Searching for an Endogenous Cannabinoid Substance

Why do cannabinoid receptors exist The experience with the enkephalins has taught neuropharmacologists that whenever receptors for a drug are present in the body, chances are that they are there to bind one or more endogenous factor(s). Not surprisingly, therefore, researchers have long been looking for chemicals, produced by the mammalian brain, that may activate cannabinoid receptors. 

How does one go about such a task One approach is based on the logical premise that an endogenous cannabinoid substance 

The chemical synthesis of anandamide confirmed this structural identification, and allowed Mechoulam, Devane and their colleagues to determine its pharmacological properties. In vitro and in vivo tests showed a great similarity of effects between anandamide and cannabinoid drugs. Anandamide reduced the electrogenic contraction of mouse vas deferens and, most importantly, closely mimicked the behavioral responses induced by 

Endogenous cannabinoid substances are released from neurons into the extracellular space by an activity-dependent process. 

Brain slices, maintained in vitro, were stimulated with a calcium ionophore 

---

Fig. 6.6. Experimental approaches taken by the laboratories of A. Howlett (A) and R. Mechoulam (B) in the search for an endogenous cannabinoid substance.

---