K2, also known as Spice, was a wildly popular product due to its psychoactive properties. Spice contained dried plant material from Canavalia rosea, Clematis vitalba, Nelumbo nucifera, Pedicularis grandifolia, Heimia salicifolia, Leonurus sibiricus and Ledum palustre; these species have all been researched for possible psychoactive activity in the past. Although it was ostensibly marketed as an herbal incense, the product was smoked much like marijuana by its users. The plants used in K2 were not found in doses large enough to be psychoactive; instead, the formulation relied upon a number of research chemicals that were similar in structure and function to Δ9-tetrahydrocannabinol, the active ingredient in marijuana. While these chemicals produced effects very similar to marijuana in the user, they were not illegal nor would they cause the user to fail a drug test. On March 1, 2011, the U.S. Drug Enforcement Adminstration made these chemicals illegal, following the lead of 16 other countries.
JWH-018, formerly named 1-Pentyl-3-(1-naphthoyl)indole, was the primary research chemical employed in K2 herbal incense. This chemical was invented by John W. Huffman, an organic chemist at Clemson University. It is considerably more potent than marijuana, gram for gram; consequently, it is diluted in K2. Unlike the partial agonist Δ9-THC, JWH-018 is a full agonist at the CB1 receptor site. There have not been any serious injuries or deaths associated with overdoses of this drug to date.
JWH-073 is another research chemical from the naphthoylindole family. It is a partial agonist at both the CB1 and CB2 cannabinoid receptors. It is somewhat selective for the CB2 subtype, roughly five times its affinity with CB1, resulting in its effects as a general painkiller. There are currently no published studies on the effects of JWH-073 in human subjects.
Unlike the JWH family, HU-210 (or 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol) was synthesized in 1988 in Professor Raphael Mechoulam's research team at the Hebrew University. This chemical is 100 to 800 times more potent than the active ingredient in marijuana, and anecdotal evidence suggests that it may last longer as well. While the naphthoyindole family chemicals are chemically unrelated to natural cannabinols, HU-210 is actually a close analog of Δ8-THC. HU-210 was a major drug of interest in the prevention and treatment of Alzheimer's Disease, before it was made illegal by the U.S. Drug Enforcement Administration.
Cannabicyclohexanol (also known as CP 47,497's 1,1-dimethyloctyl homologue) is another cannabinoid receptor agonist. It was developed earlier than the other chemicals used in K2, first synthesized by Pfizer in 1979. CP-47,497 was initially used as the active ingredient in K2, until it was discovered that its dimethyloctyl homologue was surprisingly much more potent. Like JWH-018, it is a selective CB1 full agonist, making it responsible for the vast majority of the marijuana-like psychoactive effects K2 possessed before the ban.