An update on K2/Spice, JWH-018 and synthetic cannabis

The recent meeting of the College on Problems of Drug Dependence featured a very well attended session on the emerging recreational drugs that are best described generically as synthetic cannabis. Popularly these are frequently referred to as K2 or Spice as these seem to be the best known of the initial market branding. One of the first identified and most frequently observed active compounds in these products was JWH-018, so you may see this term as well.
The past year or two has seen an explosion in the use and supply of synthetic cannabinoid “incense” products in the US and worldwide. The basic nature of the product is well established- Small packets (typically 3g in the US) of dried plant material marketed as “incense” and marked “not for human consumption” that are priced well above what you might expect. In the range of $60 at my local fine inhalation glassware establishments, last I checked. Upon analysis, these products are typically found to have a variety of plant materials, but also to be adulturated with a host of drug compounds that have agonist effects at the CB1 receptor.
As you are aware the most-active psychotropic compound to be found in cannabis, Δ⁹-tetrahydrocannabinol (THC) confers the majority of its effects through partial agonist activity at CB1 receptors.
In short, these “incense” products are a constructed, synthetic mimic of cannabis. Since the active ingredients are, in many cases, full agonists this means that the maximum CB1 activation can potentially be higher than you could achieve with any dose of the partial agonist THC.

As my readers are aware, these products are capable of producing dependence with a profile, including withdrawal effects, that are typical of cannabis dependence.
The symposium was organized and chaired by a rising star in drug abuse research, William Fantegrossi, and a legend of cannabinoid behavioral pharmacology, Jenny Wiley. The latter had been involved with much of the characterization of the JWH- compounds when they were originally created.
The DEA reported continued surveillance of products and their scheduling action that placed 5 of the more-common cannabimimetic compunds on Schedule I in early 2011. Interesting tidbit was that the delay from the intended scheduling in late Dec 2010 (30 days after their initial notice of intent to schedule) was entirely due to putting out brushfire lawsuits from convenience store / head shop interests that were making serious bank from these products. He reported that a consortium of just four shops were reporting profits (might have been sales) in the neighborhood of $5M.
One of the more interesting parts of the symposium was the participation of three members of a four institution/agency consortium or task force that has been established in the state of Arkansas. It includes people from the state’s forensic crime laboratory, the poison control service, the University of Arkansas Medical Sciences campus and the state Children’s Health service (or Children’s Hospital, I’m not remembering precisely). It seems like an ideal response to an emerging health situation of this nature- involve the two areas of front line interface (poison control and law enforcement forensics) with scientists who have experience with the health condition in question.
What I learned that was of interest to me:
-Phone calls to all US poison hotlines for marijuana or cannabis amount to about 1,000 per year. Calls for synthetic cannabinoids were 2,800-2,900 in the past two years. Given that all available epidemiology suggests that marijuana use dwarfs use of synthetic products, we can tentatively infer a greater risk.
-40 of 48 calls to the Arkansas Poison Control Hotline were from/regarding individuals already in contact with Emergency Departments / Emergency Medical Services. (1 of 48 calls was from an individual calling to report the effects were just what he wanted and to tell the agency to stop denigrating these fine products.)
-Behavioral effects of the active compounds are opposed by CB1 antagonists, in general, so there is ongoing confirmation that this is indeed the most important pharmacological activity for a range of these compounds.
-While these compounds are more potent than THC (smaller amount leads to similar effect), there is some variability across those that have been studied in animal models. And for some of the compounds, such as JWH-073, there is some indication that it may actually be a partial agonist (like THC) rather than a full agonist.
-Certain cannabimimetic combinations are frequent. One lab reports never finding JWH-073 without JWH-018. Similarly, JWH-250 and JWH-081 were frequently found together. Samples are diverse enough that it suggests an intentional recipe being followed, rather than an accidental association.
UPDATE:
In response to a query from Prof-like substance, the DEA guy mentioned that they were finding and rolling up domestic production labs. The compounds are being imported, the plant material locally sourced and the finished product being made and packaged.
The forensic scientist pointed out that since the method is to dissolve the compound in acetone and use a spray bottle to spritz the plant material the drug distribution should be uneven. And their analysis of packages shows what they call “hot spots” with some parts of it having up to 2X the drug content. So potency varies between and even within product units.
There was a distinct impression from both the DEA and the forensic side of things that there are/were many labs pumping out product, consistent with the highly diverse drug content, source material, branding/packaging, etc.
After the DEA scheduling action, apparently the packaging started using terms like “compliant” or “Does not include JWH-018, JWH-073….etc”. At least one sample that was so marked was analyzed and found to include JWH-018.