Psychedelics Are the Next Big Thing in Assisted Psychotherapy

Updated on May 24, 2024

Although many still think that psilocybin is just the active ingredient in so-called “magic mushrooms,” public opinion about psychedelics is evolving. In fact, significant research progress has been made to better understand how psilocybin, and other psychedelics, might positively impact individuals.

Research has uncovered significant benefits from combining psychedelic use with psychotherapy. Some of the most-commonly studied psychedelics include psilocybin, ketamine, and MDMA, better known as ecstasy. As these compounds are increasingly studied, regulatory changes won’t be far behind.

Let’s explore how psychedelic research as part of assisted psychotherapy is progressing and what is needed to advance these drug candidates through the U.S. regulatory paradigm.

Public opinion on psychedelics is shifting in a big way

Whether interest in medicinal use of psychedelics can be attributed to increasing scientific research or shifting cultural attitudes is an intriguing question, but what we do know is that public opinion is supportive of learning more. For example, a survey conducted by the UC Berkeley Center for the Science of Psychedelics in 2023 found that more than 60% of registered American voters support a “regulated legal framework for therapeutic use” of psychedelics.

The same survey found that 78% of voters support making it easier for researchers to study psychedelic substances. A separate survey focusing specifically on psilocybin found that 72% of participating patients utilizing mental-health services supported additional research, while 59% supported using psilocybin as a medical treatment.

Similarly, another survey found that over 78% of medical students somewhat or strongly agreed with the statement that psychedelic use “shows promise in the treatment of psychiatric disorders.”

When asked whether psychedelic use may improve outcomes if used adjunctively with psychotherapy, the percentage of students who somewhat or strongly agree surpassed 83%. Additionally, more than 70% of medical students said they strongly agree with the statement that psychedelic use “deserves further research as potential treatment for psychiatric disorders.” Another 25% of students somewhat agreed with that statement.

Australia is leading way

In 2023, Australia became the first country in the world to allow doctors to prescribe psilocybin and MDMA to treat treatment-resistant depression (TRD) and post-traumatic stress disorder (PTSD) respectively. That move coincided with a reclassification by the Therapeutic Goods Administration (TGA), which reclassified both drugs from Schedule 9 to Schedule 8 when they meet a specific set of criteria.

As a result, psilocybin and MDMA were reclassified from being prohibited drugs only allowed for use in clinical trials and research to being able to be prescribed with controls through a special access scheme for unapproved therapeutic goods. This is a different mechanism than approval of the drugs and it is important to note that there are no MDMA or psilocybin products on the Australian Register of Therapeutic Goods (ARTG).  The TGA’s reclassification came with several caveats, including the requirement that both drugs only be used as part of a psychedelic-assisted psychotherapy regimen for the specific indications of TRD and PTSD and must be prescribed by a psychiatrist.

The TGA also requires that mental-health practitioners receive Authorized Prescriber approval to be able to prescribe MDMA and psilocybin. As a result, we’re starting to see specialized facilities dedicated to psychedelic-assisted therapy — like the one recently opened by Clarion Clinics in Melbourne, the first of its kind in the world. 

Australia’s reclassification of these two psychedelics set the stage for further reforms around the world — leading to even greater interest in clinical trials that combine psychedelics with psychotherapy. For example, Incannex partnered with Monash University in Melbourne to conduct a Phase 2 clinical trial for psilocybin-assisted psychotherapy to treat generalized anxiety disorder (GAD), a condition with significant unmet treatment needs.

With results reported in early 2024, researchers found that 44 percent of patients receiving psilocybin-assisted psychotherapy reported at least a 50 percent reduction in anxiety scores from their baseline — a response rate more than four times higher than the rate observed in the placebo group. Twenty-seven percent of patients in the psilocybin group achieved full remission — a rate five times higher than that achieved via psychotherapy with placebo.

Although that trial was conducted in Australia, the U.S. Food and Drug Administration (FDA) reviewed the clinical trial design and the results as a key piece of the investigational new drug (IND) application.

U.S. regulators expedite psychedelic research and approval

Like in Australia, in the United States, the FDA is closely looking at psychedelics, potentially expediting the approval process for Compass Pathways’ psilocybin therapy for treatment-resistant depression (TRD) by granting it a breakthrough-therapy designation. The company’s Phase 2b trial was the largest psilocybin-treatment clinical trial ever conducted, including 233 patients across 22 sites in 10 countries.

That classification for a therapy involving a psychedelic drug suggests that early clinical evidence has demonstrated significant potential for the treatment versus already-approved therapies for TRD, hence, the FDA’s evolving endorsement for a drug class that has long been considered taboo. Published in the New England Journal of Medicine, researchers discovered that patients receiving the 25-milligram dose reported greater improvements in their symptoms, with 37% showing a response to the treatment at week three and 29% achieving remission at week three.

The FDA also granted priority-review status for a new drug application (NDA) filed by Lykos Therapeutics (formerly MAPS) for MDMA-assisted psychotherapy to treat PTSD in 2017, setting a target action date of August 11, 2024 and scheduling a meeting of their Psychopharmacologic Drugs Advisory Committee for June 4, 2024.  The NDA includes data from several studies, including two Phase 3 trials that examined the safety and efficacy of MDMA (ecstasy) when used alongside psychological intervention.

The future of psychedelic-assisted psychotherapy

Schedule I drugs, which include psychedelics, cannot be prescribed for any indication in the U.S., so by extension, any psychedelics that receive FDA approval to treat various conditions would have to be reclassified. In fact, we’re already seeing signs that U.S. regulators are prepared to make such changes. A key component of a drug being classified as schedule 1 by the DEA is that it has “no currently accepted medical use.” As the high-quality evidence for safety and efficacy of molecules such as MDMA and psilocybin in mental health disorders drives these molecules towards FDA approval they will have an accepted medical use and will need to be reclassified. The FDA’s interest in the potential for medical use of psychedelics was made evident in 2023, when it published new draft guidance to support drugmakers planning clinical trials involving such drugs.

As research and clinical trials evaluating the benefits of psychedelics used in combination with psychotherapy continue, we could start to see some drugs like MDMA and psilocybin be rescheduled. Thus, the question of regulatory approval of psychedelic drugs, especially in use in psychotherapy sessions, is now a matter of “when” rather than “if.”

Mark Bleackley
Mark Bleackley
Chief Science Officer at Incannex

Mark Bleackley, PhD, is Chief Science Officer at Incannex. Dr. Bleackley has a PhD in Genetics from the University of British Columbia with post-doctoral training at La Trobe University and the Australian biotechnology company Hexima Ltd. As Chief Scientific Officer, he oversees all research and development activities at Incannex, from proof-of-concept to commercialization.