Preprints.org • Kainat Riaz, Sejal Suneel, Mohammad Hamza Bin Abdul Malik et al. • 1 citation
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Half of patients with post-traumatic stress disorder (PTSD) do not respond to standard pharmacotherapy or psychotherapy. A review of six phase II randomized controlled trials indicates that MDMA-assisted psychotherapy can reduce PTSD symptoms, even in treatment-resistant cases, by increasing neurohormones such as dopamine, serotonin, norepinephrine, and oxytocin and by modulating brain regions involved in fear and anxiety. The FDA has granted MDMA-assisted psychotherapy a "Breakthrough Therapy" designation. Further research is needed to determine whether the benefits outweigh the risks and whether this approach can be integrated into existing treatment options.
Kenneth Shinozuka, Burton J. Tabaac, Alejandro Arenas et al.
preprint
MDMA, known as a party drug in the 1980s, is emerging as a powerful treatment for PTSD. Phase III FDA trials show MDMA-assisted psychotherapy has an effect size of 0.7-0.91, two to three times larger than existing antidepressants. Within 18 weeks, 67 to 71% of patients no longer meet PTSD diagnostic criteria. The literature is biased: animal studies used doses far above human levels, and human samples often involve recreational users of multiple substances. Only six clinical trials, all by MAPS, have been conducted, but preliminary evidence suggests MDMA is much more effective than current antidepressants for PTSD.
Jason B Luoma, M. Kati Lear, Kyong Yi et al.
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A man in his late 30s with generalized social anxiety disorder (SAD) received MDMA-assisted therapy that included imaginal exposure to shame-related memories and in vivo social exposures during drug sessions, plus imagery rescripting and social activation homework. His symptoms and functional impairment, measured by the Leibowitz Social Anxiety Scale and Sheehan Disability Scale, showed significant reduction. He reported increased social engagement, less anxiety in social situations, and more self-compassion. The participant found exposures during MDMA sessions particularly impactful, allowing access to intrinsic desires for social connection. The authors suggest MDMA-assisted therapy with exposure techniques may be a promising treatment for SAD, warranting further research.
Research Square • Taqwa B. Thanoon, Zeina A. Althanoon
Depression during pregnancy can harm offspring brain development and behavior. Common antidepressants like SSRIs carry risks because they cross the placenta. Ketamine is being explored as an alternative. This study in mice examined the effects of ketamine on offspring of mothers that experienced stress. Female mice were divided into groups: control, maternal stress, stress plus fluoxetine, and stress plus ketamine. Behavioral tests measured anxiety, anhedonia, and despair in the offspring. Maternal stress increased anxiety-like behaviors, and both ketamine and fluoxetine reversed some effects. However, fluoxetine was more effective at reducing despair. Ketamine moderately reduced anhedonia compared to controls. More research on dose and timing is needed to optimize ketamine treatment.
Mark Groeneveld, Thomas Harper
preprint
A framework for using MDMA therapeutically, covering professionally-guided and self-guided approaches, synthesizes research on trauma neurobiology, maladaptive schemas, and memory reconsolidation. Clinical trials show significant improvements in PTSD symptoms. Detailed guidance includes safety, dosing, session preparation, therapeutic processes, and post-session integration. Challenges like anxiety and dissociation are addressed. The framework emphasizes risk assessment, especially for self-guided use, and explores broader benefits such as expanded compassion and cognitive flexibility. The manual aims to make MDMA-assisted therapy more accessible, safe, and effective.
Mark Groeneveld, Thomas Harper
preprint
A framework for the therapeutic use of MDMA addresses both professionally-guided and self-guided approaches, synthesizing research on trauma neurobiology, maladaptive schemas, and memory reconsolidation. Clinical trials show significant improvements in PTSD symptoms. Detailed guidance covers safety, dosing, session preparation, therapeutic processes, and post-session integration, along with strategies for managing challenges like anxiety and dissociation. The paper emphasizes careful risk assessment, especially for self-guided approaches, and explores potential benefits for expanding compassion and cognitive flexibility.
bioRxiv (Cold Spring Harbor Laboratory) • Lucas Dwiel, Angela Henricks, Elise Bragg et al. • 1 citation
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Lysergic acid diethylamide (LSD) acutely reduces low-frequency electrical activity across the brain in rats, an effect that returns to normal after 24 hours. However, brain stimulation applied during a window of heightened neuroplasticity 24 hours after LSD produces larger and distinct changes in brain activity compared to stimulation after a placebo. This proof-of-concept finding suggests that psychedelic drugs may work in combination with brain stimulation to achieve enhanced effects on brain activity, with future work needed to assess impacts on behavior.
Acacia C Parks, Amanda L Woodward, Robert D Henry et al.
A telehealth-supervised at-home subcutaneous ketamine protocol for moderate-to-severe depression, anxiety, and PTSD was safe, feasible, and highly effective. Among 3,870 patients, symptom scores dropped from moderate-to-severe to mild or subthreshold ranges after about six weekly sessions: depression scores fell from 14.64 to 6.30, anxiety from 13.06 to 6.09, and PTSD from 46.7 to 27.5, with large effect sizes. Clinically meaningful improvement occurred in 80% to 84.6% of patients, depending on condition. Adverse events were low (2.8%–3.2%), and no serious complications were reported. The model offers a lower-cost, high-bioavailability alternative to in-clinic ketamine infusions.
Bryce D. Beutler, Kenneth Shinozuka, Burton J. Tabaac et al.
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Lysergic acid diethylamide (LSD) shows promise for treating alcohol use disorder, anxiety, and depression, though its therapeutic potential remains incompletely understood. In clinical trials, adverse events have almost always been mild and transient, with serious events reported in none or very few participants. For anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at one year post-treatment. A meta-analysis of randomized controlled trials found that single-dose LSD significantly improves alcohol use disorder with an odds ratio of 1.96. Large-scale prospective studies are needed to explore potential clinical applications.
Research Square • Katelyn Halpape, Raelle Pashovitz, Annabelle Wanson et al.
A small pilot program evaluated a hospital-to-outpatient intranasal racemic ketamine maintenance therapy for treatment-resistant depression. Five adult inpatients who had responded to intranasal ketamine in hospital continued treatment at a community centre, completing up to 14 sessions over 192 days. Depressive symptoms decreased or stabilized, and quality of life increased or stabilized. No serious adverse events occurred; mild side effects included anxiety and nausea, and slight blood pressure increases did not require intervention. The authors conclude the therapy appears feasible and well tolerated, but limited effectiveness conclusions can be drawn from this small study.