Your 2022 Guide to Late-Stage Psychedelic Clinical Trials

Psychedelic medicine is moving fast – blink, and you might miss something. We’re constantly gaining more evidence through innovative clinical trials happening worldwide. Mounting research is bringing us closer to FDA approval and legalization. But what trials are going on in 2022? Let’s talk about the psychedelic clinical trials happening this year. (Image credit Mush Stock)

Mental disorders are thought to affect one in three people throughout their lifetime.¹ Psychiatric medications and therapy have limited results, and many people experience relapse even while being consistent with treatment. These people depend on clinicians for answers, yet our current mental health system has few options for them. And on the clinician side, many providers feel unequipped to treat these patients.  

Psychedelic medicine could offer hope to people struggling with mental health. It may help bridge the gap for many people with treatment-resistant mental health problems. In past trials, we’ve learned that psychedelics improved depression rating scores, lessened PTSD symptom ratings, and could even be a helpful treatment for anorexia.^{2, 3, 4} 

But there’s a big pain point amongst all this promising research: most of these substances are federally illegal. It’s still possible to access legal psychedelic therapy in 2022, but this access is severely limited. We hope that’ll change and that current research will push the needle towards de-scheduling. More people should be able to experience the benefits of psychedelic therapy. 

Trials happening now add to the mounting evidence that psychedelic medicine could help improve lives. Psychedelic Support has our finger on the pulse of psychedelic medicine, so we can create the best educational resources and support networks for therapists. Let’s get into what the most influential psychedelic advocacy and research organizations are up to in 2022. Here are the psychedelic clinical trials happening this year. 

Phase III Trial in MDMA and PTSD

The Multidisciplinary Association for Psychedelic Studies is one of the largest organizations advocating and researching psychedelic medicine. And this year, they’re working on the most advanced-stage psychedelic clinical trial yet. 

For some background, Post-Traumatic Stress Disorder is consistently challenging to treat, with few patients experiencing remission. MDMA has shown significant benefit in phase I, II, and III trials with PTSD. In 2017, the FDA approved MDMA as a breakthrough treatment for PTSD. In 2020 & 2021, MAPS conducted a Phase III trial that yielded fantastic results.⁵ 

In the first phase III trial, 88% of patients with severe PTSD saw their symptoms decrease by half or more after MDMA therapy. And 67% of all participants who received MDMA no longer met the diagnostic criteria for PTSD.⁶ Medication and therapy have never achieved these results in this group. Based on these results, MDMA could change the lives of people suffering after trauma. 

This current trial is even bigger than the last, with testing sites spread across the nation. It’ll look at MDMA therapy compared to placebo treatment in patients with moderate to severe PTSD. 

Phase III MDMA Trial Structure:

1. Three weekly preparatory sessions. Each participant will go through weekly therapeutic sessions with their therapists to establish rapport and set expectations for their experimental session.
2. Three monthly treatment sessions. The patient will receive MDMA or the placebo treatment in varying doses over three spaced-out sessions. Initial doses range from 80 to 120 mg, followed by a half dose an hour later. 
3. Three integration sessions. Participants will have time with their therapists between and after each treatment session to understand and integrate their experiences.  

The results of this large-scale trial will likely mean a sea change in psychedelic medicine. Once this study is complete, MAPS will apply for FDA approval of MDMA for PTSD. They anticipate completing the study by the end of this year and approval by the end of 2023. As early as 2024, we may see MDMA used to treat PTSD in the medical setting. 

Interested in learning more about MAPS’ journey towards FDA approval for MDMA? We sat with leaders in their Public Benefit Corporation to learn about their commercialization process. Watch the talk and read the synopsis on our blog. 

MDMA is further along in the commercialization process than any other psychedelics. But others aren’t far behind. Let’s talk about the trials underway using psilocybin in major depression. 

Phase III Research in Psilocybin for Depression

Psilocybin mushrooms are perhaps the most commonly known psychedelic among the general public. Psilocybin could be an innovative treatment for depression, and much recent research focuses on Treatment-Resistant Depression (TRD). 

Severe depression and Treatment-Resistant Depression (TRD) are challenging to treat and live through. Patients with TRD are more likely to feel hopeless and suicidal. They experience a lower quality of life. Psychiatry has few treatment methods to offer after several rounds of unsuccessful treatment. 

Outcomes from researching psilocybin are more mixed than MDMA but still encouraging.

Here are the highlights from recent psilocybin clinical trials:

• In 2018, COMPASS Pathways received FDA approval for breakthrough therapy designation to study psilocybin in treatment-resistant depression. 

• A 2021 Johns Hopkins study found that psilocybin therapy rapidly decreased depression scores from patients’ baselines. Over 70% of participants showed “clinical significant responses,” and 58% of participants were in remission a month after therapy.⁷ 

• A 2021 COMPASS Pathways study in TRD patients had more mixed results. 37% of participants found decreased depression severity after psilocybin, and 29% experienced remission. 24% of patients had sustained lower depression scores after three months.⁸ This dosage-based study yielded more limited results, but it’s helping guide dosage in current research.   

• Another 2021 study compared depression outcomes in psilocybin therapy and escitalopram (Lexapro). At week 6, the two groups had no significant clinical difference in patients’ depression scores. More long-term outcomes favored psilocybin, other factors may have affected these outcomes.⁹  

This year, the first phase III study of psilocybin will be underway. COMPASS Pathways is again attempting to treat severe TRD with psilocybin. COMPASS is hoping that dosage information from their phase IIb trial last year will help them yield better results in this trial. Still, if nearly a quarter of patients with TRD can lower their depression, psilocybin could represent a breakthrough in depression treatment. 

The results of this large-scale trial will guide research in the future. It could also pressure more states to legalize and the FDA to approve psilocybin for depression. We expect to see the results of this trial in early 2023. 

Want to learn more about psilocybin-assisted therapy? Check out our free guide. 

Another late-phase trial has hopes of proceeding this year, studying a substance that few researchers have explored in this century: LSD.

Phase IIb trial in LSD and Generalized Anxiety Disorder

Nearly 20% of adults experienced an anxiety disorder in the last year, and over 30% experienced it at some point in life.¹⁰ Yet medication for anxiety is often not enough, and many people learn to live with their anxiety symptoms. 

LSD is a psychedelic that hasn’t been explored as much as psilocybin and PTSD. But it could be helpful for people with a range of anxiety disorders. Last year, MindMed completed an IIa trial investigating LSD therapy for anxiety and showed promising results. 65% of participants who received LSD showed clinically significant decreases in their anxiety scores after treatment. Effects persisted 16 weeks after treatment.¹¹ 

This year, MindMed is looking to progress into an IIb trial, but this research is currently on hold by the FDA. They’ve issued a clinical hold that prevents research for now, but we hope this will change soon. 

The Current Research Outlook in Psychedelic Medicine

2022 is shaping up to be the most exciting year yet in psychedelic research. We’re looking forward to seeing the results of the largest trials of both MDMA and psilocybin. The outcomes of this research will influence FDA approval decisions and could bring us closer to delivering legal psychedelic therapy to patients. 

At Psychedelic Support, we want to give you the tools to get involved in the fascinating world of psychedelic medicine. If you’re interested in getting into a clinical trial, check out our updated trial map and our guide on entering a trial. You can also keep checking back on our articles page to get updated on trial outcomes, articles from our speakers, and current events in psychedelic medicine. 

References

1. Müller, A. (2020). Mental health disorders: Prevalent but widely ignored in academia? The Journal of Physiology, 598(7), 1279–1281. https://doi.org/10.1113/jp279386
2. Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder. JAMA Psychiatry, 78(5), 481. https://doi.org/10.1001/jamapsychiatry.2020.3285
3. Tedesco, S., Gajaram, G., Chida, S., Ahmad, A., Pentak, M., Kelada, M., Lewis, L., Krishnan, D., Tran, C., Soetan, O. T., Mukona, L. T., & Jolayemi, A. (2021). The efficacy of MDMA (3,4-methylenedioxymethamphetamine) for post-traumatic stress disorder in humans: A systematic review and meta-analysis. Cureus. https://doi.org/10.7759/cureus.15070
4. Foldi, C. J., Liknaitzky, P., Williams, M., & Oldfield, B. J. (2020). Rethinking therapeutic strategies for anorexia nervosa: Insights from psychedelic medicine and Animal Models. Frontiers in Neuroscience, 14. https://doi.org/10.3389/fnins.2020.00043
5. Multidisciplinary Association for Psychedelic Studies. (2022, March 18). MAPS Investigator’s Brochure.
6. Slomski A. MDMA-Assisted Therapy Highly Effective for PTSD. JAMA. 2021;326(4):299. doi:10.1001/jama.2021.11748
7. Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285. Erratum in: JAMA Psychiatry. 2021 Feb 10;: PMID: 33146667; PMCID: PMC7643046.
8. COMPASS. (n.d.). COMP001 topline data – compass pathways. COMPASS Pathways. Retrieved July 27, 2022, from https://j8g9v7z6.rocketcdn.me/wp-content/uploads/2021/11/COMP001_-_topline_data.pdf
9. Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D., & Nutt, D. J. (2021). Trial of psilocybin versus escitalopram for depression. New England Journal of Medicine, 384(15), 1402–1411. https://doi.org/10.1056/nejmoa2032994
10. U.S. Department of Health and Human Services. (n.d.). Generalized anxiety disorder. National Institute of Mental Health. Retrieved July 27, 2022, from https://www.nimh.nih.gov/health/statistics/generalized-anxiety-disorder#:~:text=An%20estimated%205.7%25%20of%20U.S.,some%20time%20in%20their%20lives.
11. MindMed collaborators announce positive topline data from phase 2 trial evaluating LSD in anxiety disorders. MindMed. (2022, May 11). Retrieved July 27, 2022, from https://mindmed.co/news/press-release/mindmed-collaborators-announce-positive-topline-data-from-phase-2-trial-evaluating-lsd-in-anxiety-disorders/