The rapid evolution of psychedelic drug development is creating numerous regulatory challenges, from potential conditions of approval that can affect patient access to differences in federal and state policy regarding the drugs, according to authors of two newly published commentaries. One of the authors emphasized that public demand for psychedelics is far outpacing federal regulatory...
Patients with major depressive disorder (MDD) who received 4 weeks of buprenorphine treatment following a single infusion of ketamine experienced a significant reduction in suicidal ideation compared with ketamine plus placebo, a randomized, double‐blind trial has found. No serious treatment‐related adverse events were reported. Study results were published online May 19, 2026 in the American...
A systematic review and meta‐analysis encompassing 26 ran‐domized controlled trials (RCTs) has concluded that both single and repeated infusions of ketamine significantly improve suicidality and depressive symptoms in patients with a major depressive episode. Most of the serious adverse events that were reported in the included trials were determined to be unrelated to study treatment.
Individuals with cocaine use disorder who received a single dose of psilocybin combined with psychotherapy showed greater reductions in cocaine use relative to active placebo with psychotherapy, a randomized trial has found. No serious adverse events were reported during the trial.
Patients with treatment‐resistant depression who received psilocybin‐assisted psychotherapy showed clinically meaningful improvement in depressive symptoms relative to placebo, a Phase 2b trial has found. However, the study did not show a significant effect on the primary outcome of treatment response 6 weeks after the first of two doses of psilocybin. Study results were published online March...
A Phase 1 trial comprising 15 patients has found that repeated high‐dose administration of psilocybin was more effective than low‐dose psilocybin or placebo in reducing symptoms of obsessive‐compulsive disorder (OCD). Psilocybin was generally well‐tolerated, with no reports of serious adverse events.
An individualized one‐day dosing regimen of a vaporized formulation of the psychedelic mebufotenin (5‐methoxy‐ N,N ‐dimethyltryptamine; 5‐MeO‐DMT) was more effective than placebo in improving depressive symptoms in adults with treatment‐resistant depression, a Phase 2b trial has found. No serious treatment‐emergent adverse events were reported during the 7‐day study. Results were published...
A two‐year extension of a trial of esketamine nasal spray in patients with treatment‐resistant depression has found no new safety concerns associated with long‐term use of the drug. The overall relapse rate across both the original trial and the extension was 6.9%.
A systematic review and meta‐analysis comprising 24 trials has concluded that when both psychedelic and antidepressant trials in the treatment of depression are unblinded, psychedelics are no more effective than open‐label antidepressants. The findings call into question some optimistic projections about the efficacy of psychedelics in depression treatment.
Patients with treatment‐resistant depression who received a series of treatments with ketamine or esketamine showed a substantial reduction in emergency department visits related to suicidality over a 6‐month period, a study has found. Study participants had a 56.7% response rate of depression symptoms following the acute phase of treatment.
Four weekly doses of TSND‐201 (methylone), an analog of 3,4 methylenedioxymethamphetamine (MDMA), resulted in significant improvement relative to placebo in reducing symptoms of post‐traumatic stress disorder (PTSD), a Phase 2 study has found. Treatment‐emergent adverse events associated with TSND‐201 were generally mild to moderate in severity, with no significant suicidal ideation. Study...
Up to eight infusions of ketamine were not more effective than a psychoactive placebo in reducing depressive symptoms in patients receiving inpatient treatment for depression, a randomized trial has found. Patients receiving ketamine also showed no improvement relative to those receiving midazolam on measures of cognition and quality of life. Study results were published online Oct. 22, 2025 in...
Nearly five years of post‐approval safety data for esketamine nasal spray have uncovered no new safety concerns associated with the formulation, an analysis has found. Most adverse events occurred during the first treatment session, with incidence decreasing over the course of treatment. Results were published online Sept. 10, 2025, in the American Journal of Psychiatry .
Treatment with a single dose of a pharmaceutical formulation of lysergic acid diethylamide (LSD) resulted in a dose‐dependent reduction in anxiety in individuals with generalized anxiety disorder (GAD), a Phase 2b study has found. The two highest of four tested dose strengths of the MM120 formulation demonstrated significant improvement relative to placebo.
Twice‐weekly dosing of intranasal esketamine resulted in significant improvement in depressive symptoms compared with placebo in adults with treatment‐resistant depression, a 4‐week trial has found. Esketamine doses of 56 and 84 mg both outperformed placebo in the post‐marketing trial. Study results were published online July 2, 2025, in JAMA Psychiatry.
A meta‐analysis comprising 17 randomized trials has found that rates of control group improvement in depression studies were lower in psilocybin trials than in studies of esketamine or a selective serotonin reuptake inhibitor (SSRI). The results suggest that psilocybin's overall efficacy in the treatment of depression might be overestimated.
Use of selective serotonin reuptake inhibitor (SSRI) antidepressants has been associated with reduced intensity of emotional experience. Conversely, some research has shown that use of psilocybin in patients with depression leads to an increase in responsiveness to emotional face stimuli, suggesting that the psychedelic generates a transient elevation in mood. Investigators conducted a...
Microdosing of lysergic acid diethylamide (LSD) over a 6‐week period showed no significant benefits over placebo in reducing symptoms of attention‐deficit hyperactivity disorder (ADHD) in adults, a Phase 2A trial has found. Both the LSD and placebo groups experienced marked improvement, the investigators reported.
Results of a systematic review and meta‐analysis suggest that esketamine has only modest efficacy in the treatment of adults with treatment‐resistant depression, with initial improvement diminishing after the first few days. The results also suggest no effect of esketamine on suicidality.
Adults with alcohol use disorder who received two sessions of psilocybin‐assisted therapy demonstrated personality shifts toward normalization of abnormal trait expression, a secondary analysis of a randomized trial has found. A decrease in impulsiveness was found to be associated with reduced drinking post‐treatment, with the strongest effect for psilocybin‐treated individuals who had engaged...
The stressors that frontline healthcare workers experienced during the COVID-19 pandemic led to widespread burnout, depression, and post-traumatic stress disorder (PTSD). Based on research showing that psychedelic-assisted therapy led to improvement in symptoms of depression in various populations, investigators conducted a randomized clinical trial to evaluate the effects of psilocybin therapy...
Several sensitivity analyses of a Phase 3b trial have demonstrated that esketamine nasal spray was consistently more efficacious than extended‐release quetiapine in patients with treatment‐resistant depression (TRD). The additional analyses of the ESCAPE‐TRD trial used multiple thresholds for remission and relapse. Study results were published online Dec. 2, 2024, in The British Journal of...
Individuals who had an emergency department (ED) visit related to use of psychedelic drugs were at higher risk of developing a psychotic disorder than those in the general population, a retrospective cohort study has found. These individuals also were more likely to develop a schizophrenia spectrum disorder compared with those who had an ED visit involving alcohol or cannabis, the researchers...
Women with prenatal depressive symptoms who received a single low dose of esketamine shortly after childbirth showed a substantially lower incidence of a major depressive episode at 42 days postpartum than women receiving placebo, a new study has found. Neuropsychiatric adverse events occurred more frequently in the esketamine group, but no severe adverse events were reported.
A single 25‐mg dose of psilocybin resulted in improvement in depressive symptoms in all 15 participants in an open‐label nonrandomized trial enrolling adults with bipolar II disorder. Twelve of the 15 participants met response and remission criteria at the study's 12‐week endpoint.