Why Psychedelic-Assisted Therapies for Women’s Health Transitions
Women’s mental health is not static. Across the lifespan, key transitions like the postpartum period, the premenstrual window, and midlife are marked by profound biological shifts alongside equally profound changes in identity, meaning, and self-relationship. Yet these transitions are often treated as isolated mood disorders, divorced from the hormonal, neurological, and existential contexts in which they arise.
Psychedelic-assisted therapies offer a different lens. One that recognizes women’s health transitions as whole-system events, involving brain chemistry, nervous system regulation, emotional processing, and identity reorganization all at once.
The Neurobiology: Estrogen, Serotonin, and Glutamate
Estrogen is not just a reproductive hormone; it is a powerful neuromodulator and neuroprotective agent.
Across the brain, estrogen influences serotonergic signaling by increasing serotonin synthesis, enhancing receptor sensitivity, and slowing serotonin breakdown. It also modulates glutamatergic transmission, supporting synaptic plasticity, learning, and emotional flexibility while buffering against excitotoxic stress.
When estrogen fluctuates or declines, as it does postpartum, in the late luteal phase, and during perimenopause and menopause, these protective effects weaken. The result can include mood instability, anxiety, depressive symptoms, sleep disruption, cognitive fog, and increased vulnerability to stress, and both auto-immune and neurodegenerative diseases.
This is where the pharmacology of psychedelic-assisted therapies becomes especially relevant.
Psilocybin primarily works through the serotonin 2A receptor, a key node in mood regulation, cognitive flexibility, and meaning-making. Ketamine acts through the glutamatergic system, rapidly enhancing synaptic connectivity and restoring neural communication in circuits often suppressed during depression.
In periods when estrogen is no longer offering its usual neuroprotective support, these therapies may help temporarily fill that gap. Not by replacing hormones, but by activating the very systems estrogen once supported: serotonin signaling, glutamate-driven plasticity, and network-level brain flexibility.
Conventional Treatments
Antidepressants are often the first-line response during these transitions, yet real-world adherence is strikingly poor. Nearly half of people prescribed antidepressants discontinue them within the first year, often because they take weeks to work, carry burdensome side effects, or create a sense of emotional blunting rather than deeper understanding of what is unfolding internally.
In the U.S., millions of people attempt to taper or discontinue antidepressants each year, frequently without adequate support. In contrast, psychedelic-assisted therapies, when used safely and with clinical guidance, could promote greater emotional access rather than numbing, helping individuals feel more connected to their inner experience, identify root causes, and engage meaningfully with change. Alongside potential benefits for symptom relief, neuroplasticity, and neuroprotection, this depth of engagement may also contribute to stronger therapeutic alliance and higher adherence compared to daily pharmacologic regimens.
Midlife, Mood, and Neuroprotection
Midlife is often framed narrowly as a hormonal deficit. But what is actually happening is a broader neurological transition.
As estrogen declines, the brain loses a stabilizing force that once supported mood regulation, sleep quality, memory, and resilience to stress. This helps explain why anxiety, depression, insomnia, and cognitive changes often emerge during perimenopause and menopause, even in women with no prior mental health history.
Psychedelic-assisted therapies may offer a unique opportunity here. By promoting neuroplasticity and restoring communication across brain networks, these medicines may support emotional regulation and cognitive flexibility during a time when the brain is renegotiating its internal balance.
Importantly, this is not just about symptom relief. It is about supporting the brain through a major biological transition while honoring the psychological and existential shifts that accompany it.
Beyond Neurochemistry: The Role of Assisted Therapy
What makes these therapies especially suited for women’s health transitions is not just the drugs themselves. It is the container.
Psychedelic-assisted therapies are inherently integrative. They invite meaning, context, and embodiment into the healing process.
The postpartum period, for example, is not simply a time of hormonal withdrawal. It is a passage through the birth portal. A moment where a woman is not returned to her former self, but reshaped into someone new. There is often grief for the old identity, overwhelm at the responsibility of new life, and a profound reorientation of purpose and selfhood.
Similarly, midlife and menopause involve their own form of shedding. The letting go of fertility, familiar roles, and earlier versions of the self. This transition can carry grief, relief, fear, and unexpected freedom all at once.
These are not experiences that fit neatly into a symptom checklist!!!
In assisted psychedelic therapy, altered states can open space for emotional processing, identity integration, and existential reflection. They can help women metabolize grief, reconnect to meaning, and develop a new relationship with themselves at moments when language alone often falls short.
A Medicine for Transitions
Women’s health transitions are not problems to be solved. They are thresholds to be crossed.
Psychedelic-assisted therapies, when used responsibly within ethical and integrative frameworks, may be uniquely positioned to support these thresholds.
1) Biologically, by engaging the same neural systems influenced by estrogen.
2) Psychologically, by supporting emotional flexibility and resilience.
And 3) existentially, by offering a space to honor the grief, growth, and transformation inherent in becoming someone new.
In this way, these therapies do not simply treat symptoms. They support passage, and for many women, that distinction matters.
References
1.Potential Differences in Psychedelic Actions Based on Biological Sex. Shadani S, Conn K, Andrews ZB, Foldi CJ. Endocrinology. 2024;165(8):bqae083. doi:10.1210/endocr/bqae083.
2. Postpartum Depression: A Role for Psychedelics?. Jairaj C, Rucker JJ. Journal of Psychopharmacology (Oxford, England). 2022;36(8):920-931. doi:10.1177/02698811221093793.
3. Menstrual Changes and Reversal of Amenorrhea Induced by Classic Psychedelics: A Case Series. Gukasyan N, Narayan SK. Journal of Psychoactive Drugs. 2024 Jan-Mar;56(1):50-55. doi:10.1080/02791072.2022.2157350.
Hiroi R, Weyrich G, Koebele SV, et al. Frontiers in Neuroscience. 2016;10:517. doi:10.3389/fnins.2016.00517.
5. Depression in Women: Windows of Vulnerability and New Insights Into the Link Between Estrogen and Serotonin. Lokuge S, Frey BN, Foster JA, Soares CN, Steiner M. The Journal of Clinical Psychiatry. 2011;72(11):e1563-9. doi:10.4088/JCP.11com07089.
6.Functional and Molecular Neuroimaging of Menopause and Hormone Replacement Therapy. Comasco E, Frokjaer VG, Sundström-Poromaa I.
Frontiers in Neuroscience. 2014;8:388. doi:10.3389/fnins.2014.00388.
7.Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse. Hara Y, Waters EM, McEwen BS, Morrison JH. Physiological Reviews. 2015;95(3):785-807. doi:10.1152/physrev.00036.2014.
8. One Size Does Not Fit All: How Type of Menopause and Hormone Therapy Matters for Brain Health. Gravelsins LL, Galea LAM.
The British Journal of Psychiatry : The Journal of Mental Science. 2025;226(6):369-382. doi:10.1192/bjp.2025.52.
Sun Y, Wang H, Wang W, et al. Frontiers in Aging Neuroscience. 2022;14:993955. doi:10.3389/fnagi.2022.993955.
Chan CR, Hsu JT, Chang IT, et al. Endocrine. 2007;31(1):44-51. doi:10.1007/s12020-007-0010-2.
Engler-Chiurazzi EB, Brown CM, Povroznik JM, Simpkins JW. Progress in Neurobiology. 2017;157:188-211. doi:10.1016/j.pneurobio.2015.12.008.
12. Decreased Medial Prefrontal Cortex Glutamate Levels in Perimenopausal Women. Yap S, Luki J, Hanstock CC, et al.
Frontiers in Psychiatry. 2021;12:763562. doi:10.3389/fpsyt.2021.763562.
Yen JY, Lin HC, Lin PC, et al. International Journal of Environmental Research and Public Health. 2019;16(22):E4352. doi:10.3390/ijerph16224352.
14. Ketamine and Ketamine Metabolites as Novel Estrogen Receptor Ligands: Induction of Cytochrome P450 and AMPA Glutamate Receptor Gene Expression. Ho MF, Correia C, Ingle JN, et al. Biochemical Pharmacology. 2018;152:279-292. doi:10.1016/j.bcp.2018.03.032.
15. Ketamine Attenuates Cytochrome P450 Aromatase Gene Expression and Estradiol-17β Levels in Zebrafish Early Life Stages. Trickler WJ, Guo X, Cuevas E, et al. Journal of Applied Toxicology : JAT. 2014;34(5):480-8. doi:10.1002/jat.2888.
16. Gender Disparity in the Funding of Diseases by the U.S. National Institutes of Health. Mirin AA. Journal of Women's Health (2002). 2021;30(7):956-963. doi:10.1089/jwh.2020.8682.
17.Sex and Gender: Modifiers of Health, Disease, and Medicine. Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, et al. Lancet (London, England). 2020;396(10250):565-582. doi:10.1016/S0140-6736(20)31561-0.
18.Association of Menstruation Cycle With Completed Suicide: A Hospital-Based Case-Control Study. Behera C, Sikary AK, Mridha AR, et al.
Archives of Women's Mental Health. 2019;22(6):771-777. doi:10.1007/s00737-019-00964-6.
Prasad D, Wollenhaupt-Aguiar B, Kidd KN, de Azevedo Cardoso T, Frey BN. Journal of Women's Health (2002). 2021;30(12):1693-1707. doi:10.1089/jwh.2021.0185.
Yu Z, Burback L, Winkler O, et al. Frontiers in Psychiatry. 2024;15:1386321. doi:10.3389/fpsyt.2024.1386321.
21. Default Mode Network Modulation by Psychedelics: A Systematic Review. Gattuso JJ, Perkins D, Ruffell S, et al.
The International Journal of Neuropsychopharmacology. 2023;26(3):155-188. doi:10.1093/ijnp/pyac074.
Yu Z, Burback L, Winkler O, et al.Frontiers in Psychiatry. 2024;15:1386321. doi:10.3389/fpsyt.2024.1386321.
22. What fMRI Studies Say About the Nature of the Psychedelic Effect: A Scoping Review.
Beneš M, Páleníček T, Horáček J. Frontiers in Neuroscience. 2025;19:1606798. doi:10.3389/fnins.2025.1606798.
23. Pain and Perception: Exploring Psychedelics as Novel Therapeutic Agents in Chronic Pain Management. https://pubmed.ncbi.nlm.nih.gov/39775134/
24. The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). El Khoudary SR, et al., 2019 Oct;26(10):1213-1227. doi: 10.1097/GME.0000000000001424. PMID: 31568098; PMCID: PMC6784846.
