Cannabidiol inhibits priming-induced reinstatement of methamphetamine in REM sleep deprived rats

Abstract

Methamphetamine (METH) is a widely abused and a severely addictive psychostimulant. Relapse is the main cause of concern when treating addiction. It could manifest after a long period of abstinence. Previous studies showed that there is a strong connection between sleep impairment and relapse. Also, it has been reported that cannabidiol might be a potential treatment for drug craving and relapse. In this study, we used conditioned place preference (CPP) to investigate whether Cannabidiol (CBD), a phytocannabinoid, can prevent METH-induced reinstatement in Rapid Eye Movement Sleep Deprived (RSD) rats. In order to induce CPP, the animals were given METH (1mg/kg; sc) for five days. The effective priming dose of METH (0.5mg/kg, sc) reinstated the extinguished METH-induced CPP. In order to investigate the effect of RSD on METH-induced reinstatement, we used the inverted flowerpot technique to deprive the rats of REM sleep. We found that 24h-RSD could facilitate priming-induced reinstatement of METH. In addition to this, the ICV administration of CBD 10μg/5μl could suppress the METH-induced reinstatement even in RSD rats. In conclusion, the administration of CBD 10μg/5μl effectively prevents METH-induced CPP, even in a condition of stress. CBD can be considered an agent that reduces the risk of the relapse; however, this requires more investigation.