Psychedelic Journal Club: Microdosing for Mental Wellbeing

A commentary on the article “Adults who microdose psychedelics report health related motivations and lower levels of anxiety and depression compared to non-microdosers by Joseph M. Rootman et al., published in Scientific Reports.

In the last few years, the chilly cultural attitude toward psychedelic drugs has begun to show signs of rapid warming.

In the United States, psychedelics are still federally recognized as Schedule I controlled substances, labeled as drugs of abuse with no potential medical usefulness. However, decriminalization of psychedelics recently occurred in several cities in the United States, and similar efforts are underway at the state level around the country. Psychedelics are increasingly being considered an important new therapy for disorders of mental health, including major depressive disorder and post-traumatic stress disorder. To keep pace with the latest advances in psychedelic science, new research centers have cropped up at academic institutions including Johns Hopkins, NYU, UC San Francisco, and UC Berkeley, tasked with investigating the mechanisms by which psychedelics act in the brain and seeking to develop the safest and most effective treatment protocols possible.

The developing field of psychedelic medicine is a major factor in the shifting cultural approach to these substances. Psychedelics have a long history of use in underground and indigenous healing, but only recently has their therapeutic potency started to be evaluated within the established clinical trial framework. The use of “classical” psychedelics (like psilocybin and LSD) and psychedelic-adjacent drugs (like ketamine and MDMA), and the development of novel psychedelic analogues for the treatment of mental health disorders are now active research areas.

As such, psychedelic medicine increasingly appears to be a rich frontier with potential to deliver the first new blockbuster psychiatric medication since Prozac, and financiers have taken notice. The total value of the market is estimated to be $190 million currently, with an expected trajectory placing it in the ballpark of $2.4 billion by 20261. These big numbers are influenced by the latest clinical trial results describing the efficacy of psilocybin for treating major depressive disorder2 and MDMA for treating post-traumatic stress disorder3. In both trials, the treatment protocols involved guided therapy sessions during the drugs’ acute effects.

But what about microdosing psychedelics? Microdosing, in contrast to the treatment protocols utilized in ongoing late-stage clinical trials, is the practice of taking doses of psychedelics too small to reach the threshold level of psychoactive effects normally associated with the drugs. These sub-threshold doses are often taken at regular, frequent intervals over a long period of time. Microdosing is popularly considered to be a promotor of mental health and wellbeing, although the mechanism of action is unknown, and rigorous trials have not yet been undertaken to substantiate these claims4.

The promise of psychedelic medicine for mental health disorders, borne out in recent clinical trials, casts a warm glow over microdosing and hints at a vast new consumer market: if the effects of a microdosing routine are comparable to those of a therapist-guided high-dose treatment session, many people uninterested in challenging and intense psychedelic experiences suddenly become potential customers.

Given the mainstream openness to psychedelics, positive press, and high financial stakes, new research promoting the efficacy of microdosing should be scrutinized for design flaws and conflicts of interest.

A new paper by Rootman and colleagues, published in Scientific Reports, seems to make claims that microdosing is associated with low anxiety and depression5. However, the believability of the claims made in this paper is limited by potential bias among the co-authors and the omission of experimental design features crucially needed to appraise microdosing’s value.

The first aspect of this paper that might raise an eyebrow is the somewhat significant list of competing interests among the paper’s authors. More than one of the authors stands to gain financially from the commercialization of psychedelic medicines, and one of the authors in particular sells supplements that are part of the microdosing regimen discussed in the paper. These competing interests are clearly stated at the end of the article, and moreover, having a financial conflict of interest does not necessarily preclude rigorous science from being executed and accurately reported. But important questions could be posed about how the authors chose to frame their results. Mainly: does the presentation of the association between microdosing and positive mental health outcomes follow rigorous scientific reporting principles, or does it first and foremost serve the commercial interests of the authors?

The bigger problem with the paper is the lack of an important design feature that is necessary for evaluating the usefulness of microdosing. Simply put, the standard for evaluating the efficacy of any drug treatment is the double-blind, randomized, placebo-controlled trial. In other words, experimental evaluation of whether a drug treatment achieves its expected outcome should involve a comparison between the drug in question and an inactive substitute. Both the researchers administering the treatment and the participants receiving the treatment should be kept unaware of which of the two possible treatments is being dispensed. The procedure for deciding whether any given participant is assigned to the drug or placebo group should be fully randomized. These three experimental design elements safeguard drug studies from bias and expectancy effects. And they are not present in this report.

Instead, the study described in this article is a survey of self-selected respondents, drawing from populations of microdosers and non-microdosers. The results of this survey study are useful and interesting for illuminating the demographics and motivation of people who practice microdosing and the diversity of microdosing regimens being practiced. A key problem with the paper is how the authors discuss their survey findings of mental health outcomes.

For instance, in their Discussion section, the authors say, “The present results add to prior research that has identified positive associations between microdosing and mental health, and are the first to report associations between microdosing and reduced severity of symptoms of depression, anxiety and stress among adults with reported mental health concerns.” It is easy to imagine that the public could infer from this statement that microdosing is driving positive mental health outcomes. The authors of the article did not make it clear enough that their methodology leaves open the possibility that expectancy and placebo effects may be driving the positive health outcomes reported by survey respondents who practice microdosing. In fact, they entirely neglected to even raise the possibility of this expectancy bias in their article. Moreover, it feels like the authors are overselling their findings by claiming that they are the “first to report“ an association between microdosing and positive mental health outcomes, when there is a long history of popular reports of the benefits of microdosing4.

Undoubtedly, the claims made in this paper are exciting and intriguing. The study is certainly timely; the potential efficacy of microdosing is an important question to resolve now that psychedelic medicine is on the verge of being rolled out to the public. But because the study does not control for expectancy effects, its findings should not be taken as incontrovertible evidence that microdosing psychedelics is a useful health practice, especially given that no double-blind, randomized, placebo-controlled trial has yet been conducted. In the end, you might say this paper should be taken with a microdose of salt.

Link to journal article

What do you think about microdosing psychedelics? Tell us in the comments below!

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Written by Sean Noah
Edited by Carolyn Amir and Rebeka Popovic
Illustrated by Sean Noah

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References

  1. The Psychedelics as Medicine Report: Third Edition. Downloadable at: https://psych.global/report/
  2. Davis AK, Barrett FS, May DG, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021;78(5):481–489. doi:10.1001/jamapsychiatry.2020.3285
  3. Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 27, 1025–1033 (2021). https://doi.org/10.1038/s41591-021-01336-3
  4. Polito V, Stevenson RJ (2019) A systematic study of microdosing psychedelics. PLOS ONE 14(2): e0211023. https://doi.org/10.1371/journal.pone.0211023
  5. Rootman, J.M., Kryskow, P., Harvey, K. et al. Adults who microdose psychedelics report health related motivations and lower levels of anxiety and depression compared to non-microdosers. Sci Rep 11, 22479 (2021). https://doi.org/10.1038/s41598-021-01811-4
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Sean Noah

Sean is a postdoctoral researcher at the UC Berkeley Center for the Science of Psychedelics. He studies the link between how psychedelics change neural activity in visual cortex and their effects on visual perception. He received his PhD from UC Davis, where he studied the neural mechanisms of visual attention.

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