“I have been severely depressed for several years, and no treatment has really worked. I am desperate and I need something to give me hope. I read online that psychedelic-assisted therapy may be able to help me. Is that true? Are these therapies effective?”
When you are desperate for something that works
When someone has been severely depressed for a long time, it is completely understandable that this person wants to do anything to get better. In such a situation, psychedelic-assisted therapy can indeed be one of the options that can be tried. There is still much that is unclear about the effects, and it certainly will not help everyone, but it is completely understandable that in situations like this, patients want to try anything that may help them.
What psychedelic-assisted therapy is
Psychedelic-assisted therapies have received growing attention in recent years as possible treatments for mental disorders. These therapies combine psychotherapy with psychedelic substances such as psilocybin, LSD, ayahuasca, or ecstasy (MDMA). The idea is that these substances may enhance the effects of psychotherapy by changing perception, mood, and cognitive processes in ways that could help patients engage more deeply with treatment.
A long and interrupted history
Research on psychedelic therapies first emerged in the 1950s and 1960s. However, this work largely stopped after psychedelics were classified as illegal drugs by the United Nations in the 1960s and 1970s. At the same time, medical research regulations became stricter after the thalidomide scandal. The studies conducted during that early period generally did not meet modern scientific standards and included very few well-designed effect studies — the so-called randomized controlled trials (RCTs).
Over the past two decades, interest in psychedelic-assisted therapies has returned. Most research has focused on the use of psychedelics for depression and MDMA-assisted psychotherapy for post-traumatic stress disorder (PTSD). A smaller number of studies have also examined their effects on other conditions, including obsessive-compulsive disorder, borderline personality disorder, body dysmorphic disorder, and alcohol use disorder.
What the evidence shows so far
The available evidence appears promising. In depression and PTSD, about 20 RCTs have compared psychedelic-assisted therapies to placebo or waitlist control conditions, and the effects of the therapies were large. These findings have led some researchers and commentators to describe psychedelic-assisted therapies as a potentially transformative development in mental health care.
The available evidence appears promising — but it is important to note the limitations that make it difficult to draw firm conclusions.
It is, however, important to note that there are important limitations that make it difficult to draw firm conclusions. First, the number of studies is still small, and the total number of participants is limited. Strong evidence usually requires more large, well-conducted trials, which are still lacking in this field.
Second, several methodological concerns affect the credibility of the findings. Like many areas of mental health research, psychedelic studies may be influenced by small sample sizes, selective reporting of outcomes, conflicts of interest, and several other biases. These factors can lead to overly optimistic estimates of treatment effects.
The problem of long-term effects
A particularly important issue is the lack of long-term follow-up data. Psychedelic substances are known to have powerful short-term effects — which is not surprising, because they are also used as party drugs. However, from a clinical perspective it is much more important to know whether the benefits persist after the immediate drug effects have disappeared. So far, few studies have examined long-term outcomes, and these effects are very uncertain.
The problem of comparison groups
Another major challenge concerns the use of control groups. Because psychedelics produce obvious psychological effects, participants usually know whether they received the active treatment or a placebo. Many participants also enter studies with positive expectations about psychedelic therapies, and may be disappointed if they are assigned to a control condition. These expectations could influence outcomes and make it difficult to determine the true effectiveness of the treatment.
It also matters that participants who end up in the control group of an RCT can be disappointed, because they had hoped to receive the psychedelics. This disappointment — or perhaps finding other ways to obtain psychedelics — changes the control group. This makes it difficult to compare psychedelic-assisted therapy to the care patients usually get.
In summary
Psychedelic-assisted therapies may have the potential to improve the treatment of mental disorders, particularly depression and PTSD. However, the current evidence base is still limited, and important methodological problems mean that we cannot yet conclude that these therapies are truly effective in helping patients in the longer term.
Because this is a fast-moving field, the evidence is best followed as it develops. At Metapsy we provide access to a continuously updated, living synthesis of the trials on these treatments maintained by the SYPRES collaboration.
Pim Cuijpers is professor emeritus of clinical psychology and scientific director of Metapsy. He has been involved in more than 1,100 scientific studies, mostly on psychological treatments of mental health problems. This is one of a series of evidence summaries in which Prof. Cuijpers tries to answer questions from patients and clinicians, based on what is known in science about treatments. The knowledge is mostly drawn from collective work of the Metapsy collaboration of at least 15 years. Do you have other questions you would like Prof. Cuijpers to discuss? Feel free to contact us.
Literature
- Cuijpers P, Harrer M, Furukawa TA. (2026). Innovations to improve outcomes and uptake of psychotherapies for mental disorders: a state-of-the-art review. World Psychiatry, 25(1), 4–33.
- van Elk M, Fried EI. (2023). History repeating: guidelines to address common problems in psychedelic science. Therapeutic Advances in Psychopharmacology, 13, 20451253231198466.
- Romeo B, Karila L, Martelli C, et al. (2020). Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis. Journal of Psychopharmacology, 34(10), 1079–1085.
- Swieczkowski D, Kwaśny A, Pruc M, et al. (2025). Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials. Psychiatry Research, 344, 116337.
- Fang Q, Chan VKY, Chan SSM, et al. (2024). Efficacy and safety of psilocybin on treatment-resistant depression: A systematic review and meta-analysis. Psychiatry Research, 337, 115960.
- Smith KW, Sicignano DJ, Hernandez AV, et al. (2022). MDMA-assisted psychotherapy for treatment of posttraumatic stress disorder: A systematic review with meta-analysis. Journal of Clinical Pharmacology, 62(4), 463–471.
- Bahji A, Forsyth A, Groll D, et al. (2020). Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: a systematic review and meta-analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 96, 109735.