Peripheral cannabinoid receptor indications

A mode by which cannabinoids may exert their multiplicity of effects may be through the modulation of the expression of chemokines and cytokines which cross-signal among immune cells and play a critical role in pro-inflammatory versus anti-inflammatory activities. Blanchard et al. (1986) and Cabral et al. (1986a) reported that induction of IFN-a/ was suppressed by chronic treatment of mice with THC. Watzl et al. (1991) indicated that cytokine activity also was modulated in human peripheral blood mononuclear cell cultures by THC. However, the non-psychoactive CBD also modulated cytokine production and/or secretion, suggesting that a non-cannabinoid receptor-mediated mode of action could also be involved. The investigators indicated that a possible explanation for the capacity of cannabinoids to act through cannabinoid receptors so as to exert a broad spectrum of immune function effects was that exposure to these compounds resulted in the expression of a differential profile of cytokines. 

Cannabinoids and their synthetic and endogenous analogs are best known for their prominent psychoactive properties, but their cardiovascular effects were also recognized as early as the 1960s. The most important component of these effects is a profound decrease in arterial blood pressure, cardiac contractility, and heart rate (Lake et al. 1997a,b Hillard 2000 Kunos et al. 2000,2002 Randall et al. 2002 Ralevic et al. 2002 Hiley and Ford 2004). Although several lines of evidence indicate that the cardiovascular depressive effects of cannabinoids are mediated by peripherally localized CBi receptors, cannabinoids can also elicit vascular and cardiac effects, which are independent of CBi and CB2 receptors, as discussed in detail later in this chapter. 

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