minutes after taking the capsules. The psychedelic effect peaked at 2-3 hours, and patients were discharged 6 hours later. No serious side effects were reported, and expected side effects included transient anxiety before or as the psilocybin effects began, some experienced confusion (9), transient nausea (4) and transient headache (4). Two patients reported mild and transient paranoia.

    At 1 week post-treatment, all patients showed some improvement in their symptoms of depression. 8 of the 12 patients achieved temporary remission. By 3 months, 7 patients continued to show an improvement in symptoms and 5 of these were still in remission. Five patients showed some degree of relapse.

    The patients knew they were receiving psilocybin, and the effect of psilocybin was not compared with a placebo. The authors also stress that most of the study participants were self-referred meaning they actively sought treatment, and may have expected some effect. All patients had agreement from their GP to take part in the trial. They add that patients were carefully screened and given psychological support before, during and after the intervention, and that the study took place in a positive environment. Further research is now needed to tease out the relative influence of these factors on symptoms of depression, and look at how psilocybin compares to placebo and other current treatments.

    Writing in a linked Comment, Professor Philip Cowen, MRC Clinical Scientist, University of Oxford, Oxford, UK, says: "The key observation that might eventually justify the use of a drug like psilocybin in treatment-resistant depression is demonstration of sustained benefit in patients who previously have experienced years of symptoms despite conventional treatments, which makes longer-term outcomes particularly important. The data at 3 month follow-up (a comparatively short time in patients with extensive illness duration) are promising but not completely compelling, with about half the group showing significant depressive symptoms. Further follow-ups using detailed qualitative interviews with patients and family could be very helpful in enriching the assessment."

    https://www.sciencedaily.com/release...0517083044.htm

    -----

    Psychedelics and depression: My experience

    By Tim Williams

    I suffer from PTSD, quite severe. I have severe depression with suicidal ideation, short term memory issues, anticipative anhedonia, and aversion to interacting with others,
    to the point that I am currently listed as disabled. There ARE some things you can look at that may be of considerable help.

    The curative abilities of psychedelics are well-documented and have been noted since the 1960s. Specifically, low-dose psilocybin provokes neurogenesis (neuron birth) in the hippocampus. This is significant since the hippocampus shrinks in profoundly depressed people. Short term low-dose psilocybin has been shown to cause ‘fear extinguishment’, i.e. cessation of the nervous response when exposed to a trauma trigger. I can vouch for this being of considerable benefit for me right now.

    MDMA and LSD also have effects, though slightly different. LSD is known to weaken depression and addictive/compulsive behaviors, and MDMA was one of the most effective tools in psychoanalysis until it was banned as a party drug. Single or intermittent use of N,N-DMT (also known as just “DMT”) is also known to be of benefit – this one, personally, completely cured fear of dying on my first go.

    Ibogaine is a psychedelic but a very unusual and interesting one. It has a number of effects on a number of receptors, with stunning and profound results. One of its uses is in drug addiction, where it is up to 20x more effective than traditional detox programs,. The OTHER use – which is intertwined with the anti-addictive effects – is in non-psychotic depressive disorders.

    Its multi-pronged action simultaneously resets opiate receptor tolerance; floods the brain with dopamine, leading to re-regulation of disturbed dopaminergic effects such as anhedonia; has profound NMDA inhibitory effect (which is a whole new area of anti-depressive research right now, and also allows you to “re-process” traumatic memories); it is a stimulant (cures brain fog and lethargy); is an SSRI (cures depressive behaviours); and last but not least, it upregulates production of BDNF. BDNF is a growth factor which causes neurons to “re-sprout and repair”… think a bare tree growing new leaves. Further, taking the full “flood dose” of 25mg / kg gives you a fascinating 20 hour trip in which you have unparalleled access to all your memories (thanks, NMDA inhibition) and can literally re-visit and gain insight into any part of your life. This has been called “2 years of intensive therapy in 1 day”.

    Ibogaine can be dosed as the hallucinogenic “flood dose,” but that requires medical preparation, a minder, and is quite rough as a trip – expect nausea and ataxia. However it’s rewarding enough that many people do it once a year just for the incredible insight into one’s self that it brings.

    But the way I tend to use it is “microdose.” This is a 50mg dose per day, in a 7 days on, 3 days off pattern. The dose is not psychedelic at this point. You don’t notice it affecting you at all, but it IS there doing its work... and by the second week you will definitely notice significant improvements in many areas.

    -----

    Ketamine and depression*

    Compared with conventional antidepressants, ketamine is “remarkable,” says David Feifel, a professor of psychiatry and director of a center specializing in advanced treatments for depression at the University of California, San Diego.

    Starting in 2004, Carlos A. Zarate Jr., chief of the Experimental Therapeutics & Pathophysiology Branch of the National Institute of Mental Health, led a study in which his team used ketamine to treat 17 patients who had already been through an average of six antidepressants. They observed 12 patients (71 percent) improve within 24 hours.

    That speedy response time contrasts with conventional antidepressants such as sertraline and fluoxetine, which target serotonin pathways in the brain and typically take weeks to work. Ketamine binds to the same glutamate receptors as ibogaine. Its half-life in the body is two to three hours. But ketamine’s relief of depression lasts an average of around seven to 18 days, with some patients improving for as long as five months, Feifel says. Zarate is conducting a range of studies — including neurological imaging, proteomics, and metabolomics — to unravel ketamine’s effects in the brain. He points to dehydronorketamine as a particularly interesting metabolite. Zarate and colleagues have found that it may play a role in alleviating depression by interacting with a nicotinic receptor involved in long-term memory.

    A racemic mixture of ketamine enantiomers is currently approved and manufactured for use as an anesthetic. Doctors administer it for depression off-label as an injection or intravenous infusion, at a dose low enough to avoid unconsciousness. Johnson & Johnson’s Janssen R&D unit has an intranasal formulation of the S-(+)-ketamine enantiomer, known as esketamine, in clinical trials. In both cases, patients are dosed in clinics and monitored until the altered consciousness effects dissipate. Allergan is developing a related compound, rapastinel, that targets the same glutamate receptors but does not induce altered consciousness.

    None of the compounds provides a single-dose cure for depression—they all require continuing treatment. Nevertheless, they could be a much-needed help when other treatments do not work. “It was unlike anything I’ve seen in psychopharmacology before,” says Roland R. Griffiths, a professor of psychiatry and behavioral sciences at Johns Hopkins University, of his first trial examining the safety of psilocybin in healthy volunteers.

    Those volunteers had positive effects that could last for years. “People had increased satisfaction and quality of life,” Griffiths says. “They felt more generous, centered, optimistic, and caring toward other people in their lives.” Patients’ friends, family members, and work colleagues confirmed the differences. Griffiths has since conducted trials of psilocybin for tobacco addiction, anxiety, and depression in patients with life-threatening cancer.

    *From the article here: https://inchemistry.acs.org/content/...nic-drugs.html
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    I would love to try Ketamine - in a controlled prescribed fashion - for my depression. Or psilocybin
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    ^^

    MXE (3-MeO-2-Oxo-PCE) will be the RC closest to ketamine.

    -fireflagknown (reddit)

    ---

    I prefer 2f-ket. It is shorter lasting but feels cleaner and closer to real ket. Duration is 2-3 hours.

    -Mutagenic_pasta (reddit)

    ---

    Methoxmetamine (MXM) is probably the RC closest to ketamine. MXE is superior for me but not much like k.

    -K8hudson1 (reddit)

    ---

    MXE and O-PCE are very similar, and my all time favorite drugs ever that have extreme anti-depressive qualities.

    -RCluminati (reddit)

    ---

    Deschloroketamine (aka O-PCM, DXE, and DCK) is advertised as a ketamine replacement. It's much cheaper. I found it
    to be about 2x more potent than K, and last about twice as long.

    https://www.erowid.org/experiences/exp.php?ID=107008
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    Ibogaine rescued me from overwhelming anxiety and depression


    By Holly Stein

    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.
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    Tiny Amounts of LSD for Depression


    by Olga Khazan

    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.


    Last edited by mr peabody; 19-10-2018 at 10:12.
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