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Less than 20 years ago the field of cannabis and the cannabinoids was still considered a minor, somewhat quaint, area of research. A few groups were active in the field, but it was already being viewed as stagnating. The chemistry of cannabis was well known, ∆9-tetrahydrocannabinol (∆9-THC), identified in 1964, being the only major psychoactive constituent and cannabidiol, which is not psychoactive, possibly contributing to some of the effects. These cannabinoids and several synthetic analogs had been thoroughly investigated for their pharmacological effects. Their mode of action was considered to be non-specific. The reasons for this assumption were both technical and conceptual. On the technical side, it had been shown that THC was active in both enantiomeric forms (though with a different level of potency) and this observation was incompatible with action on biological substrates—a receptor, an enzyme, an ion channel—which react with a single stereoisomer only. The conceptual problem related to THC activity. This had been pointed out by several highly regarded research groups that had shown that many of the effects seen with cannabinoids were related to those of biologically active lipophiles, and that many of the effects of THC, particularly chronic ones, were comparable to those seen with anaesthetics and solvents. The technical problems were eliminated when it was found, by several groups, that cannabinoid action is actually stereospecific andmost of the previouswork,which had pointed to a different conclusion, was based on insufficiently purified samples. The conceptual hurdle was overcome when Allyn Howlett’s group in 1988 brought out the first evidence that a specific cannabinoid receptor exists in the brain.

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