Where Women Fit in the Science of Psychedelics

My fingers wiggling in the water, crouched down next to a stream, I listened closely to the music of the water as it dropped over the rocks in front of me. Redwood trees soared above, cathedral-like, and it was then that I had a clear understanding that everything was going to be OK. That feeling was in very short supply at the time. I was 21 years old and had just lost my grandmother—who had raised me after my abusive mother left me with her when I was four. I was truly devastated, so encased in grief that to this day, I have no memory of cleaning out our shared house by myself, and driving from New York to California to live with my best friend, who generously opened her Berkeley student apartment to me.

Just a couple of hours before my streamside realization, that friend and I had taken “magic” mushrooms together, sandwiched between bread, cheese, and fried eggplant. Then we wandered through Muir Woods and soon after began the most joyful psychedelic trip of my life. Not only did I have fun playing in the woods as a child would, but I had an unforgettable sense of the larger world cradling me, and the incredible freedom that laid before me in my life. The ancient, deep beauty of the redwoods made me feel safe, secure, and loved in a way that had been missing since my grandmother had died. A memory of that feeling of okayness has never left me, and I have long credited my recovery from the intense grief of losing my beloved grandma to those mushrooms and my friend’s care.

The dissolution of the most intense part of my grief was what psychologists call a breakthrough experience. I’m far from the only one who has found relief and an emotional transformation in psychedelic drugs. Others have had similar experiences using ketamine, LSD, MDMA, and ayahuasca, and in 2019, a study from researchers at the School of Medicine at the Imperial College London documented this phenomenon. Feelings of awe and ego-dissolution, as well as joy and contentment likely also contribute to the emotional catharsis many experience. It is likely that the positive, long-term psychological effects that have been reported for decades by people who take a psychedelic trip—things like reduction in depression, anxiety and PTSD—are linked to those breakthrough experiences.

Women’s place in the science of psychedelics

There’s been a boom in information on psychedelic drugs in recent years. That’s because while LSD and psilocybin were first studied in the U.S. in the 1950s and 1960s at Harvard, soon after that, they were criminalized. The drugs went underground and popped up again in a more significant way as party drugs in the 1990s. But there was promising clinical evidence before criminalization and there has long been anecdotal evidence that these drugs lead to breakthrough experiences and help with some of our most common and persistent mental-health ills, so researchers have been eager to test it in a rigorous, science-based way.

During the past half-decade, a variety of laws have changed in both the U.S. and other countries allowing for the use of these drugs in scientific studies—but are we making the same mistakes of the past, leaving women out of the equation?

Women’s bodies have been radically under-studied in all aspects of health: from drugs to surgical treatments, from exercise science to nutrition, medical science has long treated non-white-male bodies as “too troublesome” to test due to hormone fluctuations  (although men have them too, on a daily basis rather than monthly). Conversely, others have argued that men and women’s bodies are similar enough that women can just be treated as smaller men. Despite a 1993 Act requiring women (and female animals) to be included at equal rates in scientific testing of all kinds, we still aren’t there yet.

That equal representation is important, since since sex and associated hormonal differences may influence how some psychedelics work, as a 2001 study on MDMA suggests. “In women there are greater levels of female sex hormones and potentially the oxytocin and vasopressin response to MDMA can be somewhat sex specific,” says Dr. Matthias Liechti, MD, who has studied psychedelics for over 20 years and runs a lab at the University Hospital Basel in Switzerland exploring the psychopharmacological effects of LSD, MDMA, psilocybin, DMT, and mescaline on mental health.

“However, even in highly controlled studies in healthy subjects we could not clearly document robust sex differences. This means in some studies we did but then could not confirm in others. Thus, the substances likely act quite similar in both sexes,” says Liechti. A 2019 study found that ketamine treatments showed no difference in either efficacy or side-effects between men and women or between pre- and post-menopausal women (very few studies have included older patients, an overlooked population in this study area). Additionally, no sex differences could be detected in the acute effects of LSD or psilocybin in humans. However, all the researchers spoken to for this article agreed that there isn’t yet a definitive answer and much more research needs to be done in order to know if there truly are sex differences in psychedelics’ effects both long- and short-term and around dosages.

The good news is that, looking at dozens of studies in the area of psychedelics for mental health treatment, researchers seem to be representing men and women equally—Liechti couldn’t have done his own research on sex differences in various studies without participants of both sexes. Alexandre Piot, a clinical researcher at the University College London (UCL) and president at the UCL Society for the Application of Psychedelics, agrees that women don’t seem to be left out of this research.

“I think the bigger conversation is the inclusion of Black, Hispanic, and Indigenous people,” says Dr. Julia Mirer, MD, director of strategy at Nushama, a network of evidence-led psychedelic wellness centers. She adds that it’s important for clinicians to be prepared to work with these populations, including researchers who can understand how racism and discrimination may affect their treatment and experience, and who may need different or additional support.

The hormone question

In addition to treating PTSD, anxiety, and depression, which women experience at significantly higher rates than men, psychedelics may be uniquely useful in treating female-dominated challenges, including eating disorders, premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). “There’s mounting evidence from the underground community that both ketamine and psilocybin help with PMDD and PMS—can help with that mood. There’s also anecdotal evidence that it helps with the pain of menstrual cramps, which makes sense because it’s anti-inflammatory,” says Mirer. In these cases, it’s microdosing, or taking much smaller doses of the drug, that may help with these conditions. This is different from the stronger, trip-based treatment, and also needs more research.

But this anecdotal connection between hormones and psychedelics is promising and could explain why these drugs bring relief for depression, too. In a 2021 review paper in the journal Frontiers of Psychiatry, researchers, including Piot, looked at the connections between ovarian hormones, depression, and neuroinflammation. There is some evidence in humans of a link between fluctuation of hormones and depression for example, with postpartum depression and PMDD. While there are a few hypotheses about the cause of depression, including an imbalance of neurotransmitters like dopamine or serotonin and atrophy or neurons, Piot and his colleagues thought the neuroinflammatory hypothesis could possibly explain both possible causes. Ketamine is known to have anti-inflammatory effects in the brain in those with depression, and it also enhances synaptic plasticity. In tests, says Piot, using ketamine in female mice “required half the minimum dose male mice did to get antidepressant effects, but this was only valid when estrogen and progesterone were present. The point of this is that ovarian hormones and ketamine seem to have a synergistic effect in animal models.” He thinks that this is evidence that points to the importance of investigating this in humans and taking hormones into account when scientists are running clinical trials on ketamine. “Whether that means changing the dosages or keeping track of where women are in their cycles when you give them the dosage… It’s a call to say ‘you’ve got to pay attention to this,’” says Piot.

Ketamine is now mainstream enough that I first heard of it as a treatment for depression via Tiktok. Ketamine comes up often when talking about this class of drugs because it’s the most easily available (and legal, in the U.S., outside clinical studies) of the psychedelic treatments. Even though other psychedelics have a longer history of being studied for mental health, they are still very restricted in most places (though Mirer told me that MDMA may be approved in the same way ketamine has been in 2023). Originally developed in the 1960s and initially used as an anesthetic, ketamine was later used to treat chronic pain. “Ketamine is generally very safe. We know that because we use it in pediatric populations, instead of an anesthetic that would require us to intubate and manage breathing,” says Mirer. It’s this track record of safety that led the FDA to grant it a breakthrough therapy designation in 2019, so it can be used for off-label uses, like Mirer does at Nushama.

She says the goal is to use ketamine as a “psychedelic scaffolding” to open the door to other psychedelic treatments for mental health care. “If we can show all these techniques work with ketamine, then we can show that it’s not so scary to make another psychedelic legal when 80 percent of the treatment is, for the most part, the same,” she says.

Psychedelic research is still very young—and it’s definitely not for everyone. Mirer says an initial screen for those interested in ketamine treatment excludes those with certain medical conditions as well as diagnoses of schizophrenia or psychosis in the patient or a close relative. Anyone with an active substance abuse issue is also excluded (though in the future, ketamine might be a treatment to help those in addiction recovery, but we’re not there yet). And though the early research is very promising, and early studies indicate a good safety profile, much more research is needed generally on both the effectiveness and tolerability of these substances. “Large so-called phase 3 studies are needed in hundreds of patients to bring these substances to the market and to validly assess their benefits and risks,” says Liechti.

Currently known risks include difficult psychological situations during the acute effects of the drugs (aka “bad trips”) and anxiety.  Ongoing hallucinogenic experiences have occurred in a few subjects and there may be some cardiac effects, both which again, point to more research needed. As anyone who has tripped outside a clinical setting will attest, nausea is a very common side-effect of several psychedelics—headaches too. Post-treatment effects can include flashbacks, but overall longer-lasting negative effects don’t seem to be a problem in controlled studies according to research. Piot and Mirer both pointed to the importance of both preparation before, and integration after using psychedelics as key. “The experiences can be quite challenging, so it’s important to have a supportive and appropriate environment to take them in,” says Piot.

That’s why these drugs aren’t handed out over the counter, even where they are legal, because those offering treatments have discovered much better, more lasting results when the drugs are taken within what Mirer calls a “therapeutic container.” Researchers agree that they must be used within a defined protocol along with counseling beforehand, guidance during treatments (which vary depending on the psychedelic used—a ketamine trip is under an hour, whereas psilocybin is a six- to seven-hour experience), and contact afterward. Another word for that might be community.

That idea is echoed by Zoe Helene, founder of Cosmic Sister, who calls herself a psychedelic feminist. She’s worked with hundreds of women who have used psychedelics for healing outside clinical frameworks like those above and knowledge-shares with other women leaders in her network. “Part of the magic of psychedelics is that it helps you access the thing you want to and work on it. Having the courage to work on it is knowing that others in the group have your back.”  Helene also takes seriously the guidance of Indigenous cultures where she reminds us that most of the existing knowledge of psychedelics come from. “This is indigenous wisdom and its history is female. So that’s empowering to us because our history has been repressed. And so these psychedelics can be part of our healing.”