169. THERAPEUTIC MEMORY RECONSOLIDATION AS A TREATMENT FOR SUBSTANCE USE DISORDERS AND HOW PSYCHEDELICS ARE FACILITATING THIS INTERVENTION: THE UNITY STUDY

Abstract Background Maladaptive motivational memory (MMM) is the term given to a learned association between environmental predictors of reward (cues) and the receipt of rewarding stimuli (reward). A key characteristic of MMMs is that they drive excessive consumption behaviours in a variety of disorders such as substance use disorders (SUDs) and behavioural addictions. MMMs underlie the motivated seeking, craving and preoccupation with substance use in response to ‘trigger’ cues, that typify SUDs, and therefore represent an important clinical target for relapse prevention in SUDs. Current treatments for substance use disorders focus on the short-term and management of withdrawal symptoms and do not tackle the maladaptive environmental factors, nor neuropsychopharmacological changes, that predispose individuals to relapse. It is therefore unsurprising that relapse rates remain high with around 50% of individuals relapsing within 1-year. A promising treatment method is the process of memory reconsolidation. Reconsolidation offers a therapeutic window in which to directly target (and weaken) maladaptive motivational memory traces that promote relapse susceptibility, thus, conferring longer-lasting protection against relapse. The non-classical psychedelic and N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MMMs in hazardous drinkers when administered immediately after memory retrieval. Leading to a reduction in alcohol consumption with no return to baseline at 9-months. The UNITy project at University College London is now investigating if and how the psychedelic substance N,N-Dimethyltryptamine (DMT) may facilitate therapeutic memory reconsolidation. This is the first large randomised placebo-controlled study of DMT as an intervention in alcohol use disorder (AUD). Aims & Objectives The UNITy project aims to silence relapse-promoting maladaptive motivational memories with DMT by interfering with their reconsolidation. This novel approach to improving treatment efficacy aims to remove a key driver of craving, excessive drinking and relapse, thereby enduringly reducing alcohol consumption.

Method: The UNITy study is recruiting 120 healthy volunteers, aged 21 – 65 that drink alcohol heavily. Heavy consumption of alcohol is categorised by scoring >10 on the Alcohol Use Disorder Identification Test (AUDIT) and drinking > 3 days per week, as well as consuming 40+ units per week (males) OR 30+ units per week(females). Participants must be motivated to reduce their drinking as assessed by ‘The Stages of Change Readiness and Treatment Eagerness Scale’ (SOCRATES) and ‘Motivation to Reduce Alcohol Consumption Scale’(MRAC). The UNITy study involves 3 in-person sessions, split by 1 – 2 weeks and EEG will be recorded during and 20 minutes post-infusions (total~60 mins) including during memory retrieval and during the ‘reconsolidation window’.

Results: The UNITy Study is currently underway and this talk will present preliminary EEG data from the first few participants. Discussion & Conclusions This talk is going to present a deep-dive into the science and rationale behind the current UNITy study. What is the memory reconsolidation intervention? Why DMT? What EEG signals are we looking out for and how will this impact future therapeutic memory reconsolidation interventions.