Introduction: The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose deaths are at an all-time high, and relapse remains pervasive.Discussion: Although there are a number of FDA-approved opioid replacement therapies and maintenance medications to help ease the severity of opioid withdrawal symptoms and aid in relapse prevention, these medications are not risk free nor are they successful for all patients. Furthermore, there are legal and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone or buprenorphine, and the demand for these services far outweighs the supply and access. To fill the gap between efficacious OUD treatments and the widespread prevalence of misuse, relapse, and overdose, the development of novel, alternative, or adjunct OUD treatment therapies is highly warranted. In this article, we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight knowledge gaps and discuss cannabis' potential to prevent opioid misuse (as an analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the likelihood of relapse.Conclusion: The compelling nature of these data and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct or alternative treatment for OUD.

Over the last few years, there has been a growing tendency for opioid addicts to abuse multiple drugs, although many patients are in substitution therapy with methadone. Abuse of multiple drugs leads to a more complicated withdrawal syndrome; it is therefore necessary to investigate new drug strategies as a treatment for detoxification. Buprenorphine appears to be an effective and safe drug in opioid-addicted patient detoxification. In this study, we have compared the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid dependence and were included in this study. All patients abused various additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non-completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine, but the difference in the dropout rate was not significant. However, patients with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms after the first two weeks of treatment. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than methadone/carbamazepine in detoxification strategies for opioid addict with additional multiple drug abuse. No severe side effects occurred during treatment in either group.

Introduction: An escalating number of fatalities resulting from accidental opioid overdoses typically attributed to respiratory depression continue to define the opioid epidemic. Opioid respiratory depression results from a decrease in reflexive inspiration within the preBö tzinger complex in the brainstem. Objective: Cannabinoid receptor agonism is reported to enhance opioid analgesia, yet whether cannabinoids enhance or inhibit opioid-induced respiratory depression is unknown. Methods: Studies herein sought to define the roles of cannabinoid-1 receptor (CB1R) and cannabinoid-2 receptor (CB2R) on respiratory depression using selective agonists alone and in combination with morphine in male mice. Results: Using whole body plethysmography, the nonselective CB1R and CB2R agonist (D 9-tetrahydrocannabinol) and the CB1R synthetic cannabinoid, AM356, induced respiratory depression, whereas the well-published selective CB2 agonist, JWH 133, and the novel CB2 agonist (AM2301) did not. Moreover, a selective CB2R agonist (AM2301) significantly attenuated morphine sulfate-induced respiratory depression. Conclusion: Notably, findings suggest that attenuation of opioid-induced respiratory depression relies on CB2R activation, supporting selective CB2R agonism as an opioid adjunct therapy.

Twenty-six in-patients with Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were selected at random to receive either a combination of an 11-day low-dose buprenorphine and a 14-day carbamazepine regimen (n = 14) or a combination of an 11-day methadone and a 14-day carbamazepine regimen (n = 12) in a double-blind, randomized 14-day in-patient detoxification treatment. Patients with buprenorphine and carbamazepine showed a significantly better psychological state after the first and second weeks of treatment. Above all, the buprenorphine-treated patients demonstrated a less marked tiredness, sensitiveness and depressive state as well as a more prominent elevated mood during the detoxification process. Seven non-completers (after 7 days: four of 12 = 33.3%; after 14 days: seven of 12 = 58.3%) were treated with methadone and carbamazepine and five non-completers (after 7 days: two of 14 = 14.3%; after 14 days: five of 14 = 35.7%) received buprenorphine and carbamazepine. The difference in the overall dropout rate after day 14 was not significant. The present study supports the hypothesis that the combination of buprenorphine and carbamazepine leads to a better clinical outcome than does a combination of methadone and carbamazepine in the detoxification of opioid addicts with additional multiple drug abuse. The buprenorphine and carbamazepine-regimen provides a more effective short-term relief of affective disturbances than does methadone and carbamazepine. No severe side effects occurred during the treatment period in both groups.

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