ICER Report Public Comments - MDMA Clinical Trials
RE: Draft Evidence Report on Treatment for Post-Traumatic Stress Disorder
To whom it may concern,
In the MAPS Study Protocol Document there is reference to a paper titled Gender Differences in the Subjective Effects of MDMA which states the following:
“The fact that equal doses of MDMA per kilogram body weight produce stronger responses in women compared to men is consistent with an increased susceptibility of women to the [serotonin] 5-HT-releasing effects of MDMA.”
110. Liechti, M.E., A. Gamma, and F.X. Vollenweider, Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl), 2001. 154(2): p. 161-8.
It’s unclear why this paper was referenced by MAPS in the protocol document, but the menstrual cycle was not factored into the study design. A large literature suggests that the menstrual cycle plays a key role in the serotonergic system. A large literature also suggests that the serotonergic system plays a key role in the effects of MDMA.
It’s also unclear why outcomes are not reported by sex. This leaves many questions unanswered regarding the safety and efficacy of MDMA for both men and women.
The Evaluation of Gender Differences in Clinical Investigations, which is referenced in the Special Protocol Assessment states the following:
“The guideline identifies three specific pharmacokinetics issues to be considered when feasible: (1) effect of the stages of the menstrual cycle; (2) effect of exogenous hormonal therapy including oral contraceptives; and (3) effect of the drug or biologic on the pharmacokinetics of oral contraceptives.”
It’s unclear if this data exists at all in the broader psychedelic literature. Phenotypic differences in women related to mental health, the menstrual cycle, and serotonergic fluctuations - which may impact bioavailability and subjective effects - is also not well-represented in the broader literature. This general lack of data is being addressed further in an open letter to the FDA.
All of this said, we do believe that novel treatments such as MDMA, and natural psychedelics hold immense potential for healing mental health ailments. There are many women who have benefited from these treatment modalities for trauma-based conditions stemming from sexual assault, domestic violence and many other traumatic experiences that are more prevalent in women. Risk is relative, and for some women battling suicidality, these treatments may be a last resort.
Our intent with these comments is not to prevent access to these treatments options, but rather, to reduce harm and prevent adverse drug reactions. Historically, women have been at a greater risk for adverse drug effects, and we have an opportunity and responsibility to prevent this in psychedelic medicine.
It’s unfortunate that MAPS did not consider the paper that they themselves referenced regarding increased susceptibility of women to the [serotonin] 5-HT-releasing effects of MDMA. It is well-documented that women are a greater risk for developing PTSD and depression - conditions that MDMA is being used to treat.
More information on this topic can be provided upon request. We hope that these discrepancies will be addressed in future trials. We also hope that research which considers female biology will be prioritized as more credible, especially when compared to research that does not account for these variables.
Best regards,
Tina A. Williams
U.S Army Veteran, OIF Campaign
Director, Dysphoric Project
Hailey Llewellyn
Menstrual Health Researcher, Consultant
Director, Dysphoric Project
