ABSTRACT
Research on the therapeutic potential of psychedelic substances is expanding. A limitation within this field is the unpredictability of individual responses to psychedelics. Better understanding of factors predicting psychedelic experience is essential to clinical progress and wider harm reduction frameworks. Ketamine, MDMA, LSD and psilocybin were selected for comparison due to their promising therapeutic effects and different mechanisms of action. This study aimed to (a) identify factors that produce positive and adverse psychedelic experience, and (b) compare these potential predictors across four psychedelic substances. A thematic analysis was conducted on twenty-two first-person reports of psychedelic use (six per substance), sourced from the Erowid database. This revealed three external predictors (nature, music, and preparation) and three internal predictors (understanding, mind-set, and motivation). Each factor identified contained two sub-themes that further elucidated meaning and impact. Nature and music emerged as potential tools for deescalating adverse reactions to psychedelics. Substance-specific perceptual and sensorial effects were also examined. Finally, the importance of, and interrelationship between, preparation, mindset, understanding, and motivation was examined as common themes that emerged. The broader clinical and sociological implications are discussed, with reference to developing harm reduction frameworks. These findings constitute an early step in developing a more nuanced understanding of factors shaping psychedelic experience.