The Next Revolution In Women’s Mental Health

By Jacqui Zyl.

When it comes to mental health, major hormonal changes throughout a woman’s life, including puberty, pregnancy, and menopause, make their experiences different from men.

In fact, these major life transitions have been directly linked to an increased risk for depression and anxiety.[1],[2] However, mental health treatments are not always being tailored to women’s differing needs.[3] Unless clinicians exercise discretion based on their clinical experience, prescribing guidelines for psychotropics (drugs that affects behaviour, mood, thoughts or perception) are not gender-specific. One major reason for this, is that women have traditionally been underrepresented – or not represented at all – in clinical trials. Why? Because according to scientists, their hormonal fluctuations make them difficult to study.[4]

Today, many women are still receiving less than appropriate treatment for hormone-related mood disorders. But all that’s about to change. There is increasing demand for medicine to level up and start offering better solutions to the symptoms women experience during their reproductive and post-productive years. Women want to be more in control of their emotional wellbeing and have healthcare solutions tailored specifically for them.

Psychedelics could play a big part.  

The PMS opportunity

Many women of child-bearing age experience pre-menstrual syndrome (PMS). The associated mood symptoms can include anxiety, depression, irritability, low self-esteem and mood swings.[5] For between 3 and 8 percent of these women, these symptoms can become seriously debilitating, a condition known as premenstrual dysphoric disorder (PMDD).

While there is no cure for PMS or PMDD, symptoms are often managed with the contraceptive pill, antidepressants known as SSRIs (selective serotonin reuptake inhibitors), and other agents that suppress ovulation. For those who prefer to avoid prescription options, lifestyle changes and a host of complementary medicines are available, but their effectiveness is questionable.

When taken long-term, oestrogen-containing contraceptive pills are known to increase the risk of cervical cancer, blood clots and possibly breast cancer.[6] SSRIs carry their list of serious and undesirable side effects for women too, such as diminished sex drive, difficulty achieving orgasm, vaginal dryness, weight gain, nausea and fatigue.[7]

So, for women wanting more natural but effective solutions with less side effects, there remains a gap in the market.

The menopause opportunity

There is a taboo around menopause, and as a result, many women suffer in silence. When it comes to clinical management of this life stage, there are gaping holes in the medical care women receive.[8] Doctors – even gynaecologists – often misdiagnose symptoms and are not trained to manage the transition well.[9]

In all, there are roughly 34 different symptoms associated with menopause.[10] They can be present from months to years and can include brain fog, anxiety, depression, panic disorder and mood dysregulation. Women often describe the transition as a lonely and isolating time. Some say there is a sense of dissociation from their former selves.[11]

Low serotonin levels are largely to blame. As it turns out, the same hormones that control a woman’s menstrual cycle also influence serotonin – the brain chemical that promotes feelings of well-being and happiness.[12] When hormone levels drop during menopause, serotonin levels also fall, which contributes to increased irritability, anxiety and sadness.

Treatments for the mood symptoms of menopause have traditionally centred around hormone replacement therapy and SSRIs. And while these treatments can be effective, many women find them unsuitable due their side effects.

The promise of psychedelics

Research tells us that twice as many women than men experience depression and anxiety,[13],[14] – conditions that psychedelics are most commonly used to treat. So, it’s no surprise that more and more women are self-experimenting with these drugs to help manage a variety of mood disorders and enhance their wellbeing.[15]

Microdosing (taking a very low dose of a psychedelic drug) is a growing trend in this space. So much so that new biotech companies are emerging whose sole purpose it is to harness the benefits of psychedelics to help treat women’s mental and physical health challenges. Hormone-related mood disorders is one particular area of interest.

So, how exactly do these drugs work?

The science behind psychedelics

One of the critical properties of psychedelics is their positive impact on the serotonin system – specifically, the 5-hydroxytryptamine 2A (5-HT2A) receptors in the brain.[16]

Like SSRIs, classic psychedelics such as psilocybin (the active ingredient in magic mushrooms) and LSD (lysergic acid diethylamide) activate the serotonin system. However, instead of increasing the amount of serotonin like SSRIs do, they bind to serotonin receptors making the brain think there is more serotonin than there actually is.[17],[18] 

At the same time, these psychedelics reduce activity in the amygdala – a part of the brain that when overly activated in response to negative stimuli, has been associated with depression.[19] They also reduce activity in the anterior cingulate cortex – a part of the brain that has been associated with negative rumination and depression.

Furthermore, there is evidence that they decrease the connectivity of the brain’s default mode network (DMN), while increasing connectivity in the rest of the brain.[20]  The DMN is where our sense of self or ego resides, and it has been found to be particularly overactive in conditions such as depression, anxiety and obsessive-compulsive disorder (OCD). Psychedelics serve to disrupt this network, reducing rumination and levels of anxiety and depression, and allowing a person to be more psychologically flexible.

Where to from here?

MindBio Therapeutics is pioneering research into the clinical use of psychedelic medicines to treat a range of medical conditions such as depression, anxiety, PTSD, panic disorder, chronic pain and opiate addictions.

[1] Soares CN, Zitek B. Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability?. J Psychiatry Neurosci. 2008;33(4):331-343.

[2] Marques A, Bevilaqua M, da Fonseca A, Nardi A, Thuret S, Dias G. Gender Differences in the Neurobiology of Anxiety: Focus on Adult Hippocampal Neurogenesis. Neural Plast. 2016;2016:1-14.

[3] Sramek JJ, Murphy MF, Cutler NR. Sex differences in the psychopharmacological treatment of depression. Dialogues Clin Neurosci. 2016;18(4):447-457.

[4] Lack of females in drug dose trials leads to overmedicated women. ScienceDaily. https://www.sciencedaily.com/releases/2020/08/200812161318.htm. Published 2020. Accessed September 15, 2021.

[5] Premenstrual syndrome (PMS). Betterhealth.vic.gov.au. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/premenstrual-syndrome-pms. Accessed September 16, 2021.

[6] Butler Tobah Y. How long can I safely take birth control pills? Mayo Clinic. https://www.mayoclinic.org/healthy-lifestyle/birth-control/expert-answers/birth-control-pills/faq-20058110. Published 2020. Accessed September 17, 2021.

[7] Managing Antidepressant Sexual Side Effects. Healthline. https://www.healthline.com/health/erectile-dysfunction/antidepressant-sexual-side-effects#side-effects-in-men. Published 2019. Accessed September 17, 2021.

[8] Manson J, Kaunitz A. Menopause Management — Getting Clinical Care Back on Track. New England Journal of Medicine. 2016;374(9):803-806. doi:10.1056/nejmp1514242

[9] Wolff J. Doctors Don't Know How to Treat Menopause Symptoms. AARP. https://www.aarp.org/health/conditions-treatments/info-2018/menopause-symptoms-doctors-relief-treatment.html. Published 2018. Accessed September 16, 2021.

[10] Todd L. What are the 34 symptoms of menopause, and what helps? Medicalnewstoday.com. https://www.medicalnewstoday.com/articles/what-are-the-34-symptoms-of-menopause. Published 2021. Accessed September 16, 2021.

[11] Perry S. Menopause and mental health: finding yourself in isolation. gennev. https://gennev.com/education/social-isolation-menopause-mental-health. Published 2021. Accessed September 16, 2021.

[12] Payne J. Can Menopause Cause Depression? Hopkins Medicine. https://www.hopkinsmedicine.org/health/wellness-and-prevention/can-menopause-cause-depression. Published 2021. Accessed September 16, 2021.

[13] Gender and women's mental health. Who.int. https://www.who.int/teams/mental-health-and-substance-use/gender-and-women-s-mental-health. Accessed September 17, 2021.

[14] Facts | Anxiety and Depression Association of America, ADAA. Adaa.org. https://adaa.org/living-with-anxiety/women/facts. Accessed September 17, 2021.

[15] Winstock A, Timmerman C, Davies E et al. Global Drug Survey (GDS) 2020 Psychedelics Key Findings Report.; 2021. https://www.globaldrugsurvey.com/wp-content/uploads/2021/03/GDS2020-Psychedelics-report.pdf. Accessed September 17, 2021.

[16] Nichols D. Psychedelics. Pharmacol Rev. 2016;68(2):264-355.

[17] Selective serotonin reuptake inhibitors (SSRIs). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825. Published 2019. Accessed September 20, 2021.

[18] Jarrett C. How do psychedelics affect the brain?. BBC Science Focus Magazine. https://www.sciencefocus.com/the-human-body/how-do-psychedelics-affect-the-brain/. Published 2019. Accessed September 20, 2021.

[19] Barrett FS, Doss MK, Sepeda ND, Pekar JJ, Griffiths RR. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep. 2020;10(1):2214. Published 2020 Feb 10.

[20] Virdi J. Psychedelics and the Default Mode Network. Psychedelics Today. https://psychedelicstoday.com/2020/02/04/psychedelics-and-the-default-mode-network/. Published 2020. Accessed September 20, 2021.