Cannabinoids pharmacological effects

Before the discovery of specific cannabinoid receptors, the term cannabinoid was used to describe the biologically active constituents of the Cannabis sativa plant, including A -THC (67), cannabidiol (68) and their analogues and derivatives, many of which have characteristic pharmacological effects. 

All the foregoing pharmacological effects of anandamide, in conjunction with the well-documented existence of specific systems for its biosynthesis, catabolism, and cellular reuptake to be discussed shortly, suggest that anandamide is indeed the endogenous cannabinoid ligand. The other two less studied A -acylethanolamide endocannabinoids and also 2-AG may serve similar functions. The differential roles of each of these four endocannabinoids are still unclear. 

The most consistent pharmacological effect produced by marijuana is tachycardia, which is closely associated with the blood levels of A -THC. There is relatively little effect on blood pressure unless large quantities of marijuana are smoked, in which case there can be marked orthostatic hypotension. Cannabinoids are also vasodUatory, which results in the characteristic conjunctival reddening following marijuana smoking. They also reduce intraocular pressure and are capable of producing bronchodilation. 

The term classical cannabinoids refers to tricyclic THC-type cannabinoids. The SAR in these series have been quite extensively investigated in the past and several reviews have appeared [21, 91, 92], The structure-activity requirements formulated have withstood the erosion of time. Most of the published work refers to in vivo tests for effects now assumed to be due to CBi activation. Compton et al. have recently correlated binding to CBi with in vivo activity and have concluded that the requirements for binding to the cannabinoid receptor correlate well with activity across different species, and that receptor binding mediates most of the pharmacological effects of cannabinoids [93],... 

The primary active component of cannabis is A9-tetrahy-drocannabinol (THC), which is responsible for the greater part of the pharmacological effects of the cannabis complex. A8-THC is also active. However, the cannabis plant contains more than 400 chemicals, of which some 60 are chemically related to A9-THC, and it is evident that the exact proportions in which these are present can vary considerably, depending on the way in which the material has been harvested and prepared. In man, A9-THC is rapidly converted to 11-hydroxy-A9-THC (5), a metabolite that is active in the central nervous system. A specific receptor for the cannabinols has been identified it is a member of the G-protein-linked family of receptors (6). The cannabinoid receptor is linked to the inhibitory G-protein, which is linked to adenyl cyclase in an inhibitory fashion (7). The cannabinoid receptor is found in highest concentrations in the basal ganglia, the hippocampus, and the cerebellum, with lower concentrations in the cerebral cortex. 

Wise LE, Shelton CC, Cravatt BE, Martin BR, Lichtman AH (2007) Assessment of anandamide s pharmacological effects in mice deficient of both fatty acid amide hydrolase and cannabinoid CBl receptors. Eur J Pharmacol 557 44-48... 

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... 

The investigations conducted to date on the pharmacological effects mediated by cannabinoid receptors show that the non-psychoac-tive effects of Cannabis derivatives are mediated by CB2 peripheral receptor. Furthermore, the CB2 receptor localization proves that said non-psychoactive effects, i.e. the effects on the immune system, the anti-inflammatory, myorelaxant and antinociceptive effects, as well as the effects on pressure systems, are mediated by said receptor. 

Various preparations of the plant Cannabis saliva have been used since ancient times for their behavioral and pharmacological properties. R. Mechoulam, The Pharmohistory of Cannabis Saliva, 1-19 (1986). More recently, it has been demonstrated that the active plant constituents, known as cannabinoids, produce a variety of effects including bronchodilation, increased heart rate, reduced intraocular pressure, analgesia, antiemesis, alteration in body temperature, as well as anticonvulsant and psychotropic activities. (W. L. Dewey, Cannabinoid Pharmacology, Pharmacol. Rev., 38 45 (1986)). 

Dewey WL, Martin BR, May EL (1984) Cannabinoid stereoisomers pharmacological effects. In Smith DF (ed) CRC Handbook. Stereoisomers drugs psychopharmacology. CRC Press, Boca Raton, pp 317-326... 

Plasse T (1984) Antiemetic effects of cannabinoids. In Grotenhermen F, Russo E (eds) Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. The Haworth Integrative Healing Press, New York, pp 165-180... 

THC and a variety of cannabinoid agonists have been reliably shown to produce a constellation of pharmacological effects as evaluated in a variety of animal behavioral models, including the dog-static ataxia test, rat and monkey drug discrimination, and the tetrad test in mice (i.e., depression of spontaneous activity, antinociception, hypothermia, and catalepsy) (Dewey et al. 1972 Chaperon and Thiebot 1999 Martin 2002). These behavioral effects are well known to undergo... 

The cannabis plant has been cultivated for centuries both for the production of hemp flber and for its presumed medicinal and psychoactive properties. The smoke from burning cannabis contains many chemicals, including 61 different cannabinoids that have been identified. One of these, A-9-tetrahydrocannabinol (A-9-THC), produces most of the characteristic pharmacological effects of smoked marijuana. 

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