Present address: Laboratori de Neurofarmacologia, Facultat de Ciencies de la Salud i de la Vida, Universitat Pompeu Fabra, C/Doctor Aiguader 80, 08003-Barcelona, Spain.
Δ9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect
Article first published online: 20 DEC 2001
European Journal of Neuroscience
Volume 13, Issue 9, pages 1816–1824, May 2001
How to Cite
Valverde, O., Noble, F., Beslot, F., Daugé, V., Fournié-Zaluski, M.-C. and Roques, B. P. (2001), Δ9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect. European Journal of Neuroscience, 13: 1816–1824. doi: 10.1046/j.0953-816x.2001.01558.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received 9 June 2000, revised 8 January 2001, accepted 6 March 2001
Recent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Δ9-tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant-like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism. This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Δ9-tetrahydrocannabinol increased the release of Met-enkephalin-like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo[3H]diprenorphine binding to opioid receptors in total mouse brain. The repetitive pretreatment during 3 weeks of Δ9-tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone-induced withdrawal syndrome. However, this repetitive administration of Δ9-tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm. Taken together, these behavioural and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.