Neuroscience Forefront ReviewCannabinoid and opioid interactions: Implications for opiate dependence and withdrawal
Section snippets
Background
Overall, illicit drug abuse in the United States exceeded $180 billion in 2008 according to the National Institutes of Health. Abuse of heroin and prescription opioids have long constituted a significant economic burden to society both through the direct and indirect consequences of illicit opioid use. These costs include not only direct medical expenses, but also the costs of criminal activities associated with drug acquisition, social welfare, secondary medical issues associated with high-risk
Clinical presentation and management
Abstinence following chronic exposure to opiates is accompanied by a pronounced syndrome of aversive physical and emotional symptoms. Characteristic signs of opiate withdrawal include yawning, rhinorrhea, perspiration, dilated pupils, anxiety and restlessness, nausea and vomiting, diarrhea, increased heart rate or blood pressure, as well as a host of flu-like symptoms such as chills, joint and muscle aches, and increased body temperature (Jasinski, 1981, Gossop, 1988, Farrell, 1994, Wesson and
The endocannabinoid (EC) system
Through significant advances in our understanding of the cannabinoid system in recent years, we now understand that the endogenous cannabinoid system—or EC system—is the primary regulator of cannabinoid functions in the brain. The EC system has been implicated in a variety of physiological functions due to abundant expression of its receptors and endogenous ligands in the central nervous system (Herkenham et al., 1991, Mackie, 2005b, Mackie, 2008). The EC consists of receptors, ligands and
Cannabinoid–opioid interactions
Opioid and cannabinoid receptors are major targets for many drugs of abuse and widely-used analgesics. These receptor systems are known to mediate common signaling pathways central to clinical issues of tolerance, dependence and addiction (Manzanares et al., 1999, Pasternak, 2005, Demuth and Molleman, 2006). Drugs that target both the CB1r and MOR systems possess shared pharmacological profiles. Agonists of both receptor types have been shown to cause antinociception, sedation, hypotension,
Cannabinoid-induced decreases in opiate withdrawal expression
In the area of therapeutic utility, cannabis can be recommended as a palliative medical alternative for patients with multiple sclerosis and spinal cord problems where it has been shown to alleviate pain, muscle spasms and convulsions. In addition, it can be recommended to cancer and AIDS patients in order to prevent vomiting and nausea, which result as side effects of chemotherapy, radiation therapy and antiretroviral medications. It also stimulates appetite in people who suffer from this
Conclusions
Opioid dependence and withdrawal are complex biological processes that appear to be subject to the influence of cannabinoids. The findings from basic and pre-clinical studies in rodent models highlight several potential mechanisms through which cannabinoids may modulate the phenomenon of opioid withdrawal, and call attention to the importance of cannabinoid–opioid interactions within noradrenergic brain circuits such as the coeruleo-cortical pathway. Preclinical studies that continue to explore
Acknowledgements
This study was supported by Grants from National Institutes of Health NIDA DA020129 and DA009082 to E.J.V.B. and F31023755 to J.L.S.
References (257)
- et al.
Opiate withdrawal increases glutamate and aspartate efflux in the locus coeruleus: an in vivo microdialysis study
Brain Res
(1994) - et al.
Brain norepinephrine rediscovered in addiction research
Biol Psychiatry
(2008) - et al.
Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology
Prog Brain Res
(1991) - et al.
The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes
Brain Res Brain Res Rev
(2003) - et al.
Functionally selective cannabinoid receptor signalling: therapeutic implications and opportunities
Biochem Pharmacol
(2010) - et al.
Neuroendocrine pharmacology of stress
Eur J Pharmacol
(2003) - et al.
Direct intra-accumbal infusion of a beta-adrenergic receptor antagonist abolishes WIN 55,212-2-induced aversion
Neurosci Lett
(2011) Synergistic interactions between cannabinoid and opioid analgesics
Life Sci
(2004)- et al.
Delta 9-tetrahydrocannabinol increases proopiomelanocortin gene expression in the arcuate nucleus of the rat hypothalamus
Eur J Pharmacol
(1997) - et al.
Time-dependent differences of repeated administration with delta9-tetrahydrocannabinol in proenkephalin and cannabinoid receptor gene expression and G-protein activation by mu-opioid and CB1-cannabinoid receptors in the caudate-putamen
Brain Res Mol Brain Res
(1999)