In addition to nabilone, many other synthetic cannabinoids agonists have been described and widely tested on experimental animals to investigate the consequences of cannabinoid receptor activation (e.g., CP-55940, WIN-55212-2, JWH-018) (; ). The therapeutic application of these highly potent molecules is limited by their CB1-mediated psychotropic side effects, which presumably provide the rationale for the illicit use of some of them as an alternative to cannabis (). Preclinical and clinical data in support of this claim remain very limited, however. Internet-marketed products such as Spice, K2, and Eclipse are a blend of various types of plant material (typically herbs and spices) that have been sprayed with one of these synthetic cannabinoids (as well as other non-cannabinoid psychoactive drugs). Since 2009 more than 140 different synthetic cannabinoids have been identified in herbal mixtures consumed as recreational drugs. The synthetic cannabinoids used in “herbal mixtures” are chemically heterogeneous, most of them being aminoalkylindole derivatives such as naphthoylindoles (e.g., JWH-018 and JWH-210), cyclopropylindoles (e.g., UR-144, XLR-11), or quinoline esters (e.g., PB-22). They seem to appeal especially to young cannabis and polydrug users because they are relatively inexpensive, easily available through the Internet, and difficult to identify with standard immunoassay drug screenings. In contrast to Δ9-THC, which is a partial agonist of the CB1 receptor, many of the synthetic cannabinoids bind to CB1 receptors with high affinity and efficacy, which may also be associated with higher potential of toxicity (). According to the National Institute on Drug Abuse (, p. 2), people using these various blends have been admitted to Poison Control Centers reporting “rapid heart rate, vomiting, agitation, confusion, and hallucinations.” Synthetic cannabinoids can also raise blood pressure and cause a reduced blood supply to the heart (myocardial ischemia), and in a
The U.S. Food and Drug Administration (FDA) has licensed three drugs based on cannabinoids (see ). Dronabinol, the generic name for synthetic Δ9-THC, is marketed under the trade name of Marinol and is clinically indicated to counteract the nausea and vomiting associated with chemotherapy and to stimulate appetite in AIDS patients affected by wasting syndrome. A synthetic analog of Δ9-THC, nabilone (Cesamet®), is prescribed for similar indications. Both dronabinol and nabilone are given orally and have a slow onset of action. In July 2016 the
Apart from (dronabinol), the only synthetic cannabinoid receptor agonist to have found clinical use is nabilone — a derivative of and constituent of the proprietary preparation Cesamet®; it finds limited use for the treatment of nausea in cancer chemotherapy.