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Psilocybin: From mysticism to healing

Imagine a drug that will take you on a mystical experience where you can ride a dragon or touch the stars, but imagine the same drug can suffocate you under quicksand or imprison you in a sea of volcanic ash. These experiences are not through the mechanism of delusions, but through vivid hallucinations with the guide of a psychotherapist. Imagine one dose being able to help you through your worst nightmares or accept the fate of a terminal illness. A drug that was once used in spiritual ceremonies – psilocybin – may potentially have medicinal benefits in the thoughtfully decorated observation room.

Use cases

Depression is one of the leading causes of medical morbidity globally, and neuropsychiatric disorders are considered to be the leading cause of disability in the United States. [1] It is estimated that 1 in 6 Americans will experience a major depressive disorder episode in their lifetime. [2] In the U.S. alone, depression leads to an economic burden of $215 billion per year. [3] According to the United States Department of Veterans Affairs, roughly 8 million people suffer from post-traumatic stress disorder (PTSD) in a given year, with many of them in the veteran population [4]. Depression and anxiety often accompany PTSD symptoms and insomnia can delay recovery.

Science has been slow to catch up to these statistics and, after a decade without any new psychiatric medications, last year the FDA approved an esketamine nasal spray, Spravato®, for treatment resistant depression (TRD). Its supply and use is limited for patients who have tried and failed other antidepressant medications, and whose disease is debilitating. It is administered in a clinical setting with careful observation by a physician. In the same year, the FDA granted “breakthrough therapy” status to the previously taboo drug class, “psychedelics” for the treatment of TRD, PTSD and anxiety.


Numerous agents are often classified as psychedelics, such as ecstasy (MDMA), cannabis, amphetamines or NMDA. But when we think of classic psychedelics, the most commonly known drugs are psilocybin, LSD, DMT and mescaline. The evidence of these compounds’ existence dates back thousands of years – their evidence seen in pottery, painting artifacts and religious ceremonies, though their introduction to Western civilization is relatively new. Discovered from various indigenous plants and mushrooms, these psychedelics positively showed their effects on psychiatric conditions and were quickly brought into the laboratory for scientific research. Psilocybin, extracted from more than 200 species of Basidiomycota mushrooms, was first isolated in 1959 by a Swiss chemist, Albert Hofmann and was studied extensively by various institutions across the globe. The FDA later categorized it as a Schedule I agent under the Controlled Substance Act. However, today it is making its comeback; it is in recent phase 3 trials for FDA approval.

Psilocybin was studied in many trials during the 1960s before it was labeled as a drug with no outweighing medicinal benefit. During this time period, the enthusiasm of some lead investigators and participants often enhanced the mysticism associated with these agents. This led study results astray for many psychedelics, resulting in those trials failing to show any clinical benefit in a randomized double-blind placebo control setting.


As this therapeutic class is resurfacing, the medical community is careful in setting a study design and adequate steps are being taken to ensure the validity of the studies. Psilocybin is synthesized in a 25mg white capsule and its goal is to enhance psychotherapy. Set and setting dictates the outcomes of the therapy. In a clinical setting, the patient is prepared for the journey through psychotherapy sessions, then guided through the journey by trained facilitators, and finally discusses the outcomes after the journey. Bad trips are expected, but overcoming those experiences with the help of a guide is what makes the treatment successful. The only source of study medication is through The Usona Institute, who distributes cGMP psilocybin free of charge to all qualified researchers across the globe. Preliminary data is promising, with persistent symptoms remission, but trials are still ongoing, so we’ll have to wait to deduce any conclusions.

Future possibilities

Many of us may have heard about psychedelic microdosing as it has been in the mainstream media over the past few years. We may even have questioned the use of these drugs at a workplace. Can a person be under the influence while at work? Can it affect a person’s cognitive ability to perform job functions, or could it be protected under ADA if used for a medical condition?

Microdosing is the regular consumption of small amounts of psychedelics, such as LSD or psilocybin, to gain improvements in cognitive function. In contrast to using full-dose psychedelics, microdosing does not cause perceptual alterations. Usually 1/10th of the regular dose is taken once every three days, but consumers often vary widely in the actual amount of psychedelics they take.

Individuals who microdose report minimal acute effects from these substances, yet claim a range of long-term general health and well-being benefits. There are no double-blind placebo control trials conducted on microdosing, but what we do know are some of the negative effects of microdosing such as neuroticism, which is a personality trait often linked to anxiety, fear and frustration. Just like a full dose of psychedelics, microdosing can cause an increase in blood pressure, heart rate and is contraindicated in people with cardiovascular issues.

As we learn more about the clinical trials and the potential of psychedelics, one is eager to find if these are truly an answer for the treatment of major psychiatric disorders. Since the FDA has fast-tracked some of the studies, will the DEA reschedule certain drugs? Could we expect legalization of psychedelics prior to cannabis? Those are some of the questions we don’t have the answers to yet, but we do know certain facts:

  • Psilocybin can be synthesized in a laboratory, same drug, strength and formulation can be produced and reproduced.
  • Efficacy and safety can be measured and does not have a high abuse potential months after the last study dose for patients who have utilized it during a carefully supervised clinical setting.
  • It has a relatively short half-life and the effects diminish eight hours after ingestion.
  • Hallucinogen persisting perception disorder (HPPD) has been noted in the literature, but to date, none of the clinical trials where dose, set and setting were carefully monitored exhibit this disorder.
  • The risk of developing HPPD is high in patients who are concurrently using other hallucinogens or have substance use disorder.
  • Psychedelics are contraindicated in patients with cardiovascular issues, bipolar or schizophrenia diagnosis.

Historically used for a spiritual ceremony to reach divine transcendence or currently used for its healing benefits in a clinical setting, psilocybin advocates continue to promote its use. Some promising results in randomized double-blind, multicenter placebo control trials for the treatment of certain psychiatric disorders indicate that we must pay attention. Not every person may experience a mystical journey, but through alteration of the conscious mind along with the psychotherapy, more patients may be able to overcome their fears and emotions. We will continue to watch the trends and monitor the impact this drug and other psychedelics may have in both the individual and corporate environments.

> Sedgwick congratulates Dr. Reema Hammoud on her selection as one of this year’s Business Insurance Women to Watch! Learn more about this honor.

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