Depression, anxiety, and post-traumatic stress disorder (PTSD) are among the most intractable conditions of our time. Modern society seems to be good at creating the ground on which they thrive. We have only recently realized that simple molecules that could help these conditions have been known for decades.
Timothy Leary, a Harvard professor of psychology of the 1960s, promoted psychedelic drugs, but his goals were vague. Turn on, tune in, drop out”—Leary’s admonition was directed at people who thought their minds would be expanded, and perhaps they were, but Leary’s prescription for fulfillment was not helpful to scientists and physicians seeking therapies for depression and anxiety. The drugs also scared the FDA and other government officials because they were part of the 1960s counterculture movement. They could be dangerous. Psychedelics were banned in 1970. Now, the FDA and other agencies are in the process of reclassifying these drugs, largely because of preliminary therapeutic results.
Banned drugs, like banned books, have a way of reappearing. Ketamine, psilocybin, LSD, and MDMA can have extraordinary effects, including hallucinations and an expansive view of life. They are simple compounds and easy for chemists to make. Psychedelic drugs bind to important elements called receptors in neurons. Psilocybin, from a family of mushrooms, has been used for centuries by Native Americans as part of cultural and religious practice. Matthew W. Johnson and Roland R. Griffiths of Johns Hopkins wrote a 2017 review of the therapeutic effects of psilocybin for depression and other conditions. They and other researchers have pulled some of these drugs out of administrative limbo.
Ketamine was approved by the FDA in 1970, the same year that other psychedelic drugs were banned. It is a sedative and anesthetic for children, and it remained available for other uses. Profoundly depressed patients, who had not been helped by serotonin uptake inhibitors like Prozac, which act slowly, quickly responded to ketamine. Except for ketamine, the 1970 ban stopped research funding for psychedelic research, but their use continued underground. Michael Pollan, professor of psychology at University of California, Berkeley, recounted his own experiences taking these drugs and provides a history of their development and use in “How to Change Your Mind.” His book is a good place to start.
The bans lasted until the late 1990s when clinical trials were permitted by The National Institutes of Mental Health for patients with major depressive disorder and anxiety in terminally ill cancer patients. Post-traumatic stress disorder has also been studied. Clinical trials of these drugs are not easy to do and take time to assemble, so the numbers are small.
A specific dose of pure psilocybin or ketamine causes sedation and then a psychedelic trip, with auditory and visual hallucinations, sometimes of an extraordinary nature that can, in the patient’s perception, touch on the divine and block the ability to distinguish reality and fantasy. Patients report a loss of ego. A guide always attends and is important to the results. Relief from depression occurs quickly and lasts for months after the drug has disappeared and the patient’s brain has reassembled a rational view of the world. Most drugs act only when present in the brain above a particular concentration. That said, a bad trip can be terrifying, and the memory of it endures.
All psychiatric conditions have a physical basis in nerve cells and the circuits they form. Instinctively, many people (including me) think of non-corporeal causes, but there is no devil or evil spirit here. There are physical structures and neuronal circuits that can be touched by psychedelics or other drugs, or by electroshock. It looks like psychedelics can do that, but how they do it is unclear.
Syndromes like PTSD lead to self-treatment with opioids and alcohol. Not to study these the psychedelics would be irresponsible. But it will not be simple—there are many neurological conditions and numerous psychedelics, not all have the same effect. Drug concentrations and methods of application make a difference, as does coordinated psychotherapy. There will probably be cultural objections to using these drugs.
A few years ago, I wrote four columns that provided background and described the neurons and receptors involved in euphoria and in controlling breathing. The columns described then-current treatments for opioid addiction that worked and some that do not. We do not know how psychedelics work on symptoms. We have clues from brain-imaging studies that are now incorporated into clinical trials. Mechanism may be beyond a microbiologist like me, but medical centers with strong departments of neuroscience and psychiatry who are using new approaches to treatment are the place to start. Learning how to treat intractable conditions is always fraught, especially if it involves drugs with a prior history.
Rich Kessin is emeritus professor of pathology and cell biology at the Columbia University Irving Medical Center. Email: Richard.Kessin@gmail.com.
