Psychedelic Therapy for Women’s Health Issues

In April’s Psychedelic Support speaker series, Allison Feduccia Ph.D., Co-Founder of Psychedelic Support and a neuropharmacologist, hosted and presented on psychedelics for women’s health. 

Learn the research behind these advances and takeaways for women seeking healing through psychedelic medicine.

In this presentation, Dr. Feduccia explains the science of hormones and neurotransmitters, health challenges across the life cycle, and why psychedelic medicines could become treatment options for premenstrual symptoms, sexual health, postpartum depression, menopause, and end-of-life care.

Why Study Women?

Dr. Feduccia started by explaining why research should focus on women. 

Women make up half of the population; however, the majority of preclinical research was performed in male rodent models. Between 1909 and 2009, only 15% of these studies included both male and female sexes. 

Sex differences between males and females are important for how our brains and bodies function and how we might respond to different medications. In fact, from 1997 to 2000, 8 out of 10 drugs withdrawn from the market caused greater health risks for women.

The Menstrual Cycle

Dr. Feduccia reviewed the menstrual cycle to explain how fluctuations in female hormones have a profound effect on our brains and how we think and feel.

The menstrual cycle has 4 phases:

• Menstruation: The cycle starts with menstruation which lasts 3 to 7 days.
• Follicular phase: Starts on the first day of menstruation and ends at ovulation. Several follicles are formed and the endometrium thickens.
• Ovulation: This phase lasts between 24 and 48 hours. Estrogen is at its peak and triggers the release of one mature egg.
• Luteal phase: A sharp decline of estrogen, and progesterone starts to rise in the body.

“[Fluctuations in hormones] could actually impact the structure and function in our brain, [and] alter neurochemistry, meaning how the neurons are signalling between each other, can modulate emotion and cognition and fluctuating hormones have a big role in our risk for developing anxiety and depression,” says Dr. Feduccia.

Fluctuations in Female Hormones Contribute to an Increased Risk of Various Disorders

Although these hormone fluctuations are considered a natural process of the life cycle, women are at a heightened risk for various conditions.

• Women are two to three times more likely to develop depression and anxiety than men.
• Women have a higher prevalence of eating disorders, PTSD, and stress-related conditions.
• Women are at a higher risk for psychiatric disorders during the reproductive years and at transitional stages throughout the life cycle.

Dr. Feduccia wanted to highlight environmental factors that impact women’s health. 

• Women are more likely to experience traumatic events throughout their life.
• Women do not make as much money as men in the US; the pay gap is estimated to be about 22 to 30% between males and females.
• Women experience greater work-life balance stress including managing the household and childrearing.
• Women feel greater stress about physical appearance and body image due to social pressures and beauty standards.
• Women are more vulnerable to the stress-induced relapse of addiction disorders.

Neuroscience of Hormones and Neurotransmitters

Hormone Fluctuations and Risk of Depression Between Men and Women

Dr. Feduccia discussed a study that compared the risk of depression between men and women before puberty and during reproductive years.

The study showed that before puberty, males and females have about the same rate and risk of developing depression. However, women have a much higher risk of depression when puberty hits which corresponds to when ovarian hormone fluctuations begin.

The hormone fluctuations become even more erratic when a person reaches the phase of menopause and stops ovulation. This is typically in the forties. Menopause occurs in three phases:

• Perimenopause: This phase lasts between 2 and eight years before ovulation stops, with an average of 4 years. The ovarian hormones become very unpredictable. This is also when there is a spike in the risk of developing depression among women which does not occur for men.
• Menopause: Ovulation stops and a period has not occurred in the past 12 months.
• Post menopause: A drop off of these circulating hormones occurs.

The Role of The Endocrine System

Dr. Feduccia provided an overview of the complex endocrine system to explain potential issues and possible interventions.

The endocrine system refers to all the glands and organs throughout the body that release hormones into your bloodstream. This includes the testes, ovaries, placenta, hypothalamus, pineal gland, pituitary gland, thyroid gland, parathyroid glands, thymus, adrenal glands, and pancreas.

The hypothalamic-pituitary-adrenal (HPA) axis regulates the flow of hormones in our body. The hypothalamus produces signalling molecules that stimulate the reproductive organs to release sex hormones such as estrogen and progesterone in women and testosterone in men. When there is enough of a specific hormone in the system, signals are sent to decrease its production or to release other hormones.

“It’s a complicated system where a lot of things could potentially go wrong or have different medications…intervene,” says Dr. Feduccia.

There is a substantial interaction of sex hormones in the brain, not just in the hypothalamus. 

For example, estrogen affects every neurotransmitter system in the brain including the following:

• Serotonergic
• Noradrenergic
• GABAergic
• Dopaminergic
• Glutamatergic

All of these systems are heavily involved in mood, emotion, reward, processing, cognition, and other brain functions. 

The Life Cycle of Females

Dr. Feduccia discussed how different transition points across a woman’s life cycle can increase their risk of experiencing negative symptoms or developing physical or mental health conditions.

Premenstrual Syndrome (PMS)

A sample pulled across the world showed that PMS affects 47.8% of people. Specifically, 75% of women experience PMS symptoms in their reproductive years. Common symptoms include the following:

• Mood swings 
• Depression
• Irritability
• Abdominal cramps 
• Headaches 
• Generalized pain 
• Abdominal bloating 
• Breast swelling and tenderness 
• Appetite changes

Premenstrual Dysphoric Disorder (PMDD)

PMDD affects about 3 to 8% of women and is classified as a DSM-5 depressive disorder. PMS symptoms are exacerbated for women with PMDD and it has a severe impact on symptoms of anxiety, depression and mood swings. 

Typical treatments include SSRIs and hormonal birth control. Lifestyle changes include stress management, dietary improvements and exercise. 

It’s important to point out there is no difference in levels of circulating hormones for individuals with PMDD; however, there is an increased sensitivity to changes in gonadal hormones, and their modulation of neurotransmitter systems, predominantly serotonin and GABA.

Polycystic Ovary Syndrome (PCOS)

PCOS is a condition in which the ovaries produce an abnormal amount of androgens, which are male sex hormones usually present in women in small amounts.

Endometriosis

Endometriosis is a condition where surrounding tissues of the uterus become irritated and can potentially develop scars and flare-ups due to hormonal changes and inflammation.

Fertility Issues

For women under the age of 30, 13% experience fertility issues. Between the ages of 30 and 39, this increases to 22%. The risk increases even more for women in their 40s. Lifestyle factors such as smoking, alcohol use, weight fluctuations and stress can contribute to these issues.

Sexual Dysfunction

Sexual dysfunctions affect 43% of women, while only 31% of men are affected. This is associated with different types of medical and psychological causes. For instance, women are more likely to experience trauma and sexual abuse than men.

Postpartum Depression

Postpartum Depression (PPD) affects 10 to 20% of mothers. Fathers can also experience PPD. Symptoms include severe depression, crying, difficulty bonding, withdrawal from family, sleep issues and appetite changes

Perimenopause and Menopause

During perimenopause, 85% of women will have some symptoms such as hot flashes, night sweats, insomnia, vaginal dryness, mood disorders and weight gain.

Treatments include hormone therapy, antidepressants, gabapentin and clonidine for hot flashes, and lifestyle modifications.

Life-threatening Illnesses and End-of-Life Care

The medical system is great at addressing physical needs when treating an illness or disease. However, when it comes to end-of-life care, there are gaps in the system to help people with their psychological challenges. 

These include a sense of hopelessness, increased stress, anxiety, depression, lack of support for the person and their family in navigating death, lack of meaning and purpose during the final chapters of life and decreased quality of life and social interactions. 

Characterizing Psychedelics

How can psychedelics help women with some of these psychological and physical issues across the life cycle?

Before diving into the question, Dr. Feduccia explained what the term “psychedelics” means and how it is characterized. It’s important to understand that different compounds have distinct pharmacology.

Classic Psychedelics

Classic psychedelics include psilocybin, LSD, DMT and mescaline. They are serotonin 2A receptor agonists.

Entactogens

Enactogens include MDMA (Ecstasy), MDA and Methylone. These affect hormone release including DHEA, ACTH, oxytocin, prolactin, vasopressin and cortisol.

Dissociatives

Dissociatives include ketamine, nitrous oxide and PCP. Ketamine is the most well-known and it is an NMDA receptor antagonist.

Psychedelics May Help Women’s Health Issues

There are a few different ways psychedelics can help with women’s health issues. Dr. Feduccia spoke about how the psychological and neurobiological effects could likely play a role in potential treatments.

Psychedelic-Assisted Psychotherapy

The psychological mental aspects of psychedelic-assisted therapy have been studied. This involves having someone complete preparation and integration sessions followed by the ingestion of a full dose of a psychedelic substance with a therapist to guide them through the session. This allows them to gain perspective on the challenges in their lives and the struggles they are facing.

Modulating Reactions and Responses To Symptoms

Psychedelics have the potential to help with pain, low mood, and discomfort. For people suffering chronic pain, psychedelics may work not just by reducing the actual physical symptom of pain but can work to decrease the psychological aspects of the pain interfering with their life.

Neurobiological Interventions

Current research hasn’t explored how psychedelics could be used as a neurobiological intervention. However, psychedelic substances may be used to modulate hormones and neurotransmitter interactions.

Prevention and Well-being

Preventing disease and improving well-being could also be an application for psychedelics. This means they can help minimize the risk of developing a disorder and experiencing symptoms.

Benefits of Intermittent Use

Typically, full-dose psychedelic sessions are spaced at least a month apart. Because people are taking them intermittently, they will experience fewer side effects compared to the daily intake of traditionally prescribed medications.

This can be helpful for breastfeeding mothers who do not want to expose their babies to medications on a daily basis.

The intermittent use of psychedelics may allow someone to only use it before symptoms or during symptom presentation. For instance, psychedelics can be used at certain time points during the menstrual cycle to help prevent or ease symptoms.

Indigenous Use of Plant Medicines

Dr. Feduccia spoke about the anthropological reports that show how Indigenous tribes of Mexico and South America used psychoactive plants as aids in motherhood for hundreds of years. 

The Huichol Indians of Mexico used peyote throughout stages of pregnancy including birth and to help increase milk production after birth. Mescaline is the active compound within peyote; it stimulates the release of prolactin. Prolactin is the hormone that’s responsible for milk production and release. Mescaline can cause uterine contractions which can support labour and delivery.

Dr. Feduccia shared why we need to be cautious of our interpretations of the findings regarding the use of plant medicine in Indigenous tribes.  

“These results have not been tested in controlled clinical trials, so we can’t say that yes, this is safe….psychedelics are small molecules. They easily pass between the brain and blood barrier. They’re lipid soluble. If for these reasons, it’s very likely that they crossed the placental barrier during pregnancy and would reach the fetus.”

More information on FDA guidance on reproductive and developmental toxicity and how to study this can be found in this resource. 

Ketamine for Postpartum Depression

The appeal of ketamine for postpartum depression is that it is short-action, taken intermittently and is eliminated from breast milk within 12 hours.

Dr. Feduccia talked about the mixed results of two studies that looked at ketamine for postpartum depression.

The first study provided mothers undergoing a cesarean section with ketamine or a placebo before, two weeks and four weeks after delivery. The results were positive and there were significant group differences at two and four weeks postpartum.

The second study found no significant differences in depression or pain at three days and six weeks after delivery.

Dr. Feduccia stressed why more research is needed to understand the effect of ketamine and postpartum depression.

“It would be important to further evaluate what the appropriate dose, the timing of the administration, and just how long the antidepressant effects would be expected to last.”

Microdosing 

Dr. Feduccia briefly went over what microdosing is and some evidence of its effectiveness on various women’s health issues.

Microdosing is a method in which people take 5–10% of a full dose of a psychedelic substance every few days. Dr. Jim Fadiman is credited with starting the microdosing trend in his book The Psychedelic Explorer’s Guide in 2011.

In a 2019 survey, several women reported that microdosing helped alleviate perimenopausal symptoms. Some reported alleviation of premenstrual symptoms, including headaches, pain, fatigue, and mood swings.

In online forums, women have shared that microdosing helped regulate their periods. Higher doses either shorten or lengthen the menstrual cycle

Anecdotal Reports of Women who use Psychedelics

Dr. Feduccia gave some anecdotal reports of women sharing their positive experiences of psychedelic use.

“My period was always very severe in terms of pain. The pain even went through my entire stomach, back and legs sometimes. If I didn’t take pain relief it was vomiting, because my stomach didn’t pull the pain. I started microdosing and from that moment on I have almost no pain during and before my period.”

“I am microdosing for perimenopause and it saved me! Stopped my night sweats, reduced my hot flashes and I am back to sleeping again. Seriously a miracle I want to share with everyone! I would love to be a part of a study on the subject I just can’t find one.”

“This may sound bad but…. not completely crazy. The rollercoaster emotions that have no explanation other than hormones are lessened and the existential dread is gone as long as I dose consistently.”

Hypothesized Neurobiological Mechanisms

Dr. Feduccia explained the potential neurobiological mechanisms of psychedelics involved in helping women’s health issues.

Modulation of hormones

Psychedelics may directly or indirectly impact the circulation of hormones in major endocrine systems of the body. The neurotransmitter release triggered by psychedelic substances has a tuning effect on the hormone levels in our body.

Easing Estrogen Withdrawal and Effects of Fluctuating Hormones

Psychedelics may also have a tuning effect on how much estrogen withdrawal occurs during our normal cycle and how much that affects us. It may be reducing our psychological awareness of it or it could be a physiological effect. 

Neuroplasticity and Anti-inflammatory

Estrogen is also known to induce neuroplasticity and it can be anti-inflammatory. Women are more prone to inflammatory states, and it’s probably due to the interaction with estrogen. For instance, inflammation has been shown to contribute to conditions such as PMS, PMDD and fibromyalgia.

In non-human models, psychedelics have been shown to increase neuroplasticity and have anti-inflammatory effects.

Dr. Feduccia hypothesized how psychedelics could help with the fluctuating changes of estrogen in women’s health.

“We can use psychedelics to help facilitate what estrogen is already doing in the body, or perhaps it could act to fill in whenever estrogen is not producing these effects.” 

Individualized Approach

Dr. Feduccia explained that with the combination of biomarkers and AI, an individualized and targeted approach can be created for a specific health issue. Advanced technology can help identify specific doses or timing to administer a psychedelic or psychedelic-like compound to help with symptoms.

Psychedelic Therapy for Mental Health

Dr. Feduccia provided an overview of the different indications that are currently being studied in regard to psychedelic therapy. These include the following:

• Postpartum depression (PPD): 5-MeO-DMT (GH Research)
• Adjustment disorder
• Headache disorders (cluster, migraine)
• Fibromyalgia
• Eating disorders
• Posttraumatic stress disorder (PTSD)
• Major depressive disorder (MDD), treatment-resistant depression (TRD)
• Alcohol and substance use disorders (AUD/SUD)
• Obsessive compulsive disorder (OCD)
• Anxiety related to life-threatening illnesses / palliative care
• Social Anxiety in autistic adults
• Generalized anxiety disorder
• Suicidal ideation
• Bipolar disorder II (BDII)
• Attention deficit disorder (ADD)

The current psychedelics that are being studied include the following:

• MDMA
• Psilocybin / psilocin
• Ketamine
• DMT / DMT + harmala alkaloids
• 5-MeO-DMT
• Mescaline
• LSD
• Ibogaine

Where the Research is Heading

Dr. Feduccia spoke about the future direction of psychedelic research specifically for women. She thinks that the best way to facilitate these treatments is to look at the interaction between three factors:

Substance/Dose

This involves examining different receptor targets in the body and the brain, the desired effects versus the side effects and dose adjustments based on age and time in the menstrual cycle and life cycle.

Environmental

Lifestyle changes are always recommended before any drug intervention is given. However, lifestyle modifications are tricky to implement. Future research could explore how psychedelics might enhance our motivation to improve our diet and physical activity levels. Other environmental factors include healthy relationships, stress management, socioeconomic factors and epigenetics.

Neurobiological and Psychological

Future research will explore how psychedelic substances impact hormone levels during the menstrual cycle. A plausible place to study is the gut biome and how psychedelics can regulate our emotions, cognitions and biomarkers.

References

Women’s Health

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Becker, J. B., McClellan, M. L., & Reed, B. G. (2017). Sex differences, gender and addiction. Journal of neuroscience research, 95(1–2), 136–147. https://doi.org/10.1002/jnr.23963

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Gordon-Elliott, J. S., Ernst, C. L., Fersh, M., Albertini, E., Lusskin, S., & Altemus, M. (2017). The hypothalamic-pituitary-gonadal axis and women’s mental health: PCOS, premenstrual dysphoric disorder, and perimenopause. Psychiatric Times, 34(10). https://www.psychiatrictimes.com/view/hypothalamic-pituitary-gonadal-axis-and-womens-mental-health

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Psychedelic Research

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Kincaid, K. (2021). Birth as a potent psychedelic space: A three part model. Psychedelic Support. Retrieved from: https://psychedelic.support/resources/birth-potent-psychedelic-space/

Ketamine Research

Wolfson, P., Cole, R., Lynch, K., Yun, C., Wallach, J., Andries, J., & Whippo, M. (2022). The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of ketamine and metabolites. Journal of Psychoactive Drugs, 1–5. https://europepmc.org/article/ppr/ppr283078

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Alipoor, M., Loripoor, M., Kazemi, M., Farahbakhsh, F., & Sarkoohi, A. (2021). The effect of ketamine on preventing postpartum depression. Journal of medicine and life, 14(1), 87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982256/

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Indigenous Plant Medicines

Schaefer, S. B. (2019). Beautiful flowers: Women and peyote in Indigenous Traditions. MAPS Bulletin Spring, Vol. 29, №1. https://maps.org/news/bulletin/beautiful-flowers-women-and-peyote-in-indigenous-traditions-spring-2019/

Loures de Assis, G., & Rodrigues, J. A. (2022). Ayahuasca and Childbirth in the Santo Daime Tradition: Solidarity Among Women and Psychedelic Cultural Resistance. Chacruna Institute. Retrieved from: https://chacruna.net/ayahuasca-and-childbirth-in-the-santo-daime-tradition/

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Oliveira, C. D. R., Moreira, C. Q., de Sá, L. R. M., de Souza Spinosa, H., & Yonamine, M. (2010). Maternal and developmental toxicity of ayahuasca in Wistar rats. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 89(3), 207–212. https://onlinelibrary.wiley.com/doi/abs/10.1002/bdrb.20244

Guimarães dos Santos, R. (2013). Safety and side effects of ayahuasca in humans—an overview focusing on developmental toxicology. Journal of psychoactive drugs, 45(1), 68–78. PDF link.