(PS1-91) Exploring the Potential Psychological Drivers underlying changes in Depression, Anxiety, and Wellbeing following Naturalistic Psychedelic Use

Classic psychedelics are naturally-occurring compounds that can give rise to altered states of consciousness and marked changes in mood. These substances have demonstrated promise for treating mental disorders, yet the psychological processes driving these effects remain poorly understood. Most studies have investigated only a few psychological drivers in isolation, leaving gaps in our understanding of which factors best explain post-psychedelic mental health improvements. This study compared nineteen psychological drivers using observational data from a prospective sample of individuals planning a psychedelic experience. Surveys were administered one week before, two weeks after, and four weeks after psychedelic use. Independent variables included four covariates (i.e., age, sex, prior psychedelic use, education) and change scores – computed as the difference between one week before and two weeks after psychedelic use – for nineteen plausible psychological drivers of the effects of psychedelics (N=161; 69.67% male, mean age = 31.71). We used lasso regression – which enhances traditional regression by shrinking less relevant coefficients to zero via a process called regularization – to identify the psychological drivers that best predicted changes in well-being, depression, and anxiety between two and four weeks post-use. Higher coefficients indicated stronger associations; p-values and confidence intervals should be interpreted cautiously due to bias that results from the regularization process. Improved well-being was best predicted by increased meaning in life (β = 0.23, 95% CI [0.10, 0.36], p < 0.01), followed by higher trait agreeableness (β = 0.19, [0.08, 0.36], p < 0.05) and enhanced mindfulness (β = 0.17, [0.02, 0.38], p < 0.05). Lowered anxiety was most strongly predicted by enhanced mindfulness (β = -0.35, [-0.48, -0.22], p < 0.001), followed by higher emotional stability (β = -0.16, [-0.28, -0.02], p < 0.05) and enhanced extraversion (β = -0.15, [0.02, 0.38], p < 0.05). Lowered depression was best predicted by increased self-esteem (β = -0.22, CI [-0.37, -0.06], p < 0.05), followed by higher emotional stability (β = -0.21, [-0.26, -0.06], p = 0.13) and enhanced mindfulness (β = -0.12, [-0.26, -0.08], p = 0.15). Notably, mindfulness was the only predictor in the top three across all outcomes. Limitations include the online opportunity sampling design, the lack of assessment of race/ethnicity, and the study's observational nature.. Nevertheless, this study highlights potential pathways through which naturalistic psychedelic use may enhance mental health.