Tirzepatide to be investigated for reducing cannabis cue-reactivity in a pilot randomized crossover trial

Cannabis Use Disorder (CUD) represents a significant public health challenge, affecting millions globally and leading to substantial impairment in daily functioning, social relationships, and occupational performance. Despite its prevalence, effective pharmacological treatments for CUD remain largely elusive, with no medications currently approved by the FDA specifically for this indication. This critical gap highlights the urgent need for novel therapeutic strategies. Tirzepatide, a groundbreaking dual agonist for both the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR), has demonstrated remarkable efficacy in metabolic conditions like type 2 diabetes and obesity. Emerging research suggests that GLP-1R and GIPR signaling pathways may also play a crucial role in modulating reward circuitry and appetite regulation within the central nervous system, making these peptides intriguing candidates for investigating their potential in substance use disorders. This pilot study aims to explore this novel therapeutic avenue for CUD.

This investigation is designed as a double-blind, placebo-controlled, randomized crossover pilot clinical trial. The study plans to enroll an estimated 100 individuals diagnosed with moderate to severe Cannabis Use Disorder (CUD). Participants will be randomly assigned in a 1:1 ratio to receive either tirzepatide or a placebo. The intervention involves weekly subcutaneous injections of tirzepatide (dose not specified in abstract) or placebo. The crossover design implies that each participant will eventually receive both the active drug and placebo, allowing for within-subject comparisons. The primary objective is to examine the effects of tirzepatide on cannabis cue-reactivity, which typically involves measuring physiological, subjective, or neural responses to cannabis-related stimuli. While specific assessment methods are not detailed, these often include fMRI scans, self-report questionnaires, or behavioral tasks designed to elicit craving responses.