European journal of psychotraumatology • December 1, 2026 • Maud Rothärmel, Lila Mekaoui, François Kazour et al. • 1 citation
In a retrospective study of 22 adults with treatment-resistant depression and comorbid post-traumatic stress disorder who received esketamine nasal spray, trauma re-experiencing episodes occurred during treatment sessions. For 16 patients (72.7%) these episodes disappeared as sessions progressed. Treatment was stopped for 6 patients (27.3%) due to re-experiencing. Among those who continued esketamine, depression response rate was 45.5% and remission 22.7%; PTSD improvement rate was 45.5% and remission 18.2%. The findings suggest esketamine can be safely administered in this comorbid population and that trauma re-experiencing does not prevent clinical improvement.
European journal of psychotraumatology • December 1, 2026 • Philip Gerrans, Hugh McGovern, Jakob Hohwy et al.
Complex post-traumatic stress disorder (C-PTSD) involves lasting difficulties with emotions, self-concept, and relationships, beyond typical PTSD symptoms. This review proposes a neurocognitive explanation based on predictive processing and self-modelling, focusing on how the brain's insula integrates bodily signals, emotions, and self-awareness. The authors suggest that C-PTSD arises from maladaptive predictions shaped by prolonged interpersonal trauma, leading to unstable self-regulation. They examine MDMA-assisted psychotherapy as one intervention that may temporarily alter emotional salience, trust, and self-related thinking. The framework generates testable hypotheses about self-modelling in C-PTSD and offers guidance for developing treatments that target affective regulation and self-referential processing.
Scientific reports • July 11, 2026 • Monnica T Williams, Sonya C Faber, Jordan Sloshower et al.
A small preliminary study of five diverse individuals found that MDMA-assisted therapy significantly reduced trauma symptoms related to discrimination. Scores on the Trauma Symptoms of Discrimination Scale dropped by an average of 38% after treatment, a large effect. All participants, who had experienced multiple forms of discrimination including gender, racial, and sexual orientation bias, reported marked improvement. The results suggest MDMA-assisted therapy may help alleviate discrimination-related trauma in marginalized populations, though the small sample size calls for cautious interpretation and further research with larger, more diverse groups.
Frontiers in Psychiatry • July 8, 2026 • Lotem Zvi, Jonathan E. Handelzalts, Danny Horesh et al.
Women with histories of childhood sexual abuse (CSA) and co-occurring psychiatric disorders admitted to a specialized integrative inpatient unit in Israel showed that dissociative symptoms, particularly maladaptive absorption, were strongly linked to PTSD severity. In a cross-sectional phase with 108 women, all facets of dissociation correlated positively with PTSD symptoms. In a smaller treatment phase with 28 women, PTSD symptoms decreased after the program, and reductions in absorption were tied to improvements in overall PTSD and hyperarousal. The findings suggest dissociation should be a key therapeutic target, though larger controlled trials are needed.
The International Journal of Neuropsychopharmacology • July 6, 2026 • Shabah M. Shadli, Neda Nasrollahi, Calvin K. Young et al.
Ketamine at low doses (0.5-1.0 mg/kg I.M.) quickly reduces symptoms in treatment-resistant major depressive disorder (TR-MDD), post-traumatic stress disorder (TR-PTSD), and obsessive-compulsive disorder (TR-OCD), but its neural effects differ by diagnosis. EEG recordings of resting frontal activity before and after ketamine or fentanyl showed that TR-PTSD patients had dose- and band-frequency-dependent power changes (especially alpha at 0.5 mg/kg), while TR-MDD patients showed no such changes. TR-OCD responses differed qualitatively from both. Correlations between EEG power changes and symptom scale improvements varied by band and electrode across different disorder-specific scales. Ketamine's effects and their therapeutic links vary by brain site and frequency band depending on the DSM diagnosis, suggesting disorder-specific systems require a ketamine-sensitive factor to generate the disorder.
BMJ Open • July 1, 2026 • Kirsten C. Morley, S Arunogiri, Katherine L. Mills et al.
Combining MDMA with an integrated exposure-based therapy may improve outcomes for people with both post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a comorbidity where standard treatments help only about half of patients. This double-blind trial will randomly assign 100 participants to receive either MDMA (80–160 mg) or an active control (niacin 250 mg) alongside 12 sessions of Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE). The primary PTSD outcome is the clinician-administered PTSD Scale for DSM-5; the primary drinking outcome is heavy drinking days per week, validated by phosphatidylethanol. Secondary measures include depression, sleep disturbances, adverse events, and cost-effectiveness. Results will provide first data on safety, efficacy, and cost-effectiveness of MDMA-augmented therapy for this comorbidity.
Therapeutic Advances in Psychopharmacology • July 1, 2026 • Karthika Kasiviswanathan, Dinuli Nilaweera, M Morando et al.
MDMA-assisted psychotherapy (MDMA-AP) may help treat not only PTSD but also complex PTSD and borderline personality disorder. A systematic review of 24 studies involving 335 participants found that most reported reduced PTSD symptoms after MDMA-AP, with some noting decreased dissociative symptoms at higher doses. Although no studies directly assessed MDMA-AP for complex PTSD or borderline personality disorder, improvements in emotional regulation, interpersonal functioning, identity coherence, and abandonment concerns were reported. Adverse drug reactions were mild to moderate, though specific safety concerns remain. These findings offer preliminary insights for future research and clinical considerations.
Psychotherapy and psychosomatics • June 19, 2026 • Judith Rohde, Tyler M Moore, Kathryn Walker et al.
A systematic review and individual participant data meta-analysis of 12 studies (533 participants) found that higher baseline PTSD severity was the most robust predictor of symptom reduction after combined ketamine and psychotherapy. More psychotherapy sessions, more ketamine sessions, and shorter treatment duration were also associated with greater improvement, but these findings are tentative because most studies were of poor quality. The analysis showed that for each additional psychotherapy session, PTSD symptoms improved by an average of 1.03 points on the PCL-5, and for each additional ketamine session, improvement was 1.15 points. The results require confirmation in well-designed prospective trials.
Journal of medical Internet research • June 17, 2026 • Acacia C Parks, Amanda L Woodward, Robert D Henry et al.
A large analysis of 3,870 patients with moderate-to-severe depression, anxiety, or PTSD who used a telehealth program for at-home subcutaneous ketamine found significant symptom reductions after about six weeks. Depression scores on the PHQ-9 fell from 14.6 to 6.3, anxiety scores on the GAD-7 from 13.1 to 6.1, and PTSD scores on the PCL-5 from 46.7 to 27.5, all with large effect sizes. Over 80% of patients achieved a clinically meaningful improvement. Adverse events were low (2.8%-3.2%), and no serious complications occurred. The results suggest that supervised at-home subcutaneous ketamine is a safe and effective option that could expand access to rapid-acting treatment.
Scientific Reports • June 14, 2026 • Bar Eilat Yogev, Gal Levi, Noa Efroni et al.
Alcohol consumption before trauma increases vulnerability to PTSD-like symptoms in rats. Rats given ethanol four hours before predator scent stress showed more anxiety-like behavior, heightened startle responses, and greater hippocampal dendritic retraction seven days later. This vulnerability was linked to reduced brain-derived neurotrophic factor and neuropeptide Y, increased hyperpolarization-activated cyclic nucleotide-gated channel 1, and loss of neuropeptide Y-Y1 receptor immunoreactivity in the hippocampus—a hypoexcitable, plasticity-resistant state. A single intranasal subanesthetic dose of ketamine delivered via amylolipid nanovesicles one hour after trauma reduced cue-induced freezing and dendritic atrophy, suggesting a potential preventive strategy for alcohol-exposed trauma survivors.
Journal of addiction psychiatry • January 1, 2024 • Gianni Martire, Daniel Sipple, David Baron et al. • 341 citations
Borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) share overlapping neurobiological mechanisms, particularly reward deficiency and stress-like anti-reward processes. The authors propose reclassifying BPD as a "traumatic personality stress disorder" (TPSD) to unify therapeutic strategies that may stabilize dopaminergic reward function, such as psychedelic-assisted therapy (PAT). They argue that PAT could treat trauma-induced personality disorders by addressing these shared mechanisms. Reframing BPD as TPSD may lead to more effective, personalized interventions, reduce stigma, and improve understanding of underlying mechanisms, benefiting conditions characterized by anhedonia, negative affect, hypervigilance, and dissociation.
Nature medicine • October 1, 2023 • 400 citations
In a phase 3 trial, MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in 104 participants with moderate to severe PTSD. The average decrease in PTSD symptom severity was 23.7 points with MDMA-assisted therapy versus 14.8 points with placebo, and functional disability improved by 3.3 versus 2.1 points. Participants were ethnoracially diverse, with 27% identifying as Hispanic/Latino and 34% as other than White. Severe side effects occurred in 9.4% of the MDMA group and 3.9% of the placebo group; no deaths or serious adverse events were reported. The treatment was generally well tolerated.
Nature medicine • June 1, 2021 • Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al. • 965 citations
A phase 3 clinical trial tested MDMA-assisted therapy against placebo for severe PTSD. Participants received manualized therapy with either MDMA or placebo alongside preparatory and integrative sessions. At two months after the last session, the MDMA group showed a significantly greater reduction in PTSD symptoms (average 24.4-point drop on the CAPS-5 scale) compared to the placebo group (13.9-point drop), with a large effect size. Functional impairment also improved more with MDMA. No serious safety issues such as abuse potential, suicidality, or heart rhythm problems were observed. The findings suggest MDMA-assisted therapy is highly effective and safe for severe PTSD, including in people with common co-occurring conditions.
American Journal of Psychiatry • January 5, 2021 • A. Feder, Sara Costi, S. Rutter et al. • 239 citations
Repeated intravenous infusions of ketamine, given over two weeks, significantly reduced symptom severity in chronic PTSD compared to a psychoactive placebo (midazolam). At two weeks, the ketamine group scored nearly 12 points lower on the Clinician-Administered PTSD Scale, and 67% of participants responded to treatment versus 20% in the placebo group. Among responders, the median time to loss of response was 27.5 days after the infusion course. Ketamine was well tolerated with no serious adverse events. This is the first randomized controlled trial to show efficacy of repeated ketamine infusions for chronic PTSD.
Cell • April 1, 2020 • 330 citations
The paper argues that psychedelic psychiatry is entering a new era, characterized by a shift from prohibition to clinical investigation and therapeutic use. It describes how substances like psilocybin and MDMA are being studied for treating mental health conditions such as depression, PTSD, and anxiety, often in guided sessions with therapeutic support. The author contends that this emerging paradigm may transform mental healthcare by facilitating psychological breakthroughs and healing, though it also raises ethical and regulatory challenges. The work presents a historical and theoretical analysis of this transition, emphasizing the need for careful integration into clinical practice.
The International Journal of Neuropsychopharmacology • March 12, 2020 • Erwin Krediet, Tijmen Bostoen, Joost J. Breeksema et al. • 262 citations
Posttraumatic stress disorder (PTSD) often remains chronic after psychotherapy, and few effective medications exist. A promising new approach involves psychedelic drugs. This review discusses four compound types: MDMA, ketamine, classical psychedelics (psilocybin, LSD), and cannabinoids. It describes each compound's therapeutic rationale, administration setting, and current evidence for treating PTSD. Each offers unique qualities, from rapidly targeting symptoms to facilitating psychotherapy. The review outlines questions for future research.
Psychopharmacology • September 1, 2019 • Michael C Mithoefer, Allison A Feduccia, Lisa Jerome et al. • 364 citations
A pooled analysis of six phase 2 trials found that MDMA-assisted psychotherapy significantly reduced PTSD symptoms in adults. Participants receiving active MDMA (75-125 mg) during manualized therapy sessions showed a large treatment effect (Cohen's d = 0.8) compared to those receiving placebo or low doses (0-40 mg). After two sessions, 54.2% of the active group no longer met PTSD diagnostic criteria versus 22.6% of the control group. Depression symptoms also improved more in the active group, though this difference was not statistically significant. MDMA was well tolerated with expected side effects. These findings supported advancement to phase 3 trials and FDA Breakthrough Therapy designation.
Lancet Psychiatry • May 1, 2018 • 443 citations
A randomized, double-blind, phase 2 clinical trial tested MDMA-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers. Participants were randomly assigned to receive different doses of MDMA during psychotherapy sessions. The findings revealed that the active dose of MDMA led to significant and lasting reductions in PTSD symptoms compared to the lower dose, indicating that this innovative therapeutic approach can effectively treat this condition and provide significant relief for individuals with profound trauma.
Neuropsychopharmacology • April 26, 2017 • 680 citations
Psychedelic drugs, once a focus of psychiatric research before being banned, are now being reinvestigated for their therapeutic potential. The review traces the history of psychedelic research from the 1950s through the present resurgence, highlighting early clinical studies that suggested benefits for conditions like alcoholism and anxiety. It discusses modern controlled trials showing psilocybin and MDMA can reduce depression and PTSD symptoms, often after just one or two sessions. The authors argue these substances may work by disrupting rigid brain patterns and enhancing neuroplasticity. They call for larger, rigorous studies and careful integration into clinical practice, noting that while risks exist, the therapeutic promise is substantial.
Lancet Psychiatry • April 5, 2016 • 237 citations
Psilocybin and MDMA are emerging as novel psychopharmacological therapies for psychiatric disorders, offering potential alternatives to conventional treatments. These substances are being investigated for their ability to facilitate therapeutic breakthroughs in conditions such as depression and post-traumatic stress disorder. The text outlines their mechanisms, clinical applications, and the growing interest in their use within mental healthcare. It highlights the need for further research to establish safety and efficacy, while acknowledging the promise these therapies hold for addressing treatment-resistant psychiatric conditions.
JAMA Psychiatry • April 16, 2014 • Adriana Feder, Michael K. Parides, James W. Murrough et al. • 618 citations
A single intravenous dose of ketamine (0.5 mg/kg) rapidly reduced posttraumatic stress disorder (PTSD) symptom severity more than the active placebo midazolam in patients with chronic PTSD. Twenty-four hours after infusion, the ketamine group showed a mean reduction of 12.7 points on the Impact of Event Scale-Revised compared to midazolam. Ketamine also lessened comorbid depressive symptoms and improved overall clinical presentation. The treatment was generally well tolerated without persistent dissociative symptoms. These results suggest ketamine may offer a novel pharmacologic approach for chronic PTSD, though replication is needed.
Depression and Anxiety • April 17, 2013 • Anthony P. King, Thane M. Erickson, Nicholas D. Giardino et al. • 258 citations
Group mindfulness-based cognitive therapy (MBCT) adapted for combat posttraumatic stress disorder (PTSD) is feasible, acceptable, and associated with clinically meaningful reductions in PTSD symptom severity, particularly avoidance and numbing symptoms, and trauma-related cognitions such as self-blame. In an outpatient VA clinic, veterans with chronic PTSD who completed an 8-week MBCT group showed significant improvement on clinician-rated PTSD symptoms, whereas those in brief treatment-as-usual did not. Homework compliance was good, and drop-out rates were modest. The findings suggest MBCT as a brief adjunctive therapy for combat PTSD, but randomized controlled trials are needed to confirm efficacy.
Journal of psychopharmacology (Oxford, England) • January 1, 2013 • Michael C Mithoefer, Mark T Wagner, Ann T Mithoefer et al. • 377 citations
In a long-term follow-up of the first completed trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, all 19 original participants took part, and 16 completed all outcome measures 17 to 74 months after their final MDMA session (average 45.4 months). The mean CAPS score at follow-up (23.7) was nearly identical to the mean score at study exit (24.6), indicating that the substantial symptom relief achieved during the trial was maintained over time. Although two participants relapsed, the majority sustained clinically significant improvements, and no one reported harm from participation.
Journal of Psychopharmacology • October 31, 2012 • Peter Oehen, Rafael Traber, Verena Widmer et al. • 407 citations
MDMA-assisted psychotherapy for treatment-resistant PTSD can be safely administered in a clinical setting. In a randomized, double-blind, active-placebo controlled pilot trial, 12 patients received either a low dose (25 mg plus 12.5 mg supplemental) or a full dose (125 mg plus 62.5 mg supplemental) of MDMA during three experimental sessions, combined with weekly non-drug psychotherapy. No serious drug-related adverse events occurred. While clinician-rated PTSD symptoms (CAPS) did not show statistically significant reductions (p = 0.066), self-reported improvement (PDS) was clinically and statistically significant (p = 0.014). CAPS scores further improved at one-year follow-up, and three MDMA sessions were more effective than two (p = 0.016).