Martin A. Lee is the director of Project CBD, an educational service that focuses on cannabis science and therapeutics. He is the author of several books, including Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific, winner of the American Botanical Council’s James A. Duke Award for Excellence in Botanical Literature. Lee is also co-founder of the media research group FAIR (Fairness & Accuracy In Reporting) and the author of The Beast Reawakens and Acid Dreams: The CIA, the Sixties and Beyond.
Scientists are exploring various ways of targeting the endocannabinoid (eCB) system with synthetic drugs and isolates. Initial efforts focused on cannabinoid receptor activation or antagonism. Because direct, full-on stimulation of CB1 receptors in the brain may trigger undesirable psychoactivity, cannabinoid researchers are pursuing several strategies to deliver therapeutic benefits without conferring a marijuana-like high. These strategies include peripherally restricted CB1 agonists and antagonists that don’t cross the blood-brain barrier; selective CB2 agonists that only activate cannabinoid receptors outside the central nervous system; and allosteric modulators that can increase or decrease the efficacy of CB1 & CB2 receptor activation by endocannabinoids and plant cannabinoids. Researchers are also experimenting with synthetic compounds designed to modulate “endocannabinoid tone” without binding directly to cannabinoid receptors. Inhibitors of eCB-metabolizing enzymes (FAAH, MAGL) increase the levels of one or more endogenously released endocannabinoids at CB receptors. By targeting eCB transport molecules (fatty acid binding proteins), synthetic eCB reuptake inhibitors increase eCB levels in a manner that enhances eCB-induced protective effects. THC and CBD also function as endocannabinoid reuptake inhibitors, thereby boosting endogenous cannabinoid signaling. A comparison of the pros and cons of pharmaceutical isolates and artisanal cannabis suggests that vilifying either holistic herbal medicine or modern single-molecule medicine is not helpful. Preclinical research indicates that plant cannabinoids synergize favorably with conventional chemotherapies and radiation treatment. Patients are best served by having access to a wide range of cannabinoid-based therapeutic options. Regulatory policy should not privilege single-molecule cannabinoids over whole plant cannabis remedies.