What drug is enjoyable and, under some circumstances, might actually be good for your brain? Can smoking this substance prevent age-related memory loss, for example? To answer these and similar questions, I turn now to a neurotransmitter system in the brain that was discovered through the use of one of the most common drugs in our history. This system may not have the most familiar of names — endogenous cannabinoid neurotransmitter — but the drug that tells us most about its function is certainly a household word: marijuana. Indeed, few drugs have the kind of colorful history that marijuana has achieved. Thus, before examining the neurotransmitter that it affects, let’s look briefly at the story of the drug itself.
Among species of marijuana plants, Cannabis indica is the one grown principally for its psychoactive resins. It is likely a shorter, bushier version of the Cannabis sativa, which is used primarily for its fibers to make rope. Both plants, like catnip, contain active ingredients belonging to a family of compounds called terpenes, of which the primary psychoactive terpene is thought to be concentrated in the plants’ resin as delta-9 tetrahydrocannabinol (THC). Initially investigated more than 100 years ago by two chemists, the Smith Brothers (William and Andrew) of later cough-drop fame, the plants contain approximately 50 cannabinoid-based compounds, with 4 major cannabinoids: trans-delta-9-THC and delta-8-THC, cannabidiol (the second most abundant psychoactive ingredient after THC), and cannabinol, which may be a decomposition product of THC that accumulates as cannabis samples age. After ingestion, the trans-delta-9-THC is converted in the liver to 11-hydroxy THC, which is equally potent and psychoactive.
Probably the oldest reference to the cannabis plant, in a pharmacy book from 2737 B.C., is related to its use as a medicine. The Chinese emperor Shen Nung (the Divine Farmer) referred to it as the “liberator of sin” and recommended it for the treatment of “female weakness,” gout, rheumatism, malaria, constipation, and absent-mindedness. By 1000 B.C., its medicinal use, as indicated by available writings, had spread to India; by 500 B.C., it was familiar to the ancient Greeks.
The earliest reference to the use of cannabis as an inebriant was in 430 B.C., when the Greek historian Herodotus of Halicarnassus wrote that the Scythians burned the seeds and inhaled the smoke to induce intoxication during funerals. The plant is also mentioned several times (as “kaneh-bosem,” ) in the Old Testament (as Yahweh’s instruction to Moses in Exodus 30:23) as a bartering material, incense, and an ingredient in holy anointing oil; it was likely used by the high priests of the temple as well as by Jesus. At that time in history, the word messiah simply meant “the anointed one.” Use of the plant as an inebriant spread to the Muslim world and North Africa by 1000 A.D. and became epidemic by the 12th century. The exploring Spaniards likely brought kanehbos, by now probably pronounced as cannabis, to the New World in about 1545.