The effects of three small morning and evening doses of LSD on mood, biological and psychological measures of sleep, neuroplasticity, and well-being

Psychedelic research has seen a revival in the past decades, leading to a wave of new studies investigating the effects of psychedelic substances in clinical populations as well as in healthy volunteers. Psychedelics, such as psilocybin and LSD, have shown to be a potential alternative treatment option for psychiatric conditions, such as stress-related disorders and addiction. Also in healthy volunteers, a psychedelic acutely induced positive effects on mood and participants described it as being among the most personally meaningful experiences of their lives. Recently, the practice of repeatedly using small doses of a psychedelic has received increasing scientific interest and is better known as ‘microdosing’. Both healthy and clinical populations who microdose do this to enhance cognitive performance and mood. To understand the full potential of microdosing, knowledge about the underlying neurobiological mechanism of the positive effects on mood and behavior are pivotal. A potential mechanism underlying these positive effects that has not been investigated yet, is the effect of microdosing on sleep. Nearly all of the successful treatments for mood disorders seem to affect circadian rhythms (sleep) and enhance neuroplasticity (brain-derived neurotrophic factor, BDNF), the present project seeks to investigate the effect of small doses of a psychedelic (LSD, 20 µg) on these parameters in healthy volunteers. Studies have suggested the involvement of serotonin 1A and 2C receptors in the normalization of the circadian rhythm, and LSD is a potent agonist of these receptors, it is therefore expected that LSD affects sleep. Additionally, a recent study from our lab showed that low doses of LSD enhance BDNF levels, a marker of neuroplasticity. We hypothesize that the aforementioned effects on sleep and BDNF underlie the positive effects of LSD on mood and well-being.
Another finding is that psychedelics’ effects on sleep are dependent on the time of administration. To understand the effect of the timing of LSD administration on sleep, neuroplasticity and mood subsequently, the effect of three repeated small morning and evening doses of LSD will be compared in healthy volunteers on assessments of sleep, neuroplasticity (SW sleep and BDNF) and mood.

A positive effect on mood is expected after LSD (20 µg) compared to placebo. The effect of LSD on mood is expected to differ depending on time of drug administration (morning vs evening).

3 dosing days interspersed with one day x 4

LSD (20 µg) and to placebo