Psychedelics for Biohacking and Performance

The recent resurgence of clinical psychedelic research has produced impressive outcomes and is continuing to gain momentum. The US Food and Drug Administration recently granted “Breakthrough Therapy” designation to accelerate the investigation of psilocybin (the active ingredient in magic mushrooms) for treatment-resistant depression, while MDMA-assisted psychotherapy received the same clinical classification for post-traumatic stress disorder (PTSD). 

Scientific studies have demonstrated that classical psychedelics can catalyze a period of neuroplasticity, enhancing the brain’s ability to modify and adapt its function and structure. This process of brain reorganization is thought to contribute to the long-lasting therapeutic effects of psychedelic-assisted therapy. 

However, the intensity of a high-dose, potentially ego-dissolving psychedelic experience is not desirable for all people. Understandably, some may be intimidated by the idea of tapping into a non-ordinary state of consciousness for several hours. 

This has led to the appealing and increasingly popular practice of microdosing. What if you can receive the benefits of enhanced neuroplasticity, without having to radically alter your conscious state? 

Microdosing advocates claim that one can derive a variety of mental health and performance benefits from this increasingly popular wellness trend. Everyone from health-conscious young adults to productivity-driven entrepreneurs to high-powered Silicon Valley industrial magnates have credited microdosing as a powerful means of improving mood and performance.

Psychedelics have long been associated with creativity, too. Steve Jobs famously described his experiences with LSD as “one of the most important things in my life,” while the founder of Consciousness Hacking, Mikey Siegel, is a past faculty member of the Esalen Institute, a holistic education center geared towards the transformation of humankind that regularly hosts workshops on psychedelics.

However, thanks to the rigorous research of Adam Bramlage, founder and CEO of Flow State Micro, a functional mushroom company and microdosing education platform, we now know that microdosing is not merely a modern phenomenon. Aboriginal Australians and the Rarámuri of Northern Mexico have been taking small doses of psychoactive plants to aid in hunting, stimulation, appetite suppression, and sensory acuity for thousands of years.

All of this raises the question: Can microdosing psychedelics hack one's biology to optimize performance? 

What is Microdosing? 

Microdosing seems to have captivated biohacking enthusiasts more than any other of the many transient self-improvement trends. Concurrent with the resurgence of psychedelic science, awareness of microdosing has gained considerable popularity in recent years. So, what exactly is it?

Microdosing refers to the practice of routinely self-administering very low quantities, or, sub-threshold doses, of psychedelic drugs, such as lysergic acid diethylamide (LSD) and psilocybin. Typically, microdosing involves ingesting 5%-10% of a standard psychedelic macrodose on a fixed schedule.

While there is no consensus on the ideal dosing range of LSD or psilocybin, a recently conducted randomized controlled trial (RCT) concluded that around 13 micrograms of LSD may be a potentially safe microdose for repeated administration. Microdosers of Psilocybe cubensis - by far the most common magic mushroom species - typically ingest around 0.1 grams (or 100 milligrams), although it is important to keep in mind that different strains and species of magic mushrooms express varying quantities of psilocybin and psilocin. Also, the threshold between a sub-perceptual microdose and somewhat-perceptual low dose is thin and varies between individuals, so it's advisable to start low and dose upwards to find your sweet spot.

Popular media has characterized microdosing as a “biohack” that can enhance mood, empathy, positivity, well-being, creativity, problem-solving, focus, and all-around cognitive performance. Increased media coverage has, in a non-trivial way, influenced public discourse and personal motivation to experiment with microdosing, even though scientific research investigating this widely purported performance-enhancing phenomenon is in its very early stages.

Following the publication of Ayelet Waldman’s A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life, in which she describes profound mental health improvements as a result of microdosing LSD — the kind of psychological freedom that conventional psychiatric medications failed to produce for her — microdosing as a self-managed antidote to depression and anxiety has been the subject of increasing media attention. 

The jury is out, however, as to whether microdosing actually works, or is indeed a mere placebo effect, and whether it may be physiologically safe or potentially quite harmful. 

Is Microdosing an Effective Biohack?

Maastricht University graduate student Joel Bornemann recently published a review of all qualitative and quantitative studies investigating the alleged performance-enhancing potential of microdosing psychedelic substances. In his extensive paper — The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-beingBornemann elegantly delineates the myriad ofever-growing findings being reported in the microdosing literature. 

Microdosing Psychedelics for Creativity

In 2018, researchers in the Netherlands assessed measures of divergent thinking (Alternative Uses Task) and convergent thinking (Picture Concept Task) — both of which were presumed to be indicators of creativity — in attendees of a psychedelic festival. In this study, participants completed the creativity tasks before ingesting a sub-threshold dose of psilocybin-containing psychedelic truffles, and again while they were under the presumed influence of the substance.

Results showed significant improvements in both convergent and divergent thinking among participants, providing strong evidence for the creativity-enhancing properties of microdosing. However, the lack of a placebo control group in this study means that the perceived improvement in creativity could be an effect of placebo.

James Fadiman, highly-regarded Stanford Ph.D. in Psychology, coiner of the term "microdosing," and author of The Psychedelic Explorer’s Guide — a manual that offers comprehensive guidance for those seeking the divine within through psychedelic experimentation — recently designed a website in collaboration with Dr. Sophia Korb for people interested in conducting a self-study, which provides a protocol that recommends microdosing every third day for one month. Interestingly, for the thousands of microdosing individuals who entered daily evaluations of their experience, improved creativity was a commonly reported effect.

These positive findings regarding creativity were subsequently supported in two additional qualitative studies, one of which analyzed 21 interviews via private messaging, while the other analyzed data from a subsection questionnaire included in the Global Drug Survey answered by people who reported microdosing LSD or psilocybin within the last year. In these studies, participants reported improved mood, focus, cognition, and creativity. 

Consistently, a 2019 observational study conducted by University of Toronto researchers investigating whether microdosing may be associated with differences in creativity found similarly positive results. Analysis of self-reported data gathered via the Alternative Uses Task completed by participants both with and without microdosing experience indicated higher creativity scores among both current and former microdosers when compared to participants without such experience. 

Importantly, observed increased levels of creativity may not be a consequence of microdosing per se, as the possibility that creative people are more likely to experiment with microdosing cannot be ruled out. 

In contrast to the above largely positive findings, a systematic observational investigation conducted in 2019 that tracked microdosers daily ratings of psychological functioning over six weeks found no changes in creativity. 

Furthermore, the aforementioned double-blind controlled study that determined around 13 micrograms of LSD to be a safe microdose failed to observe any differences in creative performance. Most recently, researchers from the University of Buenos Aires, Argentina found no evidence to support that low doses of psilocybin mushrooms can enhance creativity in their double-blind placebo-controlled study

Though not generalizable, the above findings could be used to inform future investigations. 

Microdosing Psychedelics for Focus and Productivity 

The resurgence of psychedelic science appears to have been accelerated by the ever-growing number of young professionals in Silicon Valley microdosing to improve focus and productivity at work. 

In support of this purported nootropic trend, the results of several qualitative studies suggest that microdosing may lead to…

  • Improved cognitive performance 
  • Increased productivity
  • Increased efficiency
  • Decreased procrastination
  • Decreased mental fog 
  • Lower levels of distractibility 
  • Increased absorption (“focused attention characterized by deep involvement with particular aspects of subjective experience.”)

However, a questionnaire-based study published in 2019 associated microdosing with impaired focus, although participants reported twice as many positive experiences as negative ones. In the same year, a double-blind RCT in which participants received six doses of either a placebo, 5, 10, or 20 micrograms of LSD found negligible effects on cognitive performance, though findings may have been skewed by the fact that participants were confined to bed on microdosing days. 

In addition to finding no increases in creativity, as previously mentioned, psychotherapist Federico Cavanna and colleagues at the University of Buenos Aires found no evidence to support the widely espoused cognitive-enhancing properties of psilocybin mushrooms. 

Can Microdosing Improve Mood and Well-Being? 

Qualitative and quantitative studies suggest that microdosing may have the potential to:

Regarding depression, the literature to date includes some indications that psychedelic microdosing may help with depressive symptoms.

For instance, a study published in 2021 in which thousands of participants described their microdosing experience via a mobile application, showed that adults who microdose psychedelics self-report lower levels of depression. Though these results appear quite promising upon first sight, reported effects were quite small, and the lack of a control group may have influenced the outcomes of this research. 

Interestingly, the Buenos Aires research group produced no evidence to support the potential mood-enhancing properties of low doses of psilocybin mushrooms. In what were ultimately quite damning findings, the authors concluded that expectation underlies at least some of the anecdotal benefits attributed to microdosing. 

Research investigating the effects of microdosing on anxiety has also garnered mixed results, with some studies reporting lower levels of anxiety and relief from social anxiety, while others, including Fadiman’s comprehensive cross-national study, reported some incidences of increased anxiety.

Since the publication of Bornemann’s comprehensive review, 3 placebo-controlled RCTs exploring the therapeutic efficacy of microdosing have been published, also garnering mixed results. 

In one of the largest placebo-controlled trials on psychedelics to date, microdosers reported significant psychological improvements. However, participants in the placebo group reported similar improvements, and there was no significant difference between the two groups. Following this, a 2022 naturalistic, observational study showed that psilocybin microdosing may improve overall mood and mental health. 

Most recently, Mindbio Therapeutics revealed positive data from their phase 1 randomized, double-blind, placebo-controlled trial in which 80 male participants received 14 doses of either 10 micrograms of LSD or inactive placebo every third day for 6 weeks. Data from daily questionnaires suggest that participants in the LSD group experienced increases in energy, wellness, creativity, happiness, and connectedness on dose days relative to non-dose days, which persisted when controlling for expectancy effects. MindBio is developing a medicinal microdosing treatment protocol for Major Depressive Disorder (MDD), the efficacy of which will be further investigated in phase 2 clinical trials in 2023.

In summary, it remains unclear what effect psychedelic microdoses may have on anxiety and depression. A better understanding of the potential anxiolytic and antidepressant effects of microdosing will undoubtedly be enhanced by future, better-designed research. 

Possible Long-term Health Effects of Microdosing

Although psychedelics are regarded by experts as among the least harmful psychoactive substances, exhibiting no toxicity or dependence liability, no research to date has examined any potential long-term physiological effects of microdosing. 

We know that psychedelics exert their characteristic subjective effects by activating the 5-HT2A serotonin receptor, but many psychedelics also have affinity for the 5-HT2B serotonin receptor. Agonism of this receptor is implicated as a potential mediating factor in drug-induced valvular heart disease. While occasional use of psychedelics likely does not cause any cardiovascular problems, repeated microdosing for extended periods could. 

Psychedelics have also been shown to promote neuroplasticity. Specifically, these substances may improve mood and performance by developing dendritic spines in neurons and forming new synapses between neurons. This process of brain reorganization is controlled homeostatically to prevent too much or too little neuroplasticity. Stimulating too much neuroplasticity through microdosing could potentially infantilize the brain, impairing one’s ability to think and effectivelyarticulate thoughts, or perhaps even exacerbate the symptoms of psychiatric disorders. 

It is clear that the dose and frequency of exposure to psychedelic compounds matter. As we are still in the early stages of rigorous psychedelic science, researchers are yet to definitively establish the benefits and risks of ingesting varying doses of these substances over different time frames. 

Single, large doses of psychedelic substances ingested in safely controlled environments can be profoundly therapeutic. When it comes to microdosing, a considerable cohort of individuals report extraordinarily positive, life-changing benefits, and there is some evidence to support these claims. Importantly, however, there may be a risk of long-term adverse physical effects lurking beneath the surface that most certainly warrants future scientific investigation. 

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