Cannabidiol but not cannabidiolic acid reduces behavioural sensitisation to methamphetamine in rats, at pharmacologically effective doses

Abstract
Rationale Cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive components of the cannabis plant. CBD
has been well characterised to have anxiolytic and anticonvulsant activity, whereas the behavioural efects of CBDA are
less clear. Preclinical and clinical data suggests that CBD has antipsychotic properties and reduces methamphetamine self administration in rats. An animal model that is commonly used to mimic the neurochemical changes underlying psychosis
and drug dependence is methamphetamine (METH) sensitisation, where repeated administration of the psychostimulant
progressively increases the locomotor efects of METH.
Objective The aim of this study was to determine whether CBD or CBDA attenuate METH-induced sensitisation of loco motor hyperactivity in rats.
Methods Eighty-six male Sprague Dawley rats underwent METH sensitisation protocol where they were subjected to daily
METH (1 mg/kg on days 2 and 8, 5 mg/kg on days 3–7; i.p.) injections for 7 days. After 21 days of withdrawal, rats were
given a prior injection of CBD (0, 40 and 80 mg/kg; i.p.) or CBDA (0, 0.1, 10 and 1000 µg/kg; i.p.) and challenged with
acute METH (1 mg/kg; i.p.). Locomotor activity was then measured for 60 min.
Results Rats displayed robust METH sensitisation as evidenced by increased locomotor activity to METH challenge in
METH-pretreated versus SAL-pretreated rats. CBD (40 and 80 mg/kg) reduced METH-induced sensitisation. There was no
efect of any CBDA doses on METH sensitisation or acute METH-induced hyperactivity.
Conclusion These results demonstrate that CBD, but not CBDA, reduces METH sensitisation of locomotor activity in rats
at pharmacologically efective doses, thus reinforcing evidence that CBD has anti-addiction and antipsychotic properties