Limited Understanding of Synthetic Cannabinoids
"Much of our understanding of cannabinoid tolerance, dependence, and withdrawal has been based on studies involving ?9-THC, a relatively weak partial agonist at CB1 and CB2 receptors. However, the SCBs [Synthetic Cannabinoids] commonly found in quasi-legal commercial products, such as K2 and Spice, are typically full cannabinoid receptor agonists. Importantly, a drug’s efficacy determines how 'powerful' its maximal effects may be in biological systems. A low efficacy cannabinoid like ?9-THC will have a less pronounced maximal effect than a higher efficacy cannabinoid, such as the SCBs present in commercial products, and this difference in maximal effects cannot be overcome simply by increasing the dose of ?9-THC. In other words, no amount of ?9-THC can stimulate cannabinoid receptors to the same degree as the SCBs currently emerging as drugs of abuse. This has left researchers working with these high efficacy SCBs in the unusual position of having to determine whether their effects are related to the unprecedented degree of cannabinoid receptor stimulation elicited by these compounds, or whether they are produced by interactions with other, noncannabinoid receptor systems."
Sherrica Tai and William E. Fantegrossi, "Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential," Current Addiction Reports, March 15, 2014, DOI 10.1007/s40429-014-0014-y.