Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
Summary & key facts
This paper reviews research on ayahuasca and its main ingredient, DMT, and how they might help with mental health. Ayahuasca is a plant brew that makes DMT work when you drink it because it also contains chemicals that stop the body from breaking DMT down. Lab studies and a small number of clinical trials show these drugs can change brain networks and help the brain form new connections, which may reduce symptoms in people with hard-to-treat depression. The evidence is promising but still limited, so these are early findings rather than proven treatments.
- Ayahuasca is a traditional brew made from two plants: one provides DMT and the other provides chemicals that stop the body from breaking DMT down, so the DMT works when taken by mouth.
- DMT mainly affects serotonin-related receptors in the brain, which are involved in perception, thinking, and mood, and it can encourage the brain to rewire some of its connections.
- DMT by itself is usually given by inhaling, snorting, or by injection, while ayahuasca is taken orally because of the chemicals that protect DMT from being destroyed in the gut.
- Current clinical evidence is limited but encouraging: there are four phase II studies of 5-MeO-DMT and one phase II study of DMT for treatment-resistant depression, and two phase II studies of a DMT form for major depressive disorder.
- The review says the strongest and most consistent promise is for treatment-resistant depression and major depressive disorder, while studies for other mental conditions are still preliminary.
- Beyond possible treatment uses, researchers say these psychedelics are useful tools for studying how the human mind and brain work.
Abstract
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics as breakthrough therapies for mental disorders. Psychedelics can influence cognitive and emotional processes, showing solid therapeutic potential, particularly in treatment-resistant psychiatric disorders. Amongst the most promising compounds, ayahuasca and its main psychoactive component, N,N-dimethyltryptamine (DMT), have received considerable attention. Ayahuasca is a psychoactive brew traditionally prepared from the liana Banisteriopsis caapi and the leaves of Psychotria viridis. Its psychoactive properties derive mainly from DMT, while β-carbolines, which act as monoamine oxidase-A (MAO-A) inhibitors, prevent the metabolic degradation of DMT, enhancing its bioavailability and allowing oral administration. In contrast, in monotherapy, DMT or its analog 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is generally administered via alternative routes, like inhalation, intranasal, or intravenous delivery. DMT is primarily a serotonin (5-HT)2A receptor partial agonist, whereas 5-MeO-DMT has a higher affinity for the 5-HT1A receptor compared to 5-HT2A, though other receptor targets are engaged, fostering neuroplasticity and a reorganization of brain networks involved in perception, cognition, and mood regulation. Despite limited clinical trials, current evidence offers an optimistic outlook on DMT and 5-MeO-DMT efficacy for treatment-resistant depression (TRD) and major depressive disorder (MDD), whereas evidence for other mental disorders studies is still preliminary. There are four phase II studies with 5-MeO-DMT and one with DMT for TRD, while there are two phase II studies with DMT fumarate for MDD. Beyond their therapeutic potential, psychedelics also represent powerful tools for exploring the human mind, offering valuable insights into brain function and mental health.