650. HOW EARLY LIFE ADVERSITIES INFLUENCE DRUG EFFECTS LATER IN LIFE: STUDIES IN HEALTHY CONTROLS AND SUBSTANCE USE GROUPS USING ACUTE AND RETROSPECTIVE DRUG RESPONSES

Abstract Background Understanding the dual nature of drug effects - where pleasurable experiences drive continued use despite negative consequences - is critical for early identification, prevention, and treatment of drug use problems. Experiences of early life adversity (ELA), such as abuse and neglect, has been shown to influence responses to psychoactive drugs, with evidence from both preclinical and human studies supporting an increased susceptibility to positive effects. This heightened sensitivity may help to explain why exposure to ELA is a significant risk factor for addiction later in life. However, recent studies suggest that ELA is linked to greater susceptibility to both positive and negative drug effects - suggesting that while individuals with ELAs may experience stronger ‘highs’, they may also suffer more intense lows, negative psychological effects, or other harms. Aims & Objectives This study aimed to take a person-centred latent-pattern approach to examine whether ELA predicts distinct patterns of drug effects - both positive and negative. Specifically, we sought to (1) identify which positive and negative drug effects commonly co-occur together, and how this pattern may differ between people, and (2) examine whether ELA is associated with a distinct pattern of drug effects. Method 147 participants (aged 18-36) entering residential treatment for substance use disorders. Upon treatment entry, participants completed the Adverse Childhood Experiences (ACE) questionnaire, and reported on 10 positive and 10 negative drug effects experienced when using their primary drug of choice using the Net Pleasure Index (NPI). Positive effects included items such as “relief from pain and worries,” “enhanced social interactions,” and “improved relaxation,” while negative effects included “harm to close relationships,” “unpleasant psychological effects,” and “impairment in work/study abilities”. Mental health and drug use frequency were assessed at baseline and again after six months. Results Latent-pattern analysis revealed three distinct groups. The largest group (n=73) rated highly across nearly all positive and negative effects, reporting significant pain relief and social pleasure, yet also negative impacts of use on relationships, and mental and physical health. Group two (n=48) reported moderate positive effects and comparatively low negative effects when using, scoring highest for increased happiness and confidence and lowest for unpleasant acute effects. Group three (n=26) reported low positive yet high negative effects, citing relief from pain and worries as the primary positive effect, yet significant adverse impacts across nearly all domains. Respondents reported an average of 4 ACEs, and higher ACE scores were associated with belonging to two groups: those that reported high positive and negative effects, and those that reported low positive and high negative effects. Discussion & Conclusions This study supports previous findings that ELA plays a key role in shaping individuals’ responses to psychoactive drugs. Differences following ELA may arise due to neurobiological (e.g., endogenous opioid system changes) and psychological (e.g., interpretation of effects) mechanisms that should be further explored. Heterogeneity both between and within individuals with ELA underscores the need for personalised treatment approaches – for example that target the primary positive drug effects (e.g., pain relief, feeling good) that drive use over and above the negative consequences.