After a 50-year hiatus, psychedelic drugs are undergoing a research renaissance. Roland R. Griffiths, PhD, professor in the Departments of Psychiatry and Neuroscience and the Oliver Lee McCabe III, Professor in the Neuropsychopharmacology of Consciousness, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Baltimore, discusses the status of these drugs in the United States and their potential to treat psychiatric disorders.
Dr. Roland R. Griffiths
Classic psychedelics are compounds that bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include the naturally occurring compounds psilocybin, N,N-dimethyltryptamine (DMT, a component of ayahuasca) and mescaline (peyote cactus), as well as the synthesized compound lysergic acid diethylamide (LSD).
Other drugs, such as ketamine, are sometimes referred to as “psychedelics” because they can produce subjective experiences that are similar to those of people who receive classic psychedelics. However, unlike classic psychedelics, the effects of ketamine tend to be short lived. Ketamine also has addictive potential and can be lethal in high doses, which is not the case with psilocybin.
Another compound sometimes referred to as a “psychedelic” is 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy.” The Food and Drug Administration granted breakthrough approval for the study of MDMA for posttraumatic stress disorder (PTSD). FDA-approved registration trials are ongoing. MDMA differs from classic psychedelics in risk profile and pharmacology. In particular, MDMA was widely abused as part of the “rave culture,” while classic psychedelic agents do not lend themselves to that type of misuse.
What is the current legal status of psychedelic agents in the United States? Can clinicians prescribe them, or are they available only in a research setting?
All classic psychedelics are considered to be “Schedule 1” which means they are illegal to possess and use except for research and only if approved by the FDA and under licensure of the Drug Enforcement Administration (DEA), so they are not available for clinical use.
In anticipation of the possibility that phase 3 research may support the efficacy and safety of psilocybin for one or more medical or mental health disorders, our team has reviewed available evidence regarding its abuse liability and concluded that, if psilocybin were approved as medication, it could possibly be included in the Schedule IV category, with additional FDA-mandated risk management provisions. However, this is not yet the case.
Which psychedelic agents are under investigation in the United States, and for which indications?
Psilocybin is under investigation in our center, as well as elsewhere in the United States. We have previously found it to be effective for smoking cessation, and we are conducting another study that is currently recruiting volunteers for this indication. We are also recruiting volunteers for studies on the use of psilocybin for major depression, Alzheimer’s disease, and anorexia nervosa. Further information about our studies can be found on the Web site for our center, the Center for Psychedelic and Consciousness Research.
Two companies – the Usona Institute and COMPASS Pathways – have received FDA Breakthrough Therapy Designation for their programs seeking approval of psilocybin as a treatment major depressive disorder and treatment-resistant depression (TRD), respectively. In addition, an international multicenter study currently underway, which includes US centers in Houston, Baltimore, New York, San Diego, and Atlanta, is investigating psilocybin for TRD.
A number of studies, including one conducted at our center, have investigated psilocybin for depression and anxiety in patients with cancer and found it effective.
Additional research showed that psilocybin alleviated symptoms of cancer-related anxiety and depression, both in the short-term and 5 years later.
LSD has been studied and found promising in the treatment of alcohol use disorder. Additional studies of LSD that are being conducted in Basel Switzerland and at the University of Chicago are examining its impact on mood in healthy volunteers.
Ayahuasca has been studied extensively for depression and anxiety and is also currently under investigation for PTSD. We found that its use in a naturalistic group setting was associated with unintended improvements in depression and anxiety.
Lastly, a lesser-known psychedelic agent is Salvinorin A, which our center has been studying, is the psychoactive constituent of the Salvia divinorum plant. While this is not a “classic” psychedelic compound, it is nevertheless the focus of much scientific interest because its effects are mediated at opioid receptors, rather than 5-HT2A receptors, and may prove to be a novel nonaddictive opioid that may ultimately be a promising treatment for pain and addiction.