Looking Ahead: Considerations for Women’s Health in Psychedelic Research

Women have been historically underrepresented and often made to feel unseen in Western medical spaces. They are strategically excluded in research studies and often experience delays in diagnosis or disregard for their symptoms. These factors have created a trend for women to self-medicate or seek out alternatives in order to feel seen and to heal from the symptoms they are experiencing. Globally, women are more likely to experience adversity leading to the increased likelihood of developing PTSD, experiencing eating disorders and mood disruptions in their lifetime; while at the same time are less likely to be diagnosed accurately in order to get relief (Holson, 2018). This has created a trend of women being more inclined to seek out plant-based medicines to heal. With a focus being placed on treating conditions that primarily impact women, now more than ever, an emphasis should be placed on representing them in current psychedelic research studies.

After decades of prohibition, psychedelics and their therapeutic benefits are increasingly being accepted and employed as healing agents. Drugs like ketamine, ayahuasca, MDMA, and psilocybin mushrooms are being studied in clinical trials to treat PTSD, depression, substance abuse, eating disorders and a range of other maladies that have been linked to trauma and adversity. As these substances stage a comeback in the scientific community, it’s possible they could be especially promising for women (Marks, 2022). The growing popularity of women self-treating with psychedelics and finding relief is a trend that should not be ignored (Baur, 2021). At the same time, the uniqueness of female physiology calls for specialized research to provide the best possible therapies. (Marks, 2022)

Artwork by the Author: Caterina Bragagnolo

The Connection to Hormones

Classic psychedelics work by activating serotonin (5-HT2A) receptors in the brain. Activation of the 5-HT2A receptors can lead to changes in mood and promote neuroplasticity, or the brain’s ability to change and adapt, which could be important in treating mental health disorders. (Marks, 2022) Since serotonin is involved in the modulation of pain, anxiety, and depression, psychedelics which target the 5-HT2A receptor offer a hopeful prospect for women suffering from chronic pelvic pain, endometriosis and trauma.(Liechti, 2001. The literature has also shown that female hormones, particularly estrogen, have intriguing interactions with the serotonin 5-HT2A receptor. Research has demonstrated that estrogen increases the density of 5-HT2A binding sites in areas of the brain responsible for mood, mental state, emotion, cognition and behavior (Liechti, 2001).

The relationship between estrogen levels and 5-HT2A binding sites may also provide clues to gender differences in psychiatric conditions like schizophrenia and depression, which are more common in women than men. Furthermore, disruption of estrogen levels during menopause may lead to dysregulation of the 5-HT2A and brain-derived neurotrophic factor (BDNF) signalling pathway, which could predispose the brain to depression. (APA, 2017). Given that classical psychedelics, like psilocybin, MDMA and LSD, primarily elicit their effects via the 5-HT2A receptor, the presence, absence and combinations of female hormones could potentially enhance the effect of psychedelic compounds in women. However, the research on understanding the effects of psychedelics in the unique environment of the female body is still in its infancy.

Current Research

At present, there is a lack of understanding among scientists regarding how the pharmacology of psychedelic substances might impact a woman’s physiology.

“I think it speaks to a desperation in women’s health. And part of the reason for that is we all know that nobody bothers to study women, and nobody listens to women, especially when we report our specific mental health issues.”

Ayelet Waldman

A significant gap is present in our understanding of how psychedelics may impact women’s health (Liechti, 2001). Much of modern medicine is built on research performed exclusively on cisgender men: clinical research was not required to include women until the 1990s when Congress passed the National Institutes of Health Revitalization Act. This means the science that informs medicine—including the prevention, diagnosis, and treatment of disease— routinely fails to consider the crucial impact of sex and gender. As a result, women’s pain and symptoms have been, and continue to be, consistently dismissed by doctors. In the case of more than 700 diseases, women receive diagnoses significantly later than men, sometimes waiting up to 10 years for the correct diagnosis. They’re also at greater risk for adverse side effects from medication; a recent study found that 86 medications approved by the US Food and Drug Administration were more likely to cause such problems in women than men.

While research is lacking, organically women have initiated their own healing, in plant medicine spaces with hundreds of experiential accounts available to read about the benefits they received. (Borchardt, 2018) In 2017, the Global Drug Survey received 15% more women respondents than men. Also, the data showed that more women (53%) than men (42%) used psychedelics and smoked marijuana. These are dramatically different results from surveys that usually find men dominating cannabis consumption. In spite of its popularity with women, an additional survey of women found about 70% believe there is a stigma associated with psychedelic use and cannabis consumption. The same survey reported 66% of women hide the fact that they engage in plant-based medicine practices. (GDS, 2016).

Currently, there is a presenting population, with a high level of need and a willingness to be curious and explore alternative paths to healing. This landscape presents a large opportunity for research to investigate how psychedelics may influence female-specific issues such as chronic pelvic pain, mood disorders, perinatal depression and even the challenges of motherhood. It also creates opportunity to better serve a population that is in high need of support on an international scale. it may be beneficial to treat the overall health needs of women as a separate entity in psychedelic research and give it equal, if not a higher, priority.

Level of Need

Mental health needs and the everyday challenges of women are multifaceted and unique. The statistics are frightening for those not familiar with the influence of patriarchal norms. Women’s overall health also includes pregnancy, breastfeeding, menstruation, post-partum depression, perimenopause, menopause, in addition to coping with gender-based violence, miscarriage, stillbirth, and the death of a child.

According to the American Psychiatric Association, every year, one in five women in the US has a mental health problem such as depression, post-traumatic stress disorder (PTSD), or an eating disorder (APA, 2017). Depression is the most common mental health issue for women, and twice as many women experience depression in their lifetime than men. Also, women are twice as likely to experience anxiety and three times as likely to develop PTSD than men. Of people suffering from anorexia or bulimia, 85%-95% are women and women account for 65% of those with binge eating disorders.(APA, 2021)

The World Health Organization (WHO) says these statistics hold true for women worldwide. Depression, anxiety, psychological stress, domestic and sexual violence, and escalating rates of substance abuse are affecting women more than men on a global basis. WHO estimates that 80% of the 50 million people around the world affected by civil wars, violent conflicts, disasters, and displacement are women and children. At least one in five women worldwide will be the victim of rape or attempted rape in their lifetime, leading to a variety of mental conditions, including PTSD, depression, and anxiety. (WHO, 2017)

Pamela Hadfield, Cofounder of Eastra Health, believes that ‘women will naturally turn to psychedelic-derived medicines after getting little to no relief from traditional medications like SSRIs and birth control pills for issues related to PMS and menopause” (Marks, 2022).

Hadfield feels “Women's biology is different, so the reality is we need different treatments, I believe we've just seen the tip of the iceberg when it comes to what psychedelics may be able to address from a healthcare perspective.” (Parks, 2021). There is an unmet need for research to discover and understand the unique effects of psychedelic compounds in women and to create formulations with precise amounts of specific ingredients. The research going on now is groundbreaking and critical for the overall understanding of psychedelic therapy. But, consider these questions when it comes to women’s health and psychedelics. Are there certain combinations of compounds that would be more effective for treating depression, anxiety, and PTSD in women? Is the entourage effect different in women than in men? Is microdosing different for women? How? Are specific set, settings, or music more effective for women undergoing psychedelic therapy? These are a few of many unknowns in the realm of women’s health, gender differences and applied psychedelic medicine.

Gender and Depression

The majority of people using SSRIs, or prescription antidepressants, are women. The World Health Organization has found major depressive disorder the leading cause of disease burden for women internationally (WHO, 2017). Women also experience depression more often, with 1 in 4 experiencing depression and one in seven women suffering from postpartum depression (Carhart-Harris, 2016).

A study published in June 2022 led by Zach Walsh’s research team at the University of British Columbia, Kelowna, aimed to assess the impact of psilocybin on mood and mental state. Interestingly, no significant gender differences were found except for with depression, where women reported a higher improvement than men. While all can benefit from the healing potential of psychedelic medicine, more research is needed to identify and define potential gender differences around absorption, metabolism and experiential factors within psychedelic research to promote best practices.

Currently, little information is available on gender differences within psychedelic experiences. However, psychedelics show promise as a solution for certain disorders that are more prevalent in women. For instance, women are more susceptible to PTSD than men, additionally, eating disorders such as anorexia nervosa are three times more common among women than men. (Julian, 2023)

PTSD

Women are more likely to have PTSD than men, (Kronemyer, 2020). Studies suggesting positive results from doses of MDMA or psilocybin combined with therapy, have led the FDA to designate those drugs as breakthrough therapies for PTSD and treatment-­resistant depression, respectively (Kronemyer, 2020). Women have a lifetime PTSD prevalence rate of 9.7%, compared to 3.6% in men (Segebladh, et. Al, 2011). Globally, due to the level of violence women experience, in addition to cultural factors and limited resources, Women are more likely to experience trauma that goes undiagnosed and unresolved. This not only creates health concerns that impact her quality of life, but it also contributes to perpetuating a cycle of trauma that influences parenting and impacts future generations (Segebladh, et. Al, 2011).

With this endemic prevalence, cultural factors and a lack of awareness around their experience, many women go undiagnosed because these concepts are not spoken about and widely accepted in patriarchal countries. Trauma is held in the body. Women living with unresolved trauma are statistically more likely to develop physical ailments, eating disorders, premenstrual dysphoric disorder (PMDD), autoimmune issues, chronic pain, endometriosis and cardiac issues (Kronemyer, 2020).

Psychedelics like ayahuasca, psilocybin and MDMA have all shown an ability towards resolving PTSD symptoms and many experiential accounts are available sharing first-hand experiences of using these medicines to gain relief from disordered eating, chronic pelvic pain and conditions like post-partum depression and PMDD.

Trauma's Impact on the Body

Research has suggested that early traumatic experiences affect the production of stress hormones and inflammatory responses that contribute to chronic pelvic pain and other pain symptoms (Julian, 2023). Since serotonin is involved in the modulation of pain, anxiety, and depression, psychedelics which target the 5-HT2A receptor offer a hopeful prospect for women suffering from chronic pelvic pain, endometriosis and trauma (Julian, 2023).

Endometriosis is a component of 70 to 80% of the cases of chronic pelvic pain, and over 170 million women worldwide suffer from endometriosis (Kronemyer, 2020). Premenstrual dysphoric disorder (PMDD), a severe mood disorder, is characterized by mental health and physical symptoms in the week before the onset of menstruation and affects millions of women worldwide. Psychedelic medicine is currently being investigated as a potential treatment for these conditions

Premenstrual Dysphoric Disorder (PMDD), Endometriosis & Chronic pelvic pain

Currently, the first line of treatment for PMDD are selective serotonin reuptake inhibitors (SSRIs). Unlike in other mood disorders, patients with PMDD experience rapid onset of action from SSRI (Marks, 2022) Unfortunately, many women with PMDD do not respond to the traditional treatment options, often turning to microdosing psilocybin or using cannabis to find relief. Recent research shows that ketamine administered at the onset of PMDD may alleviate the treatment-resistance symptoms (Carhart-Harris,2016)).

Recent data shows that ketamine activates estrogen receptors. This is important because declining levels of estrogen during the luteal phase may be a contributing factor to PMDD. By administering ketamine at the start of the luteal phase, it may be possible to treat and reduce symptoms (Marks, 2022) The same study showed that ketamine works with estrogen to increase glutamate levels. Glutamate is a neurotransmitter that may be uniquely connected to major depression. The lack of glutamate in certain regions of the brain has been strongly linked to depression (Marks, 2022). Ketamine has been shown to activate glutamate transmission in the brain and is thought to be a key mechanism in its anti-depressant effects. Therefore ketamine may have a direct impact on mood and other signs of depression when administered at the onset of PMDD. Evidence suggests that microdosing psilocybin may have a positive effect on mood, anxiety and depression which are commonly associated with PMS and PMDD.

Psilocybin has been found to activate serotonin receptors which may contribute to its positive effects on mood and emotions. Additionally, psilocybin may have anti-inflammatory properties which could potentially help alleviate physical symptoms such as cramps, body aches, bloating and fatigue that accompany these conditions (Marks, 2022)

At the moment, no clinical trials using psychedelics for endometriosis and chronic pelvic pain are currently listed, which indicates an opportunity for research and development.

Postpartum Depression

Postpartum depression globally impacts between 20-25% of women after giving birth (Julian, 2023). Postpartum can create intense feelings of depression, and hopelessness leading to an experienced lack of connection or embodied love between mother and child.

Studies have linked Cesarean sections (C-sections) to postpartum depression (Marks, 2022). We also know that Post Partum Depression is related to reduced quality of parent-child interaction and adverse effects on maternal and child health. A recent study in the Journal of Affective Disorders suggests that in patients at high risk of postpartum depression, a single dose of ketamine administered before anaesthesia, during cesarean sections could be effective in preventing it (Liechti, 2001). The prevalence of postpartum depression was significantly lower in the ketamine group, and the study findings suggested that ketamine functions are a preventative agent against postpartum depression (Liechti, 2001).

Microdosing psilocybin has emerged in recent years as a potential solution to alleviate some of the stress and anxiety of motherhood. A Colorado-based, nationwide group called Moms on Mushrooms (M.O.M), was created to teach interested moms about using a small dose of psilocybin mushrooms. The consensus of women microdosing psilocybin have reported traditional pharmaceuticals did not work for them or made it feel like they were avoiding a root cause of the issue, while still not feeling better. Microdosing psilocybin provided women with the opportunity to feel empowered and address or confront issues that were causing their symptoms. Some mothers have reported that microdosing psilocybin has assisted them enough to slowly stop taking antidepressants or anti-anxiety medicines (Julian, 2023).

Eating Disorders

Psychedelics offer promise for those who struggle with eating disorders, which are notoriously challenging to treat relative to other mental health disorders. Traditional treatments, such as Cognitive Behavioral Therapy (CBT), have a remission rate of about 45% and a relapse rate of about 30% within one year.. Now, experts and researchers are considering psychedelic therapy as an alternative, and are analyzing the potential benefits of this treatment. (Lagarde, 2023). Ketamine, ayahuasca, MDMA, and psilocybin are the four psychedelics that have been the focus of the majority of the latest research for the potential treatment of eating disorders.

Gender is a factor in eating disorders such as anorexia nervosa, which is three times as prevalent among women as men. The Multidisciplinary Association for Psychedelic Studies (MAPS) is currently conducting a study on MDMA-assisted therapy to treat anorexia, bulimia, and binge-eating disorders; the treatment works by reducing activity in the amygdala, the part of the brain that processes fear and threat. The Centre for Psychedelic Research at Imperial College London as well as John Hopkins University are currently researching psilocybin’s effects on Anorexia Nervosa, results have not been published at this time.

These conditions primarily impact women, and now more of them are coming forward to share how psychedelics are helping them leave a constant cycle of dissatisfaction, body dysmorphia, and the accompanying anxiety, depression, and stress. They explain how the use of psychedelics helped them develop a new relationship with their eating disorders and improve their self-image. While large-scale studies are scarce, the anecdotal evidence of these shifts is powerful. (Lagarde, 2023)

The first-ever study of ayahuasca’s potential to help people heal from eating disorders was published in 2017, co-led by Dr. Adele Lafrance and Dr. Kenneth Tupper. The majority of the people in the study said that ayahuasca helped to reduce their eating disorder symptoms and showed them the root cause of the disorder. The ayahuasca experience has the ability to favorably affect behavior, stimulating self-reflection and increased awareness. Studies suggest that drinking it can aid in the treatment of anxiety, addictions, and depression, as well as eating disorders by shifting body perception To date, several studies have investigated the effects of psychedelics on eating disorders, the consensus is that the efficacy of this treatment is unclear, regardless, there is a high level of support in addition to encouraging stories that warrant further exploration.

The Future of Psychedelics for Women

Many early clinical trials, especially trials for women’s health issues are missing conclusive data on the benefits of psychedelics. This presents an opportunity for more research and development to meet these unmet needs and see if psychedelics can make an impact in women’s health (Majewski, 2022). The problems with conventional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are well-known. “SSRIs will only take you so far,” says Julie Holland, a medical advisor to MAPS.

Policy reform around psychedelic therapies with the Natural Medicines Health Act in Colorado and Australia’s recent reclassification of psilocybin and MDMA to enable prescription are leading the way and setting the example for other countries to follow. (Julian, 2023) It’s an ideal time for discussing the unique health and mental health needs of women and how psychedelics may be able to help. Keeping this focus will help prevent women from being neglected in psychedelic research. (Dyke, 2018). Historically, the unique needs and physiology of women have been underrepresented, ignored, or purposely excluded from drug development and clinical trials (Baur, 2021). Also, few female scientists have been involved in drug research, including psychedelic research. Fortunately, it’s not too late to shift this paradigm as psychedelic research steams ahead. (Dyke, 2018).

The growing popularity of women self-treating with psychedelics and finding relief is a trend that should not be ignored. At the same time, the uniqueness of female physiology calls for specialized research to provide the best possible therapies.

About the Author: Caterina Francesca Bragagnolo is an internationally licensed Art Therapist and Trauma Specialist who has worked in private practice since 2013, primarily supporting women through adverse life experiences. Currently, Caterina works at a psilocybin-assisted retreat center in Jamaica as an Art Therapist and Senior Facilitator. Throughout her personal and professional experiences, Caterina noticed the benefits of incorporating Art Therapy practice into the integration and understanding of challenging psychedelic experiences.

In noting that our subconscious often speaks in symbolism and metaphor, the creative process can be incredibly supportive when making meaning from challenging experiences. This insight allowed her to cultivate a passion for blending somatic experiencing, attachment theory and creative practice to support others as they process, define and unpack cues from the subconscious.

By using non-verbal forms of self-expression to explore, gain insight and make meaning of the metaphor and symbolism within psychedelic experiences, participants are able to gain additional understanding of themselves. Her passion is focused on empowering individuals through engagement in the creative process in order to gain understanding of the self and their experience, while providing support in the process of uncovering one’s innate healing intelligence.

In addition to being a contributing artist and author for Women on Psychedelics, Caterina is also a practicing fine artist and clinical provider within the Psychedelic Support Network. She continues to focus on increasing access to psychedelic art therapy integration and is a professional member of the European Federation of Art Therapy and Caribbean Art Therapist Association.

Catarina's work can be seen and purchased at www.cfbfineart.com

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