Tirzepatide for Stimulant Use Disorder

(TRI-MR Trial)

This trial explores a medication called tirzepatide to determine its effectiveness for individuals with moderate or severe stimulant use disorder, such as methamphetamine or cocaine addiction, who are also overweight or obese. The goal is to assess whether tirzepatide, combined with counseling and behavioral support, can improve health and reduce substance use. Participants will receive weekly tirzepatide injections for 20 weeks, undergo brain scans to monitor changes, and attend therapy sessions. Ideal participants are adults who frequently use stimulants and have a high body mass index (BMI) with related health issues, such as high blood pressure or type 2 diabetes. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

A previous study found tirzepatide to be generally safe, though some common side effects occurred. The main concerns included mild-to-moderate stomach issues, such as nausea (30-40%), diarrhea (20-25%), and vomiting (15-18%). These side effects are usually temporary and resolve on their own.

Real-world data also highlight some safety concerns, such as reactions at the injection site and occasional dosing errors. Despite these issues, tirzepatide does not lead to abuse or dependence. It is not a controlled substance, but medical supervision is recommended to monitor side effects.

Unlike the standard treatments for stimulant use disorder, which often involve behavioral therapies and medications like bupropion or naltrexone, tirzepatide offers a novel approach by targeting the body's metabolic pathways. Tirzepatide is a dual agonist, meaning it activates two receptors involved in glucose and appetite regulation, which could potentially reduce cravings and improve impulse control. Researchers are excited about tirzepatide because it represents a new way to address the neurological aspects of addiction, offering hope for more effective management of stimulant use disorder.

Research has shown that tirzepatide, initially approved for weight loss, might also aid in treating addictions to substances like methamphetamine and cocaine. Some studies suggest that tirzepatide can influence brain pathways linked to addiction, potentially reducing cravings and aiding recovery. Early results from similar drugs, known as GLP-1 receptor agonists, have shown promise in improving health outcomes related to substance use. However, while some evidence indicates potential benefits, research on tirzepatide's effectiveness for these addictions remains in the early stages. More studies are necessary to confirm these initial findings. Participants in this trial will receive once-weekly subcutaneous injections of tirzepatide over a 20-week period to further explore its potential benefits for stimulant use disorder.¹³⁵⁶⁷