There has been a recent increase in interest in MDMA therapy as Lykos Therapeutics intends to launch MDMA as a licensed medicine towards the end of 2024. This marks a significant milestone in the evolving landscape of psychedelic-assisted therapy, particularly for conditions like post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD).
MDMA-assisted psychotherapy represents a novel approach to mental health treatment. Its efficacy primarily revolves around its ability to enhance the therapeutic process by fostering a sense of openness, empathy, and reduced fear response during psychotherapy sessions. This environment is conducive for patients to process and integrate challenging emotions and memories, particularly those related to traumatic experiences.
The safety and tolerability of MDMA therapy have been major points of consideration. Recent studies indicate that when administered in a controlled clinical setting, MDMA treatment is well-tolerated by participants. Adverse events have been rare and non-life-threatening, emphasizing the controlled use of MDMA in clinical environments as a key factor for safety. Research shows that MDMA therapy for PTSD is entering the final phase of drug development, with an aim for FDA and EMA licensing in the near future. This progress indicates the potential for MDMA to become a medicine, assuming clinical efficacy criteria are achieved (Sessa, Higbed, & Nutt, 2019).
Further, MDMA-assisted therapy has shown promising results in treating social anxiety in autistic adults and anxiety associated with life-threatening illnesses. Unlike conventional drug treatments, MDMA-assisted therapy is not intended for ongoing administration. It is used on one to several occasions within a psychotherapy protocol, potentially reducing the frequency of adverse events and improving the risk/benefit ratio. This aspect may present a significant advantage over medications that require daily dosing (Danforth, Struble, Yazar-Klosinski, & Grob, 2016).
As such, there are lots of ongoing clinical research on the subject, the most important of which include:
- MDMA-Assisted Therapy for PTSD: A study analyzed brain activity and connectivity via functional MRI during both rest and autobiographical memory response before and two months after MDMA-assisted therapy in veterans and first responders with chronic PTSD. The study found reduced activation contrast after MDMA-assisted therapy in the cuneus and a correlation between recovery from PTSD and changes in functional connections during autobiographical memory recall (Singleton et al., 2023).
- DNA Methylation and MDMA-Assisted Therapy: A pilot study suggested that DNA methylation of the glucocorticoid receptor gene is associated with treatment response in severe PTSD following MDMA-assisted therapy. The study examined epigenetic changes in key hypothalamic-pituitary-adrenal (HPA) axis genes before and after MDMA and placebo with therapy, finding significant methylation changes that may predict treatment response (Lewis et al., 2023).
- Effects of MDMA-Assisted Therapy on Self-Experience in PTSD: Another study reported on the effects of MDMA-assisted therapy on patients with severe PTSD. It found that MDMA-assisted therapy, compared with psychotherapy alone, significantly altered domains of alexithymia, self-compassion, and altered self-capacities, suggesting substantial improvement in mental processes associated with poor treatment response (van der Kolk et al., 2023).
Other MDMA studies include:
| Study Type | Trial ID or DOI | Condition | Year Registered | n | Intervention |
| Phase 2 | ACTRN12619001334190 | Late-stage cancer patients, mood and anxiety | 2019 | 32 | 120mg MDMA (supplemented 60mg) with psychotherapy |
| Phase 1/2 | ACTRN12621001078842 | PTSD | 2021 | 4 | 80 or 120mg MDMA (supplemented 40 or 60mg) with psychotherapy |
| Phase 1 | No ID yet | Mechanism | 2021 | 100 | n = 100 for MDMA arm |
| Phase 0 | ACTRN12613000685718 | Tinnitus | 2013 | 40 | 30 or 70mg MDMA |
| Observational | ACTRN12620001068954 | Attitudes of psychotherapists towards MDMA-assisted psychotherapy | 2020 | 200 | MDMA-assisted psychotherapy questionnaire |
| Phase 3 / Phase 2 | ACTRN12622000883718p | Brain Activity in Healthy Adults | 2022 | 200 | 80 or 120mg MDMA; or 25, 30, 35mg psilocybin |
| Phase 2 | ACTRN12623000838617 | PTSD | 2023 | 5 | 87 + 43.5 mg |
| Phase 1 | ACTRN12622001335785 | Healthy | 2023 | 5 | 75; 125; 175; 225 mg EMP-01 (MDMA analogue) |
| Phase 2 | ACTRN12623000971639 | PTSD, veterans | 2023 | 24 | 120 + 40 mg |
| Phase 2 | ACTRN126220 01525774 | TR-OCD | 2023 | 40 | 100 mg |
Alongside this, there is a wide range of small investigator-led MDMA trials including:
- ICAN1: A Phase 2 Open-Label Treatment Development Study of MDMA-Assisted Psychotherapy in Conjunction with Cognitive Processing Therapy (CPT) for Chronic Posttraumatic Stress Disorder (PTSD)
- Influence of MDMA on Risk and Reward Circuits of the Brain
- MDMA-Assisted Psychotherapy for the Treatment of Social Anxiety Disorder
- Low-dose MDMA Versus Standard-dose MDMA in Therapy for Mood and Anxiety Symptoms in Advanced-stage Cancer Patients
- Feasibility Trial of MDMA-Assisted Psychotherapy for Depression
- Adjustment Disorder (AD) in Dyads (patient pairs) of Patients with Breast Cancer and a Concerned Significant Other
The development of MDMA-assisted psychotherapy heralds a new era in mental health treatment, promising a potentially transformative approach for patients with conditions resistant to current treatments. As Lykos Therapeutics prepares to introduce MDMA as a licensed medicine, the medical community and patients alike await with anticipation the outcomes and broader implications of this novel therapeutic approach.