Microdosing Psychedelic Substances And The Menopause

Menopause is a natural part of aging usually experienced between 45 and 55 years when your periods stop, and fertility ends. The end of the cyclic hormonal highs and lows of menstrual cycle symptoms can often usher in other symptoms with a new hormonal normal.

Symptoms that can have a significant impact on both physical and mental well-being. The commonly associated symptoms of menopause (mood swings, anxiety, insomnia, hot flushes, night sweats, low energy levels, vaginal dryness, low libido, dry skin, trouble focusing, increased abdominal fat, and weight gain) all have far from trivial impact on women's daily lives. That’s before we come to the associated chronic and systemic changes because of the lack of hormones like oestrogen, can impact bone density, increase inflammatory processes, and increase risk of acquiring certain cancers and cardiovascular illnesses – again, far from trivial.

So far there is little relief to gain for women suffering from the complications of menopause, but could microdosing psychedelic substances have potential benefits for women in the menopause, and can that benefit reach beyond just symptomatic relief?

Microdosing involves the consumption of small quantities, typically 10-20% of a regular dose, of psychedelic substances such as psilocybin (found in "magic mushrooms") or LSD, a synthetic compound. The aim isn't to induce a full psychedelic trip, but to subtly enhance cognitive, emotional, and spiritual functioning over an extended period. Psychedelics, once a taboo topic, are gradually gaining societal acceptance. They've even been labelled a "breakthrough therapy" by the US Food and Drug Administration, suggesting they may soon receive widespread medical approval.

Research into the practice of microdosing is still very much developing, though preliminary studies and anecdotal reports suggest potential benefits such as reduced anxiety and depression, enhanced mood, increased focus, and an overall boost in well-being. In talking to Dr. 1Dreah, an esteemed physician specializing in hormone optimization, the prevention of age-related diseases, and maintaining cognitive function and sexual vitality, she kindly shared her insights on the potential effectiveness of microdosing psychedelic substances for menopausal women:

“I started listening to how psychedelics, might increase blood flow to the brain, neuroplasticity, BDNF. And I'm like, wait, estradiol does that... there are a lot of parallels between what psychedelics do on a mechanistic level and what estradiol does. So, for women where estradiol is not an option for them due to a cancer status, psilocybin might be incredibly helpful.”

So what does microdosing look like?

Two notable microdosing protocols are the Fadiman and the Stamets Protocols, which outline methods for regular, low-dose psychedelic ingestion over weeks. The Fadiman Protocol (1), popularized by Dr. James Fadiman in his book "The Psychedelic Explorer's Guide," recommends a small psychedelic dose every three days for 4-6 weeks. This protocol was inspired by Albert Hoffman, the first person to synthesize LSD, who continued microdosing into his nineties.

Alternatively, the Stamets Protocol, named after Paul Stamets, advocates for a microdose taken 4-5 consecutive days with a 2-3 day break over 4-6 weeks. This method often incorporates supplements like Niacin and Lion’s Mane mushroom. Optimizing dosage is crucial to achieve tangible effects with psychedelics (2-5). LSD microdoses usually range from 10-26ug, a stark contrast to the 100-300ug used recreationally. Similarly, psilocybin mushroom microdoses span from 0.1 to 0.7 grams, compared to the recreational 3-5 grams. Studies reveal that 20 μg of LSD can reduce pain perception and increase tolerance (6).

Motivated by numerous anecdotal accounts after his book's publication, Dr. Fadiman established one of the first online microdosing forums. This platform enabled users to share experiences and track moods using the PANAS checklist. His 2019 study highlighted various reported benefits of microdosing, such as improved mood, reduced anxiety, facilitated habit formation, enhanced learning, and more (1).Several qualitative studies and online surveys reported reduced anxiety and depression and enhanced mood using the microdosing technique (1, 7-9), and even considered microdosing more effective than conventional treatment for mental health issues (8, 10). Although this research is limited by self-selecting online participants and is often in the absence of the control group.

In one of the largest trial of nearly 200, a placebo-controlled trial, using a naturalistic design, did find significant improvements in psychological outcomes from microdosing, however, the effects were considered to be because of the belief of the participants (11, 12)

So the evidence behind microdosing isn’t really there yet, but we do see continued reports of improving focus, productivity and enhancing overall cognitive function and mental health (10) (1, 13). However, others have found no effect (2, 3, 5, 14, 15) or just reporting slight impairments in cognitive function (2, 5).

Physiological studies may give us more insight in to what microdosing may, if anything, be doing. A neuroimaging study using LSD microdosing found modifications in brain connectivity in the thalamus and amygdala and this enhanced amygdala-middle frontal gyrus connectivity was associated with mood improvement (16). Microdosing psychedelics could be helpful with improving symptoms particularly psychiatric related to menopause, but does the story ends with alleviating symptoms or is there something more to it?

During menopause, heightened inflammation increases the risk of inflammatory diseases like autoimmune conditions and cardiovascular issues.

This is largely attributed to the decline in the hormone oestrogen, known for its anti-inflammatory effects. Hence, Hormone Replacement Therapy (HRT) is often seen as a preventative measure, rather than simply a symptom management strategy. Could psychedelics mechanistically on some level, substitute hormones and exhibit anti-inflammatory action? Given their impact on mental health issues, psychedelics might also have anti-inflammatory effects in the brain, where inflammation can lead to depression, addictions, impaired learning, and brain fog (17, 18)

Research suggests that microdosing psychedelics can provide anti-inflammatory benefits to the brain by activating 5-HT2A receptors (19)

However, our understanding of how psychedelics affect peripheral inflammation remains limited and warrants further investigation. A study found that psilocybin reduced the pro-inflammatory marker TNF-α, with further decreases in IL-6 and CRP observed after seven days. Additionally, improvements in mood and social interactions were associated with reductions in CRP and IL-6 (20). These results suggest that psilocybin's therapeutic effects could be tied to alterations in immune response and stress function. The 5-HT2A receptor, activated by psychedelics, is widely found in peripheral tissues. It's theorized that this receptor's activation modifies methylation and histone acetylation, which boosts the expression of anti-inflammatory genes and reduces pro-inflammatory ones. This may result in beneficial anti-inflammatory effects for menopausal women microdosing psychedelics (21). Further research is in doubt needed to better understand the half-life of psychedelics in the body and other potential receptors involved in their anti-inflammatory action.

While there are personal accounts of women finding benefits from microdosing psychedelics during menopause, no formal trials have yet established a safe and optimal protocol

As such, any decision to microdose is often left to the individual and should be approached with caution and respect, acknowledging the speculative nature of this treatment and our current limited understanding of its effects. Although the occurrences of women experimenting on their own bodies due to a lack of adequate and safe health care is not unique. Considerations about usage and dosage should account for factors like specific symptoms, overall health, potential contraindications, and medical history. Despite these considerations, many aspects will remain an estimation due to the lack of concrete research.

So finally and importantly, is it safe?

The long-term safety of microdosing has not yet been well-established and further questions around dosing, side effects, contradictions and risk factors that may be associated with menopause are awaiting investigation. We do know that microdosing can have a negative impact on cardiovascular load that is already impacted in menopausal women. Generally, psychedelics are considered relatively safe due to minimal physiological adverse effects. Research indicates that about 6% of microdosers might experience side effects such as altered thoughts, fatigue, and sleep disturbances (7). Furthermore, microdoses of LSD have been found to cause only a minor increase in blood pressure without significantly affecting heart rate (2, 16), although psilocybin raise some concern due to potential heart valve damage, linked to their 5-HT2B agonist properties (22). There's also an ongoing need to understand their interactions with other of course with medications.

Trials that collect clinical or real-world evidence are much needed in exploring how these potentially very powerful tools for a phase almost guaranteed for a woman to go through, that has so few reliable and effective tools in it presently. There is a clear need for speed of exploration given the current unmet clinical need.

In conclusion, the potential of psychedelic microdosing as a therapeutic tool for managing menopausal symptoms offers an intriguing frontier

While anecdotal evidence and initial studies hint at promising benefits, comprehensive clinical trials and real-world data collection are necessary to substantiate these claims. Balancing the noted potential for symptom relief and possible anti-inflammatory effects against safety concerns like cardiovascular impact, interaction with other medications, and optimal dosage determination calls for careful navigation. As this exploration unfolds, women's wellness during menopause may discover a ground-breaking ally in psychedelic microdosing. Yet, given our limited current understanding, caution, patient-centricity, and scientific rigor must remain paramount in this unfolding narrative.

References

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