Dried psilocybe cubensis psilocybin magic mushrooms inside a plastic prescription medicine bottle isolated on white background.

What Macrodosing Can Learn from Microdosing

By Dustin Marlan

Following a recent wave of unbridled positivity culminating in a “shroom boom,” the psychedelic renaissance now finds itself under fire amidst concerns of predatory capitalism, cultural appropriation, adverse psychological effects, and sexual abuse and boundary issues by guides and therapists.

Nonetheless, the psychedelics industry is moving ahead at full speed. Oregon will begin accepting applications from businesses to run psilocybin service centers in January 2023. MDMA clinical trials are nearing completion and expected to result in FDA approval. And corporations are readying psychedelic compounds — natural and synthetic — to produce and deliver to the masses.

All of this begs the question of how psychedelics dosage should be regulated, particularly where, as journalist Shayla Love points out, “there’s reason to worry that there hasn’t been enough preparation for negative outcomes amidst the hype.”

Indeed, psychedelics are not harmless, even in controlled environments. In addition to benefits, adverse reactions have been documented. These include hallucinogen persisting perception disorder (HPPD) and other long term negative effects from bad trips, the inability to integrate mystical experiences into our often mundane lives, spiritual bypass (i.e., the tendency to use spiritual ideas or practice to avoid facing unresolved mental issues), and deteriorating psychological health following psychedelic therapy. Ethical transgressions by guides are especially discouraging given the vulnerability of those under the effects of high doses of psychedelic substances.

Considering these issues, the expanding practice of “microdosing” — regularly taking very small amounts of a psychedelic so as not impair normal functioning — is intriguing as an alternate path forward for the embattled psychedelics industry. Yet much is still unknown about microdosing, with research finding both benefits and drawbacks. Some users report improved mood, focus, concentration, creativity, energy, social benefits, lowered anxiety, and other cognitive advantages. Others experience challenges, like physical discomfort, as well as impaired, rather than improved, mood, focus and energy, and a level of disconnection from self-identity. And it is unclear whether there are physical health risks to ingesting small amounts of a psychedelic regularly (as compared to a larger amount used only seldomly).

Further complicating matters, some of the psychological effects of microdosing could be due to the placebo effect. Yet researchers have shown changes in brain connectivity and activity through neuroimaging technology after a single low dose of LSD similar to those seen with larger doses of the substance. Another study too found that microdosing psilocybin had similar effects on the brain as compared to taking a macrodose of the substance.

Therefore, microdosing is intriguing at least insofar as the phenomenon indicates that psychedelics may have benefits at doses far below “macrodosing” — taking full doses that often lead to a loss of self-identity and out of body experiences. Perhaps a happy medium between microdosing and macrodosing could thus be calibrated.

The benefits and drawbacks of macrodosing are now well documented. Psychedelic experiences are being used to relieve conditions like depression, post-traumatic stress disorders, and anxiety. But while classic psychedelics, such as psilocybin, are typically physiologically safe, they do pose psychological risks to those who use them, particularly at higher doses. Many rate their macrodosing experience as among their top 5 most psychologically challenging experiences. While some can transform even the most terrifying trips into valuable experiences, this sort of narrative transformation is not guaranteed. For an unlucky few, reality breaks forever.

Adopting a “less is more” mentality with respect to dosing is a matter of ethics and equity. For instance, in New York Magazine and Psymposia’s popular podcast, Cover Story: Power Trip, multiple participants went on record saying that they were pressured to use higher doses of MDMA in a MAPS clinical trial for PTSD, which later haunted them. As one participant stated, “I have found now that more is not better, especially with MDMA.” Another participant noted that their higher dose “session was brutal. It had a lot of visuals right at the beginning, but they were terrifying. And I had this sensation of falling backwards into the gears of a gigantic clock. And I was getting crushed by the gears.”

The practice of microdosing indicates that full doses of psychedelics may be higher than necessary, at least for some people, in some circumstances. Lower doses may still provide insights and perspective changes, but in a less radical and more digestible manner. The assumption that macrodoses are required may derive in part from religious and spiritual uses, where the doses are so large as to effect visionary states. But it is not at all clear that what psychedelic philosopher Terence McKenna dubbed “heroic doses,” or even smaller standard doses, should be employed as part of a widespread psychedelic therapy regulatory regime.

Researchers, advocates, seekers, guides, and regulators should act with humility in determining psychedelic dosages. While standard doses of various psychedelic compounds will ostensibly be higher than a microdose, the question of just how much higher should be the topic of vigorous debate. In erring on the side of caution, the field has much to learn from the burgeoning practice of microdosing.

Dustin Marlan

Dustin Marlan is Assistant Professor of Law at the University of North Carolina School of Law. He is also a Project Affiliated Researcher for the Project on Psychedelics Law and Regulation (POPLAR) at the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.

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