Work

Persistent effects of adolescent THC on behavioral and neural responses to opioid drugs in male and female rats

Year: 2026

Type: article

Abstract: Addiction-relevant brain circuits mature during adolescence, and early-onset cannabis use is linked in humans to later-life use of harder drugs like opioids. Though this so-called “gateway effect” is heavily influenced by cultural factors in our society, preclinical studies consistently find that adolescent THC exposure (AdoTHC) increases opioid reward in rodents, suggesting that biological factors may also be involved. Here we asked how our well-characterized rodent AdoTHC protocol (5 mg/kg THC daily for 2 weeks in early adolescence) affects behavioral and neural responses to two classes of opioid drugs, heroin and remifentanil, long into adulthood. AdoTHC enhanced conditioned place preference for heroin and behavioral economic demand for self-administered remifentanil, with especially robust effects in AdoTHC females. Sex-specific AdoTHC effects on region- and network-level cFos expression patterns following heroin were also observed, which suggest preferentially altered frontal cortical networks in males, and amygdala-related networks in females. These findings support the notion that chronic adolescent exposure to moderate-dose THC causes long-term changes in opioid addiction-relevant neural networks in a manner that may relate to AdoTHC-induced vulnerability to the addictive effects of opioid drugs.

Source: Addiction Neuroscience

DOI: 10.1016/j.addicn.2026.100282

Authors: Maricela X. Martinez, Christina M. Ruiz, Christina R. Perrone, Victoria C. Inshishian, Erik Castillo, Stephen V. Mahler

Institution: University of California, Irvine

Language: English

Topic: Cannabis and Cannabinoid Research

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,660