Synthetic cannabinoid-induced changes in thalamo-prefrontal gamma synchrony and thalamic high-voltage spindles.

Hu Y.; Yu Q.; Zhuang H.; Yu Z.; Zhang Z.; Shen H. · Psychopharmacology · 2026

**Background & Methods** This review study examined the effects of acute synthetic cannabinoid exposure on thalamo-prefrontal neural oscillations using simultaneous local field potential (LFP) recordings from the mediodorsal thalamus (MD), prelimbic (PrL), and orbitofrontal (OFC) cortices in freely moving rats. The synthetic cannabinoid 5F-EDMB-PICA was administered acutely, and researchers analyzed changes in gamma power, inter-regional synchrony, and cross-frequency coupling between these brain regions. **Key Findings** • 5F-EDMB-PICA significantly suppressed both low-gamma (30-49 Hz) and high-gamma (51-80 Hz) power in the prelimbic cortex and mediodorsal thalamus, with transient low-gamma reduction observed in the orbitofrontal cortex, indicating localized suppression of neural oscillatory activity in prefrontal and thalamic regions. • The drug paradoxically increased long-range gamma coherence between the mediodorsal thalamus and prefrontal regions across both low and high-gamma sub-bands, revealing a dissociation between locally suppressed and long-range enhanced oscillatory dynamics. • 5F-EDMB-PICA increased the occurrence of high-voltage spindles (6-12 Hz) in the mediodorsal thalamus and enhanced phase-amplitude coupling between spindle/theta oscillations and prefrontal gamma amplitude, suggesting increased thalamic rhythmic output drives network reorganization. **Dosage & Administration** 5F-EDMB-PICA 0.3 mg/kg administered intraperitoneally (i.p.) **Safety & Adverse Effects** Not reported. The study focused on neurophysiological mechanisms rather than behavioral or systemic safety outcomes. **Evidence Quality** This preclinical animal study provides mechanistic insights into synthetic cannabinoid effects on thalamo-cortical circuitry but has significant limitations. The use of a single rodent model, acute dosing paradigm, and potent synthetic analog (rather than THC) limits direct translational relevance to human cannabis use. The study identifies neurobiological mechanisms potentially underlying cognitive and sensorimotor gating deficits but does not establish causal relationships or behavioral correlates. Additional research in multiple species, chronic exposure models, and integrated behavioral assessments would strengthen evidence quality. The findings contribute to understanding cannabinoid-induced neural dysfunction but remain preliminary mechanistic observations requiring validation.

More recent cannabis research