Although Ozempic has not undergone human clinical trials for cocaine addiction treatment, its established safety profile and compelling animal study results can suffice for informed physicians to prescribe it off-label. Waiting for human clinical trials may take excessively long before leveraging its use in pharmacology. Recent studies have shed light on the mechanisms behind Ozempic’s potential in reducing cocaine usage. This article will give a brief overview of the mechanisms and provide a quantitative estimate of the magnitude of its effect.

Mechanisms of Ozempic in Reducing Cocaine Usage

  • Dopaminergic Modulation:
    GLP-1 RAs, such as Ozempic, influence the dopaminergic system, which is crucial for the reward pathways associated with drug use. By reducing cocaine-induced dopamine release in the nucleus accumbens (NAc), a critical brain region involved in the reward system, Ozempic diminishes the rewarding effects of cocaine, thereby reducing its use.
  • Glutamatergic Neurotransmission:
    Ozempic also modulates glutamatergic neurotransmission by suppressing AMPA receptor-mediated excitatory post-synaptic currents in dopamine neurons. This further reduces cocaine’s rewarding effects, helping to decrease cocaine-induced conditioned place preference and self-administration.
  • Gene Expression:
    Ozempic decreases the expression of dopamine receptor genes, particularly dopamine receptor 1 (D1R) and dopamine receptor 2 long isoform (D2rlg), the kappa opioid receptor, and the glucocorticoid receptor, all located in the NAc.

Empirical Evidence


Systemic absorption self-administration of mice showed approximately a 30-50% reduction of cocaine administration after titrating Ozempic of approximately 10ug/kg into the intracerebroventricular region of the brain.

Given multiple mechanisms against addiction and up to a 50% reduction in craving for a highly addictive substance, physicians should not hesitate to prescribe Ozempic for addiction purposes, as long as the patient has a reasonable BMI or is overweight. With its established safety profile and compelling animal study results, Ozempic may be a breakthrough in cocaine addiction treatment. It is important to reiterate that the data is based on the frequency of reduction of self-administration in mice, so it may not translate in a straightforward way. However, it is still something physicians should be excited about.