Neuropharmacological and regulatory drivers of tianeptine misuse in the united states: A growing public health concern

Tianeptine is an atypical antidepressant with unique neuropharmacological properties—most notably potent mu-opioid receptor agonism—that contribute both to its therapeutic profile and to its substantial potential for misuse. Although not approved by the U.S. Food and Drug Administration, tianeptine remains widely accessible through online vendors and retail outlets where it is marketed as a dietary supplement. Over the past decade, poison center surveillance and case reports have documented a sharp rise in dependence, withdrawal, and overdose events, positioning tianeptine as an emerging public health concern often referred to as “gas-station heroin.” The intersection of neurobiological vulnerability, widespread availability, and insufficient regulatory oversight has accelerated misuse patterns in communities across the United States.

This literature review examines three interconnected pillars contributing to the growing misuse of tianeptine: neuropharmacological mechanisms, population-level epidemiologic trends, and regulatory drivers. Using Covidence for structured screening, we reviewed peer-reviewed studies describing tianeptine’s mechanism of action, U.S. poison control data, demographic patterns of misuse, accessibility through labeled and unlabeled products, and federal and state policy responses. Our synthesis highlights how tianeptine’s rapid onset, short half-life, and mu-opioid receptor activity produce withdrawal syndromes resembling those of short-acting opioids. Epidemiologic data reveal significant increases in exposure calls, particularly among adults aged 20–50 with psychiatric comorbidities or polysubstance use. Regulatory findings show that gaps in federal scheduling, inconsistent state bans, and misleading supplement labeling have enabled ongoing distribution despite documented harms.

Together, these neuropharmacologic, epidemiologic, and regulatory insights emphasize the urgency of coordinated public health action. This review supports evidence-based policymaking, calls for improved surveillance and toxicology screening, and underscores the vital role of pharmacists and healthcare providers in identifying misuse, counseling patients, and advocating for safer community practices.

Strengthening provider awareness and regulatory oversight will be essential in preventing tianeptine from becoming a persistent contributor to the evolving substance-use landscape in the United States.