Self Help

Psychedelics - Professor David Nutt

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Matheus Puppe

· 41 min read



  • Psychedelics are undergoing a revolution as new research is showing their medical potential for treating various mental health conditions like depression, PTSD, addiction, etc. This is a major change from the past 50+ years when they were banned and stigmatized.

  • The author was involved in some of the early brain imaging research on psychedelics in the 2000s which surprisingly found they reduce rather than increase brain activity, especially in areas linked to depressive thinking. This led to clinical trials showing psilocybin can be highly effective for treatment-resistant depression.

  • Other psychedelics like ketamine, LSD, ayahuasca and MDMA are also showing promise for various conditions where current treatments are inadequate. Ketamine treatment for depression is already being used as it is a licensed drug.

  • Understanding how psychedelics affect brain function and consciousness through neuroimaging is an important scientific question on par with other fields like physics. More research is needed as their mechanisms are still not fully understood.

  • The book will discuss the evidence from clinical research on psychedelics for different mental health conditions, policies around legalization/medicalization, mechanisms of action in the brain, historical and current therapeutic practices, risks/safety profiles, and the author’s own experiences.

  • The book describes 15 years of research into psychedelic drugs like psilocybin, ayahuasca, and LSD for treating mental health conditions. It discusses how these drugs work differently than antidepressants and can rapidly improve conditions like depression when combined with psychotherapy.

  • In the 1950s and 1960s, there was significant research into medical uses of psychedelics funded by government agencies. This led to many clinical trials and case studies showing promise for treating addiction, amongst other conditions. However, psychedelics also fueled social and political change in the 1960s counterculture movement.

  • In the late 1960s, LSD was banned and classified as a Schedule 1 drug due to fears it was enabling anti-war and radical social movements, not because of proven harms. This effectively censored further research for 50+ years until the current renaissance in psychedelic research.

  • The book aims to share new discoveries about how psychedelics work in the brain from the author’s 15 years of research and help answer questions about safely accessing potential medical benefits through legal means in some places.

  • Articles in the 1960s warned about the dangers of LSD, saying people might look into the sun until blind, think they could fly and jump out windows, or that LSD could damage chromosomes or corrupt youth. There were warnings that people may not be able to return to normal after tripping or may go mad.

  • This created a widespread stigma against psychedelics that persists today. However, modern research suggests the risks were overblown and psychedelics can be safely used medically with appropriate supervision and set/setting.

  • The book aims to dispel myths about psychedelics and show that while powerful, they are not as dangerous as believed and have medical potential. However, regulatory classification and stigma remain barriers to research and medical use. Politicians, regulators and some media still promote misleading scare stories rather than facts.

  • Proper research is needed to fully understand psychedelics’ impacts and medical applications. But the drug war censorship of the last 50+ years has limited scientific progress and denied patients treatments, though this is now starting to change as psychedelics gain acceptance as medicines again.

  • Serotonin is a neurotransmitter that plays a role in many brain functions like sleep, mood, emotions, learning, hunger, and sensory perceptions. It is also the target of antidepressants like SSRIs.

  • Psychedelic drugs produce their psychedelic effects by binding to serotonin 2A receptors in the brain. Different serotonin receptor subtypes have different functions.

  • Classic psychedelics like psilocybin and LSD are currently illegal in most Western countries but psilocybin research is resurging and it may become a legal prescription medicine.

  • Taking psychedelics causes changes to perception, cognition, emotion, sense of time/place/self, and can induce spiritual/mystical experiences. Effects depend on dosage, method of intake, genetics, mindset and environment.

  • Common effects are visual changes, auditory changes, altered emotions, ego dissolution, deep introspection, enhanced social bonds and problem-solving creativity.

  • LSD is taken orally and lasts about 12 hours. It was initially researched clinically but was later demonized in the 1960s counterculture era.

  • In 1938, Swiss chemist Albert Hofmann synthesized LSD from ergot fungus while working at Sandoz Laboratories. Ergot compounds were used to treat migraines and induce labor.

  • Hofmann was following standard medicinal chemistry processes to refine molecules into potential new medicines. However, he accidentally ingested some LSD in 1943 and had the first acid trip, noticing unusual effects.

  • Hofmann then intentionally took LSD to properly test it, taking a much higher dose than intended of 250 micrograms. He experienced an intense “bad trip” and had to be assisted home by bicycle, where the effects eventually turned more positive.

  • April 19th is now known as “Bicycle Day” to commemorate Hofmann’s discovery. LSD gained research interest for exploring consciousness, though it was banned in the 1960s. Research has since resumed on its therapeutic potential.

  • Meanwhile, psychoactive mushrooms containing psilocybin were used for centuries in indigenous rituals. R. Gordon Wasson publicized this in 1957 after attending a Mazatec healing ceremony with curandera Maria Sabina.

  • Sabina’s village became overrun with visitors seeking psychedelic experiences. She faced persecution until her death. Psilocybin was isolated and marketed as a medicine but is now illegal in most places though research into its therapeutic uses continues.

  • DMT is a powerful psychedelic chemical found naturally in some plants and animals. It produces intense hallucinations when smoked or injected.

  • Ayahuasca is an Amazonian brew that contains DMT along with an MAOI. The MAOI allows the DMT to take effect orally by inhibiting an enzyme that breaks it down. Ayahuasca ceremonies using this brew can last 5-12 hours.

  • Mescaline is found in peyote and san pedro cacti. It has been used ceremonially by indigenous people in North and South America for at least 6,000 years.

  • 5-MeO-DMT, or toad venom, produces a very intense but short-lived (~20 minutes) psychedelic experience when smoked or snorted. It is secreted by glands in certain toad species and is also found in some plants.

  • These substances are increasingly being studied for their therapeutic potential to treat conditions like depression, addiction and trauma. However, their use also brings safety risks which research aims to better understand.

  • The loss of traditional Native American lands and the destructive introduction of alcohol destroyed tribes’ social cohesion. Tribes adopted peyote use through the Native American Church as a way to strengthen community in the face of hardship.

  • From 1880-1994, US prohibitionists tried to ban peyote, with varying success. The Native American Church was formed in 1914 in resistance, naming peyote its sacrament. In 1994, Native Americans gained legal rights to peyote for ceremonial use.

  • Peyote is threatened due to its slow growth. Protected plantations now guarantee access for Native American Church members. San Pedro cactus is a more sustainable alternative.

  • Mescaline was the first psychedelic chemically identified in 1897. It was used in the early 1900s by scientists and thinkers to explore consciousness. Huxley’s 1954 book The Doors of Perception popularized psychedelic experiences and thinking.

  • Recent studies found peyote use correlated with better mental health for Native American Church members, and mescaline use effectively treated depression, anxiety and other issues in surveys.

  • In the past, ketamine was imported in large quantities from India labeled as “rosewater” and “massage oils.” Its recreational use was increasing, leading to more dependence and health issues like bladder damage. Around 10 people per year were dying from ketamine use in the UK.

  • In 2015, China pressed for ketamine to be made a Schedule 1 drug globally by the UN to curb abuse in Hong Kong. This would have banned its medical use.

  • The author’s group, Drug Science, lobbied against this, arguing a ban would not stop recreational use and would deny its medical benefits. Banning strong opioids like this in some countries has denied pain relief to 80% of the world’s population.

  • If ketamine had been rescheduled, medical use would have required an expensive license, effectively stopping clinical and research use. Fortunately, doctors, vets and scientists lobbied against the rescheduling, allowing further study of ketamine for depression and other disorders.

  • The author now works for a company developing psychedelic-assisted therapies, including with US ketamine clinics. Ketamine provides antidepressant effects through its action on the glutamate system in the brain.

Here is a summary of the key points about how long scopolamine lasts:

  • On its own, scopolamine typically lasts 4-6 hours when taken. However, effects vary between individuals.

  • Scopolamine became infamous when used by Dr. Hawley Crippen in 1910 to poison his wife. He used a lethal dose of scopolamine extract.

  • More recent cases of accidental scopolamine intoxication from plants like angel’s trumpet show it can cause delirium, hallucinations, memory issues and sleep paralysis for up to 12-24 hours.

  • Oliver Sacks took a high dose of a scopolamine-like drug and described experiencing a hallucinatory memory of events that never actually occurred, highlighting its strong effects on memory formation.

  • Scopolamine blocks acetylcholine receptors in the brain, disrupting memory and learning processes. This explains both its delirious effects and ability to generate false memories.

So in summary, the psychoactive and delirious effects of scopolamine typically last 4-6 hours when taken alone, but higher doses or combination with other alkaloids in plants can prolong effects for 12-24 hours or more. It also has long-lasting impacts on memory due to its mechanism of action.

  • The researcher set up a psychopharmacology department in Bristol University in 1988 with the goal of finding a painkiller that worked via kappa opioid receptors rather than mu receptors, in hopes it may be less addictive.

  • They tested a compound that targeted kappa receptors on a volunteer who had a horrifying experience of feeling detached from his body. This is why no pharmaceutical company has pursued kappa opioid receptor painkillers.

  • Salvia divinorum contains the active ingredient salvinorin A which works on kappa opioid receptors rather than serotonin receptors. Brain imaging shows effects similar to ketamine and classic psychedelics but people report distinct subjective experiences.

  • Salvia trips are often reported as unpleasant compared to serotonin-acting psychedelics, possibly due to kappa receptors being in a different brain region. Therapeutic use is unlikely as people don’t report insights from salvia experiences.

  • Researchers tested a psychedelic drug called alled ritanserin on healthy volunteers using EEG to measure brain waves. They found it increased slow-wave sleep brain activity but did not improve reported sleep quality.

  • They hypothesized it could be used to counteract a bad psychedelic trip, but this was not pursued commercially. It is now being studied to shorten LSD trips in emergency settings.

  • The researcher and their team studied psilocybin’s effects on the brain using fMRI. Contrary to expectations, they found psilocybin decreased activity in three brain regions rather than increasing it, correlated with reported psychedelic experiences.

  • Further studies with psilocybin, LSD, DMT and other psychedelics helped uncover how they affect brain networks and neural communication. Psychedelics seem to decrease activity in the default mode network, involved in self-processing and coordination between other networks.

  • Understanding psychedelics’ brain mechanisms could provide insight into consciousness, but more research is still needed due to historical stigma and regulatory barriers that have limited scientific study until recently. The researcher’s team has led studies to further uncover psychedelic neuroscience.

Here’s a summary of the key points:

  • When someone takes a psychedelic, it activates neurons in the brain that are involved in higher-level cognitive processes. This disrupts the typical synchronized brain wave patterns.

  • It causes the default mode network (DMN), which usually integrates brain activity, to go “offline.” This leads to less centralized control over different brain regions and altered consciousness.

  • Hallucinations may stem from the early stages of visual reconstruction in the brain becoming visible. Under psychedelics, the brain cannot fully fuse simple geometric shapes into a coherent image.

  • The DMN is also involved in creating one’s sense of self and typical thoughts/beliefs. With it disrupted, people can step outside habitual, often negative patterns of thinking.

  • For people struggling with mental health issues, psychedelics may help “unmanacle the mind” from damaging thought patterns and behaviors that are hard to stop, like rumination, compulsions, or addictive cravings. This could contribute to enduring positive effects on mood.

  • The passage discusses research showing that psychedelics like psilocybin and LSD increase connectivity between brain regions, disrupting the typical “small world” brain network organization and creating more connections between networks. This “large world” state resembles the brain connectivity of early childhood.

  • Increased connectivity helps explain experiences of mind expansion and insights during psychedelic trips. It allows isolated brain regions to reconnect and re-evaluate old beliefs and problems from new perspectives.

  • Enhanced neuroplasticity also allows new ideas formed during trips to persist beyond the acute effects and produce long-lasting clinical outcomes for conditions like depression.

  • The discovery of PCR DNA amplification by Kary Mullis under the influence of LSD demonstrates how psychedelic insights can catalyze major scientific innovations by opening the mind to new problem-solving approaches.

  • Opening and expanding perception through psychedelics’ disruption of typical brain functioning was a key idea discussed by William Blake and Aldous Huxley. The researcher’s own experiences with psychedelic neuroimaging research suggest they can similarly “open the mind.”

  • Non-classical psychedelics like ketamine, salvia and amanita mushrooms likely produce some distinct effects through their actions on specific neurotransmitter receptors, though they still involve broader desynchronization effects across brain networks. Effects on mood, memory, arousal and perception are discussed.

  • Enhanced color vision and musical appreciation during trips may relate to disruption of typical downplaying of these senses and opening of new cross-modal brain connections.

  • The author describes his lifelong struggle with severe depression and reluctantly participating in a clinical trial exploring the effects of psilocybin for treating depression.

  • During the trial, he had a difficult but transformative experience on a 25mg dose of psilocybin where he was able to face deep childhood traumas involving his abusive father. This led to feelings of openness, compassion, and an end to his depressive symptoms for 3 months.

  • However, the effects slowly faded over time as real-life difficulties emerged. He has since co-founded an advocacy network called PsyPAN to support further research and access to psychedelic treatments.

  • The author believes psychedelics like psilocybin have huge potential as innovative treatments for treatment-resistant depression, which is currently difficult to treat and shortens lives. He hopes future access to psychedelic medications could help many find relief.

  • Ketamine therapy is also discussed as another currently available psychedelic-assisted option for some types of severe depression. The author’s clinical experience and the promise shown in early research trials contributed to further exploration of psychedelic therapies.

  • Psilocybin, which only lasts 4 hours, seemed to improve mood and reduce depressive symptoms for weeks or months in some subjects of clinical studies.

  • Two key areas of the brain were found to be affected by psilocybin: CG25 (part of the ACC) and the default mode network (DMN, also called the self-circuit).

  • Reducing activity in CG25 through techniques like DBS surgery or medications like ketamine can effectively treat depression. Psilocybin was found to reduce CG25 activity.

  • The DMN is overactive in depressed patients and linked to rumination. Psilocybin disrupts the DMN, which could help break the pattern of depressive rumination.

  • The first modern psilocybin study for treatment-resistant depression enrolled 12 patients who had failed other therapies. After a 25mg psilocybin dose, 10/12 met the criteria for recovery from depression at the 2-week mark based on standardized scales.

  • Follow up studies at Johns Hopkins and NYU also found single psilocybin doses produced rapid and sustained reductions in anxiety, depression, and other mental health issues in cancer patients.

  • Further research is ongoing to better understand psilocybin’s long-term effects on depression and how to prevent relapse, including studies comparing it to escitalopram.

  • A clinical trial compared the antidepressant effects of psilocybin versus the SSRI escitalopram (Lexapro) in patients with major depressive disorder.

  • Psilocybin worked faster and more effectively than escitalopram based on outcomes measured at 6 weeks. 57% of psilocybin patients achieved remission vs 28% for escitalopram.

  • Brain imaging showed psilocybin had no effect on the emotional centers like the amygdala, unlike SSRIs. SSRIs blunt both positive and negative emotions.

  • Psilocybin increased functional connectivity in the brain, even days after administration when the drug had cleared. Increased connectivity correlated with improved depression.

  • Psilocybin seems to work by “resetting” rigid thought patterns and increasing mental flexibility via its effects on brain connectivity and neuroplasticity.

  • About 50% of psilocybin patients maintained their improvements at 3 months, while the other half relapsed. Factors like insight gained, mystical experiences, low anxiety during the session, and absence of deep-seated depression predicted better long-term outcomes.

So in summary, psilocybin showed superior antidepressant effects to escitalopram and appears to work via different neurophysiological mechanisms related to connectivity and plasticity rather than emotional processing. But relapse remains an issue for some patients.

Here is a three sentence summary:

Psychedelics trigger immediate neuroplasticity in the brain, which may help explain their rapid antidepressant effects. Studies have found that psychedelics like psilocybin increase the growth of dendrites and synapses in brain cells, similarly to antidepressants but more quickly. Maintaining some level of neuroplasticity over the long term through additional doses may be necessary to solidify new patterns of thinking gained during psychedelic therapy sessions.

  • In the 1950s and 1960s, both the CIA and other U.S. government researchers administered LSD to unwitting test subjects as part of experiments into mind control and interrogation techniques. These studies were unethical and caused psychological harm.

  • Around the same time, some psychiatrists began exploring the therapeutic potential of psychedelics like LSD and psilocybin. Researchers like Humphry Osmond believed these drugs could be helpful for patients when administered properly.

  • Early therapeutic studies found psychedelics reduced recidivism rates in prisoners and helped with alcoholism. However, these positive findings were overshadowed by the narrative that psychedelics caused psychosis.

  • Whether a psychedelic experience was positive or negative depended highly on factors like preparation, environment (“set and setting”) and psychological support during the experience. Therapeutic studies that included these elements saw better outcomes.

  • Pioneering researchers like Grof and Leary worked to establish protocols around set and setting that aimed to maximize benefits and minimize risks of psychedelic therapy. Their work still informs modern clinical trials exploring psychedelics.

  • The personality, suggestibility, and ability to “let go” of the person taking the psychedelic impacts their experience. Their expectations, mood, fears, and wishes also shape the experience.

  • The setting, including the physical environment (room, lighting, music), as well as the social/cultural context (legality, social acceptance) also influences the experience. A supportive setting promotes positive outcomes, while an antagonistic one can increase risk of difficult or “bad” trips.

  • Early psychedelic therapy stressed carefully preparing participants and providing a welcoming, relaxing space. Having trusted guides present during the experience helps reduce potential harms and allows difficult emotions to be processed constructively.

  • The psychedelic opens the person up emotionally and alters thinking, while the therapist guides them to get the most benefit. The drug and therapy work in combination to produce insights and neurological changes.

  • The therapist acts as a non-intervening guide, allowing the person’s own wisdom and insights to emerge. They provide support through any difficult parts and help integrate the experience after.

  • Therapy involves thorough pre-session preparation, monitoring the experience while allowing self-guided insights, and a follow-up integration session to understand and apply what was learned.

  • Psychedelic therapy typically involves preparation, drug treatment, and integration sessions after to process the experience.

  • MDMA therapy often involves 1-3 therapy sessions before using MDMA, followed by 1-3 drug sessions and longer term integration.

  • Ketamine therapy usually has 11 total sessions including 4 with ketamine.

  • Ayahuasca retreats commonly have 2-4 ceremonies over 8 days. Ibogaine retreats similarly have 2 ceremonies.

  • Music plays a central therapeutic role during psychedelic experiences by shaping emotions, thoughts and imagery. Playlists are designed to support different phases of the psychedelic journey.

  • Meditation and mindfulness may enhance psychedelic therapy effects and help integration. Some research combines psychedelics with spiritual/meditation training.

  • Psychedelic therapy draws from indigenous healing practices but also faces ethical questions around cultural appropriation, protecting origins and traditional ways of use. Protecting habitats is important as psychedelics enhance nature connection.

  • Therapists must maintain strict ethical boundaries, and any violation could undermine positive therapy outcomes even if not the study results themselves.

  • Founder of Alcoholics Anonymous, Bill Wilson, underwent the “Belladonna Treatment” in the 1930s for his alcoholism, which involved controlled substances and withdrawal. He had a profound psychedelic experience that led him to stop drinking completely.

  • Psychedelics are now being researched as a potential treatment for substance addictions like alcohol, tobacco, heroin, and cocaine. Addiction is a major health problem that is very difficult to overcome through willpower alone.

  • Staying abstinent from an addiction after treatment is challenging. Relapse is common when recovering addicts return to their old environments and social circles. Better medical treatments could help improve outcomes.

  • Early research shows psychedelics may be effective for treating addictions. Their ability to induce mystical-type experiences could help people find new perspectives to overcome substance dependencies. If proven safe and effective through clinical trials, psychedelic therapy could become an important new tool for treating conditions like alcoholism.

  • Psychedelic therapies show promise for treating addiction by helping people gain a “bigger picture” perspective beyond their addiction and enabling lasting behavioral changes to support recovery.

  • Studies from the 1950s and 1960s found that a single dose of LSD was twice to three times more effective at reducing alcoholism relapse rates compared to other existing treatments. This hidden history was suppressed when LSD was banned.

  • More recent research replicates these findings, showing psychedelics can successfully treat addictions like tobacco, heroin and other substances. For example, one study found psilocybin with CBT helped 80% of hardcore smokers quit long-term.

  • Psychedelics may work by disrupting deep-seated addiction memories through their “whole-brain” effect, giving people a way to break the cycle of compulsion. They also foster new perspectives that enhance behavioral therapies for sustained recovery.

  • If psychedelic therapies perform as well in real-world practice as initial studies suggest, they could significantly reduce addiction rates and save millions of lives by helping people overcome even difficult-to-treat addictions.

Here are the key points about rugs that can potentially cure addiction:

  • Psychedelic drugs like ketamine, psilocybin and MDMA work by disrupting the dysfunctional brain processes underlying addiction. Specifically, they may disrupt overactive links between the brain’s drive/motive and decision-making systems.

  • This allows the prefrontal cortex, the brain’s chief decision maker, to regain control over behavior and choices. It provides an opportunity for new, non-addicted patterns of thinking to take hold.

  • Studies have shown ketamine, psilocybin and MDMA can significantly reduce relapse rates and promote long-term abstinence from alcohol when combined with psychotherapy.

  • Ketamine therapy was pioneered by Dr. Evgeny Krupitsky in Russia in the 1980s-1990s, showing 50% long-term abstinence rates. Newer studies like Celia Morgan’s KARE trial are replicating these results.

  • Psilocybin studies by Michael Bogenschutz found a single dose significantly reduced heavy drinking days long-term for alcohol dependence. A larger trial in 2022 found around 50% abstinence rates after 8 months.

  • MDMA may work by suppressing excessive emotional drives and fear/anxiety that drive addiction, restoring brain balance. Ben Sessa used it to help trauma patients overcome substance abuse issues.

  • More research is still needed but these promising results suggest certain psychedelics have the potential to powerfully and durably reshape dysfunctional thought patterns underlying addiction when combined with psychotherapy.

  • PTSD causes people to relive traumatic memories and emotions, as reminders trigger the exact feelings from the original event. Many use drugs and alcohol to self-medicate and suppress trauma.

  • As victims of trauma get older, society shifts from viewing them as victims to treating them as criminals for their substance use.

  • There is evidence MDMA can help people with PTSD when used alongside psychotherapy. Sessa conducted the world’s first study using MDMA therapy for addictions.

  • The Bristol Imperial MDMA in Alcoholism (BIMA) study used MDMA-assisted therapy for alcoholics. After 9 months, the majority were abstinent compared to standard therapy alone. Some were able to drink moderately after therapy.

  • The study found MDMA had no adverse health effects on alcoholics, who are at higher risk. It also did not increase negative moods in these vulnerable individuals. In summary, the study provides preliminary evidence that MDMA-assisted therapy may effectively treat addiction by addressing underlying trauma. However, more research is still needed.

  • In the 1970s and early 1980s, MDMA was used therapeutically in psychotherapy in the US, with around 500,000 estimated doses used. Therapists found it reduced anxiety and promoted empathy, helping patients open up about difficult issues and memories.

  • However, recreational use of MDMA as a party/club drug also increased in the early 1980s. The DEA aimed to ban it, but therapists fought this to allow medical research.

  • Despite two court rulings against the DEA, MDMA was placed in Schedule 1 in 1985, banning its medical and therapeutic use. This led to a global ban by the UN.

  • In the 1990s, some therapists in Switzerland continued using MDMA illegally in therapy due to its perceived benefits, despite national bans.

  • Rick Doblin and MAPS have worked since the 1980s to advocate for MDMA research and its therapeutic potential, sponsoring clinical trials that have shown promise in treating PTSD. This could lead to approvals in the US, Canada and other countries.

  • Dr. Marcela Ot’alora Fischer held group therapy sessions on weekends using MDMA and LSD to treat clients she considered “stuck.” She used a psycholytic approach with repeated low doses over many sessions, rather than high doses a few times. She treated nearly 100 people over many years.

  • Fischer was arrested in 2009 after a patient blamed her for their marriage breaking up. At her trial, Fischer argued MDMA and LSD were psycho-integrative substances, not recreational drugs. She received a fine and suspended sentence.

  • MDMA is being studied for its potential to help people process trauma by reducing activity in the emotional and fear centers of the brain and increasing communication between areas involved in stress and memory formation. This may allow traumatic memories to be safely reprocessed.

  • Studies have found MDMA therapy can lastingly reduce PTSD symptoms even years later. It involves preparatory and integration sessions alongside non-directive MDMA sessions, where traumatic material emerges naturally. Research is exploring similar potential for other psychedelics like psilocybin.

  • The study used functional MRI to scan participants’ brains while recalling memories (3 good, 3 bad) under the effects of MDMA and a placebo.

  • They found memories were rated as more positive and vivid under MDMA compared to placebo. Bad memories were equally vivid but less negatively weighted.

  • This suggests why MDMA may help PTSD by dampening negative emotional responses to traumatic memories.

  • Memories have both a factual and emotional component stored in different brain regions. MDMA seems to reduce emotional reactivity specifically.

  • One participant with prior PTSD said MDMA allowed deeper processing of trauma memories in a way previous therapy did not, though this is not a clinical recommendation to take MDMA without therapy.

  • Future research is exploring MDMA for other anxiety disorders like social anxiety in autism and studies are planned for conditions like anorexia and addiction where underlying trauma may play a role.

  • Aldous Huxley took psilocybin mushrooms (also known as “moksha-medicine”) on his deathbed to ease his passing and die peacefully. His wife Laura facilitated this based on ideas Huxley wrote about in his book Island.

  • According to Laura’s account, the psilocybin put Huxley in a state of “complete bliss and love” and he died in a “serene and beautiful” way.

  • Laura felt this example demonstrated that Huxley’s vision in Island of using psychedelics for various beneficial purposes, including at the end of life, were plausible and not just science fiction.

  • Recent research has explored using psychedelics like LSD and psilocybin to help terminally ill patients deal with anxiety, depression and existential distress from their diagnosis. Studies show it can improve mood and quality of life.

  • Psychedelics may help near-death through antidepressant effects but also by triggering mystical/spiritual experiences that give a sense of interconnectedness and that death is a transition rather than end, easing existential fears. This can occur through ego dissolution or out-of-body experiences on psychedelics.

  • Researchers at Imperial College London studied the psychedelic drug DMT (active ingredient in ayahuasca) and its effects on the brain using fMRI scans. They gave participants intravenous injections of DMT to allow enough time for brain imaging during the trip.

  • Many participants reported profound mystical experiences on DMT like feelings of oneness/connection, encountering entities or other dimensions, sensing supernatural forces like love or God. Improvements in mood and outlook lasted for some after the acute effects wore off.

  • The researcher believes mystical experiences emerge from brain changes under psychedelics, but the exact content of experiences cannot be fully explained. While brain imaging shows altered connectivity, personal experiences cannot be objectively proven or disproven.

  • Some participants described encountering intelligent entities or passing through wormholes/doors to other universes during DMT trips. While these cannot be proven, the profound nature of the experiences felt more real than normal consciousness.

  • The researcher takes an agnostic view, acknowledging we have much to learn about consciousness and its relationship to mystical experiences. While they originate in the brain, the possibility of contact with external realities cannot be ruled out. Careful scientific study of psychedelics may provide insights.

  • Researchers gave study participants two doses of 20mg of DMT intravenously to scan their brains and detect any brain activity correlated with experiences of seeing “entities”. Analysis is ongoing.

  • Near-death experiences (NDEs) resemble DMT experiences like feeling out of body or communicating with entities. One hypothesis is that a spike in endogenous DMT at death causes NDEs. However, a scientific analysis showed the amount of DMT produced in the brain is too low to cause psychedelic experiences.

  • A study comparing DMT experiences to NDEs found considerable overlap, especially in ego dissolution and mystical experiences. NDEs had more religious and out-of-body elements.

  • Mystical experiences have been linked to improved well-being and personality changes like increased openness, extroversion, and conscientiousness. Ego dissolution, which involves the posterior cingulate cortex shutting off, may facilitate mystical experiences.

  • Breakdown of the default mode network, which defines the ego, is strongly associated with mystical experiences on psychedelics based on brain imaging studies.

  • The content of psychedelic or dream experiences is culturally determined, shaped by a person’s background and expectations.

  • Indigenous Amazonian people who take ayahuasca often report visions of animals like jaguars and serpents that are part of their culture/religion. Western users report aliens, spaceships, etc. reflecting modern sci-fi influences. Christians see images from religious art like Christ or distant churches.

  • Taking psychedelics can induce spiritual or religious experiences in believers by enhancing feelings of transcendence, presence of something beyond oneself. The “Good Friday Experiment” found psilocybin reliably induced profound religious feelings in trainee priests.

  • Non-drug means to mystical experiences like meditation may work by suppressing regions of the brain like the default mode network, as psychedelics do. They give access to unusual states that can strengthen religious belief.

  • For most, psychedelics are an easy way to access these insights by disrupting habitual patterns of thinking formed since childhood, letting novel experiences emerge that some interpret mystically or as contacting God.

  • The person began excessively sweating day and night from their hands, face, feet and back. They were also losing hair rapidly, with pillows covered in hair every morning.

  • Their behavior changed as well - they lacked emotional intelligence and vocabulary to effectively communicate with their partner, leading to frustration on both sides and arguments. Their relationship ultimately broke down, which further traumatized them.

  • Returning to psychotherapy and trying different antidepressants did not help. Two friends who had positive ayahuasca experiences in Peru recommended they try it.

  • They took a two-week holiday from work and spent 10 days alone in a simple hut deep in the Peruvian jungle, an hour walk from the nearest village. A shaman visited them twice to administer ayahuasca.

  • During the ayahuasca experiences, they had visions of an old woman spirit guide teaching them to respond with compassion rather than anger/violence to challenges from their past. This helped heal the trauma from their military experiences.

  • Upon returning home, they started an organization to help veterans access psychedelic treatments, and are conducting research studies on their potential benefits for PTSD, traumatic brain injuries, and other conditions.

  • Cluster headaches are severe, recurrent headache attacks that often occur at night. Existing treatments are often not effective.

  • Studies have found that micro- or sub-hallucinogenic doses of psychedelics like psilocybin taken every few days can not only treat cluster headache attacks but lead to long-lasting remission. However, psilocybin can also potentially cause headaches, so caution is needed.

  • The first clinical trial of psilocybin for cluster headaches showed a 30% reduction in attack frequency in 10 patients. One patient had complete remission for three weeks. Alternative treatments like LSA extracted from morning glory seeds are also used due to difficulty accessing psilocybin given its illegal status.

  • Psychedelics may treat pain by reducing inflammation, disrupting overactive pain circuits in the brain, and promoting neuroplasticity to allow the brain to reorganize pain networks. Research is underway but prescription is not yet possible given psilocybin’s illegal status.

Here is a summary of the key points about evidence related to psychedelic therapies for various mental health conditions:

  • Anorexia nervosa: Several studies are exploring psilocybin-assisted therapy to disrupt rigid thinking patterns and help with recovery process. Preliminary findings show promise.

  • OCD: Early psilocybin studies in 2006 showed reductions in symptoms lasting over 24 hours. Current trials replicating this work. Participants report symptoms dropping away after psychedelic experiences.

  • ADHD/ADD: Counterintuitively, microdosing LSD may help attention where stimulants are the standard treatment. Early research found low non-psychedelic LSD doses improved attention in healthy volunteers. Self-medication with microdoses is also reported.

  • Binge eating disorder: Tryp Therapeutics is testing their version of psilocybin which preliminary data shows an 80% reduction in binge episodes over 4 weeks.

  • The evidence rating for supporting psychedelic therapies ranges from 3-5 out of 10, with more studies still needed but promising early results, particularly for conditions like anorexia, OCD and binge eating disorder where rigid thought patterns play a role.

Here is a summary of the provided text:

  • Professor Philip Asherson of King’s College London pioneered research into treating ADHD symptoms with cannabis, which seems paradoxical given cannabis’ association with impaired attention and focus.

  • Asherson’s research aimed to treat the excessive mind wandering and repetitive thoughts that commonly occur in ADHD patients. Both psychedelics and cannabis appear able to disrupt these rumination processes.

  • Short-term trials of psychedelics to treat ADHD symptoms have shown promise so far. A long-term trial of low-dose LSD for adult ADHD patients is currently underway to further explore the treatment potential.

  • Microdosing involves taking sub-perceptual doses of psychedelics like LSD or psilocybin, amounts too low to produce hallucinogenic effects but claimed to provide benefits like improved mood, focus, creativity and productivity.

  • James Fadiman popularized microdosing in his 2011 book and research collecting anecdotal reports, though large scientific studies are still limited due to legal barriers. Personal accounts suggest a variety of psychological, cognitive, physical and relationship benefits from microdosing.

  • The science is still unclear on whether and how microdosing truly works due to the lack of rigorous studies, but it remains a popular wellness practice based on reported individual experiences.

Here are the key points about microdosing risks and research from the passage:

  • Classic psychedelics like LSD and psilocybin act on the serotonin 2A and 2B receptors. Stimulating the 2B receptor long-term, like in the fen-phen diet drug, has been linked to heart valve problems. However, microdosing is unlikely to cause this due to its irregular, infrequent dosing regimen. No heart issues have been reported from long-term microdosing yet.

  • At full doses, psychedelics stimulate neuroplasticity and brain cell growth via the 2A receptor. It’s unclear if this happens with microdosing. Microdosing may potentially promote neuron growth and protect against brain issues like dementia.

  • Anecdotal reports of microdosing benefits are numerous but biased. Observational studies show microdosing may improve mood, reduce anxiety/depression, and enhance cognition, but these don’t prove causation.

  • Double-blind randomized trials are needed but difficult for microdosing. One lab study found no effects except short-term positive mood from a larger “midi” dose. Another found expected benefits but the expectations predicted the outcomes, suggesting a placebo effect.

  • Set/mindset and expectations strongly influence psychedelic experiences and outcomes. They appear to drive microdosing benefits observed in observational studies more than the drugs themselves based on current evidence. More research is still needed.

Here is a summary of key points from the text:

  • Researchers at Imperial College conducted a naturalistic trial of microdosing psychedelics that was placebo-controlled and randomized. Participants created their own placebo capsules and were given envelopes with QR codes telling them what to take on specific days.

  • The trial found no difference in psychological outcomes like well-being and mindfulness between those who microdosed and those who took placebos. This showed the expectation and belief in microdosing can produce as strong an effect as actually microdosing.

  • However, a separate lab study found small to medium doses of LSD did produce effects on mood and attention beyond placebo. The text questions if the doses in this study can truly be considered microdoses.

  • Research on children participating in ayahuasca ceremonies in Brazil found no cognitive impairments and lower rates of anxiety/depression compared to controls. This raises questions about potential benefits of low-dose psychedelics for adolescent mental health.

  • The author was involved with advising the UK government on drug classification and found politicians often made decisions for political rather than scientific reasons. MDMA was classified as highly dangerous despite evidence it was less harmful than other Class A drugs. This influenced harsh drug policies.

The scientist felt frustrated that their scientific work providing evidence about relative drug harms was being ignored by the government in favor of policies aimed at appeasing right-wing media. Banning substances often leads to more dangerous illegal alternatives emerging.

The scientist published an article comparing the dangers of riding horses to taking ecstasy to educate people about judging relative harms. However, the home secretary shouted at them for comparing a legal and illegal activity. Their speech calling for an evidence-based drug classification system that reflects actual harms was also not accepted, and the new home secretary sacked them for campaigning against government policy.

After being sacked, the scientist continued their work measuring drug harms through their charity. Studies showed alcohol and tobacco to be more harmful than other drugs like LSD, mushrooms and ecstasy. While MDMA can have risks like overheating, those risks are often due to illicit and uncontrolled settings rather than the drug itself in regulated conditions. The scientist felt the facts about relative drug harms were being ignored for political reasons.

  • One of the key authors providing evidence that MDMA is neurotoxic was George Ricaurte of Johns Hopkins. He led studies on monkeys and claimed MDMA caused brain damage.

  • However, Ricaurte’s 2002 monkey study had to be retracted after it emerged the drug given was actually methamphetamine, not MDMA. Methamphetamine is known to be neurotoxic.

  • Arguments were made in court in 2010 (ACLU v. US) that the evidence for MDMA neurotoxicity is flawed and inconclusive. Professor Val Curran argued animal studies used much higher doses than typical human use, and human studies have small effects and cannot distinguish MDMA effects from other drug/lifestyle factors.

  • More recent studies have not found clear evidence of neurotoxicity from MDMA doses equivalent to human use. While MDMA may acutely affect serotonin levels, imaging studies suggest any effects normalize over time. Studies have not shown lasting problems with mood, cognition or sleep quality from MDMA use.

  • In summary, while early studies raised concerns, more rigorous recent work has not proven that typical MDMA use causes lasting brain damage or cognitive impairment in humans. The evidence for neurotoxicity is inconclusive.

  • The article argues that studies on MDMA (ecstasy) have not properly separated light and heavy users. Most meta-analyses have failed to find clinically significant differences between ecstasy users and controls. There is also evidence of publication bias.

  • The one effect that may have some evidence is an extremely small impact on memory. But even this effect could be due to recreational drug use in general rather than just MDMA. Follow-up studies found little to no memory impairments in former ecstasy users who had abstained for over a year.

  • Studies comparing MDMA users to non-users on memory tasks found scores were incredibly close, with MDMA users remembering only half a word less on average. However, the way the data was measured and analyzed found a “significant” difference, though the clinical relevance was limited.

  • There is now much less concern about MDMA neurotoxicity. Any effects do not appear to persist after stopping use, and large numbers of people have not developed disorders like depression from putative serotonin depletion.

  • When taken carefully as part of therapy, evidence shows MDMA can be safe. But it may not be suitable as a regular medication due to risks of frequent or heavy use.

  • The main risks come from high doses, mixing with other drugs, adulterated substances, inexperience, and environmental risks like overheating at festivals. Drug testing services can help address some of these risks.

Here is a summary of the key points about psychedelics and addiction/safety from the provided text:

  • Psychedelics like LSD, psilocybin and MDMA are not considered addictive according to standard definitions of addiction. They do not cause physical dependence or withdrawal symptoms.

  • Tolerance to psychedelic effects develops very rapidly, within a few days, so continued use does not increase effects and people cannot become dependent on them to function.

  • Animal studies also show psychedelics are not self-administered, indicating low addiction potential.

  • Psychedelics may actually have anti-addictive properties and are being studied for treating addiction to substances like opioids, cocaine, alcohol etc.

  • Ketamine and MDMA have some addiction potential but are generally less addictive than substances like cocaine, alcohol. Dependence on them is more psychological than physical.

  • Clinical use of psychedelics and ketamine eliminates addiction risk due to controlled dosing and number of treatments.

  • Risks of psychedelics arise more from black market circumstances of use rather than the substances themselves. Proper medical use can help manage risks.

  • Caution is advised for certain at-risk groups and contexts like those with heart/health issues or at heights. Needle use for any drugs is also not recommended.

  • MDMA doesn’t typically lead to dependence in the way other drugs do, as people don’t feel a persistent desire to use it outside of social contexts. However, around a quarter of MDMA users have reported some dependence symptoms according to one survey, with young women most likely.

  • Studies have found little evidence that psychedelic drug use increases risks of mental health issues like anxiety, depression or psychosis. However, certain vulnerable individuals or those with preexisting mental health conditions may be at higher risk of negative reactions.

  • Set and setting are very important - traumatic experiences under psychedelics from activities like CIA testing programs showed severe negative consequences. Safely guided therapeutic contexts seem to minimize risks.

  • Bad trips can happen due to factors like dose, expectations, environment, but attributing it simply to “bad acid” is an oversimplification. Risks of suicide attempts are very rare but may occur in vulnerable individuals. Flashbacks are rare for most but possible. Microdosing psychedelics is now being explored as a potential treatment for various conditions.

Here are the key questions and conclusions outlined in the passage:

  • Will psychedelic therapy, combined with psychotherapy, transform medicine in the same way psychedelics transformed society in the 1960s? Clinical trials show promise but more research is still needed.

  • Can real-world evidence (RWE) trials using psychological data from each patient, rather than placebo-controlled randomized trials, help accelerate knowledge about psychedelic therapies for resistant mental health conditions like depression and PTSD? Australia is pursuing this model.

  • Will monitoring actual patient outcomes through a centralized registry in Australia provide better data on psychedelic therapies than randomized trials alone? Statistical methods can analyze this real-world data.

  • How can access to therapies be expanded to help millions suffering from global crises like wars and disasters, when for-profit drug development moves slowly? Charities providing psychedelic therapies more affordably could help address this challenge.

  • In order for essential research and expanded access to continue, psychedelic drugs need to be rescheduled and taken out of the most restricted categories at both national and international levels like the WHO and UN. Campaigns are pushing for this change.

So in summary, the passage outlines key open questions around further establishing psychedelic therapies as legitimate medicine and expanding equitable global access, as regulations and research methods continue to evolve.

  • The UN has yet to approve medical cannabis and will likely try to block psychedelics as medicine due to their cautious stance. However, more governments are acting independently and progressing drug laws like Portugal, Netherlands, and Canada have with decriminalization.

  • The author supports the Latin American view that naturally growing plants/mushrooms should not be illegal in their home countries. They argue the UK ban on magic mushrooms is absurd based on picking vs possession rules.

  • If natural substances are sold, they should have regulated markets like in Netherlands and some US states, with labeling of potency, dosing details, and content thresholds. Indigenous peoples where substances originate should be compensated.

  • If synthetics like LSD and MDMA were legalized, a licensed shop model with smart card access control could provide oversight to avoid vulnerable people misusing them.

  • Non-psychedelic therapies being developed by the US may avoid legal issues but the author suspects they won’t have as good effects since psychedelic experiences seem important therapeutically.

  • Looking ahead, the author expects refined psychedelic psychotherapy as understanding and evidence grows in the next 10 years, potentially helping more internalizing conditions and those like dyspraxia. Maintaining treatment results long-term also needs exploration.

Here is a summary of the key points from the article:

  • The article discusses the history of LSD research in the 1950s-1970s. It explores how LSD became popularly known as a recreational drug of the counterculture movement in the 1960s, obscuring its earlier therapeutic uses.

  • In the 1950s, LSD was seen as having potential medical applications for treating mental illnesses like alcoholism. Researchers in the UK and US began conducting psychotherapy studies using LSD as an adjunct. Prominent researchers included Ronald Sandison in the UK.

  • In the 1960s, as recreational use of LSD spread, it became more difficult to conduct therapeutic research due to legal and safety concerns. The US government also grew wary of LSD’s association with anti-war and counter-culture movements.

  • By the 1970s, LSD and other psychedelics had been declared illegal and therapeutic research came to a standstill. The counterculture adoption of LSD as a party drug helped shape its stigma that persists today.

  • However, renewed scientific interest in recent decades has found LSD and other classic serotonergic psychedelics may have therapeutic potential for conditions like addiction, depression, and anxiety. More research is still needed to fully understand their risks and benefits.

In summary, the article provides historical context on the promising early LSD psychotherapy research in the 1950s-60s and factors that later limited its medical use due to the drug’s rise in recreational contexts.

Here is a summary of the paper:

  • The paper reports on a case study of a patient who used psilocybin mushrooms in a ritualistic context to gain insight into his depression and enhance his spiritual well-being near the end of his life.

  • The patient was a 73-year-old man with advanced colon cancer and treatment-resistant depression. He decided to incorporate psilocybin mushrooms into a spiritual ritual with the hope of improving his mental state.

  • He took psilocybin while focusing on letting go of attachment to the physical world and connecting with spiritual energies. He reported profound mystical and visual experiences that helped him find meaning and acceptance.

  • In follow-up interviews after the experience, the patient said his depression and anxiety were greatly reduced. He felt at peace and that the psilocybin experience provided comforting spiritual insights as he approached the end of his life.

  • The case study provides an example of how psilocybin, when used properly, may help some terminally ill patients find meaning and mental well-being at life’s end by facilitating mystical or spiritual experiences. However, more research is needed to fully understand risks and benefits.

This summarizes a number of key points regarding the regulation and use of MDMA in the UK:

  • MDMA was made a Class A drug in 1977 but reports in the 2000s advocated reclassifying it based on evidence it was less dangerous than other drugs. However, experts who did so were dismissed by the government.

  • MDMA deaths increased in the 2010s due to stronger more dangerous pills being sold as MDMA. Purity has declined while strength/doses have increased, complicating regulation policy.

  • Clinical research found MDMA can be used safely and effectively as an assisted therapy for various conditions like PTSD. Despite this, regulatory barriers have stalled further therapeutic research in the UK.

  • Drug checking services have provided useful safety information on adulterants in pills but faced funding difficulties. Harm reduction strategies around things like pill content are constrained by legal barriers.

  • Experts argue the current legal classification and policy approach to MDMA in the UK is mismatched with scientific understanding and may unintentionally worsen public health outcomes versus a regulated model. However, political will for reform has been lacking.

Here are the key points from the summaries:

  • MDMA (ecstasy/molly) is a psychoactive drug primarily known for its empathogenic and entactogenic effects. It works primarily by increasing the activity of the neurotransmitters serotonin, dopamine, and norepinephrine in the brain.

  • It was initially investigated medically in the 1970s for uses such as anxiety reduction and couples therapy but was restricted in 1985 over safety concerns.

  • It remains illegal for recreational use but is being investigated again for potential therapeutic uses in treating conditions like PTSD, social anxiety in autism, and alcohol use disorder. Clinical trials have shown promising results so far.

  • Potential risks from recreational use include increased heart rate/body temperature, dehydration, potential for addiction in some, and potential for serotonin depletion/neurotoxicity from frequent/high doses. However, the scientific evidence on risks is mixed.

  • It shares pharmacological properties with stimulants like methamphetamine but is considered less harmful than other illegal drugs like heroin or cocaine. There are calls for its legal status to be reassessed and for a regulated legal market rather than a ‘war on drugs’ approach.

  • Overall it describes the pharmacology of MDMA, reviews past and current research on its medical applications and therapeutic potential, discusses debates around its legal status and harms, and summarizes the current state of knowledge on the risks and safety of MDMA use.

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