Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers

Interest in low, sub-perceptual doses of psychedelics such as LSD and psilocybin—commonly called microdosing—has increased in recent years. Users report taking roughly one tenth of a recreational dose to improve daily functioning, creativity and concentration while avoiding a pronounced altered state of consciousness. Beyond performance enhancement, anecdotal accounts and interview studies indicate people also microdose to alleviate psychological and physical symptoms (for example anxiety and headache). At the same time, most clinical evidence for therapeutic effects of psychedelics has derived from regular, full doses that produce a profound acute experience; whether repeated low doses have therapeutic value remains unclear. This study set out to assess self-rated effectiveness (SRE) of psychedelic microdosing (MDP) for diagnosed mental and physiological disorders. Using an online questionnaire, the investigators compared respondents’ retrospective ratings of microdosing with (a) their conventional prescribed treatments and (b) regular (full) psychedelic doses, across three effectiveness questions: whether the treatment “worked,” whether symptoms disappeared sufficiently to restore daily functioning, and whether quality of life improved. The aim was to identify disorder-specific patterns in self-reported benefit and to inform priorities for future randomised controlled trials (RCTs).

The researchers deployed an online survey on several psychedelic websites and fora between March and July 2018. The advert did not mention microdosing explicitly in order to estimate base rates of microdosing among psychedelic users. Eligible respondents were aged 18 or older and had experience with at least one psychedelic substance; after reading study information they provided informed consent. The study received ethics approval and the questionnaire was hosted on Qualtrics. Survey items collected demographics (age, gender, continent, occupation, education), lifetime experience with a range of psychedelic substances (LSD and analogues, psilocybin, ayahuasca, DMT variants, MDMA, NBOMes, 2C compounds, mescaline, salvinorin A, etc.), and whether those substances had been used in microdoses, regular doses, or both. Respondents indicated whether a medical doctor or therapist had diagnosed them with psychiatric, neurological, or physical disorders from a pre-set list; free-text entries were re-classified afterwards into diagnostic subcategories following DSM-5 and ICD-10 frameworks, yielding 14 mental and 11 physiological subcategories. For each diagnosed disorder participants reported whether they had been offered conventional treatment (medication, therapy, or both) and then answered three binary-effectiveness questions about that conventional treatment. They also reported whether they had used a psychedelic to self-medicate that specific diagnosis, which substance was used, whether it was taken as a microdose and/or regular dose, and answered the same three effectiveness questions for each psychedelic dosing. The primary analytic approach was binary logistic regression to compare SRE of microdosing versus conventional treatment and microdosing versus regular psychedelic doses for mental and physiological diagnosis totals and, when cell counts permitted, for diagnostic subcategories. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported and significance set at p = 0.05. Analyses were not performed when cell counts were too small (less than 10 events per independent variable).

Of 5,681 people who accessed the survey, 3,590 consented, were aged ≥18 and completed the questionnaire. Roughly one third (N = 1,116; 31.1%) reported having microdosed; of those 1,116 microdosers, 410 (36.7%) reported at least one medically diagnosed mental or physiological disorder and formed the analytic sample. Mean age was 28.9 years (±10.1); 306 (74.6%) were male, 94 (22.9%) female and 10 (2.4%) identified as other. Most respondents had tertiary education (N = 290; 70.7%) and the majority originated from North America (N = 276; 67.3%). All microdosers also reported prior experience with regular psychedelic doses; the most commonly used substances for regular doses were psilocybin (N = 355; 86.6%), LSD (N = 325; 79.3%) and MDMA (N = 263; 64.1%). The most frequently reported microdosed substances were psilocybin (N = 248; 60.5%), LSD (N = 231; 56.3%), and 1P-LSD (N = 43; 10.5%). Respondents reported a total of 901 mental and 161 physiological diagnoses (some participants had multiple diagnoses; average 2.5 diagnoses per respondent). The most prevalent mental disorders were depressive disorders (N = 298; 72.7%), anxiety disorders (N = 228; 55.6%) and ADHD/ADD (N = 153; 37.3%). Leading physiological diagnoses were migraine (N = 60; 14.6%), chronic pain (N = 56; 13.7%) and cluster headache (N = 15; 3.7%). Conventional treatments had been prescribed for the majority of mental diagnoses (N = 714; 79.2%) and for most physiological diagnoses (N = 123; 76.4%). Psychedelics were used to self-medicate in over half of mental diagnoses (N = 520; 57.7%), most commonly using both micro- and regular doses (N = 413; 79.4% of those self-medicating). For physiological diagnoses, 31.7% (N = 51) reported psychedelic self-medication, with two-thirds using both dosing regimens. Comparing microdosing with conventional treatments, binary logistic regression showed that SRE of microdosing was significantly higher overall for mental diagnoses and for physiological diagnoses across the three effectiveness questions. Subcategory analyses indicated that the mental disorder effects were driven by neurodevelopmental and anxiety disorders; ad hoc testing attributed the neurodevelopmental finding specifically to ADHD/ADD rather than autism/Asperger’s. For physiological disorders the overall OR for the question “did it work” was 6.14 (p < 0.01; 95% CI [2.54, 14.86]); other physiological outcome ORs were reported as statistically significant as well. A sub-analysis of diseases of the nervous system yielded similar significant ORs (for example, OR "did it work" = 6.78, p < 0.01; 95% CI [2.63, 17.49]). Several mental and physiological subcategories could not be tested because of low cell counts. When comparing microdoses to regular psychedelic doses, microdosing was rated as less effective overall for mental disorders. Reported ORs for mental diagnoses comparing microdoses versus regular doses were: "did it work" OR = 0.15 (p < 0.01; 95% CI [0.10, 0.24]), "symptoms disappear" OR = 0.31 (p < 0.01; 95% CI [0.23, 0.42]) and "QOL improved" OR = 0.13 (p < 0.01; 95% CI [0.08, 0.21]). Subcategory analyses showed that microdosing was significantly less efficacious than regular doses specifically for depressive and anxiety disorders. By contrast, there were no statistically significant differences between microdoses and regular doses for physiological disorders: "did it work" OR = 0.45 (p = 0.27; 95% CI [0.12, 1.86]), "symptoms disappear" OR = 0.86 (p = 0.79; 95% CI [0.29, 2.55]) and "QOL improved" OR = 0.25 (p = 0.09; 95% CI [0.05, 1.25]).

Epstein and colleagues interpret the survey results as indicating that, among recreational psychedelic users who self-medicate, psychedelic microdosing is self-rated as more effective than conventional prescribed treatments for a range of disorders overall, and specifically for anxiety disorders, ADHD/ADD and certain physiological conditions such as pain. In contrast, when compared with regular (full) psychedelic doses, microdosing was rated as less effective for mental disorders overall and particularly for depression and anxiety, while no dose-related difference was found for physiological disorders. The authors suggest these patterns are disorder-specific: they propose that for depression and anxiety the acute, subjective psychedelic experience produced by regular doses may be an important therapeutic component, whereas for neurodevelopmental and some physiological conditions symptom relief might be achievable without a full subjective episode. The investigators acknowledge multiple limitations that temper interpretation. The sample was recruited via psychedelic fora and comprised recreational users who self-selected into the survey, which may bias results toward favourable views of psychedelics. Diagnostic severity and duration were not captured, nor was the longevity of symptom relief following each treatment modality; this prevents conclusions about comparative durability of effects. High rates of psychiatric comorbidity and small cell counts for many diagnostic and substance-specific comparisons limited the ability to test many subgroups and to compare particular psychedelics or specific conventional treatments (medication versus psychotherapy). Self-report and retrospective assessment of effectiveness are subject to recall and expectancy biases. Given these constraints, the authors recommend that their findings be used to prioritise indications and hypotheses for rigorous clinical evaluation rather than as evidence of efficacy. Finally, Epstein and colleagues call for randomised controlled trials in patient populations to objectively test whether observed self-rated benefits of microdosing are reproducible, dose-related, disorder-specific, and superior to conventional treatments, and to investigate the mechanisms that might account for differences between microdosing and full-dose psychedelic-assisted therapies.