Before the psychedelic renaissance: How America’s forgotten medical history is shaping the future of mental health
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Psychedelic research has renewed interest in neuroplasticity and brain-network flexibility, but the language is ahead of what we can currently prove in routine clinical care.
—Rab Nawaz, MD
The psychedelic story in medicine started in psychiatry. In the 1950s and 1960s, LSD and other psychedelics were studied in psychiatric settings in North America and Europe. Researchers tested these drugs in alcoholism, anxiety, depression, psychosomatic symptoms, and distress related to life-threatening illness.
The scale was much larger than what we’d expect it to be today. A National Academies of Sciences workshop chapter cites estimates of more than 1,000 published clinical papers and roughly 40,000 patients treated with psychedelics during the mid-20th century research period.[]
Related: Can psychedelic therapy move the needle on the US mental health crisis?A 2020 systematic review of LSD studies noted that LSD was studied from the 1950s to the 1970s for anxiety, depression, psychosomatic disease, and addiction. The review authors added an important caveat: many early studies were not performed under contemporary trial standards.[]
Thus, this early therapeutic research was limited by weak trial design, poor controls, unclear treatment models, and increasing political pressure.[]
Rostislav Ignatov, MD, Chief Medical Officer at The Haven Detox Group, says, “Early historical accounts provide evidence of the importance of humility. Initial excitement surrounding new research can lead to restarting research efforts; however, such enthusiasm should never result in moving forward faster than establishing informed-consent procedures, developing trial designs based upon empirical evidence, identifying and documenting adverse events, and ensuring patient protections.”
The modern restart
Johns Hopkins was central to the modern study of psychedelics. The institution reports that its researchers obtained US regulatory approval in 2000 to resume psychedelic research in healthy volunteers with no prior psychedelic exposure. Its 2006 psilocybin study helped restart modern clinical interest.[]
Current trials look very different from the early research era. They use screening, preparation, supervised dosing, structured psychological support, integration, adverse-event monitoring, and follow-up.
Internal medicine physician Rab Nawaz, MD, adds, “Psychedelic research has renewed interest in neuroplasticity and brain-network flexibility, but the language is ahead of what we can currently prove in routine clinical care. These may be part of the mechanism, but they are not yet reliable biomarkers that tell us who will benefit or how durable that benefit will be.”
Related: From Messi’s brain to modern medicine: Where stimulants and psychedelics converge in the performance conversationDepression has emerging evidence
The clearest recent evidence is in depressive disorders, although results remain mixed.
A 2023 JAMA trial studied a single 25 mg dose of psilocybin with psychological support in adults with major depressive disorder. The trial reported rapid and sustained antidepressant effects over 6 weeks compared with niacin placebo.[]
However, in the 2026 JAMA Psychiatry trial in treatment-resistant depression involving 144 adults, psilocybin 25 mg with psychotherapy did not significantly improve the primary response endpoint at 6 weeks, although secondary measures showed clinically meaningful reductions in depressive symptoms. The authors called the trial inconclusive and recommended replication.[]
The data are promising, but not uniform.
Addiction research
A 2022 JAMA Psychiatry trial in 93 adults with alcohol use disorder found that psilocybin-assisted psychotherapy reduced the percentage of heavy drinking days over 32 weeks compared with diphenhydramine plus psychotherapy.[]
In 2026, JAMA Network Open published a randomized clinical trial in 40 adults with cocaine use disorder.[] A single psilocybin session with psychotherapy was associated with more cocaine-abstinent days and lower lapse risk than diphenhydramine with psychotherapy.
However, across the research studies discussed so far, the authors have said further research is needed to replicate and expand the findings. The findings are still experimental, and not yet ideal for clinical inclusion.
Related: Brad Pitt opens up about his addiction—don't overlook this key factor he says was integral to his recoveryPTSD
Phase 3 results of MDMA-assisted therapy for PTSD were published in Nature Medicine in 2023.[] In that trial, 71.2% of participants in the MDMA-assisted therapy group no longer met PTSD diagnostic criteria at study end, compared with 47.6% in the placebo-with-therapy group.
Nonetheless, the FDA declined approval in 2024 and requested another late-stage trial, citing insufficient data and concerns about trial conduct and study design.[]
That decision is important. It shows that strong symptom results do not automatically solve blinding, safety, therapy standardization, documentation, or regulatory questions.
Dr. Ignatov adds, “Right now, there appear to be several promising avenues of investigation [for psychedelics]: PTSD, treatment-resistant depression, and possibly addiction.” However, he advises caution while interpreting the results of existing research and calls for the need for future studies with larger sample sizes and longer durations of study to establish the safety. With regard to addiction, he says, “Addiction is also potentially significant as long as sufficient caution is exercised, given that craving, risk of relapse, and comorbidities complicate treatment.”