Cannabidiol does not display drug abuse potential in mice behavior

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Recent evidence suggests that cannabidiol (CBD) may be useful for the treatment of different neuropsychiatric disorders. However, some controversy regarding its profile as a drug of abuse hampers the further development of basic and clinical studies. In this study, the behavioral profile of CBD as a potential drug of abuse was evaluated in C57BL/6J mice. Reinforcing properties of CBD (15, 30, and 60 mg/kg; i.p.) were assessed using the conditioned place preference (CPP) paradigm. Spontaneous withdrawal symptoms and motor activity in the open field were examined 12 h after the last CBD administration (30 mg/kg/12 h, i.p., 6 days). CBD plasma concentrations were measured at 2, 4, 8, 12, and 24 h after the administration of CBD (30 mg/kg, i.p.). Furthermore, an oral CBD self-administration paradigm (50 mg/kg; CBD water-soluble 1.2 mg/mL) was performed to evaluate whether this drug produced any effects on motivation compared with a non-reinforcing substance (water). We found that CBD failed to induce CPP, withdrawal symptoms, or altered motor behavior 12 h after its administration. At that time, only traces of CBD were detected, ensuring that the lack of alterations in somatic signs and locomotor activity was not due to residual drug in plasma. Interestingly, mice displayed similar motivation and consumption of CBD and water. Taken together, these results show that CBD lacks activity as a drug of abuse and should stimulate the development of the basic and clinical studies needed to elucidate its potential therapeutic use for the treatment of neuropsychiatric and drug use disorders.

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The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the “Instituto de Salud Carlos III” (RETICS, RD12/0028/0019), “Plan Nacional Sobre Drogas” (PNSD 2016/016), and “Ministerio de Economía y Competitividad” (FIS, PI14/00438) to JM. AVM is a predoctoral fellow supported by “Plan Nacional Sobre Drogas” (PNSD 2016/016).

Author contributions

AVM, MSGG, JMR, and CMN carried out the experimental procedures, undertook the statistical analysis, and took part in the interpretation of the results obtained. AVM, MSGG, JMR, CMN, and FN wrote the first draft of the manuscript. MSGG and JM designed the study, wrote the protocol, interpreted the results, and approved the final manuscript.

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Correspondence to Jorge Manzanares.

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  • cannabidiol
  • cannabinoid receptor
  • drug abuse
  • conditioned place preference
  • oral CBD self-administration
  • withdrawal syndrome

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