CBD Helps Rats Forget Meth-Associated Memories Through Dopamine Receptors in the Hippocampus | Research

The takeaway

CBD accelerated extinction of methamphetamine-seeking behavior in rats and prevented relapse, and both effects required D1-like dopamine receptors in the dentate gyrus of the hippocampus.

Addiction researchers; people interested in CBD for substance use disorders

D1 receptor blockade in the dentate gyrus reversed both of CBD anti-relapse effects

What the researchers found

CBD enhanced extinction of meth-conditioned place preference and prevented reinstatement. Blocking D1-like dopamine receptors in the dentate gyrus with SCH23390 reversed both of these CBD effects, establishing D1Rs as a necessary mediator.

Why it matters

There are no FDA-approved treatments for methamphetamine use disorder. Understanding how CBD reduces drug-seeking behavior at the circuit level could inform development of targeted therapies.

The numbers in context

SCH23390 at 4 microg blocked CBD enhancement of extinction. SCH23390 at 1 and 4 microg reversed CBD prevention of reinstatement. CBD doses: 10 and 50 microg intracerebroventricular.

How the study worked

Male Wistar rats received the D1R antagonist SCH23390 at three doses into the dentate gyrus before intracerebroventricular CBD. Methamphetamine-conditioned place preference measured drug-seeking behavior during extinction and reinstatement.

What this study cannot tell us

Rat model with intracerebroventricular CBD delivery, which does not mirror human oral or inhaled use. Only male rats tested. CPP is a simplified model of addiction that does not capture the full complexity of human drug-seeking.

How to read the evidence

Well-designed mechanistic animal study with dose-response data; moderate because multiple doses and clear antagonist reversal strengthen the finding.

When this study was published

2025 study with current pharmacological methods

The bigger picture

This study adds to evidence that CBD modulates addiction-related behaviors through the dopamine system, specifically in memory circuits. The hippocampus is critical for contextual memories that drive relapse.

Questions still open

Would systemic CBD achieve sufficient concentrations in the dentate gyrus to produce these effects? Do D1 receptors play the same role in human meth addiction? Could CBD be combined with behavioral extinction therapy for clinical benefit?

Common questions

Could CBD help people quit methamphetamine?

This rat study shows CBD can reduce meth-seeking behavior in an animal model, but translating this to human treatment requires clinical trials. The route of administration (directly into the brain) differs from how people would take CBD.

What role does the hippocampus play in addiction?

The hippocampus stores contextual memories, including memories of where and when drugs were used. These memories can trigger craving and relapse when a person encounters familiar drug-associated environments.

Read the original research

D1-like dopamine receptors in the dentate gyrus mediate cannabidiol's facilitation of extinction and prevention of reinstatement in methamphetamine-induced conditioned place preference.

Pharmacology, biochemistry, and behavior, 256, 174094

View on PubMed ↗Publisher’s paper ↗

Citation

Danesh, Elaheh; Saghafi, Mohammad; Mozafari, Roghayeh; Mesgar, Somaye; Haghparast, Abbas. (2025). D1-like dopamine receptors in the dentate gyrus mediate cannabidiol's facilitation of extinction and prevention of reinstatement in methamphetamine-induced conditioned place preference.. Pharmacology, biochemistry, and behavior, 256, 174094. https://doi.org/10.1016/j.pbb.2025.174094