The unique pharmacological properties of the preparations of Cannabis sativa plant have been recognized for thousands of years. There is evidence that Cannabis was cultivated in China as early as 4,000 B.C. for multiple purposes, including its use as a food and medicinal agent. In India, the use of Cannabis for medicinal purposes began approximately 1,000 BC. Cannabis extracts were used by these cultures to reduce pain, seizures, anxiety, mania and muscle spasms, and to stimulate appetite.
The introduction of Cannabis to Western medicine occurred in the mid-19th century through the writings of William B. O'Shaughnessy, an Irish physician, who became aware of indigenous use of Cannabis plant during his service under the British in India. O'Shaughnessy reported the beneficial therapeutic effects of Cannabis for convulsions and muscular spasms caused by rabies and tetanus. Jacques-Joseph Moreau, a French psychiatrist, also discovered Cannabis during his travel in the Far East and studied its psychological effects in himself and his students. Moreau published his observations regarding the use of Cannabis as an experimental psychotomimetic in Du Hachisch et de l'Alientation Mentale: Etudes Psychologiques (1840).
The beginning of the modern era of cannabinoid pharmacology is ascribed to the 1964 publication by Gaoni and Mechoulam of the structure of the psychoac-tive chemical in Cannabis, A9-tetrahydrocannabinol (THC), together with a method for its isolation from the plant. A body of scientific literature was published between 1965 and 1986 that focused on the pharmacological and cellular effects of THC. Among the important contributions of this era was the codification of a tetrad of THC effects in rodents (analgesia, reduction in body temperature, catalepsy, and spontaneous activity) that was used to characterize the cannabinoid activity of an extensive library of THC structural analogs. Levonantra-dol was found to mimic the effects of THC, although with higher potency, it was used to provide the first biochemical evidence that THC-like molecules inhibit adenylyl
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