Ayahuasca psychedelic DMT shows promise as depression therapy

A phase II clinical trial has found dimethyltryptamine (DMT), one of the psychoactive components traditionally used in the Amazonian psychedelic ritual ayahuasca, might be a promising therapy for depression.

The psychedelic pharmaceutical company Small Pharma (now Cybin UK) sponsored and designed the trial, which was led by Dr David Erritzoe, a psychiatrist and neuroscientist at Imperial College London. The results were published in Nature this month.

Seventeen participants received an injection of a DMT compound developed by Small Pharma, and 17 received placebo – all participants received psychotherapeutic support. Two weeks after the injection, participants who received DMT enjoyed a greater reduction in depressive symptoms than those who received placebo.

Tommaso Barba, a PhD candidate at Imperial College London and one of the study’s authors, emphasised the role of therapists in the study to help prepare patients for the experience and help them understand it and integrate it into their lives after it was over. He also cautioned that the trial was small and preliminary.

“There’s still more to do, but it’s promising,” Barba said.

In traditional ayahuasca, participants will drink a tea made of plants with psychedelic components as well as enzymes that slow down the body’s processing of the psychedelic components and often induce nausea and vomiting. The synthetic DMT formulation used in the trial, rather, produces a short but intense 30-minute psychedelic experience that does not induce vomiting.

Dr Daniel Perkins, a senior research fellow at the University of Melbourne‘s psychedelics research and therapeutics unit, said that the vomiting element of ayahuasca can have value on its own, although not everyone vomits when they have traditional ayahuasca compounds.

“In our research, people do report that vomiting can have quite psychologically, emotionally cathartic effects,” Perkins explained, noting that some patients vomit at the peak moment when they’re processing and releasing trauma. However, in terms of overall benefit, “we couldn’t really see that it made that much difference between people who’d reported vomiting versus people that it hadn’t”.

Psychedelic assisted therapy is similar to ayahuasca in that it involves a facilitator who guides participants through the psychedelic experience with the intent of helping them process and heal, although in ayahuasca that support comes in the form of rituals and chanting while in clinical trials like this one it is guided by contemporary psychotherapy.

The US Food and Drug Administration (FDA) approved Spravato, a ketamine based nasal spray for treatment resistant depression in 2019 – the first psychedelic adjacent depression treatment to receive FDA approval. Trials for other substances including psilocybin (the psychoactive component in “magic mushrooms” and 3,4-Methylenedioxymethamphetamine (MDMA) are also in the mix. The FDA declined to approve MDMA-assisted therapy for PTSD due to concerns about ethics and data reliability.

Perkins noted that psychedelics like psilocybin and DMT might be more appropriate anyway, because there is some evidence that they have therapeutic benefits even outside of clinical settings. In contrast, there is not strong evidence that recreational MDMA has inherent mental health benefits. MDMA also can make patients crave touch, which can put them in a compromising position with their therapists – DMT and psilocybin are not known for such effects.

While Barba said the results of the recent phase II trial are promising, there are still hurdles to consider when it comes to psychedelic therapy.

The FDA regulates drugs, not therapies, and so pharmaceutical companies are likely to reduce the therapeutic components of these treatments as much as possible in the future. While this DMT therapy might be faster than other psychedelic therapies, it still needs to be administered in a clinic, via injection and with a therapist. That just might not be as desirable to many patients as picking up a pill at the pharmacy. Also, Barba said, not everyone wants an intense, likely uncomfortable psychedelic experience.

One nuance that Barba said is difficult to capture in data is that DMT isn’t a “quick fix” for depression.

“It can act as a catalyst,” Barba said, because it can help people understand changes they need to make in their mentality or in their life. He added that often the improvement in depressive symptoms comes not just from the DMT, but from work with a therapist and “capacity to make uncomfortable decisions over time”.

For example, if DMT helps a patient realize their work is contributing to their depression, they’d likely actually have to quit that job to see real improvement.