Elsevier

Neuroscience

Volume 248, 17 September 2013, Pages 637-654
Neuroscience

Neuroscience Forefront Review
Cannabinoid and opioid interactions: Implications for opiate dependence and withdrawal

https://doi.org/10.1016/j.neuroscience.2013.04.034Get rights and content

Highlights

  • Review of the problem of opioid dependence and withdrawal.

  • Review of cannabinoid effects on noradrenergic circuitry.

  • Review of cannabinoid opioid cross-talk.

  • Targeting cannabinoid opioid interactions in novel therapeutic approaches.

Abstract

Withdrawal from opiates, such as heroin or oral narcotics, is characterized by a host of aversive physical and emotional symptoms. High rates of relapse and limited treatment success rates for opiate addiction have prompted a search for new approaches. For many opiate addicts, achieving abstinence may be further complicated by poly-drug use and co-morbid mental disorders. Research over the past decade has shed light on the influence of endocannabinoids (ECs) on the opioid system. Evidence from both animal and clinical studies point toward an interaction between these two systems, and suggest that targeting the EC system may provide novel interventions for managing opiate dependence and withdrawal. This review will summarize the literature surrounding the molecular effects of cannabinoids and opioids on the locus coeruleus–norepinephrine system, a key circuit implicated in the negative sequelae of opiate addiction. A consideration of the trends and effects of marijuana use in those seeking treatment to abstain from opiates in the clinical setting will also be presented. In summary, the present review details how cannabinoid–opioid interactions may inform novel interventions in the management of 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.

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