Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

Abstract

Although the first studies regarding the endogenous opioid system and addiction were published during the 1940s, addiction and cannabinoids were not addressed until the 1970s. Currently, the number of opioid addiction studies indexed in PubMed-Medline is 16 times greater than the number of cannabinoid addiction reports. More recently, functional interactions have been demonstrated between the endogenous cannabinoid and opioid systems. For example, the cannabinoid brain receptor type 1 (CB1) and mu opioid receptor type 1 (MOR1) co-localize in the same presynaptic nerve terminals and signal through a common receptor-mediated G-protein pathway. Here, we review a great variety of behavioral models of drug addiction and alcohol-related behaviors. We also include data providing clear evidence that activation of the cannabinoid and opioid endogenous systems via WIN 55,512-2 (0.4-10 mg/kg) and morphine (1.0-10 mg/kg), respectively, produces similar levels of relapse to alcohol in operant alcohol self-administration tasks. Finally, we discuss genetic studies that reveal significant associations between polymorphisms in MOR1 and CB1 receptors and drug addiction. For example, the SNP A118G, which changes the amino acid aspartate to asparagine in the MOR1 gene, is highly associated with altered opioid system function. The presence of a microsatellite polymorphism of an (AAT)n triplet near the CB1 gene is associated with drug addiction phenotypes. But, studies exploring haplotypes with regard to both systems, however, are lacking.

∆9-Tetrahydrocannabinol Decreases NOP Receptor Density and mRNA Levels in Human SH-SY5Y Cells

“…Our results demonstrate that Δ 9 -THC is able to modulate NOP receptor density; these data are in agreement with previous studies showing the interaction between the cannabinoid and opioid system (Cichewicz 2004;Parolaro et al 2005;López-Moreno et al 2010;Parolaro et al 2010). Fig.…”

“…Endogenous opioid and cannabinoid systems interact in a variety of physiological processes such as nociception, anxiety, and immuno-mediate responses (Parolaro et al 2010). They also display functional interactions in the pathogenetic mechanisms underlying drug abuse and addiction (i.e., reward, tolerance, and abstinence syndrome) (Navarro et al 2001;López-Moreno et al 2010;Parolaro et al 2010).…”

Propofol increases μ-opioid receptor expression in SH-SY5Y human neuroblastoma cells

“…Stimulation of the activity of distinct components of the endogenous opioid system by opioids or by other drugs of abuse, may mediate some of their reinforcing effects (17). Recent studies suggest that MOR and µ-opioid peptides are involved in the addictive processes induced by cannabinoids, nicotine and alcohol (18)(19)(20). Our findings suggest that by increasing MOR expression in neuronal cells, propofol has the potential to enhance the activity of the endogenous µ-opioid system and thus has the potential for abuse.…”

The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis

“…19 There is evidence indicating that microsatellites can affect transcription efficacy and gene function. 20 This polymorphism has been related to different disorders, such as drug abuse, [21][22][23][24] Parkinson's disease, 25 anorexia nervosa 26 and schizophrenia, 27,28 with variable results. The long alleles of (AAT) n repeat polymorphism of the CNR1 gene have been recently reported to represent a genetic risk factor for the primary progressive form of MS, 29 but their role in disease progression in relapsing-remitting MS (RRMS) has never been explored.…”