FDA rejects Lycos Therapeutics’ MDMA-assisted Therapy Trials
The Rejection is a Reflection Point for the Industry
The FDA’s recent decision to reject Lykos Therapeutics' New Drug Application (NDA) for MDMA-assisted therapy for PTSD has sparked considerable debate and introspection in the psychedelic community. This decision highlights the challenges in developing psychedelic therapies and raises important questions about the rigorous standards required for new drug approval, especially in psychedelic medicine.
The Federal Drug Administration rejected the New Drug Application for MDMA
The rejection emphasizes the need for transparent, well-designed studies that prioritize patient safety and the transparency of results.
What is MDMA?
MDMA (chemically 3,4-Methylenedioxymethamphetamine) is a psychoactive amphetamine that has gained significant attention for its potential in therapy, particularly in treating Post-Traumatic Stress Disorder (PTSD). Initially popularized as a recreational drug under the names Ecstasy or Molly, it remains popular in the electronic music, club and rave scene. Like many other drugs, it was criminalized in the 1980s with the War on Drugs, and still similarly, has scene a recent resurgence of interest and research due to its unique pharmacological properties. Rick Doblin, the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), has been a prominent advocate for MDMA-assisted therapy and research into the drugs efficacy. Despite progress, MDMA remains a Schedule I drug as designated by the FDA, rejecting the idea that it holds therapeutic value.
MDMA is both structurally and functionally distinct from classical psychedelics like psilocybin. While it does have the effect of altered perception and visual effects, the mechanisms of action and effects significantly differ. Classical psychedelics primarily exert their effects by binding to the 5-HT2A serotonin receptors in the brain, leading to profound effects are often described as deeply introspective. In contrast, MDMA’s primary action is the release of large amounts of serotonin, dopamine, and norepinephrine, which contributes to its unique combination of stimulant, empathogenic, and mild psychedelic effects. This release of neurotransmitters leads to heightened feelings of euphoria, increased sociability, and emotional closeness making it a promising candidate for assisting in the treatment of PTSD, where patients often struggle with emotional numbness.
Research into MDMA-assisted therapy has indicated significant reductions in PTSD symptoms following therapy sessions. The therapy protocol typically involves a combination of MDMA administration in a controlled setting, accompanied by psychotherapy to help patients process and integrate their experiences. Still, concerns about its safety, potential for abuse, and the need for more comprehensive long-term and ethically transparent studies have led to a cautious approach with approval for therapeutic use.
An MDMA assisted therapy session peformed as part of MAPS research.
The program was criticized for lacking sufficient ethical controls and for underreporting adverse reactions, particularly incidents of suicidal ideation observed the day after treatment. These concerns highlighted the integrity of the clinical trial process.
Background on MAPS and Lykos Therapeutics
The Multidisciplinary Association for Psychedelic Studies (MAPS), was founded by Rick Doblin in 1986 as a non-profit organization dedicated to researching and developing MDMA assisted therapy. Under Doblin's leadership, MAPS became a pioneer in the field, conducting many groundbreaking studies that highlighted the potential of MDMA and strengthening the rest of the field of psychedelic research.
In January 2024, MAPS transitioned into Lykos Therapeutics, a for-profit entity, a move that caught many in the psychedelic community by surprise. This shift from a non-profit to a for-profit model shifted the organization's approach from research to commercializations. The transition was part of a broader corporate strategy to secure the necessary funding and resources to bring MDMA to market as a pharmaceutical product. Many also saw this change as being a good sign for imminent approval of the ongoing Phase III clinical trials.
However in August 2024, the FDA after raising questions about the completeness of the research and possible underreporting of negative impacts, made the decision to reject Lykos' New Drug Application (NDA) for MDMA and MDMA-assisted therapy for PTSD. The rejection led to an immediate layoff of 75% of the staff and was humbling for the company, its leaders, and the industry.
In the wake of the rejection, Doblin resigned from his position leading Lykos, making statements that seemed to put him at odds with the direction that Lykos was beginning to take the process. The board of directors responded by appointing a pharmaceutical industry veteran to lead the organization, tasking them with restarting the clinical trial process under a more conventional pharmaceutical model. This is expected to take another 2-3 years, delaying the availability of MDMA for treatment more broadly.
The shift towards a traditional drug development model represent a departure from MAPS' original mission and methods, as noted by Doblin in a letter. While this transition may ultimately help Lykos navigate this issue. it has led to questions about the organization and its commitment to the broader, visionary goals it has espoused.
Key Issues Leading to FDA Rejection
Functional Unblinding: Participants often knew whether they received MDMA or a placebo, which compromised the trial’s integrity. The FDA recommended using an active placebo like Ritalin to help ensure better blinding. This criticism of blinding studies is common in other psychedelic drug testing, since it’s often obvious to the patient if they are under the influence of a substance with those effects.
Underreporting of Negative Effects: The trials faced serious ethical concerns, such as reports that some therapists encouraged participants to view worsening symptoms as progress. Underreporting of adverse events, including suicidal ideation following treatment, an effect of the “hangover” that often comes from releasing so many positive neurotransmitters, raised further safety concerns.
Sexual Misconduct Allegations: Some study participants made serious allegations of sexual misconduct by therapists administering the trial. These serious allegations, now part of ongoing legal proceedings, led to the retraction of three papers, including those covering previous Phase II clinical trials, by The Journal of Psychopharmacology, and suggested a substantial lack of oversight, and ethical conduct from some therapists involved.
Therapeutic Approach and Methodology: The FDA also questioned the validity of the psychotherapy methods used with MDMA. They noted inconsistencies in how it was delivered and that the studies lacked sufficient validation and control of how therapists treated participants, which made drawing reliable conclusions difficult to assert.
Efficacy and Safety Concerns: Ultimately the FDA was not convinced that MDMA’s benefits outweighed its risks, especially for vulnerable patients suffering emotional distress. Additional safety concerns included the recognized potential for drug abuse and increased blood pressure.
Retractions of Key Research Papers
Following the FDA’s rejection, The Journal of Psychopharmacology retracted several key research papers published by the organization that were key to the phase 2 and 3 clinical trials evaluating MDMA's efficacy as a treatment for PTSD. The decision to retract these papers was based on the FDA’s findings that called into question the reliability of the data reported in the trials, including discrepancies in patient outcomes, unreported adverse effects, and inconsistencies in the methodology that may have skewed the results.
The journal's statement accompanying the retractions emphasized that this was done out of an abundance of caution and they stressed the importance of maintaining strict ethical standards in research, particularly in the field of psychedelic therapies, which is already subject to intense scrutiny. They further stressed the importance of ethical conduct when dealing with vulnerable populations, such as those suffering from PTSD.
MDMA is targeted as a Pharmaceutical Product
MDMA will reportedly be resubmitted to the FDA by Lykos Therapeautics under its new leadership. Expect a stricter focus on the drug as a traditional pharmaceutical product.
Implications for the Future Research
The decisions by The Journal of Psychopharmacology and the FDA both highlight the importance of upholding high ethical standards and employing robust research methodologies in the development of psychedelic therapies and underscore the unique challenges associated with conducting clinical trials in this emerging field.
Clinical trials involving these types of substances are inherently complex due to the profound psychological effects these substances can induce. Ensuring the safety and well-being of participants requires not only rigorous study designs but also meticulous attention to ethical considerations, such as informed consent, ethical conduct by researchers and clinicians, accurate reporting of adverse effects, and strict adherence to defined protocols.
This is significant given the current momentum in the field of psychedelic research. Over the past decade, there has been a resurgence of interest in exploring the therapeutic potential of psychedelics for a variety of mental health conditions, including PTSD, depression, anxiety, and addiction. This renewed focus has led to a growing number of clinical trials, some of which have shown promising results and excited the field.
The lessons learned will likely influence the design and conduct of future research. Regulatory bodies, journals, and researchers alike may implement more stringent oversight measures to ensure that studies meet the highest standards of scientific and ethical rigor. This could include enhanced monitoring of trial protocols, more rigorous peer review processes, and greater transparency in the reporting of results. It has already led to broader discussions within the research community about best practices in psychedelic research. Longer term, these developments could lead to more effective and reliable therapies for mental health conditions, backed by more stringent research methodologies.
The Importance of Oregon’s Psilocybin Program
With the FDA’s rejection, those awaiting MDMA-assisted therapy face at least a two-year delay. However, Oregon offers a legal alternative with psilocybin, which is available in licensed Service Centers like Lucid Cradle. Oregon’s program is crucial at this time, providing immediate access to legal psychedelic therapies with a secure supply chain of naturally produced psilocybin for those in need.
Patients who had been hoping for this innovative treatment now face an extended delay of at least two years. However, an alternative available in Oregon, where psilocybin—the active compound in magic mushrooms—has been legalized for therapeutic use under a regulated framework.
Oregon's psilocybin program allows adults 21 and older to access psilocybin services through licensed Service Centers, such as Lucid Cradle, where they can receive regulated, lab-tested psilocybin in a controlled, supportive environment. This program provides immediate access to legal psychedelic therapies for individuals seeking alternative treatments. Oregon’s program offers several key advantages:
Regulated Environment: Oregon’s psilocybin services are conducted in licensed Service Centers, ensuring that the therapy is administered by trained facilitators in a safe and controlled setting. This regulated environment helps mitigate the risks associated with psychedelic use, providing a structured space and a safe setting.
Immediate Access: Psilocybin is legally available in Oregon and individuals seeking psychedelic therapy do not have to wait for federal approval and can access these services now, potentially offering relief to those struggling with conditions like depression, anxiety, and PTSD.
Secure Supply Chain: Oregon’s program is supported by a secure supply chain of naturally produced psilocybin. Licensed manufacturers cultivate and process psilocybin mushrooms ensuring that the mushrooms used in therapy is high quality and free from contaminants.
Broad Applicability: Psilocybin has shown promise across a broad range of conditions, including depression, anxiety, addiction, and existential distress.
While the FDA's rejection of MDMA-assisted therapy represents a setback for the industry, Oregon's psilocybin program offers a immediate and legally accessible alternative for those seeking repreive. As the field of psychedelic medicine continues to evolve, Oregon's efforts serve as a blueprint for expanding access.
Book a Personalized Psilocybin Retreat with Stable Pathways Group to experience this for yourself.
