The second age of psychedelic therapies for mental health

Psychedelics like psilocybin and ketamine are being touted as the next generation of treatment for depression, anxiety, and other mental health issues. There’s no question that a next generation is needed. But it’s not like flipping a switch: These therapies involve a novel administration paradigm, acceptance by regulatory bodies, and public appreciation of their unique medicinal value.

The most common first-line treatments for depression, selective serotonin reuptake inhibitors (SSRIs) like Prozac, were introduced nearly a half century ago. While these medicines have had a major impact on treating depression, SSRIs do not work for around 30% of people with major depressive disorder. And even when they are effective, it can take several weeks for them to begin working, and they must be taken continuously for years. Side effects and adverse events like dry mouth, nausea, weight gain, and sexual dysfunction cause people to stop taking them, take them infrequently, and/or switch from one to another in search of improved effectiveness or tolerability.

The advent of psychedelic therapies

Problems with SSRIs led to a revival of research into the mental health benefits of psychedelics that began in the early 1990s, after a 25-year hiatus due to the war on drugs and related prohibitive drug scheduling of psychedelics. Thirty years later, the field is past the “early promise” stage. Johns Hopkins University in Baltimore, the University of California, Berkeley, and the Icahn School of Medicine at Mount Sinai in New York City, among others, have opened centers devoted to studying psychedelics for mental health.

There’s growing scientific consensus regarding the therapeutic potential of psychedelic drugs, and regulatory agencies are beginning to accept how psychedelics treat depression and other mental issues. But it will take some doing to make these therapies ready for prime time. For one thing, it will be essential to develop psychedelic therapies with psychoactive states lasting less than four hours, something my company, Reunion Neuroscience, and others are working toward.

Unlike taking a simple SSRI pill, psychedelic therapies require three distinct stages: preparation, the session, and integration.

In the preparation stage, the clinician must establish trust with the patient and reassure them that the treatment will be safe and effective. Being able to reassure a patient, especially one who has never before had a psychedelic experience, that the psychoactive state is short should serve to ease anxieties and lead to a better overall experience.

During the session, a shorter psychoactive state is useful from a practical point of view. If a psychedelic experience lasts up to eight hours, two trained monitors must be available the entire time. But there’s a limit to how many trained monitors are available — at double the cost — so the possibility of needing only half as many monitors opens the door to treating more patients.

After the session, psychological support is used to help the patient reflect on the insights gained during the psychedelic experience, unpacking them for ongoing use. This is distinct from psychotherapy, because it’s limited to a short time immediately after the session.

In addition to the details of providing psychedelic therapy, another real challenge is the need for stronger intellectual property for psychedelic products. Many of these are currently generic products, which may limit companies from broadly investing in clinical development and commercialization. As a result, companies may find they lack the financial strength to help overcome the inevitable barriers to widespread adoption.

Another thing to consider is how traditional behavioral psychotherapy will interact with psychedelic treatment. It will require collaborative efforts to creatively integrate a new paradigm of administering these products to patients with chronic depression and anxiety. While more research is needed on the durability of psychedelic therapies, depending on the disease state there’s a possibility that a single-dose treatment may be sufficient to provide long-term symptom control, particularly in areas where the mental health condition is acute, like postpartum depression.

I believe that passion and staying power will both be needed: the right kind of stubbornness and the right kind of resources to fund the right kind of teams.

Let’s make the second age of psychedelic therapies a reality.

Greg Mayes is the CEO of Reunion Neuroscience, a biotech developing novel psychedelic solutions for underserved mental health conditions.