Examining the effects of naturalistic hallucinogen use on internalizing symptoms in a longitudinal sample of young adults

Massachusetts General Hospital, Boston MA

Investigators

Abstract

Hallucinogens are a heterogeneous group of substances that cause visual and auditory hallucinations, profound changes in one’s perception of time and space, and changes in mood. Many hallucinogens are also referred to as psychedelics. In recent years, there has been a massive resurgence of interest in hallucinogens within clinical research and popular culture, as clinical trials suggest that many hallucinogens hold promise for treating a range of mental disorders (e.g., depression, anxiety). Rates of hallucinogen use have risen sharply in recent years, particularly for young adults, for whom rates of hallucinogen use have nearly doubled in just three years (2018-2021). Moreover, evidence suggests that individuals are increasingly self-medicating using hallucinogens due to their reported mental benefits. Yet, a major gap in our knowledge is that we lack information about how naturalistic (i.e., real-world, non-clinical) hallucinogen use impacts mental wellbeing. Clinical trials provide very limited information about the real-world health impacts of these substances, and existing research on naturalistic hallucinogen use is severely limited (e.g., cross-sectional studies). Furthermore, many hallucinogens can have adverse health consequences when used in non-clinical settings (e.g., extreme anxiety, paranoia). In light of rising rates of use, there is an urgent need for rigorous studies to fill the aforementioned knowledge gap. Thus, the proposed DP5 project will assess the impact of naturalistic hallucinogen use on internalizing symptoms (e.g., depressive affect) in young adults; I will focus on young adults given that rates of use have increased disproportionately quickly within this age group. For my project, I will use data from Monitoring the Future (MTF), an NIH-funded longitudinal study on substance use and health in American youth (N = 100,000+). Further, I will use g-methods, a well-established set of statistical approaches that are designed to facilitate causal inference with observational data. Aim 1a will use inverse probability weighted marginal structural models (IPW-MSMs) to assess the impact of hallucinogens (e.g., LSD, MDMA, ketamine, “other hallucinogen use”) on internalizing symptoms (depressive affect, self-esteem, self-derogation, loneliness). Aim 1b will further assess the impacts of hallucinogen use on internalizing symptoms using a second g-method: structural nested mean models (SNMMs) with g-estimation. I hypothesize that hallucinogen use will have negative effects on internalizing outcomes; this hypothesis is not ethical to test in the context of a randomized trial, warranting this observational approach. Aim 2 will assess how individual characteristics (age, marital status, income, education, religious importance, rurality) impact the link between hallucinogen use and internalizing symptoms; I will use SNMMs with g-estimation for this aim. In sum, this project stands to provide valuable information about the real-world health impacts of hallucinogen use, identify individual-level factors that are closely linked to the possible negative effects of hallucinogens, inform public policy, and set the stage for future investigations in this area.