Cannabinoids cardiovascular

Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S (2005) Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweightpatients 1 -year experience from the RIO-Europe study. The Lancet 365(9468) 1389-1397... 

The mechanisms involved in THC s central nervous system (CNS) and cardiovascular effects have not been well delineated. Specific cannabinoid receptors in the cerebral cortex may be responsible for the pharmacologic effects of THC. THC also has immunosuppressive effects and results in depression... 

Cannabinoids are able to cause different effects at the level of various systems and/or organs the most important effects occur on the central nervous system and on the cardiovascular system. In fact, they are able to affect mood, memory, motor coordination and cognition, and they increase heart rate and variate the systemic arterial pressure. Furthermore, it is well known the capability of cannabinoids to reduce intraocular pressure and to affect the respiratory and endocrine systems (L. E. Hollister, Health Aspects of Cannabis, Pharmacological Reviews, 38,1-20,1986). More recently, it was found that they suppress the cellular and humoral immune response and have antiinflammatory properties (A. W. Wirth et al.. Antiinflammatory Properties of Cannabichromene, Life Science, 26,1991-1995,1980). 

The most abundant member of this group is the cannabinoid Al-THC-7-oic-acid. When tested in humans as well as in the rhesus monkey, this cannabinoid did not show the behavioral activity or the cardiovascular effects characteristic of the parent substance, THC. (Perez-Reyes, M. In Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs, Barnett, G. and Chiang, N. (eds), Biomedical Press, 1985, pages 287-310 Mechoulam, R. and Edery, M. ln Marijuana, Mechoulam, R. (ed.), Academic Press, New York, 1973). Thus, little attention has been given to the possible pharmacodynamic properties of this metabolite or any of the other acid metabolites of THC. 

Hiley, C.R. Ford, W.R. Cannabinoid pharmacology in the cardiovascular system potential protective mechanisms through lipid signaling. Biol. Rev. Camb. Philos. Soc. 2004, 79 (1), 187-205. 

Batkai S, Pacher P, Osei-Hyiaman D, Radeva S, Liu J, Harvey-White J, Offertaler L, Macie K, Rudd MA, Bukoski RD, Kunos G (2004) Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 110 1996-2002... 

It is well known that the acute consumption of THC causes tachycardia in humans without any significant effect on blood pressure, whilst the chronic ingestion of cannabinoids leads to hypotension and bradycardia (Benowitz and Jones 1975). Pharmacological studies using selective CBi receptor antagonists (Varga et al. 1995 Lake et al. 1997) have suggested that some of these cardiovascular responses are mediated by CBi receptors. 

Randall MD, Harris D, Kendall DA, Ralevic V (2002) Cardiovascular effects of cannabinoids. Pharmacol Ther 95 191-202... 

Niederhoffer N, Szabo B (1999) Effect of the cannabinoid receptor agonist W1N55212-2 on sympathetic cardiovascular regulation. Br J Pharmacol 126 457-466... 

Niederhoffer N, Schmid K, Szabo B (2003) The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression. Naunyn-Schmiedeberg s Arch Pharmacol 367 434-443... 

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. 

Role of Central Versus Peripheral Mechanisms in the Cardiovascular Effects of Cannabinoids... 

Finally, Zygmunt et al. (1999) described an unusual indirect pathway. They demonstrated that anandamide induces vasorelaxation in rat mesenteric and hepatic arteries, and in guinea pig basilary artery through the activation of TRPVl receptors on sensory neurons, causing the release of the vasodilatory peptide calcitonin gene-related peptide (CGRP) (see also Sect. 4 below, Role of Vanilloid TRPVl Receptors in the Cardiovascular Effects of Cannabinoids ). 

---