A CBD-rich hemp extract is superior to CBD alone in reducing relapse to methamphetamine-seeking in rats

In preclinical models, the non-intoxicating cannabis component cannabidiol (CBD) reduces relapse to methamphetamine (Meth)-seeking and Meth-induced hyperactivity in rats. Cannabis products containing multiple cannabinoids (“full spectrum”) may offer greater therapeutic potential than single cannabinoid (“isolate”) products. However, few studies tested this. This study examined whether a hemp extract (HE) containing multiple cannabinoids might be superior to CBD alone in reducing Meth-induced behavioural sensitisation and relapse, and whether serotonin 1 A receptors (5-HT 1A ) are involved. Male Sprague-Dawley rats self-administered either Meth or sucrose via lever press, followed by extinction and reinstatement by Meth injection (1 mg/kg; i.p.) or sucrose access. Rats received vehicle, CBD isolate (80 mg/kg), HE (containing 2.5 mg/kg of CBD and other phytocannabinoids), or HE with CBD added to match the 80 mg/kg amount of the CBD isolate (CBD + HE condition). The 5-HT 1A antagonist WAY-100635 was co-administered to assess receptor involvement. Separate rats were tested for conditioned place preference (CPP) to assess possible intrinsic rewarding properties of the cannabinoids. A final group was tested for Meth-induced behavioural sensitisation. All CBD containing treatments reduced Meth-primed reinstatement, with HE and CBD + HE more effective than CBD isolate. There was no effect of any treatment on reacquisition of sucrose seeking. WAY-100635 did not block the effects of any treatment. Neither cannabinoid treatment produced CPP. All treatments reduced the expression of Meth-induced sensitised hyperactivity with CBD + HE showing some superiority over CBD or HE alone. This study suggests that CBD + HE may be more effective than CBD in reducing Meth relapse-like behaviour. • CBD-rich hemp extract surpasses CBD alone in reducing relapse to Meth-seeking. • CBD, Hemp-extract, and CBD-rich hemp extract have no effect on sucrose relapse. • CBD, Hemp-extract, and CBD-rich extract do not exert their effects via 5-HT 1A R. • CBD and CBD-rich hemp extract decrease Meth-induced behavioural sensitisation. • CBD, Hemp-extract, and CBD-rich extract do not induce conditioned place preference.