The Biggest Risk to the Psychedelic Industry is Underestimating Female Biology
Here's Why
(This article has been revised to include the NIH Revitalization Act which was signed into law in 1993.)
“In women’s cases, we needed to standardize where they were in their menstrual cycle when we studied them. We timed the doses for the first 10 days after their menstrual cycle bleeding stopped.”
- Dr. Rick Strassman, DMT the Spirit Molecule
In the 1990s, Dr Rick Strassman jumped through every hoop imaginable to study N,N-dimethyltryptamine, also known as DMT. A potent psychedelic and schedule one controlled substance, Dr. Strassman was diligent and determined to get approval to study the drug in human patients.
Throughout the lengthy, overly bureaucratic process of studying an illegal substance, Dr. Strassman carefully designed his studies on DMT, and ensured that he covered all possible bases - including adding the menstrual cycle phase as a research variable.
The menstrual cycle is often confused with menstruation, which is the time a woman bleeds. The menstrual cycle lasts the entire month and should really be thought of as the fertility cycle.
Ovulation, menstruation and post-menstruation are all part of the menstrual cycle and have different hormone profiles that interact with the serotonin system in different ways.
Even in the 1990s, research on the menstrual cycle and serotonin was plentiful. With the understanding that the psychedelic process relies on the serotonergic system, Dr. Strassman understood that timing in women should be considered a variable in psychedelic research.
Dr. Strassman’s DMT trials were also in accordance with the newly passed NIH Revitalization Act of 1993:
DESIGN OF CLINICAL TRIALS.—In the case of any clinical trial in which women or members of minority groups will under subsection (a) be included as subjects, the Director of NIH shall ensure that the trial is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect women or members of minority groups, as the case may be, differently than other subjects in the trial.
Dr. Strassman was wise beyond his years, because standardizing the menstrual cycle phase as a research variable is not yet a common practice in psychedelic research. In fact, the menstrual cycle has been largely ignored in the current wave of psychedelic research.
It’s difficult to say why, after Strassman’s work in the 90s, the menstrual cycle receives little to no attention in psychedelic research, other than ignorance. I’m open to more positive explanations, but I’m really coming up with nothing on this one.
Let’s not Repeat the Ambien FAIL in Psychedelic Medicine
Before the 1990s, including women in research was not required for FDA drug approval. Not including women in research was largely driven by concerns about harming unborn children if women became pregnant during trials.
The result was an increase in harm to women who were adversely affected by drugs that were never tested on women. Ambien, a popular prescription sleep aid was prescribed to both men and women at the same dosage from 1992 to 2013 until the FDA realized that the drug stayed in women’s systems longer than men.
As it turns out - brace yourself for the shocking news - women and men metabolize the drug differently. Researchers found that 3% of men had enough of the drug in their system the next morning to impair driving, compared to 15% of women.
In the case of psychedelic research, differences between men and women in the pharmacokinetics - the study of how the body interacts with administered substances for the entire duration of exposure - is not well understood.
A recent paper titled “Knowledge gaps in psychedelic medicalisation: Clinical studies and regulatory aspects” discusses pharmacokinetics and how individual differences like gene expression may play a role in the psychedelic process. Still, there is no mention in this paper about the menstrual cycle or fluctuating female hormones.
Neuroplasticity, Serotonin and BDNF
It’s not just that the serotonin system interacts with both the menstrual cycle and psychedelics - it’s that the menstrual cycle interacts with all of the main hypotheses psychedelic researchers are pointing to:
Changes in neuroplasticity are observed over the course of the menstrual cycle, and with psychedelic use.
Changes in serotonin are observed over the course of the menstrual cycle and is believed to be the main mechanism of action for the psychedelic experience.
Changes in brain derived neurotrophic factor (BDNF) are observed over the course of the menstrual cycle and with psychedelic use.
The question of whether or not the menstrual cycle and psychedelics interact with each other is silly at this point. The real question is how they interact with each other.
This is Everyone’s Problem
Not understanding how menstrual cycle phase interacts with psychedelics has a wide range of implications from harm reduction to legal risk. This is not just a problem for women, but for anyone interested in the safety of psychedelics as they become more widely available - both medically and in traditional ceremonial settings.
The same dose, taken at different times in the cycle may have different effects, and psychedelic substances may be metabolized differently in men and women. This puts women at risk for increased harm, especially because so much of the early literature focused on combat veterans who are predominantly male. For more on this topic, check out Women are the Psychedelic Medicine Market, Here’s Why it Matters.
Dosage adjustments may also need to be considered across the menstrual cycle, especially in women with menstrual conditions like premenstrual dysphoric disorder or premenstrual exacerbation.
Information on Harm Reduction:
I’m no lawyer, but according to the NIH Revitalization Act of 1994, clinical trials in the United States that do not consider timing of dose as a research variable that affects women differently than men, may be adding unnecessary risk to their projects.
Women are now required in clinical trials thanks to the Act, but are we missing the point entirely by adding women to trials without factoring in the menstrual cycle? I’m pretty sure that’s what they meant by this:
“NIH shall ensure that the trial is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect women or members of minority groups, as the case may be, differently than other subjects in the trial.”
While this law may not apply to privately funded research, why would researchers not want to understand these variables? According to the current research on the menstrual cycle, serotonin, neuroplasticity and BDNF, there is a baseline understanding of how female physiology changes over the menstrual cycle.
In my research, I’m unable to find a single paper other than Strassman’s that factors the menstrual cycle into psychedelic research. That doesn’t mean the research doesn’t exist - perhaps there are more examples that I’m unable to find - but it does mean that the overwhelming trend is to remain oblivious to female biology.
Clinical trials are currently being conducted for FDA approval, but have any of them considered timing of dose for women? I’ve heard plenty of explanations about why this isn’t happening - notably complexity in study design - but my question is:
If Dr. Strassman could do it in the 90s, when there was no support or funding for psychedelic research, is that really an explanation, or just an excuse to ignore female physiology?
This is the reason a law had to be passed, to force researchers to account for physiological differences in women. It deeply saddens me that psychedelic research is following the same trend that has historically led to increased harm in women.
The data clearly demonstrates that major depression and PTSD are more common in women, and that’s before we get into female specific mental health conditions like premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation (PME) which have been largely ignored by psychedelic research institutions.
If we believe that this issue is the result of ignorance in psychedelic research, than the solution is education and awareness. If we want psychedelics to have a bright future of healing for both women and men, we must take action - like yesterday - to educate people who have a vested interest in psychedelic harm reduction, decrimalization and / or legalization.