Cellular and behavioral basis of cannabinioid and opioid interactions: Implications for opioid dependence and withdrawal.

The brain's endogenous opioid and endocannabinoid systems are neuromodulatory of synaptic transmission, and play key roles in pain, memory, reward, and addiction. Recent clinical and pre-clinical evidence suggests that opioid use may be reduced with cannabinoid intake. This suggests the presence of a functional interaction between these two systems. Emerging research indicates that cannabinoids and opioids can functionally interact at different levels. At the cellular level, opioid and cannabinoids can have direct receptor associations, alterations in endogenous opioid peptide or cannabinoid release, or post-receptor activation interactions via shared signal transduction pathways. At the systems level, the nature of cannabinoid and opioid interaction might differ in brain circuits underlying different behavioral phenomenon, including reward-seeking or antinociception. Given the rising use of opioid and cannabinoid drugs, a better understanding of how these endogenous signaling systems interact in the brain is of significant interest. This review focuses on the potential relationship of these neural systems in addiction-related processes.