Opioid addiction, a chronic relapsing disorder, continues to impose great health and economic burden on our society. America’s opioid crisis has become an epidemic due in part to the lack of effective treatments for the negative physical and emotional states suffered by the individuals during withdrawal from chronic opioid use. These symptoms might be major contributing factors to relapse. Recently, Cannabis and cannabinoids have emerged as a potential therapeutic strategy in the treatment of opioid addiction. This review differs from many other reports in the field by focusing on the possible mechanisms underlying the effects of cannabinoids on the negative physical and emotional states induced by opioid withdrawal. We start by briefly outlining the current opioid crisis and how both opioids and cannabinoids affect the mammalian central nervous system (CNS). Next, we present findings that illustrate how cannabinoids may be used to enhance opioid analgesia and to mitigate opioid withdrawal syndromes. Finally, we summarize these findings and propose directions for future research.