Cannabidiol reverses fentanyl-induced addiction and modulates neuroinflammation

Introduction: Fentanyl and non-pharmaceutical fentanyl use have been the leading causes of opioid-induced death worldwide. Being 50 times stronger than heroin and 100 times stronger than morphine, fentanyl is a potent opioid with overdoses causing over 250,000 deaths since 2018 in the US alone. The treatment of fentanyl addiction is a complex process and a clinical challenge. There is a dire need to find other innovative and alternative modalities in the fight against fentanyl crisis. Increasing evidence suggests a correlation between neuroinflammation and symptoms of drug abuse, opening up the possibility of immunoregulatory agents as therapy for fentanyl addiction as well as a other opioid-induced addiction. Cannabidiol (CBD) is a non-opioid, relatively safe, non-psychoactive phyto-cannabinoid produced by cannabis plants. Importantly, recent reports have documented benefits of CBD in the treatment and management of complications related to opioid withdrawal. We investigated if inhaled CBD could reverse the fentanyl addiction and whether the CBD treatment could ameliorate the addiction symptoms by regulating neuroinflammatory signals and re-establishing the homeostasis in CNS. Method: We used a fentanyl-induced conditioned place preference (CPP) model in mouse to test whether inhaled CBD could reverse the fentanyl addiction and ameliorate the adversarial symptoms. By employing a combination of flow cytometry as well as behavioral tests, we further assessed the impact of fentanyl addiction on cells and neuroinflammatory signals in CNS and we measured the effects of CBD in the treatment of addiction symptoms and inflammatory signals. Results: Our findings suggest that CBD inhalation could be used effectively in the treatment of fentanyl addiction. CBD mitigated the excessive fentanyl-induced neuroinflammatory responses and decreased cellular stress and senescence. Conclusion: inhaled CBD could alleviate the fentanyl addiction and regulate neuroinflammatory responses. This novel approach is non-invasive, accessible, effective, and warrants further, translational and research.