A randomised, double-blind, placebo-controlled trial of repeated microdoses of lysergic acid diethylamide in healthy volunteers

Abstract

Microdosing refers to the practice of regularly ingesting low doses of psychedelic drugs which are below the level required to produce consciousness-altering hallucinogenic effects. This largely unsanctioned practise has become increasingly popular for the purposes of self-optimisation and the management of mental and physical health symptoms. While there have been efforts to investigate the effects of microdosing under controlled conditions, these studies have been limited by a low number of doses and administration in non-naturalistic environments. This thesis documents the first study of long-term repeated microdoses in participants’ home environments. The first aim of this thesis was to investigate the safety of repeated microdoses of the psychedelic drug lysergic acid diethylamide (LSD) in healthy adult males. Eighty participants were recruited into a double-blind study with parallel groups (n = 40 in each). Participants were given 10 μg of LSD or placebo under supervision and took a subsequent 13 microdoses at home (one every third day for six weeks). Participants completed daily questionnaires which collected adverse events and mood scales. Safety was assessed using reported adverse events, and assessments of vital signs. The second aim of this thesis was to assess the mood, personality, and cognitive effects of the microdosing protocol. As well as the daily questionnaires, a comprehensive battery of questionnaires and tasks were administered at baseline and at the end of the six-week protocol. The third aim of the thesis was to assess the neurobiological effects of the microdoses using electroencephalography (EEG) recordings during tasks associated with neuroplasticity. Event-related potentials from two tasks and advanced computational modelling was used to investigate changes to microcircuitry connectivity. This thesis demonstrates that microdosing psychedelics in healthy male adults is relatively safe and has acute positive mood effects, but no durable effects were detected. This thesis also demonstrates changes to connectivity during a plasticity-associated task, indicating a possible neurobiological mechanism of these mood effects. These results suggest that investigation of microdosing as a treatment for conditions such as mood disorders is viable and warranted.