Cannabinoid receptors and pain.

Marihuana Chemistry: Recent advances in cannabinoid chemistry open the area to more sophisticated biological research.

A sample of hashish was extracted consecutively with petroleum ether, benzene, and methanol. When tested intravenously in monkeys only the petroleum-ether fraction was active. This material was further fractionated. The only active compound isolated was Delta(1)-tetrahydrocannabinol. Cannabinol, cannabidiol, cannabichromene, cannabigerol, and cannabicyclol when administered together with Delta(1)-tetrahydrocannabinol do not cause a change in the activity of the latter, under the experimental conditions used. These results provide evidence that, except for Delta(1)-tetrahydrocannabinol, no other major, psychotomimetically active compounds are present in hashish.

http://science.sciencemag.org/content/sci/169/3945/611.full.pdf

Chemical Basis of Hashish Activity

Cannabinoids are antinociceptive in animal models of acute, tissue injury-, and nerve injury-induced nociception. This review examines the biology of endogenous cannabinoids (endocannabinoids) and behavioral, neurophysiological, and neuroanatomical evidence supporting the notion that cannabioids play a role in pain modulation. Behavioral pharmacological approaches, in conjunction with the identification and quantification of endocannabinoids through the use of liquid and gas chromatography mass spectrometry, have providedinsight into the functional roles of endocannabinoids in pain modulation. Here we examine the distribution of cannabinoid receptors and endocannabinoid-hydrolyzing enzymes within pain modulatory circuits together with behavioral, neurochemical, and neurophysiological studies that suggest a role for endocannabinoid signaling in pain modulation. This review will provide a comprehensive evaluation of the roles of the endocannabinoids 2-arachidonoyl-glycerol and anandamide in stress-induced analgesia. These findings provide a functional framework with which to understand the roles of endocannabinoids in nociceptive processing at the supraspinal level.

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Endocannabinoid mechanisms of pain modulation.

A large body of literature indicates that cannabinoids suppress behavioral responses to acute and persistent noxious stimulation in animals. This review exax mines neuroanatomical, behavioral, and neurophysiological evidence supporting a role for cannabinoids in suppressing pain at spinal, supraspinal, and peripheral levels. Localization studies employing receptor binding and quantitative autoradiography, immunocytochemistry, and in situ hybridization are reviewed to examine the distribution of cannabinoid receptors at these levels and provide a neuroanatomical framework with which to understand the roles of endogenous cannabinoids in sensory processing. Pharmacological and transgenic approaches that have been used to study cannabinoid antinociceptive mechanisms are described. These studies provide insight into the functional roles of cannabinoid CB1 (CB1R) and CB2 (CB2R) receptor subtypes in cannabinoid antinociceptive mechanisms, as revealed in animal models of acute and persistent pain. The role of endocannabinoids and related fatty acid amides that are implicated in endogenous mechanisms for pain suppression are discussed. Human studies evaluating therapeutic potential of cannabinoid pharmacotherapies in experimental and clinical pain syndromes are evaluated. The potential of exploiting cannabinoid antinociceptive mechanisms in novel pharmacotherapies for pain is discussed.

Mechoulam R

Papers

Pharmacological effects of two active constituents of marihuana.