medRxiv Preprint Server
March 27, 2026
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey et al.
preprint
A living systematic review and meta-analysis of six randomized controlled trials with 286 participants found that MDMA-assisted therapy reduces PTSD symptoms more than control conditions (Hedges' g = -0.71). More dosing sessions and higher cumulative doses were linked to larger effects. MDMA also led to higher response (risk ratio 1.35) and remission (risk ratio 2.25) rates. Most studies had low risk of bias per Cochrane guidelines, though issues like expectancy and functional unblinding remain. The evidence was rated low certainty using GRADE, and the authors note more trials are needed.
Medicine Advances
March 27, 2026
Thomas Edward Cutting, Richard Evans Hartman
Ketamine and its stereoisomers show efficacy for PTSD and treatment-resistant depression, with (R)-ketamine having fewer side effects. The therapeutic mechanisms involve specific brain regions: the dentate gyrus, prefrontal cortex, CA3 region of the ventral hippocampus, dorsal raphe nucleus, and the prelimbic–dorsal raphe nucleus circuit. For PTSD, ketamine attenuates serotonin signaling in the dorsal raphe nucleus and activates that circuit. When given before stress, it increases purine and pyrimidine metabolism, potentiates inhibitory neurotransmitters, and dampens excitatory ones except glutamic acid. Brain-derived neurotrophic factor activation of tropomyosin-related kinase B appears necessary for treatment effects, but N-methyl-D-aspartate receptor antagonism may not be.
bioRxiv (Cold Spring Harbor Laboratory)
March 24, 2026
Kenneth Shinozuka, Mattia Rosso, Anna Chaiken et al.
1 citation
A single dose of the atypical psychedelic ibogaine can be highly effective at treating PTSD in veterans up to twelve months later, according to an observational study of 30 veterans. Using a novel EEG analysis method, researchers found that ibogaine shifted high-beta (24 and 25 Hz) brain networks from frontal areas toward posterior regions, an effect seen both three to four days and one month after treatment. This posterior shift correlated with improvements in PTSD symptoms and was replicated in an independent dataset on ibogaine for opioid use disorder. Neural modeling suggested the shift reflects increased corticocortical, not corticothalamic, connectivity. The reconfiguration of high-beta networks may be a robust biomarker for ibogaine's therapeutic effects.
European Neuropsychopharmacology
March 12, 2026
Natalia E. Fares-Otero, Yuki Furukawa, Marit Sijbrandij et al.
A systematic review and meta-analysis of randomized controlled trials found that MDMA-assisted therapy (MDMA-AT) was associated with reductions in PTSD symptom severity and dissociative symptoms, and may improve functioning, compared with control conditions. No clear benefit was observed for depressive symptoms. The analysis included 8 trials with 298 participants for the primary outcome. However, the overall certainty of the evidence was very low due to high risk of bias in outcome measurement, deviations from intended interventions, small sample sizes, and lack of active controls in most studies. Larger, higher-quality trials with active controls and long-term follow-up are needed to determine efficacy.
Journal of Traumatic Stress
March 12, 2026
Leslie A. Morland, B O Rothbaum, Lauren M. Sippel et al.
2 citations
MDMA-assisted psychotherapy for PTSD shows promising results in recent randomized controlled trials, with high response and remission rates, but the FDA declined to approve it in August 2024 due to insufficient evidence. This review examines the current scientific literature on MDMA-AT, covering proposed mechanisms, methodological strengths and limitations, evidence gaps, and clinical, ethical, and regulatory issues. Key limitations include challenges with blinding, lack of active comparator conditions, no head-to-head comparisons of different therapy models, inadequate safety monitoring, and limited sample generalizability. Emerging research integrates MDMA with established trauma-focused therapies like prolonged exposure and cognitive processing therapy to leverage MDMA's effects on cognitive behavioral mechanisms.
American Journal of Health-System Pharmacy
March 4, 2026
Jennifer E. Thomas, Anna Dellarole, Robin J. Jacobs
Current literature most strongly supports MDMA and intravenous ketamine as treatments for PTSD. Under professional supervision, these agents may reduce PTSD symptoms and are generally well tolerated. However, findings require cautious interpretation because of limitations including treatment expectancy effects and potential inadequate blinding. Additional randomized controlled trials of other psychedelics, such as psilocybin and lysergic acid diethylamide, are necessary to evaluate their effectiveness for PTSD.
Psychiatr Res Clin Pract
March 3, 2026
The term "flashback" has been used differently across psychedelic and post-traumatic stress disorder (PTSD) research over time. This historical analysis traces how the concept originated in the 1960s with psychedelic experiences, then was later adopted in PTSD literature to describe involuntary re-experiencing of traumatic events. The paper argues that the term's meaning has shifted and sometimes become conflated, leading to confusion in clinical and research contexts. It examines the historical development of the term and its current usage, highlighting the need for clearer definitions to improve diagnostic accuracy and scientific communication.
Neuroscience and biobehavioral reviews
March 1, 2026
Andrew Laurin, Hugo Bottemanne, Samuel Bulteau et al.
2 citations
A review proposes that post-traumatic stress disorder (PTSD) involves disrupted body awareness, specifically the sense of body ownership and sense of agency, which current models overlook. Using predictive processing theory, it distinguishes two PTSD subtypes. In non-dissociative PTSD, hyperprecise trauma-related prior beliefs and heightened interoceptive signals (due to amygdala and anterior insula hyperactivity) produce rigid self-representations, with cognitive processing ranked as prior, interoception, then exteroception. In the dissociative subtype, emotional over-inhibition and anterior insula hypoactivity weaken priors and interoception, while exteroception dominates (exteroception, interoception, prior). Sense of agency impairments are specific to the dissociative subtype, linked to angular gyrus hyperactivity and glutamate hypofunction. The framework suggests a dimensional model of body consciousness disruption across the PTSD spectrum and discusses therapeutic implications for top-down and bottom-up interventions.
Biological psychiatry global open science
March 1, 2026
Noam Goldway, Taly Markovits, Naomi Fine et al.
1 citation
Dissociation—feeling detached from one's body, environment, or self—often accompanies posttraumatic stress disorder (PTSD), but its neural basis is poorly understood. Using network control theory on resting-state functional MRI data, researchers examined brain dynamics during dissociative states in healthy volunteers given ketamine (n=30) and in PTSD patients (n=78) before and after treatment. Ketamine induced brain dynamics similar to those in untreated PTSD patients: increased dominance of the default mode network (DMN) meta-state and decreased dominance of the somatomotor network (SOM) meta-state. After treatment, reduced DMN meta-state dominance correlated with fewer dissociative symptoms. Treated patients also showed more organized, less entropic brain states, though ketamine did not significantly alter entropy indices. Dissociative states, whether drug-induced or clinical, involve increased DMN and reduced SOM dominance.
The Nursing clinics of North America
March 1, 2026
Amanda Canada
Posttraumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD) frequently co-occur, leading to worse outcomes and higher relapse rates. Ketamine can produce rapid and lasting reductions in PTSD symptoms and AUD relapse. Prazosin effectively treats PTSD-related nightmares and may lower alcohol consumption in people with high autonomic reactivity. Because these drugs work through complementary mechanisms—modulating glutamatergic transmission and reducing noradrenergic hyperactivity—combining them may improve stabilization, readiness for trauma-focused therapy, and broader symptom control. Although this combination has not been tested in clinical trials, it warrants nurse practitioner-led research to evaluate safety, efficacy, and integration into multidisciplinary care.