Catalysts for change: Psychedelic-assisted therapies for PTSD

Psychedelic-based therapies are poised to change the treatments that psychiatrists can offer patients.

"I often talk about psychedelic treatments as catalysts for change, for both the individual and the field of psychiatry," said Medical University of South Carolina psychiatrist Jennifer Jones, M.D., who conducts research on these treatments.

The highly anticipated approval of MDMA, or "ecstasy," to treat post-traumatic stress disorder would be the first for a psychedelic drug, ushering in changes for patients, mental health providers and society. The Food and Drug Administration is expected to issue a decision on MDMA-assisted therapy for PTSD in early 2024.

How well this revolutionary research will be implemented into practice will depend on patients' willingness to undergo psychedelic-based treatments and their ability to access those treatments, said Jones. Jones' latest research, published in Frontiers in Psychiatry, examines these potential barriers in a population that stands to benefit greatly from psychedelic therapies for PTSD: individuals that use substances.

Changing treatments and outcomes

Approval of psychedelic therapies could help patients with mental illnesses, particularly those with multiple or treatment-resistant disorders. PTSD is an often severe mental disorder that can occur after being exposed to a traumatic event. Current treatments, while improving symptoms in some patients, leave many without any benefit at all.

For the many people who have PTSD and habitually use alcohol or other substances, rates of nonresponse to treatment are even higher. Jones thinks this is unacceptable, so she started researching new approaches to treat patients with both PTSD and a substance use disorder.

A promising 'new' treatment option for patients with both PTSD and SUD may come from an 'old' group of drugs called psychedelics. Psychedelics include both natural (psilocybin, mescaline, DMT) and synthetic (LSD, MDMA) drugs. Natural psychedelics have been used medicinally and spiritually in traditional cultures for centuries. However, they were described scientifically mostly in the 1950s and 1960s.

"It is really interesting—in these early studies looking at psychedelic therapy for one indication, like PTSD, they noticed improvements in symptoms of another mental health disorder, like depression or SUD," said Jones.

Since 2009, approximately 80 clinical trials involving MDMA have been completed or are ongoing, according to Clinicaltrials.gov. These trials investigate the use of MDMA in a wide range of disorders, including anxiety, depression, obsessive compulsive disorder, SUD and PTSD. These diverse studies highlight the potential effects of MDMA across multiple disorders, something that prior treatments have lacked.

"This is really important," said Jones. "It is very common to have concurrent mental health disorders, so having a treatment like MDMA that could, for example, improve both PTSD and SUD symptoms is really exciting for the field."

Currently, drugs used to treat PTSD may be given with or without another form of therapy, broadly referred to as "talk therapy." For MDMA-assisted therapy, the talk therapy component is a fundamental part of the treatment.

"In the context of MDMA-assisted therapy for PTSD, MDMA is thought to dampen the fear response around the traumatic memory, allowing the participant to engage with the therapy team to process this memory, sometimes for the first time in their lives," said Jones. "Instead of running from it, they can process the traumatic memory and move past it."

This processing may also apply to other mental functions, perhaps accounting for MDMA's ability to improve symptoms for other disorders, like SUD.

"Participants in psychedelic clinical trials have lasting benefits that come from changes in their behaviors, their thought processes and their interactions with others," said Jones. "Participants often point to these changes as what made the difference in their symptoms."

The immediate effects of MDMA during therapy are not without concern, however. Jones is often asked whether the MDMA will produce feelings of "ecstasy." "Ecstasy is a common descriptor for the effects caused by recreational MDMA, used so frequently that it became a nickname for the drug. However, because this therapy is a difficult process of self-healing, MDMA in this context does not usually produce ecstasy, Jones said. This common concern points to some of the possible barriers that Jones wanted to assess in her recent publication.

Changing minds

For some, reluctance to receive MDMA-assisted therapy is tied to negative views of psychedelics and their recreational uses. In the 1970s, all psychedelics were classified as Schedule I substances, drugs with high-abuse potential without clinical benefits, tarnishing political and public perceptions of these drugs. Their recreational use and representations in media have continued to perpetuate this stigma.

Negative views of psychedelics and increasing regulatory control halted early promising research on psychedelics in Western medicine in the 1970s, reported the Multidisciplinary Association for Psychedelic Studies. It wasn't until the 1990s that officially sanctioned psychedelic research resumed on a small scale, only accelerating in the 2010s. New government policies allowed psychedelic clinical research to resume, but public perceptions of psychedelics will determine the success of these drugs as treatments.

In Jones' study, approximately 70% of survey respondents indicated their support for MDMA-based research and belief that MDMA could be useful for treating mental health disorders. A smaller group, 59%, would be willing to receive an MDMA-based treatment if it were recommended by a mental health provider. The survey results suggest that most people who use substances are open to MDMA research and would be willing to try an MDMA-based therapy.

Jones also examined the role of race and ethnicity on opinions about MDMA-assisted therapy. Despite their underrepresentation in psychedelic clinical trials, racial and ethnic groups had similar levels of support for MDMA research. However, there were small, but potentially important, differences in willingness to try an MDMA-based therapy. "While largely a hypothesis," said Jones, "differences in willingness to participate in clinical trials are probably related to prior use or cultural beliefs."

While this research brings up additional questions for Jones and colleagues, she believes these results can help researchers and mental health providers to understand how to develop and implement treatments more equitably for different patient and ethnic populations.

By discussing these issues prior to the FDA decision, Jones hopes steps can be taken to address patient concerns.

"It is my heartfelt goal that everyone who might benefit from MDMA-assisted therapy is able to receive treatment once it is available, and that they will not be held back by worries or stigma about the treatment," said Jones. "For that to be a reality, we have to seek input directly from those most likely to benefit from the treatments that we are developing."