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<sub>1A</sub>) 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<sub>1A</sub> 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.
Authors
- L. W. Anderson (ORCID: https://orcid.org/0009-0008-8563-0496)
- Priscila A. Costa (ORCID: https://orcid.org/0000-0001-7926-4823)
- Jennifer L. Cornish (ORCID: https://orcid.org/0000-0002-9754-8069)
- Christina J. Perry (ORCID: https://orcid.org/0000-0002-6155-1469)
- Iain S. McGregor (ORCID: https://orcid.org/0000-0002-9307-7159)
- Sarah J. Baracz (ORCID: https://orcid.org/0000-0002-9938-1936)
- Laísa S. Umpierrez (ORCID: https://orcid.org/0000-0002-5548-7878)
- Maral J. Korkozian
- Jonathon C. Arnold
Institutions
- The University of Sydney (AU)
- Macquarie University (AU)
Publication Details
- Journal
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Published
- 2026-01-26
- DOI
- https://doi.org/10.1016/j.pnpbp.2026.111629
- Primary Topic
- Cannabis and Cannabinoid Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00