Preface to Psychedelic Tricksters:
A True Secret History of LSD
by David Black
JUNE 3, 2020



Preface to Psychedelic Tricksters:

 A True Secret History of LSD by David Black

BPC Publications. London 2020 

Preface

Like atomic power and artificial intelligence, lysergic acid diethylamide (LSD) was discovered in the closing years of World War Two. Since then, atomic bombs and computers have been the constant source of fears that combined they might bring about the destruction of humanity. LSD has aroused similar fears. Albert Hoffman, the Swiss chemist who discovered its effects in 1943, likened the LSD trip to an ‘inner bomb’. He warned that, if improperly used and distributed, LSD might bring about more destruction than an atomic detonation. But it has also been argued that, if properly used and distributed, LSD use might actually change people’s consciousness for the better and help to prevent nuclear war. Professor David Nutt, who sat on the British Labour government’s Advisory Committee on the Misuse of Drugs until he was sacked in 2009, argues that the study of psychedelics is essential for understanding the nature of consciousness itself:

‘This is core neuroscience. This is about humanity at its deepest level. It is fundamental to understanding ourselves. And the only way to study consciousness is to change it. Psychedelics change consciousness in a way that is unique, powerful, and perpetual – of course we have to study them’.

As is well known, in the 1950s and early ‘60s the US Central Intelligence Agency used LSD, in secret and illegal experiments, on unwitting subjects. The CIA did so according to Cold War logic: if the Russians could work out how to use LSD in bio-chemical warfare — or in ‘brain-washing’, as a ‘truth drug’, or even as a ‘Manchurian Candidate’ — then the USA needed to work it out first.

In 1953, the CIA launched a top-secret ‘mind-control’ project, code-named MK-Ultra. The CIA’s assets in the US medical profession ‘officially’ labelled LSD as ‘psychosis-inducing drug’, only of use in psychiatric analysis and research. Many CIA officers, contractors and assets however, became enthusiastic trippers themselves, in full knowledge that LSD could produce atrocious as well as enchanting hallucinations. Knowing the secrets of LSD, they thought of themselves as a kind of anti-communist spiritual elite who, unlike the US citizenry at large, were ‘in the know’.

But by the end of the 1950s, with no sign of the Russians contaminating the water supply with LSD, there were plenty of signs in the United States that the psychedelic experience was escaping its captors. Some of the researchers in American hospitals – who had little awareness that their work was being secretly sponsored by the CIA — realised that LSD had ‘spiritual’ implications, i.e. for developing an ‘integrative’ enlightened consciousness, conducive to visionary creativity. These researchers stressed the importance of ‘set and setting’ in properly supervised LSD sessions. The English scholar, Aldous Huxley, who took his first LSD trip in 1955, related in his essay Heaven and Hell the hallucinogenic experience to the visionary works of William Blake:

‘Visionary experience is not the same as mystical experience. Mystical experience is beyond the realm of opposites. Visionary experience is still within that realm. Heaven entails hell, and “going to heaven” is no more liberation than is the descent into horror. Heaven is merely a vantage point, from which the divine Ground can be more clearly seen than on the level of ordinary individualized existence’.

Huxley, though an advocate for psychedelic drugs, wanted them strictly controlled. In contrast, Timothy Leary, who first took LSD in December 1961, became the ‘guru’ of psychedelia as LSD ‘escaped’ into the counter-culture of the 1960s. The ‘escape’ has been the subject of conspiracy theories which have been weaponised in today’s so-called Culture Wars. According to one widely-held view, the entire psychedelic counter-culture of the 1960s was engineered by the CIA as part of a plot by some secret global elite bent on mass mind-control. For elements of the Right, the psychedelic counter-culture undermined ‘traditional values’ such as patriarchy, nationalism and subservience to authority. On the Left, some see the 1960s hedonism of ‘Sex, Drugs and Rock’n’Roll’ as having been a distraction from politics. The theory, as it has spread, has thrown in extra villains for good measure: satanists, MI6, the psychiatrists of the Tavistock Institute, the Grateful Dead, and Theodor Adorno of the Frankfurt School of Critical Theory, etc, etc.

In truth, the extent of the CIA’s involvement in the psychedelic counter-culture of the 1960s has always been difficult to determine; not least because Sidney Gottlieb, head of MK-Ultra, illegally destroyed the project’s operational files in 1973. Nonetheless, some leading figures of the counter-culture, such as Timothy Leary, can hardly be discussed without reference to the CIA – not least because Leary himself had so much to say about it. In the present work, whilst I pay only scant attention to conspiracy theories, I make no apologies for investigating, where necessary, real conspiracies.

The underground networks of acid producers and distributors on both sides of the Atlantic were described after their downfall in the nineteen-seventies in such terms as ‘Hippie Mafia’ or ‘Microdot Gang’: so out of their heads that they didn’t know any better; or were ‘only in it for the money’; or were tools of organised crime and/or state agencies. In an earlier ebook I noted that nearly everyone involved – the psychedelic revolutionaries, the financiers, intelligence and anti-drugs agencies, CIA-sponsored scientists and researchers – operated to a greater or lesser extent outside of accepted standards of ‘legality’, or didn’t even recognise them; hence the title: Acid Outlaws: LSD, Counter-Culture and Counter-Revolution. But although the term ‘outlaw’ certainly fits many of people in this study, it doesn’t fit all of them by any means. Stephen Bentley, ex-undercover police officer and author of Undercover: Operation Julie – The Inside Story, takes exception to my use of the term ‘questionable legality’ regarding of some of the surveillance methods he and his colleagues used:

‘Questionable by who? Illegal – mostly not… Yes, I smoked a lot of hash… and did some cocaine. Technically, that was illegal. Tell me what I was supposed to do given I was undercover. I wasn’t Steve Bentley. I was ‘Steve Jackson’ – wild, carefree, giving all the impression I was a dealer. I’m now 72 years’ old. I don’t care for the historical revisionism applied to Operation Julie recently. It was a highly successful and unique police investigation carried out professionally under difficult circumstances’.

On my reference to the ‘ham-acting of drunken undercover officers’, Bentley retorts:

‘Maybe you should try living a lie for the best part of a year; doing things alien to you; becoming a different person. Those who know will scoff at the thought of it being an act. It’s not. You become someone else – believe me’.

The point is, I concede that although Stephen Bentley mixed with ‘acid outlaws’ and behaved like one when he was infiltrating them in north Wales in the 1970s, he certainly wasn’t one himself. Steve Abrams – who inspired me twenty years ago to write about this subject in the first place – wasn’t an outlaw either. He is described in an obituary in Psychedelic Press – quite accurately — as a ‘psychedelic trickster’. Many of the leading players who feature in this tale were certainly outlaws at various times but primarily they were tricksters. In Carl Gustav Jung’s definition of archetypes, the ‘Trickster’ surfaces in many stories in mythology, folklore and religion. More generally, anthropologists studying indigenous cultures in various parts of the world identify the trickster with cunning crazy-acting animals such as the fox or coyote, shape-shifting gods such as Loki in Norse mythology and rustic pranksters in human form. In the literature of Greek antiquity, Prometheus, the son of a Titan, tricks the gods with his buffoonery and steals fire from heaven for the benefit of human kind, for which he is severely punished by Zeus. As the historian of religion, Klaus-Peter Koepping, puts it:

‘In European consciousness Prometheus becomes the symbol for man’s never-ceasing, unremitting, and relentless struggle against fate, against the gods, unrepentingly defying the laws of the Olympians, though (and this again shows the continuing absurdity) never being successful in this endeavor, which, however, is necessary for the origin of civilized life (the ultimate paradox of rule breaking as a rule)’.

Like fire, psychedelic drugs can be dangerous as well as beneficial. In various ways the tricksters who feature in this book tended to believe that their antics were beneficial to humanity as well as themselves; and in most cases had to suffer the consequences of their actions. CIA MK-Ultra chief, Sidney Gottlieb, believed that that his immoral and dishonest actions were outweighed by his patriotism and dedication to science, but his reputation has been posthumously trashed (a biography by Stephen Kinzer calls him as ‘the CIA’s Poisoner-in-Chief’). On the ‘other’ side, the reputation of Timothy Leary, who likewise believed he was acting as a patriot and saviour of civilisation, has shape-shifted from brilliant scientist to mystical guru, wanted criminal, wild-eyed revolutionary, renegade informer and finally self-aggrandising ‘showboater’.

I sent a copy of the previous book to Tim Scully, a most significant actor in the events unfolded in this story. Scully is a meticulous researcher (he is compiling a history of LSD production in the US) and, as it turns out, a very reliable witness. Scully, born 1944, was in 1966 taken on as apprentice to the famous LSD chemist Owsley Stanley (AKA Bear Stanley). After Owsley withdrew from LSD production following a bust of his tableting facility in December 1967, Scully was determined to continue. After making LSD in successive laboratories in Denver, Scully began to work with fellow psychedelic chemist, Nick Sand (another trickster). Their collaboration led to the establishment in November 1968 of a lab in Windsor, California, which ultimately produced well over a kilo (more than four million 300 μg doses) of very pure LSD that became known as Orange Sunshine. Scully, in writing to me, pointed to a number of errors in my writings regarding events in the USA. Generously, he provided me with a lot of very useful information: firstly, on how underground LSD production was organised in the United States in the 1960s; secondly, on the relations between the American LSD producers in the United States, their collaborators in Great Britain, and the ‘Brotherhood of Eternal Love’; and thirdly on the alleged CIA asset, Ronald Stark, who Scully knew and did business with. With further research and fact-checking I realised that none of the previous books on the subject (including mine) have accurately covered these three issues. I hope – whilst making no claim to have written anything like a comprehensive or definitive history of the LSD underground – that this one does.

Contents

1 – MK-Ultra: The CIA’s ‘Mind Control’ Project

Sorcery

Midnight Climax

Heartbreak Hotel: the Death of Frank Olson

Human Ecology: an MK-Ultra Front

Personality Assessment

2 – How the CIA Failed the Acid Test

Magic Mushrooms

Harvard Trips

Timothy Leary and Mary Pinchot

‘Captain Trips’: Alfred Hubbard

Coasts of Utopias

3 – London Underground

Centre of the World

Psychedelic Situationists

The 1967 ‘Summer of Love’

4 – David Solomon and the Art of Psychedelic Subversion

Psychedelic Jazz

Acid Revolution

5 – Steve Abrams: E.S.P., C.I.A., T.H.C.

Parapsychology

Potboilers

SOMA, Solomon and Stark

6 – The New Prohibition versus the Acid Underground

Psychedelic Alchemy

Owsley and the Grateful Dead

Heat

The Brotherhood of Eternal Love

Money Matters

Orange Sunshine

7 – The Atlantic Acid Alliance

Richard Kemp – Liverpool’s LSD Chemist

Tripping with RD Laing

8 – The British Microdot Gang and the Veritable Split

9 – The Downfall of the Brotherhood of Eternal Love

Ronald Stark and the Brotherhood

Takeover

Operation BEL

The Scully-Sand Conspiracy Trial

10 – Timothy Leary’s Reality Tunnels: One Escape After Another

Political Intoxication

Weather Underground: Stalinism on Acid

Armed Love

Hotel Abyss

Leary ‘Co-operates’

11 – Operation Julie: the Hunters and the Hunted

S.T.U.F.F.

The Chase

Showtrial

12 – The Many Faces of Ronald Hadley Stark

Busted in Bologna

Italy’s ‘Years of Lead’

The Red Brigades

Lebanon

Prison Wager

13 – Tricksters

14 – Acid 2.0: Redux or Recuperation?

The Barbarism of Pure Culture
Psychedelic Culture, Situationist Poetics and Films, Radical Politics, Working-Class History

http://thebarbarismofpureculture.co.uk/wp/preface-to-psychedelic-tricksters-a-new-secret-history-of-lsd-by-david-black/

SEE

LA REVUE GAUCHE - Left Comment: Search results for LSD 

 

Psychedelic psilocybin-assisted therapy reduces depressive symptoms in adults with cancer and depression

Clinical trial results support further study of this psychedelic substance, administered with psychological support from trained therapists, in affected patients

Peer-Reviewed Publication

WILEY

Results from a phase II clinical trial indicate that psilocybin, a hallucinogenic chemical found in certain mushrooms of the genus Psiloybe, may benefit individuals with cancer and major depression. Trial participants treated with psilocybin not only experienced a lessening of depressive symptoms but also spoke highly of the therapy when interviewed at the end of the trial. The findings are published by Wiley in two articles appearing online in CANCER, a peer-reviewed journal of the American Cancer Society.

By binding to a specific subtype of serotonin receptor in the brain, psilocybin can cause alterations to mood, cognition, and perception. Psilocybin is currently classified as a Schedule I drug—defined as having no accepted medical use and a high potential for abuse—and is not approved by the US Food and Drug Administration for clinical use. However, multiple randomized controlled trials have demonstrated the safety and potential efficacy of psilocybin-assisted therapy—which combines psilocybin with psychological support from trained therapists—to treat major depressive disorder. Additionally, ongoing research is looking into the use of psilocybin-assisted therapy for various other mental health conditions, such as anxiety, addiction, and post-traumatic stress disorder.

In this latest phase II open-label trial involving adults with cancer and major depression, 30 participants at Sunstone Therapies in Rockville, Maryland received a single 25 mg dose of synthesized psilocybin plus a 1:1 session with a therapist and group therapy support.

“This study was differentiated by its group approach. Cohorts of 3-4 patients were simultaneously treated with 25 mg of psilocybin in adjacent rooms open at the same time, in a 1:1 therapist:patient ratio. The cohorts had preparation for the therapy as well as integration sessions following the psilocybin session as a group,” explained lead author Manish Agrawal, MD, of Sunstone Therapies.

Participants enrolled had moderate to severe depression scores at baseline. After eight weeks of treatment, Dr. Agrawal and his colleagues observed that patients’ depression severity scores dropped by an average of 19.1 points, a magnitude that would indicate the majority no longer experienced depression. Furthermore, 80% of participants experienced a sustained response to treatment, and 50% showed full remission of depressive symptoms after one week, which was sustained for eight weeks. Treatment-related side effects such as nausea and headache were generally mild.

“As an oncologist for many years, I experienced the frustration of not being able to provide cancer care that treats the whole person, not just the tumor,” said Dr. Agrawal. “This was a small, open-label study and more research needs to be done, but the potential is significant and could have implications for helping millions of patients with cancer who are also struggling with the severe psychological impact of the disease.”

Dr. Agrawal is also the senior author of a second study led by Yvan Beaussant, MD, MSc, of Dana-Farber Cancer Institute that gathered input from patients in the trial during exit interviews. Participants described generally positive experiences. In terms of safety, they noted that being a part of the group calmed their fears and increased their sense of preparedness to engage in therapy. Regarding therapeutic efficacy, they felt that being connected to the group deepened and enriched their experience, ultimately contributing to their experience of self-transcendence and compassion for one another. Also, the use of both individual and group sessions was found to support the therapy in different ways. For example, the implementation of individual and group sessions allowed the therapy to remain an intimate introspective process while adding a sense of “togetherness” to it.

“As a hematologist and palliative care physician and researcher, it was profoundly moving and encouraging to witness the magnitude of participants’ improvement and the depth of their healing journey following their participation in the trial. Participants overwhelmingly expressed positive sentiments about their experience of psilocybin-assisted therapy while emphasizing the importance of the supportive, structured setting in which it took place,” said Dr. Beaussant. “Many described an ongoing transformative impact on their lives and well-being more than two months after having received psilocybin, feeling better equipped to cope with cancer and, for some, end of life.”

Before this intervention is implemented into clinical practice, additional studies should include larger numbers of patients, along with a control arm to compare its effects with other treatments or placebo. 

 

Additional information
NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. A free abstract of this article will be available via the CANCER Newsroom upon online publication. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com

Full Citations:
“Psilocybin-assisted Group Therapy in Patients with Cancer Diagnosed with a Major Depressive Disorder.” Manish Agrawal, William Richards, Yvan Beaussant, Sarah Shnayder, Rezvan Ameli, Kimberly Roddy, Norma Stevens, Brian Richards, Nick Schor, Heather Honstein, Betsy Jenkins, Mark Bates, and Paul Thambi. CANCER; Published Online: December 18, 2023 (DOI: 10.1002/cncr.35010). 

URL Upon Publication: http://doi.wiley.com/10.1002/cncr.35010  

“Acceptability of Psilocybin-assisted Group Therapy in Patients with Cancer and Major Depressive Disorder: Qualitative Analysis.” Yvan Beaussant, Elise Tarbi, Kabir Nigam, Skye Miner, Zachary Sager, Justin J Sanders, Michael Ljuslin, Benjamin Guérin, Paul Thambi, James A. Tulsky, and Manish Agrawal. CANCER; Published Online: December 18, 2023 (DOI: 10.1002/cncr.35024). 

URL Upon Publication: http://doi.wiley.com/10.1002/cncr.35024

Contact for Dr. Agrawal: Tracy Cheung/Chris Gardner/Andrew Stern, at SunstoneTherapies@consilium-comms.com

Contact for Dr. Beaussant: Nicole Oliverio, Senior Media Relations Specialist, Department of External Communications, at nicole_oliverio@dfci.harvard.edu, or +1 617-257-0454

About the Journal
CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online. Follow CANCER on Twitter @JournalCancer and Instagram @ACSJournalCancer, and stay up to date with the American Cancer Society Journals on LinkedIn.

About Wiley
Wiley is a knowledge company and a global leader in research, publishing, and knowledge solutions. Dedicated to the creation and application of knowledge, Wiley serves the world’s researchers, learners, innovators, and leaders, helping them achieve their goals and solve the world's most important challenges. For more than two centuries, Wiley has been delivering on its timeless mission to unlock human potential. Visit us at Wiley.com. Follow us on Facebook, Twitter, LinkedIn and Instagram.

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JOURNAL

Cancer

DOI

10.1002/cncr.35010 

ARTICLE TITLE

Psilocybin-assisted Group Therapy in Patients with Cancer Diagnosed with a Major Depressive Disorder

ARTICLE PUBLICATION DATE

18-Dec-2023

Trip or treat?

Scientists at the Medical College of Wisconsin make strides in designing non-hallucinogenic psychedelic treatments that may accelerate research on mental health benefits; research findings published in Nature Communications.

Peer-Reviewed Publication

MEDICAL COLLEGE OF WISCONSIN

 

IMAGE: 

SCIENTISTS AT THE MEDICAL COLLEGE OF WISCONSIN MAKE STRIDES IN DESIGNING NON-HALLUCINOGENIC PSYCHEDELIC TREATMENTS THAT MAY ACCELERATE RESEARCH ON MENTAL HEALTH BENEFITS; RESEARCH FINDINGS PUBLISHED IN NATURE COMMUNICATIONS.

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CREDIT: MEDICAL COLLEGE OF WISCONSIN

NEWS RELEASE

FRI, DEC. 15

 

Trip or Treat?

Scientists at the Medical College of Wisconsin make strides in designing non-hallucinogenic psychedelic treatments that may accelerate research on mental health benefits; research findings published in Nature Communications.

Milwaukee, Wis. – Dec. 15, 2023 – There is nothing magic about the recent increase in interest around the study of psychedelic drugs as potential treatments for patients suffering from a myriad of mental health conditions.

“The excitement follows the science,” says John McCorvy, PhD, assistant professor of cell biology, neurobiology and anatomy at the Medical College of Wisconsin (MCW). “The number of landmark studies continues to grow, and the potential has caught the attention of academia and the pharmaceutical industry.”

The legal status of psychedelic compounds slowed research progress to a crawl for decades before some studies began to garner regulatory approval in the early 2000s. Even in approved clinical trials, the hallucinogenic properties of these drugs lead to additional hurdles. Research participants need to take the substances under strict supervision in a clinical setting. Trained therapists monitor participants for a long time as the length of a hallucinogenic experience ranges from about four to 12 hours depending on the drug and the individual. The treatment can cause confusion and anxiety for some patients who do not respond well to hallucinations, underscoring the need for vigilant healthcare personnel. For those who have tolerated the drugs and associated hallucinations, however, promising studies have indicated that participants have experienced a substantial and sustained improvement in symptoms after taking a single dose. 

“We’ve seen double-blind, placebo-controlled trials with psilocybin where patients with major depressive disorder reported improved symptoms for months,” Dr. McCorvy says. “It is unheard of to get those kinds of results, especially without the patient having to take a pill every day.” Psilocybin is a naturally occurring psychedelic compound made by hundreds of types of fungi, often referred to as “magic” mushrooms.

As promising as these and other results may be, however, the legal and practical hurdles for scientists and would-be research participants continue to loom large. But what if you could remove the hallucinogenic properties of possible psychedelic treatments without reducing their therapeutic potential?

MCW scientists published results in Nature Communications in December 2023 from experiments investigating what causes a psychedelic compound to elicit hallucinogenic experiences and how this characteristic can be manipulated by drug designers to create new psychedelic treatments for depression.  

“There was no clear answer as to why a drug is hallucinogenic just based on chemical structure,” Dr. McCorvy says.

To better understand the source of hallucinogenic potential in these compounds, the scientists began by investigating a serotonin receptor called 5-HT2A that is found on the surface of cells throughout the central nervous system. It appeared likely to be involved in hallucinogenic potential based on other research findings. The team knew that psilocybin and other well-known psychedelics would increase activity in this receptor, but it was unknown whether the compounds would favor one of two potential cellular signaling pathways. The scientists found that psychedelics did not completely favor either the Gq signaling pathway (the G protein responsible for typical cellular signaling) or the β-arrestin pathway (a protein that competes with Gq for the binding site to decrease signaling activity into the cell). 

“We know that G protein signaling pathways are like the gas pedal for signaling and the β-arrestin pathway is like the brakes,” Dr. McCorvy says. “Our question was, which of these signaling pathways is responsible for the hallucinogenic effects?”

To find out, scientists at St. Joseph’s University, led by assistant professor Jason Wallach, PhD, synthesized hundreds of compounds and Dr. McCorvy’s lab profiled their ability to selectively activate one of the two pathways through the serotonin 5-HT2A receptor. Compounds that feature this type of pathway-selective activation are known as biased agonists. Ultimately, the team found the most effective option for discovering biased agonists is by adding additional molecular bulk to one of the compounds they had synthesized. This atomic manipulation reduced the Gq signaling while preserving the β-arrestin activity. Then, Adam Halberstadt, PhD, and his lab at the University of California San Diego began testing the compounds in mice using an automated head twitch measurement that predicts psychedelic potential in humans. They found that these modified psychedelic biased agonist compounds with reduced Gq signaling did not induce a number of head twitches that correlates to hallucinogenic experiences, suggesting Gq signaling from the 5-HT2A receptor is necessary for psychedelic effects.   

“We took a psychedelic and made it non-psychedelic, and we did it in a structure-based fashion,” Dr. McCorvy says. “Hopefully in the future this will help increase study of these compounds if the hallucinogenic hurdles can be removed.”

Dr. McCorvy would like to see industry build on this research by developing and testing new potential psychedelic treatments without the hallucinogenic trip.

“My vision is to get some of these compounds properly vetted in trials and out to clinics in my lifetime,” Dr. McCorvy says. “I know too many people who have suffered from posttraumatic stress disorder and other mental health conditions without enough relief from current therapies. They need new treatment options as soon as it is prudent and possible.”

Reference: Jason Wallach, Andrew B. Cao, Maggie M. Calkins, Andrew J. Heim, Janelle K. Lanham, Emma M. Bonniwell, Joseph J. Hennessey, Hailey A. Bock, Emilie I. Anderson, Alexander M. Sherwood, Hamilton Morris, Robbin de Klein, Adam K. Klein, Bruna Cuccurazzu, James Gamrat, Tilka Fannana, Randy Zauhar, Adam L. Halberstadt, John D. McCorvy. Identification of 5-HT2A Receptor Signaling Pathways Associated with Psychedelic Potential. Nature Communications, 15 December 2023.

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About the Medical College of Wisconsin

With a history dating back to 1893, The Medical College of Wisconsin is dedicated to leadership and excellence in education, patient care, research, and community engagement. More than 1,400 students are enrolled in MCW’s medical school and graduate school programs in Milwaukee, Green Bay, and Central Wisconsin. MCW’s School of Pharmacy opened in 2017. A major national research center, MCW is the largest research institution in the Milwaukee metro area and second largest in Wisconsin. In the last 10 years, faculty received more than $1.5 billion in external support for research, teaching, training, and related purposes. This total includes highly competitive research and training awards from the National Institutes of Health (NIH). Annually, MCW faculty direct or collaborate on more than 3,100 research studies, including clinical trials. Additionally, more than 1,600 physicians provide care in virtually every specialty of medicine for more than 2.8 million patients annually.

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JOURNAL

Nature Communications

DOI

10.1038/s41467-023-44016-1 

METHOD OF RESEARCH

Experimental study

ARTICLE TITLE

Identification of 5-HT2A Receptor Signaling Pathways Associated with Psychedelic Potential

ARTICLE PUBLICATION DATE

15-Dec-2023

COI STATEMENT

JW, ALH, and JDM submitted a patent application for the novel compounds in this study entitled “Selective, partial, and arrestin-biased 5-HT2A agonists with utility in various disorders,” PCT WO2022241006A1. AKK is currently an employee of Gilgamesh Pharmaceuticals. All other authors declare no competing interests.

ALDOUS HUXLEY WORK ON PSYCHEDELICS

The Doors of Perception and Heaven and Hell

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https://yes-pdf.com › electronic-book

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The untalented visionary may perceive an inner reality no less tremendous, beautiful and significant than the world beheld by Blake; but he lacks altogether the ...

Intensity of psychedelic experiences after taking psilocybin does not depend on body mass index, study suggests

Researchers in the United Kingdom studied whether the effects of psilocybin, a naturally occurring hallucinogenic drug, depend on the body mass index of the person, thereby requiring higher doses for the same effect in heavier people. The results showed that the overall intensity of psychedelic experiences after consuming a 25 mg dose of psilocybin was unaffected by differences in body mass indices of respondents. The study was published in the Journal of Psychopharmacology.

Psilocybin is a psychedelic drug obtained from certain sorts of fresh and dry mushrooms (“magic mushrooms”). In the human body, it acts as a serotonin type 2A (5-HT2A) receptor agonist, activating serotonin receptors on brain cells, mostly in the prefrontal cortex region of the brain. In this way, it reduces the energy needed for the brain to switch between different activity states.

Although illegal in the United States and considered a Schedule I substance by the Drug Enforcement Administration (high abuse risk, no medical use), there is a recent increase of interest for its potential use in psychiatric treatment. However, due to its legal status, research on dosing of the drug has, so far, been limited and it is unknown whether the dosage needs to be scaled to achieve the same psychedelic effect for people of different body weight or a fixed dosage can be used for everyone.

“There is already a lot of research supporting the importance of the acute experience in psilocybin-assisted therapy, and that this is not solely dependent on the dose used. The acute experience is also shaped by extra-pharmacological factors; commonly referred to as the set and setting,” explained study author Meg J. Spriggs, a research associate at the Centre for Psychedelic Research at Imperial College London.

“While body weight adjusted dosing is the ‘gold standard’ in pharmacological research, it was unclear from previous research whether bodyweight adjustment is necessary in psilocybin-assisted therapy, given what we know about these extra-pharmacological factors. Here, we wanted to test whether the acute experience and outcome are impacted by a participants BMI when using a fixed 25 mg dose (a ‘therapeutic’ dose) of psilocybin.”

“As we look towards a future where psychedelic-assisted therapy may become accessible, we need to be thinking about how to facilitate safe and equitable clinical roll out,” the researcher said. “Bodyweight adjustment is standard practice in research, but it adds practical and financial complexity to standardization, validation and large-scale distribution. A greater understanding about whether fixed doses can be used will help facilitate this transition to the clinic.”

Spriggs and her colleagues analyzed data from three different studies using psilocybin. Two of the studies were clinical studies on potential use of psilocybin for treating depression and the third was a study on healthy volunteers who have never taken a psychedelic drug before aiming to examine long-term psychological and brain changes. The researchers analyzed data on the effects of a 25 mg dose of psilocybin from all three studies. The three studies included 77 participants. Average age was 43 years.

The researchers measured body weight and height of participants to calculate their body mass indexes. Body mass index is calculated by dividing the body weight of a person expressed in kilograms by the square of the person’s height in meters. It is used to indicate whether a person is underweight, normal-weight or overweight.

Participants also completed an assessment of the altered states of consciousness related to the psychedelic state they were experiencing after taking the psilocybin dose (The Altered States of Consciousness Questionnaire, ASC), of emotional breakthrough experienced during the psychedelic state (Emotional Breakthrough Inventory, EBI) and of well-being (Warwick-Edinburg Mental Well-being Scale).

“Body mass index does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower body mass index,” Spriggs and her colleagues wrote. However, further analysis suggested that even this link with body mass index disappeared when age and sex of participants are taken into account.

“While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not,” the researchers concluded.

“This helps us understand that psychedelic-assisted therapy is more than just pharmacology, it is psycho-pharmaco-therapy,” Spriggs told PsyPost. “The drug is only one aspect of the therapy ‘package,’ which also includes extensive psychological preparation before, and integration after, the dosing session which takes place in a supportive and therapeutically-oriented environment.”

This research further demonstrates that there is more than just the ratio of dose-to-bodyweight in determining the acute experience and the outcome.

“This is a great demonstration of where ‘support for the null hypothesis’ is really important. Using standard (‘frequentist’) statistical methods, the results of this study are non-significant — meaning that there is no evidence for the effect of BMI, and so the results are inconclusive. A common problem in science is that null results are often not published. Not only does this mean that the wider science community cannot learn from null findings, but it can put pressure on researchers to ‘find’ significant results if they want a study to be published.”

“Here we took a different statistical approach (Bayesian statistics) that allowed us to draw conclusions about evidence in support of the null hypothesis. i.e., we can say that there is evidence against BMI being a predictor of acute experience and outcome. So, what would typically be a null result is actually really informative. I hope that this helps people to look at science in a different way, and inspires scientist to explore new statistical approaches.”

The study results provide strong evidence that scaling psilocybin dose according to body weight is not necessary and that a fixed dosage for all persons is sufficient to achieve acute psychedelic experience. However, it also has certain limitations. Notably, only the 25 mg dosage was studied and it is possible that effects of different dosages would depend on body weight. Also, there were much more obese participants than underweight ones.

“Fixed vs bodyweight adjusted dosing also has implications for clinical applications in populations where BMI is part of the diagnostic criteria, e.g., anorexia — I am currently working on a trial of psilocybin-assisted therapy for anorexia at Imperial College London,” Spriggs noted.

The study, “Body mass index (BMI) does not predict responses to psilocybin”, 

was authored by Meg J. Spriggs, Bruna Giribaldi, Taylor Lyons, Fernando E. Rosas, Laura S. Kärtner, Tobias Buchborn, Hannah M. Douglass, Leor Roseman, Christopher Timmermann, David Erritzoe, David J. Nutt, and Robin L. Carhart-Harris.


2022/12/31
© PsyPost

Can microdosing psychedelics boost mental health? Here’s what the evidence suggests.

Meryl Davids Landau - Yesterday 

National Geographic

When Jaclyn Downs, a 43-year-old nutritionist in Lancaster, Pennsylvania, stumbled upon the concept of microdosing psilocybin, or taking a tiny amount of a psychedelic for a subtle effect, she immediately recalled an incident in college where friends made tea with “magic mushrooms,” which contain the drug. Downs had only one sip, but she spent the rest of the night feeling grounded, peaceful, and present. Looking back, she realized what she had experienced was a microdose.

Three years ago Downs began microdosing to prepare for certain situations, such as when she had to stay later at a social event than she might want to. The drug soothed her angst and made her a better conversationalist, she says. Six months ago, she began a more structured routine, taking a tincture of microdose psilocybin every three days. It has made her calmer and more accepting, she says, especially when her six- and nine-year-old daughters argue with one another or push back on her requests. “Before I was more reactive—getting angry or irritated—but now I respond more evenly,” Downs says. “The general atmosphere of our home is more positive.”


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Diana Bui, Wendell Phipps, and Carlyn Hope Davis went hiking in the Pacific Palisades after microdosing and then chose to roller skate at their favorite location on Venice Beach.

In recent years, psychedelic drugs have evolved from a taboo topic to one gaining acceptance in mainstream quarters of society. Psychedelics are even heading for general medical approval, having been designated as a “breakthrough therapy” by the U.S. Food and Drug Administration.

But many who are intrigued by the promise of psychedelics—a category that includes psilocybin, lysergic acid diethylamide (LSD), ayahuasca, mescaline, and other substances that alter consciousness—are eager to reap the benefits without having to take a dose strong enough to provoke an hours-long journey down the rabbit hole. A growing number are turning to microdosing, regularly ingesting five to 10 percent of the mind-bending amount in a quest to enhance well-being, improve work, or diminish depression and other psychological demons without triggering the drug’s full effects.


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Many people who microdose consume foods or teas containing psychedelic drugs, which can trigger warm emotions and pleasure. Here a baker spritzes cookies with a microdose of a psychedelic brew including MDMA—also known as ecstasy or Molly—as well as LSD and 2C-B, a synthetic drug first synthesized in the 1970s.

But experts say there is little scientific evidence so far to support this approach.

“As far as we know, there are not many risks associated with microdosing. But it’s not at all clear, aside from user testimonials, that there are benefits,” says John Krystal, chair of psychiatry at the Yale School of Medicine, who has closely followed the field.

A key reason is that microdosing, as it is done in real life, is challenging to study. Users generally consume a dose for one or two mornings, skip the next one or two, and repeat this regimen for months or years. Because psychedelics are illegal, U.S. law prohibits researchers from giving them to people to take on this schedule at home. But providing the drug and overseeing users day after day in a laboratory isn’t practical, says Albert Garcia-Romeu, a researcher at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore.

That presents a problem for both the scientists and the microdosers. When active users respond to surveys about their experiences for observational research, the scientists can’t be sure each person is taking the same amount. After all, there aren’t standardized products a person can pick up at the local pharmacy. It’ s especially challenging for someone to determine an exact psilocybin microdose from a batch of dried mushrooms or a lick of an LSD tab, says Jerome Sarris, executive director of the Psychae Institute in Melbourne, Australia.

A growing phenomenon


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Alli Schaper is cofounder and CEO of Supermush, which sells various mouth sprays made from non-psychedelic mushrooms called cordyceps. Here, Schaper chills out at her home in Marina Del Rey, Los Angeles, after taking a microdose of psilocybin.

No one knows how many people in the U.S. currently microdose, although its popularity seems to be growing. An analysis in 2018 of a Reddit discussion group devoted to microdosing recorded 27,000 subscribers; in early 2022, the group had 183,000. At a recent business conference focusing on psychedelic drugs in Miami, when audience members were asked how many currently microdose, hundreds of hands went up.

“When it first became popular about a decade ago, microdosing was hush hush, with tech entrepreneurs and businesspeople the primary users,” says Steven Holdt, the 24-year-old founder of Tune In Psychedelics, an app that lets microdosers track their dosing schedules and record drug effects for their own information. In the past few years, a broad range of people have jumped on board, Holdt says, thanks to podcasts on the topic, articles in mainstream newspapers, and writer Ayelet Waldman’s popular book, A Really Good Day, which chronicled how microdosing LSD lifted her intractable depression.


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he Hillbilly is one of the most common varieties of magic mushroom. The psychedelic pan-tropical giant grows wild in states lining the Gulf Coast, and is found in Central and South America, the Caribbean, and Southeast Asia. This one was grown in the Hollywood Hills of Los Angeles.

Erica Zelfand, a naturopathic physician in Portland, Oregon, says dozens of her patients currently microdose, mostly in a bid to improve their depression or attention deficit disorder. Zelfand supports their efforts but makes it clear they are lab rats in a grand experiment. “I let them know that we don’t have the research yet. And we especially don’t know the long-term risks,” she says. To help build a body of knowledge, she encourages patients to report their experiences on crowdsourced research sites like microdose.me or microdosingsurvey.com.


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After microdosing and taking a walk in the nearby hills, Colin Benward sits at his altar to meditate at his home in Topanga Canyon, Los Angeles.

High versus low doses


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An earthy platter showcases the many shapes of the Hillbilly mushroom. The psychedelic effects of these fungi can kick in as quickly as 15 to 30 minutes after a microdose, peak in 60 to 90 minutes, and mostly disappear after about six hours.

None of the current studies on microdosing reach standards that enable scientists to draw firm conclusions. But results from recent studies using a single high-dose psychedelic have illuminated the mental-health potential of these long-shunned drugs. One potent dose of synthetic psilocybin along with psychological support improved treatment-resistant depression, according to unpublished results from a randomized study of more than 200 people released in November by the company Compass Pathways, whose proprietary formulation is one of the F.D.A. breakthrough-therapy designees. And in May 2021 scientists reported in the journal Nature that a high dose of MDMA (aka Molly or Ecstasy, which is not a classic psychedelic but produces a similar effect) greatly diminished severe post-traumatic stress disorder (PTSD).

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But these results can’t be generalized to microdoses, says Matthew Johnson, acting director of the Johns Hopkins Center, which has conducted numerous studies on high-dose psychedelics.

A review of psychedelic research that Sarris published in January 2022 underscored problems facing studies that seek to discover both micro- or high-dose effects of a psychedelic drug: few large randomized trials have been done in humans.

Studies of medications in people typically begin with what is known as a phase one clinical trial, designed to determine levels of safety and tolerability in a small number of people. Such a study has not yet been undertaken for microdosing, although the drug manufacturer Diamond Therapeutics announced in November that it is about to embark on such a trial, minutely escalating the quantity of psilocybin until the ideal microdose, one that causes positive effects with the fewest negative ones, is found.

A handful of laboratory studies that included a small number of healthy people have sought to uncover the effects of microdosing after taking one or a few doses. A 2020 review published in Therapeutic Advances in Psychopharmacology counted 14 of these small experimental studies, with most finding that microdosing LSD or psilocybin yields subtle positive changes to emotions and to thought processes involved in problem-solving. The reviewers noted that some users did feel anxious or overly euphoric. Since all studies were done in healthy individuals it isn’t known whether microdosing might consistently benefit people with mental-health concerns.

One European study of 30 people, published in April 2021, found that people who microdosed psychedelics for several weeks were more in awe when viewing videos and artworks than during the weeks they took a placebo. But the study was flawed because many people were able to figure out what they were taking based on side effects like increased sweating so the researchers were unable to separate people’s actual experiences from their expectations.
Placebo effect?

Larger studies have primarily asked current users about their experiences. One tapped more than a thousand microdosers who reported increased energy, better work results, and more positive moods. Another compared 4,000 microdosers to a similar group of nonusers and found that among people with prior mental-health issues, those who microdosed reported having lower levels of anxiety and depression.

But in addition to the issue of users taking non-standardized doses, participants were all microdosing before the studies began, so they may have been biased. “We have to be cautious about not overinterpreting the encouraging retrospective reports that have appeared in the literature,” Yale’s Krystal says. “The concern about first-person experiences is that there is often tremendous potential for placebo effects to color the interpretation.”

In fact, the best study of microdosing to date shows just this effect. This was a “citizen science initiative” involving some 200 LSD and psilocybin microdosers. Some of the participants were chosen at random by scientists at Imperial College London to swap their drugs for placebos, with neither group knowing for sure which they were getting. After a month everyone was surveyed about their well-being, life satisfaction, cognition, and other factors. Psychological outcomes improved significantly for people taking the psychedelics—but they also did for those downing the placebos.

This was a clever way to study a large number of microdosers in the current regulatory environment, says Garcia-Romeu, who helped to evaluate the research for the journal eLife. The fact that so many placebo-takers reported benefits “calls into question the whole phenomenon of microdosing,” he says.

Nonetheless, imaging studies do make clear that something is happening.

In one, 20 healthy people were scanned with an fMRI several hours after taking a microdose of LSD or a placebo. The amygdala, considered the emotion center of the brain, changed how it interacted with other brain regions in the microdosers, indicating the potential to better regulate negative emotions, says study coauthor Katrin Preller, a neuropsychologist at the University of Zurich. In fact, those whose brains experienced the improved connectivity also subjectively reported feeling more upbeat, Preller says. Another study used electroencephalography (EEG) to measure brain activity in 22 LSD microdosers and documented more activity in the brain than usually occurs during rest, something also seen with high-dose psychedelics.
The effects of microdosing

Despite the paucity of research, people are turning to microdoses for a variety of reasons. Holdt says microdosing psilocybin helps him have fun around other people. He suffers from social anxiety, so without the drugs his mind constantly ruminates about all the things he might say or do. “Microdosing helps me stop that inner monologue so I can be more comfortable and present,” he says. He has had the same effect using high-dose psychedelics, which he first experienced in high school, but says the subtler effects of microdosing make it easier to incorporate into everyday life. “You don’t need to take a day off work or have someone watching you [to make sure a trip doesn’t turn ugly],” he says.

Many microdosers find it helps them with work. Dusty, a 40-year-old audio engineer in Philadelphia (who asked that only his nickname be used), says the tiny bit of LSD he takes once each week boosts his productivity, desire to collaborate, and creativity on the job. For example, when setting up sound systems for live concerts, “there are a million little problems that you need to solve every day, and there’s not always a good road map,” he says. On days he microdoses, he’s noticed he has “a little extra excitement to solve a problem that leads to long-term solutions, rather than just making it work for now.”

Others microdose to self-treat mental-health conditions. Karen Gilbert, a 69-year-old retired nurse in Lopez Island, Washington, is hoping microdosing psilocybin, which she started in November, might help with the depression she has suffered for more than two decades. One of Zelfand’s patients, Gilbert says she noticed a difference almost immediately. “For the first time in a long time I am excited about the projects I want to do, which are feeling like opportunities rather than obligations,” she says.

Zelfand herself tried microdosing a few times but didn’t enjoy the effects. “I don’t feel well when I do it. It seems to make me a little edgy,” she says.

Some of Zelfand’s patients have had similar unwanted experiences. People with general anxiety disorders and, especially, bipolar disorder should probably avoid microdosing because it can lead to agitation or mania, she says.

Experts also worry that microdosing on a regular basis for a long period of time could theoretically weaken heart valves, like the damage caused by the diet drugs phentermine and fenfluramine (Phen/Fen) in the 1990s. Both Phen/Fen and psychedelics act on one of the body’s serotonin receptors, known as 5-HT2B, Johns Hopkins’ Garcia-Romeu says.

Even if microdosing proves to be safe and effective, some experts fear widespread recreational use could render it useless later in life if it turns out to be valuable for important mental-health purposes but people are tolerant to it after frequent use. “If we introduce more of these types of substances, that might undercut their therapeutic efficacy when we really need them for medicine, such as for end-of-life distress,” says Conor Murray, a neuroscientist at UCLA who conducted the EEG research.

And while they don’t trigger the same wild thoughts and images as taking high doses of these drugs do, some microdosers have reported some impairment, Johnson says. “If this turns out to be the case, it may be hard to drive, take care of your toddler, or make important decisions at work.”

Plus, of course, psychedelics are illegal, which means there’s no quality control on supply. What’s more, “people have lost their jobs because they’re microdosing, and they can and do get incarcerated,” Garcia-Romeu says.

But even those who are concerned about the growing use of psychedelics say microdosing may eventually prove beneficial for some people. Johnson from Johns Hopkins thinks depression might be relieved by microdosing—although he’s much more jazzed about the prospect that a person could get more relief after one or two high-dose sessions, something his research is bearing out.

Krystal believes until more is known about microdosing, people should hold off. “Right now, it should only be done in the context of experimental research,” he says. “There, protections can be in place, and the data generated will inform our understanding about these doses and drugs.”

Additional microdosing studies could also yield insights about our brains. For example, experts don’t fully understand the role of another serotonin receptor activated by psychedelics, 5-HT2A, Johnson says. “We have a whole lot to learn about [this receptor]. Is it involved with naturally occurring mystical experiences like near death experiences, even alien abduction encounters?” he wonders. “How can we use microdosing research to understand more about the nature of the human mind?”