Overview

Psilocybin is a psychoactive compound that is found naturally in wild-grown fungi. The compound provides its user a variety of experiences, which include, hallucinations, mystical-type experiences, along with other therapeutic effects. Psilocybin is more commonly referred to as “magic mushrooms” because psilocybin is contained naturally within the mushroom. More than 180 species of mushrooms contain psilocybin or its derivative psilocin.

Psilocybin has deep roots in history. The first evidence of psilocybin dates back to between 4,000-7,000 B.C.E. Within mountain ranges in Tassili, Algeria, there are ancient rock carvings that suggest ancient psilocybin use. In one carving, a row of masked figures hold up mushrooms in their right hands. Two parallel dotted lines from each mushroom connect to the top of the figures’ heads. In another carving, a large, masked figure is shown with mushrooms growing from its hands, forearms, and thighs. Furthermore, around 1,000-500 B.C.E, tribes and indigenous persons in Mexico and Guatemala erected temples for mushroom gods. In addition, mushroom-carved stones and other mushroom motifs from 200 A.D. also appeared throughout Central America. Ancient psilocybin use indicates that psilocybin has been used for thousands of years to facilitate religious and spiritual experiences.

In 1957, psilocybin gained notoriety in the United States after mycologist R. Gordon Wasson wrote an article in Life Magazine. Mr. Watson described the use of psilocybin mushrooms in a ritual ceremony Mr. Watson witnessed on a trip in Mexico. In the years following, several clinical studies were conducted using psilocybin to aid in treating alcoholism, schizophrenia, autism, obsessive-compulsive disorder, and depression. Yet, the Food & Drug Administration (FDA) labeled psilocybin a schedule 1 controlled substance in the Controlled Substances Act in 1970. A schedule 1 controlled substance is defined as a substance that has “no currently accepted medical use and a high potential for abuse.” Consequently, medical research of psilocybin halted until 1992, when the National Institute on Drug Abuse partnered with the FDA to allow for psychedelic research. Today, several organizations have been created for the purpose of studying psilocybin in a clinical setting. The goal of these organizations is to study the medical benefits of using psilocybin to treat a variety of illnesses and to effectively lobby local, state, and national governments to change psilocybin’s Schedule 1 classification.

Medical Benefits

Psilocybin gained popularity in the 1960s and 1970s following the discovery psilocybin by R. Gordon Wasson. Research suggested that psilocybin could be used to treat a variety of ailments. After the Controlled Substances Act went into effect in 1971, medical studies related to psilocybin came to a halt. However, early research and anecdotal experiences have prompted medical researchers to investigate the therapeutic compounds of psilocybin mushrooms. Today, there are several organizations that have already completed clinical trials and are currently undergoing clinical trials using psilocybin. The goal of all clinical trials is to determine how the substance may help treat symptoms of a verity of illnesses. Specifically, psilocybin may effectively treat symptoms of depression, addiction, OCD, cancer-related anxiety, cluster headaches, anorexia, Alzheimer’s Disease, among others.

Depression

The use of psilocybin to treat depression has shown the most promise when compared to using psilocybin to treat other ailments. The FDA has designated psilocybin as a “breakthrough therapy” for depression, which could accelerate the process of psilocybin drug development and review.

In 2016, Johns Hopkins CPCR published its study on using psilocybin mushrooms to treat symptoms of depression and anxiety.[1] Specifically, the study involved 51 cancer patients with life-threatening diagnoses that had symptoms of depression and/or anxiety. Johns Hopkins CPCR studied the effects of a very low dose (1 or 3 mg for every 70 kg of bodyweight) vs. a high dose (22 or 30 mg for every 70 kg of bodyweight) of psilocybin administered in an alternating sequence with 5 weeks between sessions. The moods, attitudes, and behaviors of the patients were observed by medical professionals throughout the study. The researched found that high-dose psilocybin produced substantial decreases in feelings of depression anxiety. Furthermore, researchers concluded that participants using high-dose psilocybin testify to a higher quality of life, contentment with life, optimism, and a decrease in anxiety related to death. Subsequently, participants still felt the positive changes of psilocybin at the 6-month follow-up. Specifically, about 80% of participants showed clinically significant decreases in depressions and anxiety and showed clinically significant improvements in attitudes about life/self, mood, relationships, and spirituality. In addition, over 80% of the study’s participants testified that psilocybin at least moderately increased well-being and life satisfaction.

In 2017, the Beckley Institute published the results of its 6-month study about using psilocybin mushrooms to treat depression.[2] Using twenty patients with mostly severe and treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart). Medical professions assessed the symptoms were assessed from 1 week to 6 months post-treatment. The researchers found that psilocybin significantly reduced depressive symptoms for the first 5 weeks post-treatment. Furthermore, participants experienced reduced depressive symptoms at 3 and 6 months. Importantly, none of the participants sought conventional antidepressant treatment within the 5 weeks of the last administration of psilocybin. Ultimately, researchers concluded that patients reacted positively to psilocybin, and symptoms experienced by participants after two psilocybin treatment sessions remained significant 6 months post-treatment. As a result, the researchers felt psilocybin is a promising treatment for reducing symptoms of depression.

Currently, the Usona institute in conducting a Phase 2 clinical study using psilocybin to treat symptoms of depression. A Phase 2 clinical trial is the second step in a typical four-step drug approval process. During the drug approval process, the safety of psilocybin is tested in larger groups of people as the drug moves through the phases. Specifically, Phase 2 studies can involve up to several hundred volunteers. The goal of the study is to research the safety and effect of a  single dose of psilocybin compared to a placebo in participants with depression. Each participant will be randomized to receive either a one-time dose of psilocybin or a placebo. The study started in Fall 2019 and is expected to be completed in Spring 2021. Right now, 5 locations across the nation are accepting volunteers to be part of this study (including Segal Trials in Lauderhill, Florida) and 2 locations will be accepting volunteers in the near future. To learn more about this ongoing study, click the link below.

https://usonaclinicaltrials.org/major-depressive-disorder-psilocybin-clinical-trial-psil201

Another ongoing Phase 2 clinical study using mushrooms to treat symptoms of depression is being conducted by John Hopkins CPCR. There are 24 participants that receive a moderately high psilocybin dose in the first session and receive either a moderately high or high psilocybin dose in the second session. The study began in August 2017 and is expected to be complete by December 2020.[3]

Addiction

In 2014, Johns Hopkins University School of Medicine published a study on the use of psilocybin to treat tobacco addiction.[4] The study used 15 participants who received moderate (20 mg for 70 kg of body weight) and high (30 mg for 70 kg of bodyweight) doses of psilocybin within a 15-week smoking cessation treatment. Participants on average had attempted to quite smoking cigarettes 6 times and smoked an average of 19 cigarettes per day.  Medical professionals assessed the participants’ health and testimony of participants’ smoking behavior. The researchers concluded that 80% of the participants abstained from smoking for an average of 7 days at 6-month follow-up. Researchers found that the 7 day abstinence from smoking substantially exceeds the abstinence time reported by other pharmacological therapies by around 35%. The early findings suggest psilocybin may be effective at getting individuals to overcome addiction.

In 2015, a study funded by the Heffter Research Institute was published about the use of psilocybin to treat alcohol addiction.[5] In the study, ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions. Furthermore, the participants received Motivational Enhancement Therapy and therapy sessions to prepare for and debrief from the psilocybin sessions. During the first four weeks of the study, the participants engaged in weekly therapy and did not receive any psilocybin. The researchers found that participants did not significantly abstain from alcohol during the first 4 weeks of the study. Yet, researchers determined that participants reported a significantly reduced number of drinking days and heavy drinking days for the 32 weeks that followed the participant’s use of  psilocybin. As a result, researchers concluded that the findings indicate that psilocybin could be an effective treatment for alcohol addiction, and further studies with larger sample sizes are required.

Currently, John Hopkins CPCR, the Beckley Institute, and the Heffter Research Institute are collaborating on a clinical study using psilocybin to treat symptoms of nicotine dependence.[6] The study follows psilocybin studies in treating addiction conducted in the 1960s, 1970s, and from previous studies that found psilocybin can cause participants to have important experiences for the participant’s self-meaning and spiritual significance (Griffiths et al., 2006, 2008). The study is estimated to have around 95 participants. The purpose of the study is to compare the use of psilocybin or transdermal nicotine patch when administered under highly supportive conditions to individuals who are nicotine-dependent cigarette smokers, who have had multiple unsuccessful quit attempts, and who continue to desire to quit smoking. Participants in the study will receive a 13-week course of cognitive behavioral therapy for smoking cessation, with Target Quit Date set for week 5. Participants will have either a single day-long psilocybin session using a high dose (30 mg for 70 kg of body weight), or a standard 8 to 10-week course of nicotine patch treatment. Medical professionals will monitor participant smoking status for 8 weeks after the Target Quit Date. Smoking status will also be assessed at three follow up sessions approximately 3, 6, and 12 months after the Target Quit Date. In addition, 50 participants will undergo MRI scanning before and after Target Quit Date to assess the effect of both treatments on the brain-based mechanisms associated with overcoming nicotine addiction. The study is still seeking volunteers, but volunteers must live within driving distance of John Hopkins Bayview campus in Baltimore, Maryland.

Obsessive-Compulsive Disorder

In 2006, Francisco A. Moreno, MD; Christopher B. Wiegand, MD; E. Keolani Taitano, PhD; and Pedro L. Delgado, MD published a study entitled Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder.[7] The study used nine participants  with DSM-IV-defined OCD and no other current major psychiatric disorder. Each participant  was administered 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to hallucinogenic. Specifically, each participant was first given a low dosage (100 microgram per kg of bodyweight), then medium dosage (200 microgram per kg of bodyweight), and finally high (300 microgram per kg of bodyweight) doses were assigned in that order. Yet, each participant received an administration of a very low dose (25 microgram per kg of bodyweight) at a random time after the first dose. The test days were separated by at least 1 week and each session lasted 8-hours. Subsequently, participants stayed overnight at a psychiatric inpatient unit for overnight observation. The researchers found that participant’s showed between a 23%-100% reduction in OCD symptoms. Furthermore, participants reported that the reduced symptoms of OCD lasted well  Improvement generally lasted well-beyond 24 hours Therefore, researchers concluded that psilocybin caused a significant reduction in OCD symptoms of its test subjects.

Cancer-Related Psychological Distress

In 2020, The Heffter Research Institute published an Early Phase 1 study it conducted on using psilocybin to treat cancer-related psychological distress.[8] 15 volunteers participated in the study over the span of 3-4.5 years. Each participant received a single dosage (0.3mg per kg of bodyweight) of psilocybin. The participants reported reduced anxiety, depression, hopelessness, demoralization, and death anxiety at the first and second follow-ups. Specifically, 60-80% of participants met criteria for clinically significant antidepressant responses. Moreover, 71-100% attributed positive life changes to the psilocybin-assisted therapy experience and was considered among the most personally meaningful and spiritually significant experiences of the participants’ lives. The researchers determined that psilocybin promotes long-term relief from cancer-related psychiatric distress and enhances psychological, emotional, and spiritual well-being for patients with life-threatening cancer.

In 2011, a study funded by the Heffter Research Institute, the Betsy Gordon Foundation, the Nathan Cummings Foundation, among others was published about the use of psilocybin to treat cancer-related psychological distress.[9] 12 volunteers with advanced-stage cancer participated in the study over the span of 4 years. 8 volunteers completed the 6-month follow-up assessment, 11 completed the first 4 months of assessment, and all 12 volunteers completed at least the first 3 months of follow-up. Each volunteer had two experiences, a single dose of psilocybin (0.2mg per kg of bodyweight) on one occasion and a placebo on one occasion. Reserachers noted a significant reduction in anxiety and depression. As a result, the researchers concluded that psilocybin may provide effective treatment for anxiety caused d by advanced-stage cancers.

Cluster Headaches

A cluster headache is a special type of headache. Cluster headaches are shorter in duration than migraines, but are more intense. A person suffering from cluster headaches often describe the pain as significant, disruptive, and interferes with a person’s quality of life. Currently, the Heffter Research Institute is conducting a Phase 1 study on using psilocybin to treat symptoms of cluster headaches. [10] The study began in November 2016, and is expected to conclude in December 2020. There are 24 participants that will receive either receive an oral placebo, low dose psilocybin (1 mg), or high dose psilocybin (10mg) in three experimental sessions. Each administration of psilocybin is separated by 5 days. The study is expected to be published by November 2021.

Anorexia Nervosa

Anorexia is a type of psychological disorder that is characterized by a distorted body image, with a fear of being overweight. Individuals suffering from anorexia are underweight and often exercise to excess. Currently, Johns Hopkins CPCR is conducting a Phase 1 study of using psilocybin to see (1) if individuals diagnosed with anorexia nervosa can safely use psilocybin and (2) if psilocybin will improve an anorexia nervosa patient’s quality of life.[11] Participants will undergo two moderate to high dose psilocybin sessions. At the first session, each participant will receive will be the lesser of 20 mg or 0.6 mg per kg of body weight. At the second session, each participant will either remain at participant’s initial dose, or increase to the lesser of 25 mg or 0.6 mg per kg of bodyweight based upon the discretion of the study team. The total time commitment for the main portion of the study is about 8-10 weeks, with long-term follow-ups conducted for an additional 6 months. The study began in August 2019 and is expected to finish in December 2022.

Alzheimer’s Disease

Currently, Johns Hopkins CPCR is recruiting volunteers for an Early Phase 1 study on the use of psilocybin by individuals diagnosed with early Alzheimer’s disease (or Mild Cognitive Impairment).[12] Specifically, Johns Hopkins CPCR will study (1) if individuals with early Alzheimer’s disease can safely use psilocybin and (2) if psilocybin will improve an early Alzheimer patient’s quality of life. Participants will complete an 8-weeks of treatment including two psilocybin sessions. In the first session, participants will be administered a psilocybin dose of 15 mg per 70 kg of bodyweight in week 4. The second session, participants will receive a psilocybin dosage of 15 or 25 mg per 70 kg of bodyweight. Subsequently, all participants will receive follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants prior to treatment through post-treatment. The study is expected to begin in late July 2020 and is expected to be completed in March 2022.

Mr. Psychedelic Law Members Highlight

Scott Fisher, MD.

What research are you currently involved in relating to psychedelics and what is your role in that research?

I am lead facilitator for the Fort Lauderdale site of the Usona-sponsored PSIL201, a randomized, double-blind, placebo-controlled, FDA-registered Phase 2 clinical trial assessing the effectiveness of a single dose of psilocybin for the treatment of major depressive disorder.

How did you get involved in the psilocybin industry?

 I became involved when I realized the incredible potential that psychedelic-facilitated spiritual experience has for helping to heal a variety of emotional and mental health problems.  The field of psychiatry has unfortunately neglected the importance of spiritual and religious growth on mental health.  I believe psilocybin treatments represent an important step towards addressing this glaring gap in helping our patients and clients.

Have you taken any specific course work related to psychedelics?

I hold a Certificate in Psychedelic Therapy and Research from the California Institute of Integral Studies, the only program of its kind at an accredited institution of higher learning.  As part of that program, I have completed the majority of the Multidisciplinary Association of Psychedelic Studies training for MDMA-assisted psychotherapy to treat post-traumatic stress disorder, in addition to significant clinical coursework in psilocybin-assisted therapy.  I have also completed training from the Usona Institute for facilitators assisting in their studies of psilocybin to treat depression.

What does progress in the psilocybin industry mean to you?

FDA approval of psilocybin-assisted therapy to treat major depressive disorder, a strong possibility in the next 4-5 years, would be the next step towards progress.  Beyond that, further studies will hopefully clear a path forward for a broader legalization of responsible use.  I believe research done in the future is likely to prove psilocybin, when used in the right setting with good intentions, helpful for what has been called the improvement of already basically healthy people.

Policy

Psilocybin is a Schedule 1 controlled substance under the Controlled Substances Act. As a result, possession and use of psilocybin is federally illegal. Furthermore, psilocybin is illegal in all 50 states. As a result, only organizations with approval from the FDA and DEA may lawfully administer psilocybin to conduct clinical trials. Moreover, three cities which include Denver, Santa Cruz, and Oakland have both signed legislation to decriminalize psilocybin and magic mushrooms. In those cities, decriminalization opens the door for researchers to explore potential medical benefits. While psilocybin remains illegal, psilocybin mushroom spores are legal to possess in the United States with the exception of California, Georgia, and Idaho. Yet, the act of cultivating psilocybin spores into psilocybin mushrooms is considered illegal.

At Mr. Psychedelic Law, we envision a RESPONSIBLE legal framework that allows people to reach a higher level of consciousness through psilocybin mushrooms and other psychedelics while also accounting for the potential negative effects of taking these compounds under the wrong set and setting. We will accomplish this goal by gathering the brightest medical, scientific, spiritual, and legal minds in Florida to speak about psilocybin mushrooms so as to open the minds of Florida citizens to the need for, and concept of RESPONSIBLE legalization of this ancient healing plant medicine.

[1] Griffiths, Roland R, et al. “Psilocybin Produces Substantial and Sustained Decreases in Depression and Anxiety in Patients with Life-Threatening Cancer: A Randomized Double-Blind Trial.” Journal of Psychopharmacology, vol. 30, no. 12, 2016, pp. 1181–1197., doi:10.1177/0269881116675513.

[2] Carhart-Harris, R. L., et al. “Psilocybin with Psychological Support for Treatment-Resistant Depression: Six-Month Follow-Up.” Psychopharmacology, vol. 235, no. 2, 2017, pp. 399–408., doi:10.1007/s00213-017-4771-x.

[3] ClinicalTrials.gov Identifier: NCT03181529

[4] Johnson, Matthew W, et al. “Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction.” Journal of Psychopharmacology, vol. 28, no. 11, 2014, pp. 983–992., doi:10.1177/0269881114548296.

[5] Carhart-Harris, R. L., et al. “Psilocybin with Psychological Support for Treatment-Resistant Depression: Six-Month Follow-Up.” Psychopharmacology, vol. 235, no. 2, 2017, pp. 399–408., doi:10.1007/s00213-017-4771-x.

[6] ClinicalTrials.gov Identifier: NCT01943994

[7] Mareno, MD., Francisco A., et. al. “Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder.” Maps.org, Multidisciplinary Association for Psychedelic Studies; the Heffter Research Institute, 2006, maps.org/research-archive/w3pb/2006/2006_Moreno_22868_1.pdf.

[8] Agin-Liebes, Gabrielle I, et al. “Long-Term Follow-up of Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Patients with Life-Threatening Cancer.” Journal of Psychopharmacology, vol. 34, no. 2, 2020, pp. 155–166., doi:10.1177/0269881119897615.

[9] Grob, Charles S., et al. “Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer.” Archives of General Psychiatry, vol. 68, no. 1, 2011, p. 71., doi:10.1001/archgenpsychiatry.2010.116.

[10] ClinicalTrials.gov Identifier: NCT02981173

[11] ClinicalTrials.gov Identifier: NCT04052568

[12] ClinicalTrials.gov Identifier: NCT04123314