The Poison Review

We recently talked about the endogenous cannabinoid receptor (CR) in a post discussing K2, packets of herbs and spices laced with specific CR agonists.  There are two major classes of CRs: CR(1) — located mainly in the central nervous system; and CR(2) — located in T cells, macrophages, and other components of the immune system.  The psychoactive effects of cannabinoids are mediated almost entirely by the CR(1) units.  K2 typically contains the research chemical JWH-018, a synthetic CR(1) stimulator.

In an interesting twist on this story, a recently published paper in International Journal of Obesity (16 Feb 2010; advance online publication)  reports the findings from a large study investigating the use of taranabant – a CR(1) antagonist — as a weight-loss agent.  The paper states that:

“Endocannabinoids are believed to promote appetite and food intake by activating cannabinoid-1 receptors (CB1Rs) expressed in hypothalamic centers that regulate energy balance, the limbic system that regulates reward pathways, and other cortical and subcortical regions.”

Previous studies indicated that taranabant reduced appetite and increased energy output.  Although this present study indicated that groups on varying doses of taranabant all lost more weight compared with controls, the study was stopped because because of unacceptable and dose-related adverse effects, including dysphoria, depression, anxiety, and suicidal ideation.  Because of these effects, Merck stopped the phase III clinical trials of taranabant in October 2008.

The blog Neuroskeptic has a very interesting discussion of this paper. Hats off — yet again — to DoseNation for linking to that post.