Background: The pharmacodynamic effects of Lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by personality traits and mood states.

Aim: To determine pharmacological and psychological predictors of the LSD effects in healthy human subjects.

Method: This analysis is based on 9 double-blind, placebo-controlled, cross-over studies with a total of 213 healthy subjects receiving between 25–200µg of LSD. The influence of sex, age, dose, body weight, pharmacogenetic, drug experience, personality, setting, and mood before drug intake on the peak autonomic and total subjective responses to LSD was investigated using multiple linear mixed effects models. Results were adjusted for LSD dose and corrected for multiple testing. Least Absolute Shrinkage and Selection Operator regression was employed to identify and prioritize the significance of predictors in the model.

Results: The LSD dose emerged as the most influential predictor, exhibiting a positive correlation with most response variables. Pre-drug mental states such as "general well-being”, "emotional excitability", and "anxiety" were also important predictor for a range of subjective effects but also heart rate and body temperature. The trait "openness to experiences" was positively correlated with elevated ratings in "oceanic boundlessness" and mystical-type effects. The acute response on “anxiety” negatively correlated with the genetically determined functionality of the Cytochrome 2D6 enzyme.

Conclusion: Besides the amount of drug consumed, non-pharmacological factors also significantly predicted the subjective drug experience. Sex, body weight, and prior experience were not significant factors in influencing the drug experience.