This editorial paper aims to inform the attitude of medical health professionals towards psychedelics, with regard to evaluating their therapeutic potential in accordance with a rigorous application of the scientific method, while taking social, historical, political, and cultural factors that have influenced their legal status and the discontinuation of prior research. The paper highlights the need for psychiatrists to engage with a rational and evidence-based discourse on drug policy that neither glorifies or demonizes psychedelic substances, in step with the ongoing efforts to apply modern standards of randomized placebo-controlled clinical trials. An outstanding challenge for psychiatrists is the manner of communication with patients seeking advice on psychedelic self-medication, in face of alienating by refusing to discuss the matter due to their legal status, while conveying a realistic picture that is proportionate to the degree of scientific evidence that is currently available.

Abstract

“These are interesting times for the practice and teaching of psychopharmacology. For instance, the repurposing of ketamine, the dissociative anesthetic, from anesthesiology into the practice of psychiatry, has garnered considerable interest as a potential innovation in the treatment of major depression. Similarly attracting attention is the re-emergence of psychedelic drugs as potential treatments for a wide range of psychiatric disorders. Baby-boomer psychiatrists will remember the age of psychedelics in the 1960s, while subsequently trained generations of psychiatrists rarely, if ever, heard about them as potential treatments. A hiatus occurred for psychedelic research, from the mid-1970s into the mid-1990s . Despite this hiatus, careful scientific studies with psychedelics began in the mid1990s, by a few investigators. A July 31, 2020, ClinicalTrials.gov search using the term psychedelics  listed 268 National Institute of Health trials for the treatment of both medical and psychiatric conditions, the latter of which include depression, anxiety, obsessive compulsive disorder, posttraumatic stress disorder (PTSD), substance use disorders, and cognitive impairment. Psychedelic drugs include “classical” psychedelics like lysergic acid diethylamide (LSD), psilocybin, and ayahuasca, which are agonists at the serotonin 2A receptor, and empathogens like 3,4-methylenedioxymethamphetamine (MDMA), which release and inhibit the reuptake of serotonin and dopamine. Sometimes, other compounds, like ketamine, and atypical hallucinogens are also called psychedelics. Psilocybin, found in some mushrooms, and ayahuasca, consisting of two plant-based compounds, have been part of sacred ceremonies of ancient cultures and provide an interface between Western psychiatry and traditional indigenous healing approaches. State-of-the-art human studies with psychedelics are not easy to conduct given regulatory challenges and complex design issues, including providing an appropriate control group and blinding. Nevertheless, over the past couple decades, enough evidence has gradually accumulated to warrant Food and Drug Administration (FDA) trials. Psilocybin is currently in early phase 2 trials for the treatment of major depressive disorder and treatment-resistant depression under an FDA breakthrough therapy designation. MDMA is in the midst of phase 3 trials for PTSD , also under a breakthrough therapy designation. Time will tell whether these treatments will ultimately gain FDA approval, but their re-emergence may represent a teachable moment. This editorial focuses on teaching residents about these fascinating and ancient compounds called psychedelics, because they present an opportunity to educate our residents regarding aspects of the scientific method, including its relationship to the social, historical, political, and cultural factors that influence research, the clinical response to public experimentation, and policy. We have parsed the teachable moments into basic, practical, and curious lessons from psychedelics.”

Authors: Alan K. Louie, Eugene V. Beresin, John Coverdale, Richard Balon, Anthony P. S. Guerrero, Mary K. Morreale, Rashi Aggarwal & Adam M. Brenner

Summary

Academic Psychiatry 2020

These are interesting times for the practice and teaching of psychopharmacology, with the re-emergence of psychedelic drugs as potential treatments for a wide range of psychiatric disorders, including depression, anxiety, obsessive compulsive disorder, posttraumatic stress disorder, substance use disorders, and cognitive impairment.

Psychedelic drugs are agonists at the serotonin 2A receptor and include lysergic acid diethylamide (LSD), psilocybin, and ayahuasca. They are also called empathogens, and are used in sacred ceremonies of ancient cultures.

Human studies with psychedelics are not easy to conduct given regulatory challenges and complex design issues, but enough evidence has gradually accumulated to warrant Food and Drug Administration trials.

This editorial focuses on teaching residents about psychedelics, including the scientific method, social, historical, political, and cultural factors that influence research, and policy.

Basic Lessons

Trainees may ask why psychedelics weren’t noted previously. The answer is that 1000 studies were conducted back in the 1960s, but they were conducted before scientifically rigorous clinical trial methodologies were implemented.

Studies on psychedelics were shut down in the 1970s due to legal restrictions, public opinion turning against psychedelics, and reports of adverse outcomes. The field of psychedelic research has only begun to reappear over the last 25 years.

The lesson here for trainees is part scientific and part sociological. Researchers must conduct rigorous scientific studies and clinical trials, and psychiatrists must advocate for rational drug policies based on science, without glorification or demonization of psychedelics.

Practical Lessons

Psychedelics are not yet approved by the FDA for use as a treatment for psychiatric symptoms. Patients are asking psychiatrists about the use of psychedelics, but psychiatrists cannot provide scientific information about psychedelics as a treatment.

Faculty must help residents to address this knowledge gap by providing information about clinical trials that have occurred since the 1990s, as well as ongoing trials for FDA approval. Residents should learn how to respond to patients’ questions.

Curious Lessons

Investigators of drugs like psilocybin have noted that the effects of these drugs are substantially influenced by the setting in which they were administered.

Trainees should be aware that during modern clinical trials with these drugs, subjects are continuously monitored and cared for by two trained researchers, a man and a woman. If psychedelics are approved by the FDA, a Risk Evaluation and Mitigation Strategy protocol is anticipated.

Psychedelic exposure may have long-term effects, even after the drug is cleared from the system. This would support a paradigm in which a psychopharmacological agent enhances long-lasting learning, similar to the paradigm in which transcranial magnetic stimulation augments extinction learning.

Psychedelics may alter behavior in a long-term manner due to new learning enhanced by the drug experience. The set and setting of the experience might play a critical role in determining new connections being laid down.

Psychedelics have been reported to cause lasting behavioral changes, including lowering of blood pressure and smoking cessation, yet researchers are not yet able to differentiate the fMRI images of subjects under the influence of psychedelics and other altered states of consciousness.

Conclusions

Psychedelic drugs have a long history and are currently available illicitly. Psychiatry needs to conduct scientific research to determine the clinical utility of psychedelic drugs and to formulate policies governing their use.