Modulatory role of asymmetric dimethylarginine (ADMA) in cannabinoid tolerance and dependence.

Numerous studies have shown that opioids and cannabinoids share some pharmacological properties. Accordingly, similarly to opioids, tolerance and dependence develops after chronic use of cannabinoids. Nitric oxide (NO) has been shown to play important roles both in opioid- and cannabinoid-induced tolerance and dependence. The endogenous nitric oxide synthase (NOS) inhibitor, ADMA, levels have been shown to elevate, and L-arginine/ADMA ratio has been shown to reduce in many cardiovascular/metabolic disorders. Recently, ADMA has also been proposed as a modulator of nociception in opiate tolerance and dependence. Taken together, we hypothesized that ADMA and/or L-arginine/ADMA ratio may play a modulatory role in tolerance and dependence to cannabinoids.