by Alyson Martin and Nushin Rashidian
New Press, 264 pp., $17.95 (paper)In the summer of 2006, a young scientist from Israel joined my laboratory. He came to learn how viruses attack cells, a major focus of my research program. And I looked forward to drawing on his expertise in an emerging area of science that intrigued me: the biological effects of cannabinoids, the active chemical compounds in the marijuana plant. The Israeli researcher had trained at Jerusalem’s Hebrew University with Professor Raphael Mechoulam, a chemist credited with the discovery in 1964 of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana. Mechoulam later characterized cannabidiol (CBD), a related substance plentiful in the plant, as distinct from THC in that it had no discernible effects on mood, perception, wakefulness, or appetite.1
The work of the young scientist proved productive. In short order, he tested the effects of several cannabinoids on a herpes virus that promotes the development of Kaposi’s sarcoma, a disfiguring and sometimes fatal tumor among people with impaired immunity, like those with AIDS. It turned out that CBD, the plentiful, nonpsychoactive compound, could switch off the malignant effects of the virus.2Scientists in my department also found that cannabinoids could alter how white blood cells migrated in response to physiological stimuli, a key aspect of immune defense; other research teams found that THC inhibited the growth and spread of lung cancer and CBD of breast cancer in laboratory models.3 Clearly, chemicals in the plant could have diverse and potent effects on normal and malignant cells.
But what I found most fascinating was that we have a natural or “endogenous” cannabinoid system. In 1988, researchers identified a specific docking site, or receptor, on the surface of cells in the brain that bound THC. This first receptor was termed cannabinoid receptor 1, or CB1.4 Five years later, a second receptor for cannabinoids, CB2, was found.5 This latter docking protein was less plentiful in the central nervous system but richly present on white blood cells. Again, it was Raphael Mechoulam who discovered the first endogenous cannabinoid, a fatty acid in the brain, which he termed “anandamide.” (The name is derived from the Sanskrit word ananda, which means “bliss.”) When anandamide attached to CB1 it triggered a cascade of biochemical changes within our neurons.6
Other endogenous cannabinoids were later identified. This makes evolutionary sense, since the CB1 and CB2 receptors would not be present on our cells if we did not normally make molecules to dock on them. The physiological ramifications of endogenous cannabinoids appeared quite broad; their most impressive effects were related to perception of and response to pain.
Cannabis is one of the oldest psychotropic drugs in continuous use. Archaeologists have discovered it in digs in Asia that date to the Neolithic period, around 4000 BCE. The most common species of the plant is Cannabis sativa, found in both tropical and temperate climates. Marijuana is a Mexican term that first referred to cheap tobacco and now denotes the dried leaves and flowers of the hemp plant. Hashish is Arabic for Indian hemp and refers to its viscous resin. An emperor of China, Shen Nung, also the discoverer of tea and ephedrine, is held to be among the first to report on therapeutic uses of cannabis in a medicinal compendium that dates to 2737 BCE. In 1839, William O’Shaughnessy, a British doctor working in India, published a paper on cannabis as an analgesic and appetite stimulant that also tempered nausea, relaxed muscles, and might ameliorate epileptic seizures. His observations led to widespread medical use of cannabis in the United Kingdom; it was prescribed to Queen Victoria for relief of menstrual discomfort.7
The cannabis plant contains some 460 compounds, including more than 60 cannabinoids. . .