Microdosing Psychedelics: Untapped Potential in Psychiatry?

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is returning. What she’s looking for, she tells the reader, is a really good day — something that has been elusive in her turbulent life.

Although psychedelics remain illegal for both recreational and therapeutic use, they are being studied at academic centers; And there is hope that they will offer something that our traditional medications might not. However, these are not “micro” doses, but full doses of psychedelic agents that induce clinically-monitored “trips” in order to treat conditions such as depression, anorexia nervosa, or for smoking cessation, to name just a few.

Yet few relatively few studies have examined the therapeutic potential of psychedelic agents used in microdoses.

Because these drugs are illegal under most circumstances, many of the studies surveys of users involve in their natural environments who are already microdosing in an uncontrolled manner. In a 2019 study published in PLOS One, Vince Polito and Richard Stevenson, from Macquarie University in Sydney, Australia, gave daily surveys of psychological functioning to 98 microdosers over 6 weeks. Several participants were excluded for using doses that were too high or for concurrent use of other illicit substances.

Whereas the authors found that many people claimed to have positive experiences, there was an increase in neuroticism in some of the subjects. There was no control group and no uniformity to what the subject claimed to be ingesting with regard to dose, frequency, substance, or verification of the chemical content.

University of Chicago neuroscientist Harriet De Wit, PhD, leads one of the few laboratories that conducts controlled, double-blind studies looking at microdosing LSD.

“With microdosing there are expectations, and we don’t know if it’s the expectation or the agent that is making a difference,” she explained to Medscape. And when asked who in her experience is experimenting with microdosing psychedelics, she expounded “Everybody under the sun!”

De Wit notes that people microdose to increase their creativity, productivity, focus and energy, to heighten their spiritual awareness, improve empathy and social relational skills, and to improve their mood — all purported benefits of low-dose psychedelics.

Earlier this year her group published a study in Addition Biology in which 39 subjects were administered low doses of LSD four times over 2 weeks. To address the issues of expectation, the subjects were not told they were participating in a study of hallucinogens specifically, but instead were given a list of pharmaceuticals in different classes that they might be given. Microdoses of LSD did not improve either mood or performance, but they did appear to be safe and they produced no adverse effects..

To date, studies on microdosing have looked at their effects on healthy populations and the practice has been associated with “Silicon Valley techies” looking for performance enhancement. Waldman, however, is different.

She is open about her diagnosis of bipolar disorder, and her long history with therapy and medications. As she describes herself in the beginning of her book, she is emotionally uncomfortable, and both irritable and reactive to the point that her life is propelled by interpersonal chaos. In her uncontrolled ‘study,’ she is an N of 1, and she is pleased with the results. Microdosing, she believes, helped her become less irritable, more resilient, and in fact, have some very good days.

By the end of her memoir, she was looking for a way to continue microdosing, but was unsure how to safely obtain more LSD and be certain of its purity. Her experience does raise the possibility that microdoses may have therapeutic benefits in people with certain psychiatric conditions, but this has yet to be studied.

J. Raymond DePaulo Jr, MD, is the chair of the National Network of Depression Centers and a distinguished service professor at Johns Hopkins Hospital in Baltimore. “Microdosing of psychedelics is very problematic for two equally serious reasons,” he cautioned. “There is no control over what it is that people are actually taking, it is completely unstudied scientifically, and there is no agreement on what a ‘micro’ dose is.”

He noted that one of his patients thought he was taking psilocybin. A chemical analysis was done that revealed the agent to contain a combination of THC, a stimulant, morphine, and fluoxetine. There wasn’t a trace of psilocybin. “Mislabeling is the rule, not the exception,” DePaulo has concluded.

He also believes the placebo effect has a powerful role with microdosing. “It’s not working because of what is in the pill, more likely it is working because of what is advertised to be in it.”

De Wit noted that when she started her study she tried to find people who were elevated on measures of depression or anxiety, but was not looking for a specific clinical population of patients with these clinical diagnoses. “We found a handful of people and they improved, but so did those in the placebo group; they all got better.”

Psychedelic agents interacting with antidepressants, so subjects in controlled studies need to go off their medications before enrolling — this is a limiting factor in studies of both macro- and microdosing. De Wit also notes that there are logistical and practical obstacles — it is difficult to get approval to use these agents and the patients have to remain in the lab and be observed for several hours after they are administered, just as with standard doses.

As might be expected, data collection and anecdotal microdosing experiences are rampant on the internet. The social media forum Reddit alone boasts 192,000 members in its microdosing group, while the Imperial College of London invites microdosers to take part in surveys intended to add to the body of knowledge. But despite its popularity, there is little in the way of prospective, agent-verified, placebo-controlled research exploring whether or not microdosing is truly beneficial beyond just anecdotal.

Perhaps microdosing is a fad, or perhaps it offers some benefits to some people. Given the current interest in the therapeutic uses of psychedelics, it would be useful to have controlled studies of lower doses that don’t carry the risk of “bad trips.”

Certainly, psychiatry could use more agents to address mental health issues, and society might benefit from the use of agents that are proven to be evidence-based options for improving creativity and productivity. Anything that has potential to reduce psychiatric suffering seems worthy of further study to delineate which populations could be helped or harmed.

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