Cannabidiol modulates the brain rhythms within the hippocampal-prelimbic pathway in reinstatement of extinguished methamphetamine-induced conditioned place preference.

Sedehi R.; Karimi-Haghighi S.; Hooshmandi E.; Haghparast A.; Dehkordi Z. · Neuroscience · 2026

**Background & Methods** This experimental study investigated neural mechanisms in the hippocampal-prelimbic pathway during reinstatement of methamphetamine-induced reward-seeking behavior using a conditioned place preference (CPP) paradigm in rats. The research examined how cannabidiol (CBD) modulates brain oscillations and phase-amplitude coupling following methamphetamine exposure at doses of 0.5 and 0.25 mg/kg. **Key Findings** • Methamphetamine administration modulated phase-amplitude coupling between hippocampal alpha-beta (α-β: 8-30 Hz) phases and prelimbic beta-gamma (β-γ: 13-100 Hz) amplitudes, demonstrating hippocampal influence over prelimbic oscillations during reward-seeking behavior, with no significant direct modulation observed in the prelimbic area itself. • CBD administration decreased beta-gamma (β-γ) oscillation power within the hippocampus and attenuated phase coupling between hippocampal α-β phases and prelimbic γ amplitudes, suggesting potential modulation of addictive drive and altered neural dynamics underlying drug-seeking behavior. • CBD decreased the strength of sustained alpha-beta (α-β) oscillations in the hippocampus, providing evidence for a potential preventive mechanism against relapse in methamphetamine addiction. **Dosage & Administration** Methamphetamine was administered at 0.5 and 0.25 mg/kg doses. Specific CBD dosage, route of administration, and treatment timeline are not reported in the abstract. **Safety & Adverse Effects** Not reported. **Evidence Quality** This is a preclinical animal study (rats) published in 2026, representing basic neuroscience research with potential translational relevance. The study employs sophisticated neurophysiological techniques including phase-amplitude coupling analysis to elucidate mechanisms. However, findings are limited to animal models and cannot be directly extrapolated to human addiction treatment. The abstract lacks critical methodological details including sample size, blinding procedures, statistical analysis approaches, and control conditions. The restriction to a single animal species and behavioral paradigm limits generalizability. This represents early-stage mechanistic research requiring replication and eventual human clinical validation before clinical application. The work provides valuable neurobiological insights into CBD's potential anti-addictive properties but should not inform clinical practice without further evidence from controlled human trials.

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