The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955–2021) and recommendations for the field

Polito, Vince; Liknaitzky, Paul

doi:10.1016/j.neubiorev.2022.104706

Cited by 40 publications

(43 citation statements)

References 74 publications

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“…A key question for researchers is whether the effects of microdosing have clinical or optimization benefits beyond what might be explained by placebo or expectation." (Polito & Liknaitzky, 2022). In short, microdosing leads to perceivable effects, explaining why CGR is universally high across trials (Cavanna et al, 2022;Murray et al, 2021;Szigeti et al, 2021;van Elk et al, 2021), but at this point none of these effects seem to be related improved mental health and the other hypothesized benefits.…”

Section: Discussionmentioning

confidence: 96%

The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing

Szigeti¹,

Nutt²,

Carhart-Harris

et al. 2022

Preprint

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In medical research, the gold standard experimental design is the blinded randomized controlled trial. Despite the central role of blinding, it is rare for trials to assess blinding integrity and to incorporate this information into the interpretation of results. Here we use computational modelling to show that the combination of weak blinding and positive treatment expectancy can lead to activated expectancy bias (AEB), which is an uneven distribution of expectancy effects between the treatment arms due to patients recognizing their treatment allocation. We show that this bias can inflate estimates of treatment effects and potentially create false positive findings. To counteract this bias, we introduce the Correct Guess Rate Curve (CGRC), a novel analytical tool that can estimate what would be the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. We apply CGRC to pseudo-experimental data generated by our computational model and show that the method produces AEB corrected results. Furthermore, to demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed data from a previously published self-blinding microdose trial. Results suggest that the observed placebo vs. microdose differences are susceptible to AEB, therefore, at risk of being false positives. These results demonstrate that a placebo control group is in itself not sufficient to control for expectancy effects, arguing that placebo-controlled studies are more fallible than conventionally assumed, which has implications for evidence-based medicine and numerous public health policies.

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Section: Discussionmentioning

confidence: 96%

The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing

Szigeti¹,

Nutt²,

Carhart-Harris

et al. 2022

Preprint

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“…In this article, our discussion focuses on microdosing with the classic serotonergic psychedelics: LSD and psilocybin. Most surveys and experimental evidence on microdosing come from either or both of these substances (Bershad et al, 2019;Johnstad, 2018;Kuypers et al, 2019;Passie, 2019;Polito and Liknaitzky, 2022;Yanakieva et al, 2018). Various online surveys on microdosing report that 48% to 68% of respondents used LSD or 1P-LSD (a chemical analog of LSD), 28% to 58% used psilocybin, 2% used mescaline (Hutten et al, 2019;Polito and Stevenson, 2019), and between 6% and 16% used "other" psychedelics (Anderson et al, 2019b;Polito and Stevenson, 2019).…”

Section: Microdosing With Lsd and Psilocybinmentioning

confidence: 99%

“…Microdosers of psilocybin typically ingest a median microdose of 300 mg dried psilocybin-containing mushrooms, the most common method of obtaining psilocybin outside a research context (Fadiman and Korb, 2019; Johnstad, 2018; Polito and Stevenson, 2019; Prochazkova et al, 2018). Few human experimental studies have solely focused on psilocybin microdosing (aside from incidental evidence obtained from “very low dose” arms of a larger study), compared with the number of controlled laboratory studies examining the effect of a full-dose via oral synthetic psilocybin (Carhart-Harris et al, 2018; Griffiths et al, 2006; Polito and Liknaitzky, 2022; Wackermann et al, 2008). Using the rule of thumb where a microdose is 10% of a “full dose” (itself is a contested quantity), the corresponding microdose for orally ingested pure psilocybin would be around 1–3 mg.…”

Section: Introductionmentioning

confidence: 99%

Microdosing with classical psychedelics: Research trajectories and practical considerations

Wong

Raz

2022

Transcult Psychiatry

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Microdosing—the intermittent ingestion of minute, sub-hallucinogenic amounts of psychedelic substances, repeatedly and over time—has become a widespread, albeit largely understudied, phenomenon. Regulations around using psychedelics at any dose—micro, mini, macro, or mega—pose all sorts of difficulties for those who wish to systematically study the effects of Schedule I drugs, especially in the United States. Microdosers commonly claim that taking a sub-hallucinogenic (pre-hallucinogenic or sub-perceptual) dose improves higher brain functions, including creativity, productivity, and mood. If true, these results would provide an important experimental edge in distinguishing psychosocial effects (e.g. caused by expectation) from those related to the active psychedelic ingredient. In this critical integrative synthesis, we explore the psychobiological science of dose amounts and how it informs microdosing with classical psychedelics (e.g. lysergic acid diethylamide [LSD] and psilocybin) to highlight and fuel research into questions (e.g. in cognitive neuroscience, consciousness studies, and metacognition). We sketch the hurdle-laden regulatory landscape and the procedures that shroud research with Schedule I drugs. Finally, we offer some future directions relevant to both scholars and clinicians in the social and behavioral sciences as well as in mental health and neurological science.

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“…Research into psychedelic microdosing began in 1955, with the majority of studies being published recently (i.e., since 2018). Polito and Liknaitzky (2022) carried out a systematic review on low-dose psychedelics between 1955 and 2022. The authors found that several outcomes stood out across these studies with several sources of data indicating direct drug effects.…”

mentioning

confidence: 99%

“…Establishing well-controlled studies using adequate blinding methods, and the long-term effects and safety of microdosing are important. With microdosing becoming increasingly popular, as well as having a prominent effect on people's lives, research must continue (Polito & Liknaitzky, 2022).…”

mentioning

confidence: 99%

Psilocybin as a healer

Golia¹

2022

Conscious Spiritual Transpers Psychol

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This phenomenological research explored the fast-growing societal trend in psilocybin microdosing, whereby a sub-perceptual amount of the psychedelic is consumed regularly. Anecdotal reports of microdosing have suggested that individuals can experience the relief of depressive symptoms, greater creativity and focus, deeper connections, and improvements in several mental health issues. Research on the lived experience of psilocybin microdosing, however, is lacking. Semi-structured interviews were conducted with 12 individuals to explore their lived experiences of microdosing. Seven central themes were observed in most individuals: 1) Mental Health; 2) Dose effects; 3) A feeling of connection to self, nature, or something ‘bigger’; 4) An increase in productivity; 5) An increased state of wellbeing; 6) Navigating problems more effectively; 7) Participants with a musical background experienced an increase in their levels of creativity. By providing support for the use of psilocybin microdosing, the findings are valuable in the growing field of psychedelic research. However, as these purported benefits are based on self-reports, further controlled studies are necessary.

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The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955–2021) and recommendations for the field

Cited by 40 publications

References 74 publications

The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing

The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing

Microdosing with classical psychedelics: Research trajectories and practical considerations

Psilocybin as a healer

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