How Psychedelics Interact with Hormones

Written by Martha Allitt

Throughout medical history, scientists have long-overlooked women's-specific biology, ignoring how factors like menstruation, reproduction, and menopause may affect or be affected by drugs

In fact, it wasn't until 1993, under the National Institutes of Health Revitalization Act, that health authorities even required women to participate in clinical trials.

Psychedelic research has made significant advances in approaches to healthcare and therapy

Yet, when it comes to the unique needs of women, the psychedelic field is no different from other areas of research, and there’s still very little we know about how psychedelics affect women’s-specific needs. As well as psychological impacts, it’s likely that the menstrual cycle could have a biological influence over the effect of psychedelics. Hormones could change the strength of psychedelic effects. Classical psychedelics, including LSD, psilocybin and DMT. interact with  5-HT2A receptors, proteins which normally respond to the chemical messenger serotonin. In the 1990s, a rodent experiment found oestrogen increased the amount of 5-HT2A binding sites in the brain. A later study found impaired oestrogen signalling reduced 5-HT2A action in the brain, again demonstrating the impact of oestrogen on 5-HT2A action.
With 5-HT2A thought to underlie the psychoactive effects of psychedelics, these findings suggest that  when a woman's oestrogen is at its highest, psychedelic effects may be more potent. This suggestion could be important for women when deciding what dose of a psychedelic substance to take during different times of the month. 

Another reason psychedelic effects may change throughout the month is because of synergy between oestrogen and progesterone with psychedelic substances

For example, both high levels of oestrogen and progesterone receptors and psychedelics have been associated with greater communication between the two hemispheres of the brain, which could lead to synergy and stronger psychoactive effects.  As well as serotonin function, oestrogen can also increase the synthesis and function of dopamine. Dopamine has been shown to play a role in the psychoactive effects of psychedelics, mainly LSD, and so changing hormones throughout the month could also psychedelic psychoactivity by influencing the dopamine system. 

Psychedelic substances may impact hormone levels

Regarding the impact of psychedelics on menstrual function, one study showed that blocking 5-HT2A inhibited the release of LHRH (luteinizing hormone-release hormone), which plays a key role in regulating ovulation and release of other reproductive hormones. As such, by having the opposite effect and activating 5-HT2A, psychedelics may be able to stimulate the release of LHRH.

In addition, psychedelics have been shown to regulate levels of the stress hormones, prolactin and cortisol, which are known to suppress the production of reproductive hormones and affect the cycle. However, the impact of psychedelics on these hormones may be different for different substances because of variation in their nervous system effects. For example, whereas psilocybin was shown to decrease prolactin in healthy volunteers in one study, another found LSD increased prolactin in cells through activating specific dopamine receptors. Since stress hormones are also thought to be responsible for infrequent and absent periods (oligomenorrhea and amenorrhea), psychedelics which are able to decrease prolactin and cortisol, could potentially even prevent, or reverse these conditions. 

It’s clear that determining this two-sided relationship could have crucial implications

Both for public health, and for the quickly-evolving psychedelic therapy landscape. Addressing the need to better understand psychedelics and women's biology – menstruation and beyond – at Hystelica we are currently making ties with clinical and observational trials to include woman specific data.