Yet More Data on Psychedelics in Veterans with Depression
And it's early, but it's good.
Greetings from Seattle! I am writing a column that is not very child psychiatry-focused today because I could write it quickly. That is how much I care, dear readers, to feed your almost unquenchable hunger for health-themed journalism. This is The Frontier Psychiatrists, live from AACAP 2024. Now, today’s column.
Contra the claims of Midofedamine evangelicals, claiming that MDMA-AT was desperately needed because, as Nutt Et. Al. Argued in an editorial published on October 10th:
there has been an urgent need for innovation in the treatment of PTSD for decades1
As if there had not been innovation (a falsehood, given the other innovative treatments that have been demonstrated at various stages of development):
the FDA held a public advisory committee (AdCom) hearing in early June 2024. This committee almost unanimously rejected both the evidence of efficacy and the benefit–risk profile for MDMA-assisted therapy (MDMA-AT) submitted by Lykos. This decision surprised many in the field given that the clinical efficacy data had been available in peer-reviewed and often high-impact journals (e.g. Mitchell et al. 2021, 2023) and appeared to meet the FDA requirements of two placebo-controlled randomised controlled trials (RCTs) for proof of efficacy.
Except, you know, it didn’t demonstrate that sufficiently. Three major publications have had to be retracted. There is, however, hope for psychedelic medicine in veterans. Researchers will likely circle back to an MDMA-related molecule, absent the baggage of the -AT manual, in due time. One of these other contenders for “first novel psychedelic” is, of course, psilocybin. We already had phase II data on COMP360 in PTSD— the COMPASS/Pathways proprietary version of the naturally occurring mushroom, described in this newsletter as a Christmas miracle just last year. It has multiple trials describing single-dose and multidose schedules in treatment-resistant depression and regular old depression. My co-authors and I even authored a helpful review in April of 2024:
In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%–57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses.2
More data on its use in veterans is out this month. This study was a depression trial—the population was veterans with depression who also had PTSD in some cases. The issue in the treatment of veterans with depression is that it’s often very “resistant.”
Today’s topic is an open-label trial, in a cohort of individuals with low placebo response rates anyway, had treatment-resistant depression and were treated with a single dose of psilocybin:
15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score.
And it worked:
60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes.3
So, veterans….there is hope for your depression—with or without PTSD. More veteran-focused research needs to be conducted—they don’t typically have the same response data as other populations and deserve the best healthcare we can offer. This is an excellent start, and more needs to be done. The most important detail? Two hundred individuals volunteered for this 15-person trial. If we conduct ourselves ethically, these studies will continue to enroll robustly.
Nutt DJ, Hawrot T, Hunt P, Schlag AK. Allaying the fears: Midomafetamine with therapy is a medicine. Drug Science, Policy and Law. 2024;10. doi:10.1177/20503245241274079
Tabaac, Burton J. MD, FAHA1,2; Shinozuka, Kenneth BA3,4,*; Arenas, Alejandro MD5; Beutler, Bryce D. MD6; Cherian, Kirsten PhD7; Evans, Viviana D. BA8; Fasano, Chelsey BA9; Muir, Owen S. MD, DFAACAP10,11. Psychedelic Therapy: A Primer for Primary Care Clinicians—Psilocybin. American Journal of Therapeutics 31(2):p e121-e132, March/April 2024. | DOI: 10.1097/MJT.0000000000001724
Ellis, S., Bostian, C., Feng, W., Fischer, E., Schwartz, G., Eisen, K., Lean, M., Conlan, E., Ostacher, M., Aaronson, S., & Suppes, T. (2025). Single-dose psilocybin for U.S. Military Veterans with severe treatment-resistant depression – A first-in-kind open-label pilot study. Journal of Affective Disorders, 369, 381-389. https://doi.org/10.1016/j.jad.2024.09.133
Thank you!
Promising! Thanks for sharing esp while you’re busy at a conference!