Review
Pharmacological and biochemical interactions between opioids and cannabinoids

https://doi.org/10.1016/S0165-6147(99)01339-5Get rights and content

Abstract

Opioids and cannabinoids are among the most widely consumed drugs of abuse in humans. A number of studies have shown that both types of drugs share several pharmacological properties, including hypothermia, sedation, hypotension, inhibition of both intestinal motility and locomotor activity and, in particular, antinociception. Moreover, phenomena of cross-tolerance or mutual potentiation of some of these pharmacological effects have been reported. In recent years, these phenomena have supported the possible existence of functional links in the mechanisms of action of both types of drugs. The present review addresses the recent advances in the study of pharmacological interactions between opioids and cannabinoids, focusing on two aspects: antinociception and drug addiction. The potential biochemical mechanisms involved in these pharmacological interactions are also discussed together with possible therapeutic implications of opioid–cannabinoid interactions.

Section snippets

Common pharmacological properties of opioids and cannabinoids

Hypothermia, sedation, hypotension, inhibition of intestinal motility and motor depression are just some of the effects elicited by both opioids and cannabinoids1, 2. However, the most important interactions were found in antinociception1, 2, 3, 4, 5 and, to a lesser extent, in drug reinforcement6, 7, 8, 9, 10.

Biochemical mechanisms involved in opioid–cannabinoid interactions

Despite data that support an interaction between the opioid and the cannabinoid systems in antinociception and drug addiction, as well as in other less-studied pharmacological effects such as hypothermia2, the nature of such interactions remains unclear. Several authors have suggested that both drugs share common links in their molecular mechanisms of action, although this has been a matter of controversy. In this respect, it is important to consider that the nature of cannabinoid–opioid

Concluding remarks

According to the results discussed in this review, it appears that opioids and cannabinoids share a number of pharmacological actions that could be relevant in understanding the therapeutic potential of cannabinoids, particularly as analgesics. There is also an interconnected role for cannabinoid and opioid receptors in brain regions mediating addictive behaviours that might be of clinical interest. Although some hypotheses have been presented and discussed here on the basis that they are not

Chemical names

CP55940: (−)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol

SR141716A: N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)4-methyl-3-pyrazolecarboxamide

SR144528: N-([1s]-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide

WIN552122: r(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphtalenyl)methanone

Acknowledgements

The authors are indebted to all the researchers (M. Ruiz-Gayo, I. Reche, G. Vela and E. Ambrosio) who directly collaborated in the studies presented here, and to Dr J. M. Walker (Brown University) for critically reading the manuscript. J. Corchero is a predoctoral fellow and J. Romero a postdoctoral fellow, both supported by the Comunidad Autónoma de Madrid. J. Manzanares is a Senior Research Fellow supported by the Spanish Ministry of Education.

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