Researchers urge caution around psilocybin use

Survey assesses both risky behaviors and positive outcomes

December 30, 2016

Science Daily/Johns Hopkins Medicine

In a survey of almost 2,000 people who said they had had a past negative experience when taking psilocybin-containing "magic mushrooms," Johns Hopkins researchers say that more than 10 percent believed their worst "bad trip" had put themselves or others in harm's way, and a substantial majority called their most distressing episode one of the top 10 biggest challenges of their lives. Despite the difficulty, however, most of the respondents still reported the experience to be "meaningful" or "worthwhile," with half of these positive responses claiming it as one of the top most valuable experiences in their life.

The results of the survey were published in the Dec. 1 print issue of the Journal of Psychopharmacology.

The researchers caution that their survey results don't apply to all psilocybin mushroom use, since the questionnaire wasn't designed to assess "good trip" experiences. And, the survey wasn't designed to determine how often bad trips occur.

"Considering both the negative effects and the positive outcomes that respondents sometimes reported, the survey results confirm our view that neither users nor researchers can be cavalier about the risks associated with psilocybin," says Roland Griffiths, Ph.D., a psychopharmacologist and professor of psychiatry and behavioral sciences and neurosciences at the Johns Hopkins University School of Medicine. Griffiths has spent more than 15 years conducting studies of psilocybin's capacity to produce profound, mystical-type experiences, treat psychological anxiety and depression and to aid in smoking cessation.

Psilocybin and use of other hallucinogens became popular in the U.S. in the 1960s due to charismatic proponents, who suggested anecdotally that users would experience profound psychological insights and benefits. But drugs such as psilocybin and LSD were banned for supposed safety reasons shortly thereafter, in the 1970s, without much scientific evidence about risks or benefits.

In recent years, Griffiths and his team have conducted more than a dozen studies confirming some of those benefits. The current study was designed, he said, to shed light on the impact of so-called "bad trips."

For the new survey, Griffiths' team used advertisements on social media platforms and email invitations to recruit people who self-reported a difficult or challenging experience while taking psilocybin mushrooms. The survey took about an hour to complete and included three questionnaires: the Hallucinogen Rating Scale, the Mystical Experience Questionnaire, developed by Griffiths and colleagues in 2006, and parts of the 5D-Altered States of Consciousness Questionnaire.

Participants were asked in the survey to focus only on their worst bad trip experience, and then to report about the dose of psilocybin they took, the environment in which the experience occurred, how long it lasted, and strategies available and used to stop this negative experience and any unwanted consequences.

Of 1,993 completed surveys, 78 percent of respondents were men, 89 percent were white, and 51 percent had college or graduate degrees. Sixty-six percent were from the U.S. On average, the survey participants were 30 years old at the time of the survey and 23 years old at the time of their bad trips, with 93 percent responding that they used psilocybin more than two times.

Based on the survey data that assessed each respondent's absolute worst bad trip, 10.7 percent of the respondents said they put themselves or others at risk for physical harm during their bad trip. Some 2.6 percent said they acted aggressively or violently, and 2.7 percent said they sought medical help. Five of the participants with self-reported pre-existing anxiety, depression or suicidal thoughts attempted suicide while on the drug during their worst bad trip, which the researchers say is indicative of requiring a supportive and safe environment during use, like those conditions used in ongoing research studies. However, six people reported that their suicidal thoughts disappeared after their experience on their worst bad trip -- the latter result coinciding with a recent study published by Griffiths showing the antidepressive properties of psilocybin in cancer patients.

Still, Griffiths said, a third of the participants also said their experience was among the top five most meaningful, and a third ranked it in the top five most spiritually significant experiences of their lives. Sixty-two percent of participants said the experience was among the top 10 most difficult ones in their lifetime; 39 percent listed it in their top five most difficult experiences; and 11 percent listed it as their single most difficult experience.

"The counterintuitive finding that extremely difficult experiences can sometimes also be very meaningful experiences is consistent with what we see in our studies with psilocybin -- that resolution of a difficult experience, sometimes described as catharsis, often results in positive personal meaning or spiritual significance," Griffiths says.

¬In all of Griffiths' clinical research, people given psilocybin are provided a safe, comfortable space with trained experts to offer support to participants. "Throughout these carefully managed studies, the incidence of risky behaviors or enduring psychological problems has been extremely low," Griffiths says. "We are vigilant in screening out volunteers who may not be suited to receive psilocybin, and we mentally prepare study participants before their psilocybin sessions."

"Cultures that have long used psilocybin mushrooms for healing or religious purposes have recognized their potential dangers and have developed corresponding safeguards," says Griffiths. "They don't give the mushrooms to just anyone, anytime, without a contained setting and supportive, skillful monitoring."

The researchers say that survey studies like this one rely on self-reporting that cannot be objectively substantiated, and that additional scientifically rigorous studies are needed to better understand the risks and potential benefits of using hallucinogenic drugs.

According to the Substance Abuse and Mental Health Services Administration's National Survey on Drug Use and Health, about 22.9 million people or 8.7 percent of Americans reported prior use of psilocybin. While not without behavioral and psychological risks, psilocybin is not regarded as addictive or as toxic to the brain, liver or other organs.

https://www.sciencedaily.com/releases/2016/12/161230180654.htm

Potential of psilocybin to alleviate psychological and spiritual distress in cancer patients is revealed

January 31, 2013

Science Daily/New York University

Improvements in the diagnosis and treatment of cancers in recent years have led to a marked increase in patients' physical survival rates. While doctors can treat the physical disease, what is not well understood is how best to address the psychological needs of patients with cancer.

In addition to the physical pain associated with cancer, many patients also experience psychologically harmful symptoms of anxiety, depression, anger, and denial. Social isolation, in addition to hopelessness, helplessness and loss of independence, has also been associated with significant psychological suffering in patients coping with advanced-stage cancer.

A recently published book chapter "Use of the Classic Hallucinogen Psilocybin for Treatment of Existential Distress Associated with Cancer," reviews the potential of a novel psychoactive drug, psilocybin, in alleviating the psychological and spiritual distress that often accompanies a life-threatening cancer diagnosis.

The chapter, published in Psychological Aspects of Cancer: A Guide to Emotional and Psychological Consequences of Cancer, Their Causes, and Their Management, was co-written by Anthony P. Bossis, PhD, Clinical Assistant Professor of Psychiatry and Oral and Maxillofacial Pathology, Radiology, and Medicine at the New York University College of Dentistry (NYUCD) and Langone Medical Center.

The hallucinogen treatment model with psilocybin has been shown to induce a mystical or spiritual experience and is a unique therapeutic approach to reduce the anxiety of terminal cancer patients.

"Mystical or peak consciousness states in cancer patients have been associated with a number of benefits including improved psychological, spiritual, and existential well-being," said Dr. Bossis.

Psilocybin (a serotonergic psychoactive agent) is a naturally occurring active component of many species of mushrooms, and is rapidly metabolized to psilocin, a highly potent activator of serotonin receptors. In addition to receiving the psilocybin compound, patients enrolled in the study also receive psychological preparation prior to the psilocybin dosing followed by a brief series of integrative psychotherapeutic sessions.

The chapter includes a clinical case vignette of a patient in the ongoing Psilocybin Cancer Anxiety Study at the Bluestone Center for Clinical Research. Participants undergo two drug administration sessions in which psilocybin is administered on one occasion and a placebo on the other.

"The primary objective of this phase I, double-blind, controlled pilot study is to assess the efficacy of psilocybin administration on psychosocial distress, with the specific primary outcome variable being anxiety associated with advanced and/or recurrent cancer," said Bossis. "Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, existential/psychospiritual distress, attitudes toward illness, quality of life, and spiritual/mystical states of consciousness," said Bossis.

The clinical vignette describes a patient who, over the course of three years, experienced extreme fatigue, pain, overall body aches, discomfort and psychological distress due to cancer and intensive biweekly chemotherapy. The patient became increasingly anxious and depressed and was enrolled in two study sessions; in one he received psilocybin and the other placebo. Despite continuing the arduous chemotherapy schedule, suffering from illness, and undergoing additional surgical procedures, the patient continued to report a marked improvement in attitude, coping, and mood 18 weeks after his session and stated, "my quality of life is dramatically improved," the patient said.

Stephen Ross, MD, Assistant Professor of Psychiatry and Child and Adolescent Psychiatry at the NYU School of Medicine and Clinical Assistant Professor of Psychiatry and Oral and Maxillofacial Pathology, Radiology, and Medicine at the NYUCD is the principal investigator for the study; Dr. Bossis and Jeffrey Guss, MD, Clinical Assistant Professor of Psychiatry are co-principal investigators.

The co-authors of the chapter were: Charles S. Grob, MD, Professor of Psychiatry and Biobehavioral Sciences at Harbor-UCLA Medical Center and Roland R. Griffiths, PhD, Professor of Psychiatry and Behavioral Science and Neuroscience at Johns Hopkins University.

The Psilocybin Cancer Anxiety Study was also recently highlighted in a News article, "Opening Doors of Perception: Psychedelic Drugs and End-of-Life Care" in the Journal of the National Cancer Institute.

"The emotional, spiritual and existential distress that can often accompany a diagnosis of cancer often goes unidentified and untreated in cancer patients. Patients who have benefited from psilocybin clinical research have reported less anxiety, improved quality of life, enhanced psychological and spiritual well-being, and a greater acceptance of the life-changes brought on by cancer. It is a welcome development that this promising and novel clinical research model utilizing psilocybin has begun to gain clinical and academic attention," Bossis notes.

The Psilocybin Cancer Anxiety Study is currently recruiting additional subjects. To enroll or learn more, please visit BluestoneCenter.org or http://www.nyucanceranxiety.org/.

https://www.sciencedaily.com/releases/2013/01/130131095040.htm

Magic mushrooms' effects illuminated in brain imaging studies

January 24, 2012

Science Daily/Imperial College London

Brain scans of people under the influence of the psilocybin, the active ingredient in magic mushrooms, have given scientists the most detailed picture to date of how psychedelic drugs work. The findings of two studies being published in scientific journals this week identify areas of the brain where activity is suppressed by psilocybin and suggest that it helps people to experience memories more vividly.

In the first study, published January 23 in Proceedings of the National Academy of Sciences (PNAS), 30 healthy volunteers had psilocybin infused into their blood while inside magnetic resonance imaging (MRI) scanners, which measure changes in brain activity. The scans showed that activity decreased in "hub" regions of the brain -- areas that are especially well-connected with other areas.

The second study, due to be published online by the British Journal of Psychiatry on January 24, found that psilocybin enhanced volunteers' recollections of personal memories, which the researchers suggest could make it useful as an adjunct to psychotherapy.

Professor David Nutt, from the Department of Medicine at Imperial College London, the senior author of both studies, said: "Psychedelics are thought of as 'mind-expanding' drugs so it has commonly been assumed that they work by increasing brain activity, but surprisingly, we found that psilocybin actually caused activity to decrease in areas that have the densest connections with other areas. These hubs constrain our experience of the world and keep it orderly. We now know that deactivating these regions leads to a state in which the world is experienced as strange."

The intensity of the effects reported by the participants, including visions of geometric patterns, unusual bodily sensations and altered sense of space and time, correlated with a decrease in oxygenation and blood flow in certain parts of the brain.

The function of these areas, the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC), is the subject of debate among neuroscientists, but the PCC is proposed to have a role in consciousness and self-identity. The mPFC is known to be hyperactive in depression, so psilocybin's action on this area could be responsible for some antidepressant effects that have been reported. Similarly, psilocybin reduced blood flow in the hypothalamus, where blood flow is increased during cluster headaches, perhaps explaining why some sufferers have said symptoms improved under psilocybin.

In the British Journal of Psychiatry study 10 volunteers viewed written cues that prompted them to think about memories associated with strong positive emotions while inside the brain scanner. The participants rated their recollections as being more vivid after taking psilocybin compared with a placebo, and with psilocybin there was increased activity in areas of the brain that process vision and other sensory information.

Participants were also asked to rate changes in their emotional wellbeing two weeks after taking the psilocybin and placebo. Their ratings of memory vividness under the drug showed a significant positive correlation with their wellbeing two weeks afterwards. In a previous study of 12 people in 2011, researchers found that people with anxiety who were given a single psilocybin treatment had decreased depression scores six months later.

Dr Robin Carhart-Harris, from the Department of Medicine at Imperial College London, the first author of both papers, said: "Psilocybin was used extensively in psychotherapy in the 1950s, but the biological rationale for its use has not been properly investigated until now. Our findings support the idea that psilocybin facilitates access to personal memories and emotions.

"Previous studies have suggested that psilocybin can improve people's sense of emotional wellbeing and even reduce depression in people with anxiety. This is consistent with our finding that psilocybin decreases mPFC activity, as many effective depression treatments do. The effects need to be investigated further, and ours was only a small study, but we are interested in exploring psilocybin's potential as a therapeutic tool."

The researchers acknowledged that because the participants in this study had volunteered after having previous experience of psychedelics, they may have held prior assumptions about the drugs which could have contributed to the positive memory rating and the reports of improved wellbeing in the follow-up.

Functional MRI measures brain activity indirectly by mapping blood flow or the oxygen levels in the blood. When an area becomes more active, it uses more glucose, but generates energy in rapid chemical reactions that do not use oxygen. Consequently, blood flow increases but oxygen consumption does not, resulting in a higher concentration of oxygen in blood in the local veins.

In the PNAS study, the volunteers were split into two groups, each studied using a different type of fMRI: 15 were scanned using arterial spin labelling (ASL) perfusion fMRI, which measures blood flow, and 15 using blood-oxygen level-dependent (BOLD) fMRI. The two modalities produced similar results, strongly suggesting that the observed effects were genuine.

The studies were carried out with a Home Office licence for storing and handling a schedule 1 drug and were approved by NHS research ethics committees. All the volunteers were mentally and physically healthy and had taken hallucinogenic drugs previously without any adverse response. The research involved scientists from Imperial, the University of Bristol and Cardiff University and was funded by the Beckley Foundation, the Neuropsychoanalysis Foundation, Multidisciplinary Association for Psychedelic Studies, and the Heffter Research Institute.

https://www.sciencedaily.com/releases/2012/01/120123152043.htm

Mechanism of Hallucinogens' Effects Discovered

February 2, 2007

Science Daily/Cell Press

The brain mechanism underlying the mind-bending effects of hallucinogens such as LSD, mescaline, and psilocybin has been discovered by neuroscientists. They said their discoveries not only shed light on the longtime mystery of how hallucinogens work, but that the findings also offer a pathway to understanding the function of drugs used to treat neuropsychiatric disorders, which are now being used largely without an understanding of their fundamental mechanism.

Stuart Sealfon, Jay Gingrich, and colleagues published their findings in the February 1, 2007 issue of the journal Neuron, published by Cell Press.

Researchers have long known that hallucinogens activate specific receptors in the brain, called 5-HT2A receptors (2ARs), that are normally triggered by the neurotransmitter serotonin. Neurotransmitters are chemicals that one brain cell launches at receptors on another to trigger a nerve impulse in the receiving cell. However, a fundamental mystery has been why other compounds that activate the same receptors are not hallucinogenic.

In their studies, the researchers compared the differences between the effects of LSD and a nonhallucinogenic chemical that also activates 2AR receptors on the mouse neural machinery. Since the animals could not report the kinds of perception-altering effects that humans experience on hallucinogens, the researchers determined hallucinogenic properties by measuring a head twitch response the mice characteristically showed when under hallucinogens but not when under nonhallucinogens.

The scientists concentrated their studies on the cortex of the brain, which earlier studies had shown to be the center for action of the hallucinogens. Their analysis revealed that LSD produced genetic, electrophysiological, and internal cellular signaling responses that were distinctively different from those induced by a nonhallucinogenic compound.

They also explored whether 2ARs were central to the hallucinogenic effect of LSD by producing mice lacking the receptors, but in which receptor activity could be selectively restored in the cortex. The researchers found that mice without functioning receptors showed no hallucinogenic response to LSD, but restoring the receptors rendered LSD hallucinogenic in the animals.

The researchers wrote that "These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens."

They also concluded that "The strategy we developed to elucidate [hallucinogen] action should be applicable to [central nervous system]-active compounds, with therapeutic potential in other disorders. Thus, our findings may advance the understanding of neuropsychiatric disorders that have specific pharmacological treatments whose mechanisms of action are not fully understood."

https://www.sciencedaily.com/releases/2007/01/070131135536.htm