Cannabidiol enhances the antinociceptive effects of morphine and attenuates opioid-induced tolerance in the chronic constriction injury model

Author(s)

Jesus, Carlos Henrique Alves ; Ferreira, Matheus Vinicius ; Gasparin, Alexia Thamara ; Rosa, Evelize Stacoviaki ; Genaro, Karina ; Crippa, Jose Alexandre de Souza ; Chichorro, Juliana Geremias ; da Cunha, Joice Maria

• Document type: Journal article
• Source: Behavioural Brain Research; v. 435, p. 12-pg., 2022-08-26.

Abstract

Neuropathic pain (NP) is a complex health problem that includes sensorial manifestations such as evoked and ongoing pain. Cannabidiol (CBD) has shown potential in the treatment of NP and the combination between opioids and cannabinoids has provided promising results on pain relief. Thus, our study aimed to investigate the effect of treatment combination between CBD and morphine on evoked and ongoing pain, and the effect of CBD on morphine-induced tolerance in the model of chronic constriction injury (CCI) of the sciatic nerve in rats. Mechanical thresholds (i.e., evoked pain) were evaluated before and 7 days after surgery. We also employed a 4 -day conditioned place preference (CPP) protocol, to evaluate relief of ongoing pain (6-9 days after surgery). Treatment with morphine (2 and 4 mg/kg) or CBD (30 mg/kg) induced a significant antinociceptive effect on evoked pain. The combination of CBD (30 mg/kg) and morphine (1 mg/kg) produced an enhanced anti-nociceptive effect, when compared to morphine alone (1 mg/Kg). Treatment with morphine (1 and 2 mg/kg) or CBD (30 mg/kg) alone failed to induce significant scores in the CPP test. However, combined treatment of CBD (30 mg/kg) and morphine (1 mg/kg) provided significant positive scores, increased the number of entrances in the drug-paired chamber in the CPP test and did not alter locomotor activity in rats. Lastly, treatment with CBD partially attenuated morphine-induced tolerance. In summary, our results support the indication of CBD as an adjuvant to opioid therapy for the attenuation of NP and opioid-induced analgesic tolerance. (AU)

• FAPESP's process: 08/09009-2 - Crack/cocaine chronic use: dopamine transporters availability, genetic factors, and executive functioning
• Grantee: Acioly Luiz Tavares de Lacerda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/05416-4 - Experimental strategies in the context of COVID-19-induced anosmia: is neurodegeneration involved?
• Grantee: Alline Cristina de Campos
• Support Opportunities: Regular Research Grants