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Synergistic interactions of endogenous opioids and cannabinoid systems.
Brain Res. 1999 Nov 27; 848(1-2):183-90.BR

Abstract

Cannabinoids and opioids are distinct drug classes historically used in combination to treat pain. Delta(9)-THC, an active constituent in marijuana, releases endogenous dynorphin A and leucine enkephalin in the production of analgesia. The endocannabinoid, anandamide (AEA), fails to release dynorphin A. The synthetic cannabinoid, CP55,940, releases dynorphin B. Neither AEA nor CP55,940 enhances morphine analgesia. The CB1 antagonist, SR141716A, differentially blocks Delta(9)-THC versus AEA. Tolerance to Delta(9)-THC, but not AEA, involves a decrease in the release of dynorphin A. Our preclinical studies indicate that Delta(9)-THC and morphine can be useful in low dose combination as an analgesic. Such is not observed with AEA or CP55,940. We hypothesize the existence of a new CB receptor differentially linked to endogenous opioid systems based upon data showing the stereoselectivity of endogenous opioid release. Such a receptor, due to the release of endogenous opioids, may have significant impact upon the clinical development of cannabinoid/opioid combinations for the treatment of a variety of types of pain in humans.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Box 980613, Virginia Commonwealth University, Richmond, VA 23298-0613, USA. S.Welch@hsc.vcu.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10612710

Citation

Welch, S P., and M Eads. "Synergistic Interactions of Endogenous Opioids and Cannabinoid Systems." Brain Research, vol. 848, no. 1-2, 1999, pp. 183-90.
Welch SP, Eads M. Synergistic interactions of endogenous opioids and cannabinoid systems. Brain Res. 1999;848(1-2):183-90.
Welch, S. P., & Eads, M. (1999). Synergistic interactions of endogenous opioids and cannabinoid systems. Brain Research, 848(1-2), 183-90.
Welch SP, Eads M. Synergistic Interactions of Endogenous Opioids and Cannabinoid Systems. Brain Res. 1999 Nov 27;848(1-2):183-90. PubMed PMID: 10612710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic interactions of endogenous opioids and cannabinoid systems. AU - Welch,S P, AU - Eads,M, PY - 1999/12/29/pubmed PY - 2000/3/4/medline PY - 1999/12/29/entrez SP - 183 EP - 90 JF - Brain research JO - Brain Res VL - 848 IS - 1-2 N2 - Cannabinoids and opioids are distinct drug classes historically used in combination to treat pain. Delta(9)-THC, an active constituent in marijuana, releases endogenous dynorphin A and leucine enkephalin in the production of analgesia. The endocannabinoid, anandamide (AEA), fails to release dynorphin A. The synthetic cannabinoid, CP55,940, releases dynorphin B. Neither AEA nor CP55,940 enhances morphine analgesia. The CB1 antagonist, SR141716A, differentially blocks Delta(9)-THC versus AEA. Tolerance to Delta(9)-THC, but not AEA, involves a decrease in the release of dynorphin A. Our preclinical studies indicate that Delta(9)-THC and morphine can be useful in low dose combination as an analgesic. Such is not observed with AEA or CP55,940. We hypothesize the existence of a new CB receptor differentially linked to endogenous opioid systems based upon data showing the stereoselectivity of endogenous opioid release. Such a receptor, due to the release of endogenous opioids, may have significant impact upon the clinical development of cannabinoid/opioid combinations for the treatment of a variety of types of pain in humans. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/10612710/Synergistic_interactions_of_endogenous_opioids_and_cannabinoid_systems_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(99)01908-3 DB - PRIME DP - Unbound Medicine ER -