Microdosing Research

This experimental study (n=37) explored the integration of psilocybin-assisted neurofeedback in individuals with psychiatric disorders and executive function deficits. The participants received three microdose sessions followed by three psilocybin-assisted neurofeedback sessions. While there were no immediate improvements in experimental tasks assessing executive functions, significant self-reported improvements in daily life executive functions were observed, including working memory, shifting, monitoring, and inhibition, with high effect sizes.

This preclinical study using rats established and validated a regimen for psilocybin microdosing, administering repeated low doses of psilocybin at a level below the psychedelic threshold. The rats tolerated the regimen well without showing signs of anhedonia, anxiety, or altered locomotor activity. Additionally, the treatment imparted resilience against stress, reduced self-grooming behaviours associated with compulsiveness, and increased 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus.

This review (2023) covers in vitro, animal, and clinical studies to assess the potential risk of valvular heart disease (VHD) from microdosing psychedelic substances, focusing on LSD, psilocybin, mescaline, DMT, and MDMA due to their interaction with the serotonin 5-HT2B receptor. Findings show that all these compounds, except mescaline (due to low potency), were partial agonists at the 5-HT2B receptor. While safety margins from typical microdoses were greater than known valvulopathogens, there remains a potential risk. No studies directly evaluated VHD risk for the four psychedelics, but some evidence suggests chronic ingestion of full doses of MDMA might be linked to VHD.

This observational within-subjects study (n=17) repeatedly assessed participants during their psychedelic microdosing regimen using the CNSVS neurocognitive battery in a naturalistic setting. Results indicate that neither the day of microdosing nor the day after showed significant links to enhanced or diminished performance across various cognitive functions. The study concludes that microdosing psychedelics might influence psychological pathways rather than neurocognitive ones, leading to a subjective feeling of performance enhancement.

This Phase I RCT (n=80) examined the effects of microdosing LSD (10μcg; 14x; 6w) on sleep in healthy adult male volunteers, with doses self-administered every third day and sleep monitored through a commercially available sleep/activity tracker. The results showed that participants in the LSD group slept an extra 24.3 minutes per night on the night after microdosing compared to the placebo group, with no changes in sleep stages or physical activity.

This survey study (n=18) of microdosers over a month finds that on the microdosing day and the day after participants reported higher state authenticity. The researchers also found that they engaged in more activities on both days, but satisfaction was only higher on the microdosing day itself.

This review (2024) critically assesses the available evidence from dose-controlled studies investigating low doses of LSD and psilocybin. It proposes eight potential issues, such as small sample sizes, a limited number of controlled studies, and the possibility of selection bias, that challenge the claims that microdosing is predominantly a placebo effect. It suggests that it is currently inconclusive whether microdosing is merely a placebo.

This pre-print re-analysis (n=48) of microdosing LSD (5-20μg) finds that LSD reduces the influence of our expectations (precision-weighted local priors) on what we think time should feel like (under-reproduction bias). When controlling for the expectations, the bias disappears, indicating that LSD microdosing reduces the relative weighting of priors (expectations).

This placebo-controlled, randomized, naturalistic study (n=80) of repeated microdoses of LSD (10μg, 14x, 6w) finds improved ratings, on dosing days, on creativity, connectedness, energy, and other wellness ratings. Though these transient changes were found, no enduring changes to mood and cognition were observed.

This text-based interview study (n=13) explores the experiences and perceived mental health and well-being changes of microdosing psychedelics. The results identified three superordinate themes: 1) Seeking a solution: Agency and rationale; 2) Microdosers as scientists; 3) Catalysing desirable and beneficial effects.