Cannabidiol enhanced the development of sensitization to the expression of methamphetamine-induced conditioned place preference in male rats

Cannabis and ecstasy are illicit substances, and currently, there are no approved treatments for methamphetamine (METH) use disorder. Some studies have proposed that cannabidiol (CBD) decreases the motivation for METH seeking, but reports indicate that the therapeutic benefits are only for heroin. Here, we studied the interaction between CBD and METH during the sensitization phase on the rewarding effect of METH, using the conditioned place preference (CPP) paradigm to measure possible alterations in sensitivity. Our data showed that i. p. injection of METH created METH-induced CPP at two of the highest applied doses (1 and 2 mg/kg), and injection of METH during the sensitization period caused an establishment of METH-induced CPP at lower doses (0.25 and 0.5 mg/kg). Data also revealed that i. c.v. administration of CBD during the sensitization phase, shifted the establishment of METH-induced CPP toward a lower dose (0.5 mg/kg). Concurrent administration of CBD (10 μg/5 μl, i. c.v.) and METH (0.25 mg/kg, i. p.) during sensitization phase established METH-induced CPP with sub-threshold doses of METH (0.125, 0.25, and 0.5 mg/kg). Our results suggest the involvement of CBD and prior exposure to METH in creating sensitization to METH CPP. •METH pre-treatment during 3-day sensitization period increased the METH reward-associated behaviors.•ICV application of cannabidiol during the sensitization period potentiated the METH-induced CPP.•Concurrent administration of low doses of CBD and METH during the sensitization period induced METH-CPP.