Psychedelics are moving through the drug-development pipeline, and the results are exciting! In a phase 2 trial of 233 adults with treatment-resistant depression, the highest dose of a synthetic psilocybin cut depression scores 6.6 points more than control at three weeks (P<0.001). In a phase 2b trial of 198 adults with generalized anxiety disorder, a single dose of MM120 (LSD) cut anxiety up to 6.0 points more than placebo at four weeks. Phase 1 trials of two short-acting compounds, DMT and 5-MeO-DMT, reported no serious adverse events, and a review counted 241 registered psychedelic trials, with registrations accelerating after 2019. Encouraging to see staged research moving forward!
Key studies
Study 1. SPL026 (DMT fumarate) in 32 healthy participants (James, 2023)
No serious adverse events in 32 healthy volunteers given escalating infusions of SPL026 (DMT fumarate), which was well tolerated!
In a phase 1, randomized, double-blind, placebo-controlled dose-escalation trial, researchers gave 32 psychedelic-naive healthy participants an intravenous infusion of SPL026 at one of four dose levels or placebo, with psychological support from two therapy team members! Researchers reported that SPL026 was well tolerated, with an acceptable safety profile and no serious adverse events, and some evidence that higher blood levels went with more intense experiences. The trial achieved its goal of selecting a dose to carry into patients with major depressive disorder.
“SPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events.”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: James E, Erritzoe D, Benway T, et al. Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial. Front Psychiatry. 2023;14:1305796. https://doi.org/10.3389/fpsyt.2023.1305796
Study 2. BPL-003 (intranasal 5-MeO-DMT) in 44 healthy participants (Rucker, 2024)
Profound, highly emotional effects with a rapid onset and short duration, and 60% had a complete mystical experience at the higher intranasal BPL-003 doses in a 44-person trial!
In a phase 1, double-blind, placebo-controlled, single ascending dose trial, researchers gave 44 psychedelic-naive healthy participants an intranasal formulation of 5-MeO-DMT (BPL-003) or placebo and measured blood levels and subjective effects! Researchers reported that BPL-003 was well tolerated with no serious adverse events, that profound and highly emotional consciousness-altering effects began rapidly and were short-lasting, and that 60% of participants had a 'complete mystical experience' at the higher doses. They concluded that the short duration of action and induction of mystical experiences suggest clinical potential.
“Profound and highly emotional consciousness-altering effects were observed with BPL-003, with a rapid onset and short-lasting duration.”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Rucker JJ, Roberts C, Seynaeve M, et al. Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. J Psychopharmacol. 2024;38(8):712-723. https://doi.org/10.1177/02698811241246857
Study 3. A synthetic psilocybin formulation in 233 adults with treatment-resistant depression (Goodwin, 2022)
The highest dose of a synthetic psilocybin cut depression scores 6.6 points more than control at three weeks (P<0.001) in 233 adults with treatment-resistant depression!
In a phase 2 double-blind trial, researchers randomly assigned 233 adults with treatment-resistant depression to a single dose of a proprietary synthetic psilocybin at one of three dose levels, the lowest serving as the control, along with psychological support! Researchers reported that the highest dose reduced depression scores significantly more than the control at three weeks (difference of 6.6 points on the MADRS; P<0.001), and that response and remission at three weeks generally supported the primary results.
“psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Goodwin GM, Aaronson ST, Alvarez O, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022;387(18):1637-1648. https://doi.org/10.1056/nejmoa2206443
Study 4. MM120 (lysergide D-tartrate) in 198 adults with generalized anxiety disorder (Robison, 2025)
6.0 points greater anxiety reduction than placebo at four weeks with the highest MM120 (LSD) dose in 198 adults with generalized anxiety disorder!
In a phase 2b, multicenter, randomized, double-blind, placebo-controlled trial at 22 US sites, researchers gave 198 adults with moderate to severe generalized anxiety disorder a single dose of MM120 (lysergide D-tartrate) at one of four dose levels or placebo, with anxiety rated by blinded central raters! Researchers reported statistically significant reductions in anxiety at four weeks for the two higher doses, with differences of 5.0 and 6.0 points versus placebo on the Hamilton scale. The authors concluded that a single dose of MM120 produced a dose-dependent reduction in anxiety, informing dose selection for phase 3 pivotal trials.
“In participants with moderate to severe GAD, a single dose of MM120 produced a dose-dependent reduction in anxiety.”
Abstract of the published study (text from Europe PMC), key sentence highlighted in yellow. Source: Robison R, Barrow R, Conant C, et al. Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial. JAMA. 2025;334(15):1358-1372. https://doi.org/10.1001/jama.2025.13481
Related reading
- Uyar A, Forbrich L, Lueken U, et al. Landscape analysis of pre-registered clinical trials involving classical psychedelics. J Psychopharmacol. 2026;40(5):720-731. https://doi.org/10.1177/02698811251371690 — A review of 241 registered psychedelic trials, showing registrations rising exponentially after 2006 and accelerating after 2019.
- Silva F, Butlen-Ducuing F, Guizzaro L, et al. A review of psychedelics trials completed in depression, informed by European regulatory perspectives. Neurosci Appl. 2025;4:105516. https://doi.org/10.1016/j.nsa.2025.105516 — Brings together 8 completed depression trials of psilocybin, LSD, ayahuasca and DMT, and maps the path to the larger studies ahead.
Related pages on this site
Brain Imaging Research · Inflammation and the Immune System · Personality and Traits · Creativity · Wellness of the 'Well' · Spiritual Wellness · Wellness of the Planet
This page summarizes published research for education only. It is not medical advice. Any change to a medication remains the decision of that person’s own prescriber.
Keep reading
All Educational Resources · About This Archive · For Practicum Supervisors