Understanding Neuroplasticity Induced by Tryptamines (UNITy): Understanding Neuroplasticity Induced by Tryptamines: Rewiring Maladaptive Memories in Hazardous Drinking with Memory Reactivation and Dimethyltryptamine (DMT)

This registered clinical study investigates whether N,N-dimethyltryptamine (DMT), alone or combined with reactivating alcohol-related memories, can produce lasting changes in the brain, cognition, and drinking behavior in people with mild alcohol use disorder who are hazardous drinkers but not seeking treatment. Up to 120 participants will be assigned to one of four groups: alcohol memory retrieval plus DMT, alcohol memory retrieval plus placebo, control memory retrieval plus DMT, or control memory retrieval plus placebo. Drinking levels will be measured over three lab sessions and a nine-month follow-up using timeline follow-back and blood tests.

Study at a glance

Abstract

This study examines the existence and mechanistic underpinnings of lasting neural, cognitive, and behavioural plasticity in response to N-N-dimethyltryptamine (DMT) in a hazardous drinking population. It combines behavioural, neuroimaging, ecological momentary and qualitative data to gain a holistic understanding of potential mechanisms of therapeutic change following DMT. Primarily, we test the effects of dimethyltryptamine (DMT) in people with mild Alcohol Use Disorder (AUD), in the form of non-treatment-seeing hazardous drinking. We will assess whether leveraging the mechanism of memory reconsolidation can modify learned reward associations (maladaptive memories) and enhance the anti-drinking effects of DMT. A maximum N = 120 will be allocated to 4 groups as follows: Alcohol Memory retrieval (AMR) + DMT; AMR + placebo, Control Memory Retrieval (CMR) + DMT, CMR+Placebo. Total N will be determined based upon interim stopping rules as outlined in this registration. We will examine the effects of DMT alone and in combination with alcohol memory reactivation on drinking levels (as measure by timeline follow-back and dried blood spot phosphatidylethanol), over the course of three in-lab sessions and over a 9 month follow up. Participants will also complete batteries of questionnaires and cognitive tasks, qualitative interviews and full-length movie fMRI scans prior to and two weeks following an infusion of DMT or placebo. Between sessions, they will complete daily journals and VAS measures of mood and drinking using an EMA app. acutely pre-, post- an on -drug, we will record brain activity with EEG. Beyond examining primary outcomes of drinking behaviour, we will use these secondary measures to explore mechanisms of action of DMT that predict lasting behavioural and cognitive change at the neural, experiential and mnemonic levels. We thereby aim to conduct the most complete mechanistic study of a psychedelic drug in alcohol use to date.