Mindfulness meditation enhances positive effects of psilocybin

October 24, 2019

Science Daily/University of Zurich

Recent years have seen a renewed interest in the clinical application of classic psychedelics in the treatment of depression and anxiety disorders. Researchers of the University of Zurich have now shown that mindfulness meditation can enhance the positive long-term effects of a single dose of psilocybin, which is found in certain mushrooms.

Hallucinogens such as LSD or psilocybin, the active ingredient in "magic mushrooms," alter the perception of those who take them: The boundaries between the self and the world begin to dissolve and feelings of bliss and unity are triggered. Such experiences of self-transcendence and reduced self-focus are similar to those brought about by mindfulness meditation. They can reduce stress, prompt feelings of enduring happiness and increase empathy and altruism. In contrast to this, exaggerated self-focus, recurring negative thoughts and emotions about one's self, and impaired social interactions are characteristic features of psychiatric disorders such as depression.

Enhanced experience of self-transcendence

Researchers at the University Hospital of Psychiatry Zurich have now for the first time examined the potential synergistic effects of combining mindfulness meditation and psilocybin. The scientists recruited 40 meditation experts who were taking part in a five-day mindfulness retreat. In the double-blind study, the participants were administered either a single dose of psilocybin or a placebo on the fourth day of the group retreat. Using various psychometric and neurocognitive measurements, the team of researchers were able to show that mindfulness meditation increased the positive effects of psilocybin, while counteracting possible dysphoric responses to the psychedelic experience. "Psilocybin markedly increased the incidence and intensity of self-transcendence virtually without inducing any anxiety compared to participants who received the placebo," says first author Lukasz Smigielski, who conducted the study directed by UZH professor of psychiatry Franz Vollenweider.

Sustained beneficial effects

At the four-month follow-up, the meditation experts who had been given psilocybin demonstrated more beneficial changes in psychosocial functioning, better self-acceptance and more empathy than the placebo control group. According to Vollenweider, the intensity of self-transcendence experienced during the retreat played a key role for these enduring changes. In a previously published study, he and his team used magnetic resonance imaging to show that experiences of self-transcendence result in lasting changes to neural connections in the brain, and more specifically in the regions that are active when we think about ourselves.

The research group found that besides meditation depth, the participants' openness and optimism were conducive to a positive response to psilocybin. "These factors can help us predict a positive response," says Vollenweider. At the same time, skills that are trained during mindfulness meditation -- such as regulating one's attention and reappraising emotions -- seem to buffer potential negative reactions to psilocybin.

Potential for treating affective disorders

"Our findings shed light on the interplay between pharmacological and extra-pharmacological factors in psychedelic states of mind," says Vollenweider. "They indicate that mindfulness training enhances the positive effects of a single dose of psilocybin, and can increase empathy and permanently reduce ego-centricity. This opens up new therapeutic avenues, for example for the treatment of depression, which is often accompanied by increased self-focus and social deficits."

https://www.sciencedaily.com/releases/2019/10/191024075003.htm

Reclassification recommendations for drug in 'magic mushrooms'

Reclassification recommendations for drug in 'magic mushrooms'

If phase III clinical trials are successful, researchers suggest categorizing the drug as schedule IV

September 26, 2018

Science Daily/Johns Hopkins Medicine

In an evaluation of the safety and abuse research on the drug in hallucinogenic mushrooms, Johns Hopkins researchers suggest that if it clears phase III clinical trials, psilocybin should be re-categorized from a schedule I drug -- one with no known medical potential -- to a schedule IV drug such as prescription sleep aids, but with tighter control.

 The researchers summarize their analysis in the October print issue of Neuropharmacology.

 "We want to initiate the conversation now as to how to classify psilocybin to facilitate its path to the clinic and minimize logistical hurdles in the future," says Matthew W. Johnson, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We expect these final clearance trials to take place in the next five years or so."

Following the Controlled Substances Act of 1970, any drug with the potential for abuse is categorized based on criteria that take into account whether the drug has accepted medical use, and its safety and the potential for abuse. Although preliminary research studies suggest that psilocybin may be effective for smoking cessation and for disorders such as cancer-specific depression and anxiety, it must clear phase III clinical trials before the Food and Drug Administration can be petitioned to reclassify it.

Studies in animals and humans both show low potential for abuse, the researchers say. When rats push a lever to receive psilocybin, they don't keep pushing the lever like they do for drugs such as cocaine, alcohol or heroin. When it comes to human studies, people who have used psilocybin typically report using it a few times across their lifetime.

As for safety, studies show it frequently falls at the end of the scales with the least harm to users and society, say the researchers. Psilocybin also is lowest in the potential for lethal overdose as there is no known overdose level.

"We should be clear that psilocybin is not without risks of harm, which are greater in recreational than medical settings, but relatively speaking, looking at other drugs both legal and illegal, it comes off as being the least harmful in different surveys and across different countries," says Johnson.

That being said, although psilocybin is relatively less harmful than other drugs and not prone to compulsive abuse, the researchers don't recommend releasing psilocybin into patients' hands even with a prescription. "We believe that the conditions should be tightly controlled and that when taken for a clinical reason, it should be administered in a health care setting monitored by a person trained for that situation," says Johnson. The researchers foresee that the process for psilocybin use in the clinic would be similar to how an anesthesiologist prescribes and administers a drug, minimizing the potential for abuse or harm.

https://www.sciencedaily.com/releases/2018/09/180926082159.htm

Hallucinogenic drug psilocybin eases existential anxiety in people with life-threatening cancer

December 1, 2016

Science Daily/Johns Hopkins Medicine

In a small double-blind study, Johns Hopkins researchers report that a substantial majority of people suffering cancer-related anxiety or depression found considerable relief for up to six months from a single large dose of psilocybin -- the active compound in hallucinogenic "magic mushrooms."

The researchers cautioned that the drug was given in tightly controlled conditions in the presence of two clinically trained monitors and said they do not recommend use of the compound outside of such a research or patient care setting.

The Johns Hopkins team released its study results, involving 51 adult patients, concurrently with researchers from New York University Langone Medical Center, who conducted a similarly designed study on 29 participants. Both studies are published in the Journal of Psychopharmacology on Dec. 1.

The Johns Hopkins group reported that psilocybin decreased clinician- and patient-rated depressed mood, anxiety and death anxiety, and increased quality of life, life meaning and optimism. Six months after the final session of treatment, about 80 percent of participants continued to show clinically significant decreases in depressed mood and anxiety, with about 60 percent showing symptom remission into the normal range. Eighty-three percent reported increases in well-being or life satisfaction. Some 67 percent of participants reported the experience as one of the top five meaningful experiences in their lives, and about 70 percent reported the experience as one of the top five spiritually significant lifetime events.

"The most interesting and remarkable finding is that a single dose of psilocybin, which lasts four to six hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions," says Roland Griffiths, Ph.D., professor of behavioral biology in the Departments of Psychiatry and Behavioral Sciences and of Neuroscience at the Johns Hopkins University School of Medicine. He notes that traditional psychotherapy offered to people with cancer, including behavioral therapy and antidepressants, can take weeks or even months, isn't always effective, and in the case of some drugs, such as benzodiazepines, may have addictive and other troubling side effects.

Griffiths says his team's new study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which found that psilocybin can consistently produce positive changes in mood, behavior and spirituality when administered to carefully screened and prepared participants. The study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.

"A life-threatening cancer diagnosis can be psychologically challenging, with anxiety and depression as very common symptoms," says Griffiths. "People with this kind of existential anxiety often feel hopeless and are worried about the meaning of life and what happens upon death."

For the study, the investigators recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic. They were chosen from a total of 566 individuals reached through flyers, web advertisements and physician referrals. Most participants had breast, upper digestive, GI, genitourinary or blood cancer, and each had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.

Half of the participants were female with an average age of 56. Ninety-two percent were white, 4 percent were African-American and 2 percent were Asian.

Each participant had two treatment sessions scheduled five weeks apart, one with a very low psilocybin dose (1 or3 milligrams per 70 kilograms) taken in a capsule and meant to act as a "control" placebo because the dose was too low to produce effects. In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 milligrams per 70 kilograms).

To minimize expectancy effects, the participants and the staff members supervising the sessions were told that the participants would receive psilocybin on both sessions, but they did not know that all participants would receive one high and one low dose. Blood pressure and mood were monitored throughout the sessions. Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.

In addition to experiencing changes in visual perception, emotions and thinking, most participants reported experiences of psychological insight and often profound, deeply meaningful experiences of the interconnectedness of all people.

The researchers assessed each participant's mood, attitude about life, behaviors and spirituality with questionnaires and structured interviews before the first session, seven hours after taking the psilocybin, five weeks after each session and six months after the second session. Immediately after the sessions, participants completed questionnaires assessing changes in visual, auditory and body perceptions; feelings of transcendence; changes in mood; and more.

Structured clinical interviews, such as the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, and patient questionnaires, like the Beck Depression Inventory and the State-Trait Anxiety Inventory, assessed depression and anxiety. Other questionnaires assessed quality of life, death acceptance, meaningful existence, optimism and spirituality -- generally defined as a search for the meaning of life and a connection to something bigger than one's self. To measure the changes in attitudes, moods and behavior over time, the researchers administered a questionnaire that assessed negative or positive changes in attitudes about life, mood and behavior.

With regard to adverse effects, Griffiths says 15 percent of participants were nauseated or vomited, and one-third of participants experienced some psychological discomfort, such as anxiety or paranoia, after taking the higher dose. One-third of the participants had transient increases in blood pressure. A few participants reported headaches following the session.

"Before beginning the study, it wasn't clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy," says Griffiths. "I could imagine that cancer patients would receive psilocybin, look into the existential void and come out even more fearful. However, the positive changes in attitudes, moods and behavior that we documented in healthy volunteers were replicated in cancer patients."

Up to 40 percent of people with cancer suffer from a mood disorder, according to the National Comprehensive Cancer Network.

Anticipating wide interest in the psilocybin research from scientists, clinicians and the public, the journal solicited 11 commentaries to be co-published with the study results written by luminaries in psychiatry, palliative care and drug regulation, including two past presidents of the American Psychiatric Association, a past president of the European College of Neuropsychopharmacology, the former deputy director of the U.S. Office of National Drug Control Policy, and the former head of the U.K. Medicines and Healthcare Products Regulatory Authority. In general, the commentaries were supportive of the research and of using these drugs in a clinical setting as tools for psychiatry.

https://www.sciencedaily.com/releases/2016/12/161201094448.htm