Cannabis Cannabidiol

Group of compounds which naturally occur in the hemp plant, Cannabis saiiva. Most of them are unsoluble in water. The most abundant cannabinoids are A9--tetrahydrocannabinol (THC), its precursor cannabidiol and cannabinol, which is formed spontaneously from THC. Cannabinoids exert their effects through G-protein coupled cannabinoid receptors (CBi/CB2). 

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. 

A -THC, the main psychoactive component of cannabis, is a moderately potent partial agonist of the CBi and CB2 receptors, while cannabidiol has little affinity for either receptor (Table 6.7). The term classical cannabinoids is used to describe cannabinoid receptor modulators structurally related to (67), which have a tricyclic dibenzopyran core. While several other structural types of cannabinoid receptor modulators have been discovered in recent years, the classical cannabinoids are still by far the most extensively studied group in terms of SAR and pharmacology. 

Cannabinoids Chemicals synthesised from precursor terpenes in Cannabis sativa including cannabidiol, cannibinol and THC. 

Lindstrom P, Lindblom U and Boreus L (1987). Lack of effect of cannabidiol in sustained neuropathia. Paper presented at Marijuana International Conference on Cannabis, Melbourne, June. 

A few studies have been conducted on cannabis and its derivatives. Alozie et al. (3) measured the radioactivity accumulated in various brain areas following the intravenous injection of 3H-THC, 3H-cannabinol, and 3H-cannabidiol to adult male rats. Five minutes after injection, these three labeled compounds exhibited a homogeneous distribution in brain, suggesting that no specific binding occurred. Such studies must be completed by examining the time course of the evolution of 3H-cannabis derivatives in various brain areas before any firm conclusion can be drawn. 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

Gas chromatography coupled to tandem mass spectrometry (GC-MS/MS [49]) prior to analysis of the three primary active components of cannabis (THC, cannabidiol and cannabinol) by this technique, airborne particulates were extracted in an ultrasonic bath with chloroform. The extracts were combined and concentrated under a stream of nitrogen. The residue was filtered through pre-washed disposable PTFE membranes, dried and finally reconstituted with cyclohexane. After separation and solvent partitioning, the extracts were analysed by GC-MS/MS. 

There is much interest in the medical applications of Cannabis sativa L. (marijuana). An oral spray consisting of the marijuana constituents, cannabidiol (CBD,19) and A -mzw-tetrahydrocannabinol (THC, 20), has been approved recendy in Canada for the treatment of neuropathic pain associated with multiple sclerosis (MS), and it is possible that this drug will be approved elsewhere in the near future. ... 

Until the mid 1960 s the only plant cannabinoid whose structure was fully elucidated was cannabinol (CBN) — a constituent which actually may represent an oxidation artifact. However, on the basis of CBN, the main cannabinoid structure skeleton became known. Thus, cannabidiol (CBD), which had been independently isolated in pure form by Adams and by Todd, was correctly assumed to be, like CBN, a terpenoid derivative attached to olivetol. But its exact structure was not elucidated. The psychoactive components of cannabis were assumed to be related tricyclic derivatives. On the basis of the tentatively elucidated constituents, Todd suggested that the cannabinoids may be formed initially in the plant by condensation of a menthatriene with olivetol. 

A second cannabis constituent, cannabidiol (CBD) was also isolated, but its structure was only partially clarified. Synthetic tetrahydro-cannabinols, which showed cannabis-like activity in animal tests, were prepared, but they obviously differed from the active natural product, on the basis of their UV spectrum. 

Taura F, Morimoto S, Shoyama Y, Purification and characterization of cannabidiolic-acid synthase from Cannabis sativa L. Biochemical analysis of a novel enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic 2lcsA, J Biol Chem 271 17411—17416, 1996. 

Jacob A, Todd AR, Cannabis indica. Part 11. Isolation of Cannabidiol from Egyptian Hashish. Observations on the Structure of Cannabinol, J Chem Soc... 

Malfait AM, Gallily R, SumariwaUa PF, The non-psycho active cannabis-constituent cannabidiol is an oral anti-arthritic therapeutic in murine coUagen-induced arthritis. Prod Nat Acad Sci USA 97 9561—9566, 2000. 

Constitution of the cannabidiolic acid, M.P.133, isolated from Cannabis sativa. Acta Univ Palacki Olomuc Fac Med 1958 16 9. 

Stromberg, L. Minor components of Cannabis resin V. Mass spectrometric data and gas chromatographic retention times of cannabinoid components with retention times shorter than that of cannabidiol. J Chromatogr 1974 96 179. 

Turner, C. E., K. W. Hadley, J. H. Holley, S. Billets and M. L. Mole, Jr. Constituents of Cannabis sativa. VIII. Possible biological application of a new method to separate cannabidiol and cannabichromene. J Pharm Sci 1975 64 810. 

CS298 luvone, T., G. Esposito, R. Esposito, R. Santamaria, M. Di Rosa, and A. A. Izzo. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PCI2 cells. J Neurochem 2004 89(1) 134-141. CS299 Ng, R. S., D. A. Darko, and R. M. 

Parker, L. A., R. Mechoulam, and C. Schlievert. Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport 2002 13(5) 567-570. 

Cannabis chinensis Del. C. sativa L. Huo Ma Ren or Da Ma Ren (Hemp) (fruit, seed) Vitamin Bj, vitamin B2, muscarine, choline, trigonelline, l(d)-isoleucine betaine, cannabinol, tetra-hydrocannobinol, cannabidiol.33-450 Purgative, stimulate intestinal mucosa causing an increase in secretions and peristalsis. 

At least 60 bioactive compounds are contained in herbal cannabis. A9-Tetrahydrocannabinol (A9-THC) (Mechoulam and Gaoni, 1967), cannabidiol and cannabinol are the major psychoactive or adjuvant ingredients. Cannabinoids act through at least two different G-protein coupled receptors named CBi and CB2 receptors. 

Taura, F., Morimoto, S., Shoyama, Y. Purification and characterization of cannabidiolic-ac/d synthase from Cannabis sativa L., J. Biol. Chem. 1996, 271, 17411-17416. 

Figure 30-29 Structures of the active components of cannabis, tetrahydrocannabinol, and cannabidiol, and structures of endogenous cannabinoids and of the vanilloid lipid capsaicin.

More than 400 chemical compounds have been identified in marijuana. Approximately 60 of these are unique to the cannabis plant, substances called cannabinoids. Of the cannabinoids, a group of isomers (chemically similar substances) called tetrahydro-cannabinols (THC) are thought to be the most psychoactive. These are Ai-THC (also called A9-THC) and A6-THC (also called A8-THC). Other cannabinoids include cannabidiolic acid (CBDA), cannabidiol (CBD), and cannabinol (CBN). Their role in marijuana intoxication is less well understood. The amount of THC produced depends on the strain of cannabis and on environmental factors such as growth, harvest, and storage conditions. 

The psychoactive and medicinal chemical compounds found in the resin of the marijuana plant are known as cannabinoids. The cannabis plant contains more than 460 known compounds over 60 of these have a cannabinoid structure. The only cannabinoid that is highly psychoactive and present in large amounts in the resin of the cannabis plant is tetrahydrocannabinol, or THC. The other two major cannabinoids are the cannabidiols and the cannabinols. It appears that the cannabis plant first produces the mildly active cannabidiols, which are converted to the more psychoactive THCs and then broken down to relatively inactive... 

The main active ingredients of cannabis are cannabinol, cannabidiol and several isomers of tetrahydrocannabinol, of which delta-9-tetrahydro-cannabinol (THC) is probably responsible for most of the psychoactive effects of the various preparations. It is of interest to note that THC does not contain nitrogen in its three-membered ring system. The structure of THC is shown in Figure 15.8. 

Phytocannabinoids are natural compounds present in Cannabis sativa, responsible for the pharmacological and toxicological properties of this plant. About 70 compounds belong to this class, the most important are A9-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD). 

Cirimele, V., Sachs, H., Kintz, R, and Mangin, R, Testing human hair for cannabis. III. Rapid screening procedure for simultaneous identification of A -tetrahydrocannabinol, cannabinol and cannabidiol, J. Anal. Toxicol, in press. 

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