Gus Alva, MD

Future Research Priorities for MDMA-Assisted Therapy, with Gus Alva, MD

, and public health as a whole, wait with anticipation surrounding the US Food and Drug Administration’s decision on 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in the management of 

A subject mired in controversy as a result of decades-old stigma, MDMA-assisted therapy has, with extensive research efforts and clinical trial data, proven its potential. Beyond MDMA-assisted therapies, clinical programs and trials for other psychedelic agents, including psilocybin, ketamine, and other compounds, have furthered discussions around the roles of these therapeutic options in psychiatric care.

Backed by positive data from the phase 3, randomized, double-blind, placebo-controlled MAPP1 and MAPP2 trials, the application for MDMA-assisted therapy  PTSD seemed poise to usher in a new era in management. 

However, the road to a potential approval has seemingly turned into an even greater uphill battle in the wake of an FDA Psychopharmacologic Advisory Committee on June 4, 2024, which saw the committee vote 2-9 against supporting the effectiveness of MDMA in the treatment of adult patients with PTSD followed by a subsequent 1 to 10 vote against the notion that the benefits of MDMA in combination with the FDA’s proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD.

Despite this, leading researchers, psychiatrists, as well as patients and advocacy organizations, have vocalized their concerns surrounding the unmet need in PTSD management and the need to research further the use of psychedelic therapies for use in psychiatric conditions.

In this 5-part video series, we spotlight the perspective of leading subject matter expert Gus Alva, MD, a psychiatrist and medical director of ATP Clinical Research, on the subject, with segments dedicated to:

Interpreting Trial Data for MDMA-Assisted Therapy

Addressing Stigma Surrounding MDMA and Psychedelic Therapies

Future Research Priorities for MDMA-Assisted Therapy

In this final segment, Alva discusses the critical need for long-term data on MDMA-assisted therapy, emphasizing the importance of understanding potential long-term effects. The conversation highlights concerns about the possibility of negative outcomes over extended periods, which underscores the necessity for ongoing research. Despite these concerns, Alva acknowledges the promising data already available, which extends beyond PTSD to other conditions like alcohol dependence. 

The discussion touches on the potential benefits of MDMA-assisted therapy for various psychiatric and addiction disorders, advocating for a cautious yet open-minded approach. Alva also mentions the importance of adhering to established psychotherapeutic guidelines to ensure safe and effective treatment. The segment concludes by stressing the need for post-marketing studies to monitor long-term outcomes and fulfill regulatory commitments, ultimately aiming to broaden the therapeutic applications of MDMA in a controlled and scientifically sound manner.

Relevant disclosures for Alva include Teva Pharmaceuticals, Otsuka America Pharmaceuticals, AbbVie Inc., Axsome Therapeutics, Janssen Pharmaceuticals, and more.

Mitchell JM, Ot'alora G M, van der Kolk B, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. 

. 2023;29(10):2473-2480. doi:10.1038/s41591-023-02565-4

Kunzmann K. FDA Psychopharmacologic Advisory Committee votes against supporting effectiveness of MDMA FOR PTSD. HCP Live. June 4, 2024. Accessed July 26, 2024. https://www.hcplive.com/view/live-updates-fda-psychopharmacologic-advisory-committee-meeting-mdma-ptsd.

Campbell P. First Study of Psilocybin in PTSD shows promise, safety of treatment approach. HCP Live. May 9, 2024. Accessed July 26, 2024. https://www.hcplive.com/view/first-study-of-psilocybin-in-ptsd-shows-promise-safety-of-treatment-approach.

Videos

In this part of our 5-part series, Gus Alva, MD discusses the next steps in research for long-term effects and broader applications of MDMA-assisted therapy.


Prospect of Psychedelic Therapies in Psychiatry, with Gus Alva, MD

Prospect of Psychedelic Therapies, with Gus Alva, MD

In this segment, Alva emphasizes the importance of a cautious and evidence-based approach to integrating MDMA-assisted therapy into clinical practice for PTSD. Highlighting their active participation in ongoing studies, Alva stresses the necessity of thorough research and data analysis before adopting new treatments. 

The discussion covers the use of off-label treatments like ketamine and esketamine, which, despite lacking FDA approval, have shown promise in treating resistant depression and suicidal ideation. Alva details the neurochemical pathways involved, such as the glutamatergic pathway for ketamine and the impact on monoamines and hormones like oxytocin and cortisol for MDMA. This segment underscores the need to keep an open mind while rigorously evaluating new therapies, emphasizing the potential of MDMA-assisted therapy to address long-standing treatment challenges.

In this part of our 5-part series, Gus Alva, MD explores MDMA’s neurochemical impact and the need for ongoing research.

Future Research Priorities for MDMA-Assisted Therapy in PTSD, with Gus Alva, MD

Addressing Stigma Surrounding MDMA and Psychedelic Therapies, with Gus Alva, MD

In this segment, Alva discusses the critical role of education in overcoming stigma and misconceptions about MDMA-assisted psychotherapy for PTSD. Highlighting the importance of providing accurate information to both healthcare professionals and the public, the discussion addresses common concerns about the potential for abuse and misuse of MDMA.  

Alva emphasizes the difference between recreational and controlled clinical use, where MDMA is administered in a carefully regulated environment with professional supervision. The segment explores the historical context of PTSD, noting how it was once dismissed and misunderstood, and draws parallels with the current skepticism surrounding MDMA-assisted therapies. 

Alva provides a detailed explanation of the dosing regimen and therapeutic process, clarifying that treatment involves a few carefully spaced sessions with precise dosing. The conversation also touches on the broader challenges of gaining trust in new therapies amidst a climate of media skepticism and public distrust.

In this part of our 5-part series, Gus Alva, MD highlights the importance of education and overcoming skepticism about MDMA-assisted therapy.

Interpreting Trial Data for MDMA-Assisted Therapy, Gus Alva, MD

In this segment, Alva examines the growing body of evidence supporting the efficacy of MDMA-assisted psychotherapy in the treatment of PTSD. Despite some criticism regarding study design issues, the data consistently demonstrate that MDMA significantly enhances the therapeutic process. The discussion addresses common concerns, including the potential for abuse and misuse of MDMA, often highlighted by its association with recreational use at events like raves. However, Alva emphasizes the critical differences between controlled clinical use and recreational abuse. In a therapeutic setting, MDMA is administered in a controlled environment, with precise dosing and constant supervision by 2 therapists, ensuring patient safety and maximizing therapeutic benefit. The segment also touches on the FDA's cautious approach to this novel treatment modality, noting that while some skepticism remains, the established efficacy of MDMA-assisted psychotherapy is promising. 

In this part of our 5-part series, Gus Alva, MD talks about MDMA's efficacy in controlled settings and addresses misconceptions.

Gus Alva, MD

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