Erritzoe, David, Wingert, Aleksandra, Weiss, Brandon, Pronovost-Morgan, Chloé, Szigeti, Balázs, and Mallon, Orla
Classic psychedelic molecules, such as lysergic acid (LSD), psilocybin (the active ingredient of “magic mushrooms”), and N,N-Dimethyltryptamine (DMT) are 5-hydroxytryptamine 2A (5-HT2A) receptor agonists that can alter perception, mood and cognition (Nichols, 2016). Over the last 10-15 years, new scientific evidence has emerged on the therapeutic potential of psychedelic compounds in patients with depression, anxiety and post-traumatic stress disorder (Carhart-Harris, 2016; Griffiths, 2016; Grob, 2011; Ross, 2016; dos Santos, 2016; Thomas, 2017). In the same period, a novel use paradigm of psychedelics has also emerged, called ‘microdosing’, which is the regular usage of psychedelic drugs at sub-perceptual doses (Fadiman 2011). A considerable number of experience reports claims that microdosing can improve psychological well-being and cognitive functioning (Experience reports 1-3; Fadiman, 2011; Waldman, 2017). However, more rigorous research has failed to demonstrate an effect of microdosing on psychological outcomes while controlling for placebo effects and blind-breaking. We propose a laboratory-based study to investigate the effects of psychedelic microdosing on cognitive performance, biological and genetic indices relevant to neural plasticity, immune functioning, and mental and physical health symptoms. Our study has an observational design with the addition of an innovative self-blinding procedure that allows self-experimenters to implement their own placebo control. Participants will be allocated 1:1 to the microdosing (MD) or placebo (PL) condition. The primary objectives of the study are to test whether psychedelic microdosing has an effect beyond placebo on cognitive function, neurophysiology, and mental health domains (e.g., depression or anxiety). The strength of this study design is (1) the substantial expected sample size (up to 80 participants) relative to what is typically feasible in a clinical study at lower cost, while also controlling for expectations/placebo effects that are likely to bias other observational studies; (2) our focus on a unique cohort of microdose users who are self-medicating mental health problems, bearing greater relevance to clinical applications of microdosing; and (3) the ability to probe more deeply into biological/genetic changes that may accompany psychological and cognitive improvements.