Microdosing Psilocybin

Microdosing has become increasingly popular over the last decade. A microdosing regimen typically entails the ingestion of a psychedelic substance at a sub-hallucinogenic dose, usually 5–10% of a standard dose. Psilocybin and lysergic acid diethylamide (LSD) are the most common psychedelics used for microdosing and users commonly follow the Fadiman protocol, which suggests that one should dose every third day to achieve optimal effects (Fadiman, 2011; Hutten et al., 2019). Anecdotal reports and observational studies suggest that microdosing can have antidepressant and anxiolytic effects (Anderson et al., 2019; Cameron et al., 2020; Fadiman and Korb, 2019; Johnstad, 2018; Kaertner et al., 2021; Lea et al., 2020; Petranker et al., 2020; Polito and Stevenson, 2019; Webb et al., 2019). Users with mental health conditions, such as anxiety and obsessive-compulsive disorder (OCD), report microdosing as a form of self-medication (Hutten et al., 2019; Johnstad, 2018).

However, the available evidence regarding the efficacy of Microdosing Psilocybin for mental health remains inconsistent. Three of the four existing experimental studies on humans found no evidence for the alleged antidepressant and anxiolytic effects (Bershad et al., 2019; Family et al., 2020; Szigeti et al., 2021). The fourth, Hutten et al. (2020), found that 20 μg LSD increased positive mood but also anxiety. These inconsistencies may well be related to differences in study designs. The observational studies investigated the effects of microdosing longitudinally, either by gathering cross-sectional data from a subpopulation of individuals who regularly practice microdosing, or via prospective observational design that gathered data from before, during, and after a predetermined microdosing period (Bornemann, 2020). These studies did not control for psychedelic substances or dosages. In contrast, three of the four experimental studies focused only on the effects of LSD microdosing compared with placebo and investigated the acute effect of varying doses (Bershad et al.: 6.5, 13 and 26 μg; Family et al.: 5, 10 and 20 μg; Hutten et al.: 5, 10 and 20 μg). Participants of the fourth self-blinded experimental study self-administered psychedelic microdoses of their choice (i.e. primarily LSD and psilocybin), over 4 weeks. The authors assessed both acute and post-acute effects and controlled for varying dose quantities (Szigeti et al., 2021). The two experimental studies investigating the effect of microdosing on rats also reveal mixed results. Horsley et al. (2018) found a modest anxiogenic effect in the elevated-plus maze when the rats were tested 48 h after the third microdose of both psilocin and ketamine. In contrast, Cameron et al. (2019) found no effects of a 2-month dimethyltryptamine (DMT) microdosing protocol on anxiety but did find reduced immobility in the forced swim paradigm, which is considered an antidepressant-like effect, and less freezing behaviour following fear extinction training, which may reflect enhanced fear extinction.