On her blog, Dr. Nora Volkow called attention to the potential use of psychedelics to treat various mental health issues. She noted where a variant of ketamine known as esketamine is already FDA approved to treat treatment-resistant depression. And the FDA has designated formulations of psilocybin and MDMA as “breakthrough therapies” for depression and PTSD respectively. As the Director of the National Institute on Drug Abuse (NIDA), she also acknowledged they represent “a potential paradigm shift in the way we address substance use disorders.” However, there is a lot we still do not know about these drugs, “and there is danger of the hype getting out ahead of the science.”
Dr. Volkow said the promise of psychedelic compounds was likely because of their ability to promote rapid neural rewiring. Recent studies have suggested the “neuroplastogen” properties of psilocybin might be related to its ability to bind to serotonin receptors inside neurons, something that serotonin cannot do. (Neuroplastogens are compounds that are capable of rapidly promoting structural and functional neuroplasticity.) This rewiring may explain the long-lasting effects of psilocybin and other psychedelic compounds. “What is needed is sound scientific research including clinical trials that can substantiate therapeutic efficacy, duration, and safety in large numbers of participants.”
As part of a research study, psychedelics are administered by clinicians within highly controlled settings. This is important not only for safety reasons but because contextual factors and expectations play a crucial role in their effectiveness. Whether a patient has a positive or negative experience depends to a significant extent upon their mindset going into the experience and whether the setting is one in which they feel secure. This raises an important question—the extent (if any) to which the clinician’s time and attention and/or therapeutic approach play a role in psychedelics’ therapeutic efficacy—where much more research is needed. The extent to which psychotherapy is necessary in conjunction with psychedelics and which methods work best is an open question.
She noted several challenges to studying psychedelics in clinical trials, beginning with the lack of effective placebos that make clinical trial participants unsure whether they received the placebo, or the psychedelic drug being studied. Patients who take psychedelics in clinical trials are in a highly vulnerable state, and there are no widely accepted therapeutic protocols to ensure their safety. Some groups, like veterans with PTSD, who might benefit the most from treatment with psychedelics may also have a high potential risk of harm from psychedelic-based treatment. In addition to developing training protocols for clinicians, there is no standard yet for their credentialing. And lastly, given that adjunctive psychotherapy with these treatments would be expensive, “there must be a model for reimbursing providers to facilitate equitable access.”
Psychedelics and Psychotherapy
David Nichols and Walter Hanna wrote in “The History of Psychedelics in Psychiatry” that initial interest in the value of psychedelic drugs was in the possibility they might produce mental effects like those of schizophrenia or other psychiatric disorders. Early studies with peyote and mescaline described the nature of their effects on the psyche. In time, interest focused on whether the effects of psychedelics resembling mental illnesses could enlighten the underlying basis for understanding how to treat psychiatric disorders. Then the role of psychedelics as adjuncts to psychotherapy began to evolve and became the primary focus of work with psychedelics through the present time.
A psychiatrist named Humphry Osmond heard of the discovery of LSD by Albert Hoffman and tried it himself. He discovered it produced profound changes in consciousness. By inducing a new level of self-awareness, Osmond theorized LSD could have therapeutic benefits for individuals suffering with schizophrenia. Some of his early volunteers in LSD experiments described this feeling as “a new sense of spirituality.”
Osmond’s co-researcher, Abram Hoffer, had the idea to try LSD with alcoholics because he thought LSD experiences were similar to descriptions of delirium tremens. In 1953, he and Osmond wondered if a controlled LSD-produced delirium would help alcoholics stay sober because of their fear of experiencing delirium tremens from drinking. Over the next ten years they tried this procedure on over 700 patients, one of who was Bill Wilson, cofounder of Alcoholics Anonymous.
For more on Bill Wilson and LSD, see “As Harmless as Aspirin?” and “Bill W. and His LSD Experiences,” Part 1 and Part 2.
In “The History of Psychedelics in Psychiatry,” Nichols and Hanna noted by 1951, more than 100 articles on LSD and its psychiatric uses had appeared in medical journals. By 1961, that had increased to more than 1,000 articles. Hoffer and Osmond quickly abandoned their idea of inducing a fear of delirium tremens and began to emphasize the psychedelic aspects of LSD with alcoholics. “From the beginning, it was not considered that LSD by itself could produce a major change in the alcoholic but was looked upon as an essential factor in an overall treatment program based on several therapeutic variables.”
In her article, Dr. Volkow commented that Wilson believed that, by inducing spiritual experiences, psychedelics would help with the spiritual awakening in Step Twelve. She said one of the most interesting questions around psychedelics is whether the commonly reported spiritual experiences and other subjective effects are essential to their therapeutic effects. Conversely, are they side effects that could be potentially decoupled to make a safer and easier-to administer pharmacologic compound? “There are contrasting schools of thought on this question, and thus far the evidence remains inconclusive.”
Nichols and Hanna said Sandoz Pharmaceuticals and Albert Hofmann didn’t anticipate that a drug developed for understanding mental illness would become widely used recreationally. Additionally, the FDA began using new, rigid criteria required by the Drug Amendments of 1962, which mandated a drug had to be shown to be safe and effective to be approved. “In contrast to most drugs, proving effectiveness for LSD and psychedelics was not easily defined, let alone measured.” The passage of the 1962 drug amendments meant that no new studies with psychedelics would be approved by the FDA.
Then in the late 1990s brain imaging technologies began to be applied to the study of psychedelics. The first new research study to explore the potential therapeutic value for a psychedelic occurred in 2006—a small proof-of-concept safety study of psilocybin given to 9 patients suffering from obsessive-compulsive disorder (OCD). Marked decreases in symptoms were observed in all subjects. Given the small number of subjects, the study was not conclusive. Clinical studies began to proliferate in a new wave of research.
They all reported statistically significant therapeutic improvement in the participants. Follow-up studies for this research have been carried out, as well as a number of studies using modern imaging technologies to understand better the effects of psychedelics on brain function. The growing number of such trials shows that we are entering a new phase of research with psychedelics.
Nevertheless, there are unique psychological risks with psychedelics, even if there is a low degree of physical risks. The most likely risk is having a “bad trip” during the drug effect, which could lead to potentially dangerous behavior such as leaving the study site. Psychiatry is now rethinking the promise of psychedelics. “As a result psychiatry may be undergoing a paradigm shift with respect to treatment of depression, anxiety, addictions, and other illnesses.”
Researchers and the public need to take to heart the cautions expressed by Nora Volkow in her blog article. The serious problem of the lack of effective placebos means when there are positive results in psychedelic clinical trials, they need to be taken with a grain of salt. The highly vulnerable state of patients using psychedelics means therapeutic protocols must be developed AND adhered to ensure patient safety. There was a report of an unlicensed MDMA-assisted therapist working for MAPS being sued for sexually assaulting a subject under MDMA’s influence. See “The Long Strange Trip of MDMA-Assisted Therapy.”
I don’t think we’re at the place to say psychiatry is undergoing a paradigm shift in treatment with psychedelics. We need significantly more research before we can claim psychedelics are changing how we treat depression, anxiety, addictions, and other illnesses. For more on the problems and concerns with psychedelic-assisted therapies, see “Psychedelics Are Not a Magic Bullet,” “Psychedelics as the Newest Psychiatric Craze,” Part 1 and Part 2, “Psychedelics and Veterans,” and “Pursuing Psychedelic Therapy.”
