Ready or not, psychedelic medicine is coming to market

On The Cover

In February, FDA accepted Lykos Therapeutics’ new drug application (NDA) for midomafetamine (MDMA) capsules, used in combination with psychotherapy, for the treatment of PTSD. If the treatment is approved, a decision that could come as soon as August 2024, it will be the first in what is expected to be a growing number of FDA-approved psychedelic-assisted therapies.

Clinical trials of psilocybin are underway as well. If the trials are successful, this psychedelic agent found in magic mushrooms could see FDA approval for the treatment of severe depression in the next few years.

Evidence for these once-illicit drugs is part of a growing body of research that supports their benefits in several mental health conditions. The question is no longer if psychedelic medicine will one day be among the treatment options for mental health conditions, but rather when.

Patients are ready for these new drugs, too—that is, if they aren’t using them already. Two-thirds of Americans support regulated, therapeutic use of psychedelics, according to an online survey conducted by UC Berkeley Center for the Science of Psychedelics. An estimated one in four Americans has tried at least one psychedelic drug in their lifetime, another survey found. And that number seems to be rapidly climbing; the number of Americans over 12 years old who report using hallucinogens has doubled in the last 10 years.

“Upon the FDA approval of these compounds, we need pharmacists to be a part of that discussion, a part of the care framework, so that we can ensure that access, safety, accountability—all the things that pharmacists are already providing now—can be translated into psychedelic care systems,” said Sa’ed Al-Olimat, PharmD, cofounder of the Psychedelic Pharmacists Association.

Lykos Therapeutics’ NDA includes results from two randomized, double-blind, placebo-controlled Phase 3 studies, MAPP1 and MAPP2, published in Nature Medicine in 2023. In both trials, patients who received MDMA plus psychotherapy saw significantly more improvement in PTSD symptom severity and functional ability than those on a placebo plus psychotherapy.

As for psilocybin, in a 2021 head-to-head comparison of the psychedelic agent and SSRI escitalopram plus psychotherapy published in NEJM, the psychedelic was not superior to the conventional antidepressant. But subsequent trials have shown it relieves depression compared to placebo. Numerous other trials are currently underway to further measure psilocybin’s benefits in treatment-resistant depression.

MDMA and psilocybin are the psychedelic drugs closest to earning FDA approval for mental health conditions and coming to the U.S. market in the near term. But they are just two among numerous psychedelic agents that have some degree of evidence to support their benefits for mental health conditions such as treatment-resistant depression, PTSD, OCD, eating disorders, and SUDs.

Psychedelics in addition to MDMA and psilocybin that have been investigated for these benefits include lysergic acid diethylamide (LSD); N,N-dimethyltryptamine (DMT); ayahuasca, a psychoactive brew originating from the Amazon basin that contains both DMT and naturally occurring MAOIs; 5‐methoxy‐N,N‐dimethyltryptamine (5-MeO-DMT); and mescaline (3,4,5-trimethoxyphenethylamine), the psychedelic agent found in the peyote plant.

Psychedelic-assisted psychotherapy

Many of the benefits of these drugs have been seen in the context of psychedelic-assisted therapy. That is, the drugs are seen to enhance the effects of psychotherapy and achieve results that neither the drug nor psychotherapy alone could.

“Psychedelics act on specific serotonin receptors to increase glutamatergic activity in the brain,” Al-Olimat said. This, researchers believe, fosters new neuronal connections in the brain. When normal brain functioning is disrupted, psychedelics seem to repair or reset these broken networks.

“What this allows,” Al-Olimat said, “is for novel insights to take place, so enhanced perception, enhanced perspective. These experiences that come from the macrodose experience are insights that patients can take away from, reflect on, and integrate into their daily lives for habit change.”

Psychedelics’ actions in the brain allow patients to make meaning out of what they see or feel during the dissociative, psychedelic experience, and facilitate meaningful insights and changes in talk therapy.

Some physicians are using ketamine—a dissociative, but not technically a psychedelic drug—in the same way: as an adjuvant to psychotherapy. Depending on the protocol, patients may receive a ketamine infusion in a physician’s office or sublingual lozenges under video supervision at home on what’s called their “dose day,” and follow up the dose on another day with what’s called “integration”—a talk therapy session in which the patient unpacks and makes sense of the psychedelic experience and its applications to their recovery from their mental health condition.

The psychedelic-assisted therapy model is predicated on the idea that both the neuroplastic and psychedelic effects of the drug are needed to achieve the mental health benefits. Depending on the drug and the treatment protocol, this model may require a time-consuming medication washout, hours of preparation with a therapist, multiple dose days during which a dissociative experience takes place and may last several hours, and hours of integration therapy after dose days.

Some research underway aims to isolate compounds from psychedelic agents that would cause the neuroplastic effects without the psychedelic trip to determine whether it would be beneficial in the treatment of mental illnesses.

A multi-institutional team of researchers from UCSF, Yale, and Duke has isolated compounds from the African medicinal plant ibogaine that may act on serotonin in the same way as the natural psychedelic does—to treat depression and SUDs—but without its many dangerous adverse effects that can include heart arrhythmias.

“Not everyone has the time or luxury to do hours and hours of preparation, followed by a 4- to 6- or 8-hour experience, one to three times, followed by integration afterwards,” Al-Olimat said. Others may not meet inclusion criteria for psychedelics due to health risks.

“If those patients are able to take a pill to get that neuronal growth without having a full-blown mystical experience that should be an option,” Al-Olimat said.

Paradigm shift

The entrance of psychedelics onto the mainstream prescription drug market will mark a major paradigm shift as the psychoactive substances in these drugs have been illegal until now. With this shift, pharmacists may need to take stock of their own biases.

“If you had no idea it was a psychedelic, and you read the literature,” Al-Olimat said, “you’d say, ‘Wow! One to three doses of this novel compound and we see alleviation of symptoms of depression, anxiety, PTSD, and other potential indications. Why aren’t we doing more research on this? Why aren’t we talking about this?’”

Pharmacists have likely encountered people—many of whom have suffered for years on traditional antidepressants with no relief—who are already accessing psychedelics for mental health purposes or seriously considering it. Besides through clinical trials, patients may be accessing psychedelics through wellness retreats or religious ceremonies both in the United States and abroad.

“These are viable treatment options for people either now or in the future,” said Benjamin Malcolm, PharmD, founder of Spirit Pharmacist, an online service through which he provides consulting and education on psychedelics. “The train has left the station.”

For this reason, pharmacists may prepare themselves to provide objective answers to patients’ questions about psychedelics.

“People deserve to have all the information about all the options when they make decisions about their health,” Malcolm said.

It’s in the name of providing people the information they deserve that Malcolm has found a role for himself as a pharmacist in the field of psychedelic medicine. Through video chats, he provides psychedelic education and psychopharmacological consulting. His clients range from individuals who have used or are interested in using psychedelics and have questions, to providers such as psychiatrists designing clinical trials, psychedelic-assisted therapy facilitators, organizations, and others.

Malcolm stresses that not every community pharmacist needs to become an expert in psychedelic medicine. They just need to be prepared to listen and respond without judgment.

“It would be best to say something along the lines of, ‘I’m not an expert in this area, but I hear there could be some promise with psychedelics, but I also know you have to be careful about who receives them and under what circumstances’,” he said.

Malcolm knows from his experience consulting patients who are curious about the potential benefits of psychedelics that “In those 30 seconds or 1 minute at the pharmacy counter, if you can just let the person know that they are not crazy or criminal for thinking about this, that should be the goal.”

To further normalize and destigmatize the encounter, pharmacists could prepare a printed handout including the potential benefits and risks of psychedelics in the treatment of mental health conditions and a list of resources for patients to consult.

Resources to consider include:

MAPS.org: The Multidisciplinary Association for Psychedelic Studies offers articles, resources, and downloadable exercises.

The Fireside Project provides telephone-based peer support during or after a psychedelic experience.

Information about some of the few pharmacists who provide online education and consultation on psychedelic medicine, such as Malcolm at SpiritPharmacist.com and Emily Kulpa, PharmD, at DrEmilyKulpa.com.

Roles for pharmacists

Patients are already accessing psychedelics for mental health care with or without a pharmacist’s involvement.

“The psychedelics space is rapidly evolving and no one’s talking about pharmacists,” Al-Olimat said. “When these compounds have FDA approval, pharmacies will be utilized—but at the very bare minimum. We can do much more and many pharmacists want to do much more.”

If patients mention to their pharmacist an interest in psychedelics for a mental health condition, pharmacists can counsel them on the impact their current psychiatric medications may have on the experience.

SSRIs, for example, can blunt the impact of MDMA and psilocybin and prevent patients from having a full psychedelic experience.

“That doesn’t sound dangerous, but if someone is putting in hours of preparation and they’re already teetering on the brink, in terms of their mental health, and they spend hundreds or thousands of dollars to have this experience, and they go to the dose day and nothing happens—then what?” Al-Olimat said.

Pharmacists, he said, should encourage patients to talk to their physicians about coming off their antidepressants before trying psychedelics.

As these drugs come to market, pharmacists can be part of the patient’s screening and medical intake process. They can check for and mitigate drug interactions and assist in deprescribing where needed. As some treatment protocols will call for clinical supervision on dose days, some pharmacists may train to provide that support.

What next

Pharmacists who want to know more have options. Online courses are available, such as those offered by the Psychedelic Pharmacists Association and Spirit Pharmacist. But pharmacists might also start to carve out their role in psychedelics right in their own communities.

Search for “psychedelics” and your city on Facebook or Meetup. “You might be surprised how many local clubs you find,” Al-Olimat said. “It’s not a bunch of people trying to trip and hallucinate. It’s just people who want a safe place to talk about psychedelics. And for you to be a pharmacist and go there—not only will you validate them, but you might also help reduce risk in your local community, which is what we should all be doing.” ■