Psychology › Therapy & treatment › Psychiatric medicine: drugs and brain treatments
Psychedelic-assisted therapy (psilocybin, MDMA)
Revived 2006; FDA rejected MDMA 2024· Therapy or method
Mixed evidenceSome support; effects smaller or less consistent than once thought.
Treatment pairing a few supervised doses of a drug such as psilocybin or MDMA with preparatory and follow-up talk therapy.
See it on the Psychology map →What it says
LSD was studied for alcoholism and other conditions in the 1950s–60s until the drugs were banned around 1970. In 2006 Roland Griffiths at Johns Hopkins published a psilocybin study in which volunteers reported lasting, deeply meaningful experiences, reviving the field. Trials followed in depression, end-of-life distress, smoking and alcohol use. MDMA, not a classic psychedelic, was tested for PTSD, but the FDA declined to approve it in 2024. Australia allowed limited prescribing in 2023; Oregon and Colorado legalized supervised psilocybin.
Why it matters
It could change how psychiatric drugs are used: a few guided sessions instead of daily pills, if the benefits hold up in rigorous trials.
The evidence
Status: mixed. Small trials report large effects, but blinding is weak because nearly everyone knows whether they got the drug. Several trials were run by researchers or companies with strong stakes in success.
Open questions
Whether the mystical experience itself heals or the chemistry alone does, how long benefits last, and how safe it is outside careful research settings.
Connections (3)
▸Psychedelic-assisted therapy (psilocybin, MDMA) acts on receptors for SerotoninWell replicated
The connection
The body converts psilocybin to psilocin, which activates serotonin 5-HT2A receptors, especially in the cortex, producing altered perception and loosened habits of thought. MDMA works differently: it floods synapses with serotonin and raises oxytocin, which may make painful memories easier to talk about.
Who showed it and when
Albert Hofmann at Sandoz in Basel made LSD (1938) and isolated psilocybin (1958); Franz Vollenweider's Zurich team confirmed the 5-HT2A link in humans in 1998.
The evidence
Blocking 5-HT2A receptors with the drug ketanserin largely blocks the psilocybin experience in volunteers, and PET scans show receptor occupancy tracks how intense the trip feels.
Open questions
Whether the therapeutic benefit needs the trip itself; companies are testing non-hallucinogenic drugs that hit the same receptors.
▸Psychedelic-assisted therapy (psilocybin, MDMA) was denied FDA approval for Post-traumatic stress disorder (PTSD)Well replicated
The connection
MDMA-assisted therapy for PTSD reached late-stage trials reporting large improvements, and the FDA granted it 'breakthrough' status in 2017. But in August 2024 the FDA declined to approve it and asked for another trial, after an advisory panel voted against it over blinding, data quality and safety concerns.
Who showed it and when
Sponsored by the nonprofit MAPS and its spin-off Lykos Therapeutics; Phase 3 trials 2018–2022; advisory panel vote June 2024; rejection August 2024.
The evidence
FDA and advisory committee records are public; the Phase 3 results appeared in Nature Medicine (2021, 2023), and Psychopharmacology retracted three earlier MDMA papers in 2024.
Open questions
Whether MDMA itself or expectation drove results, since most patients guessed their group; misconduct at one trial site deepened doubts. Supporters plan new trials.
▸Psychedelic-assisted therapy (psilocybin, MDMA) shows early promise for Depression and mood disordersMixed evidence
The connection
In trials, one or two psilocybin sessions, with preparation and follow-up therapy, have reduced depression for weeks or longer. Researchers think the drug may loosen rigid, self-critical thinking patterns, opening a window in which therapy can work.
Who showed it and when
Robin Carhart-Harris at Imperial College London (from 2016), Alan Davis and colleagues at Johns Hopkins (2020), and Compass Pathways' company trials (results from 2022).
How solid is it?
A 2021 trial found psilocybin roughly matched the SSRI escitalopram on its main measure; a 2022 trial of 233 patients found modest benefit at three weeks that faded by twelve.
Open questions
Whether effects hold up with better blinding and longer follow-up, and how they compare with existing treatments in everyday clinics.