Tetrahydrocannabinol 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). 

Synthesis of A9-Tetrahydrocannabinol from Natural Cannabidiol (Semisynthetic A9-THC)... 

There are over 400 constituent compounds in marijuana. More than 60 of these are pharmacologically active cannabinoids, of which 4 are the most important. The most psychoactive is delta-9-tetrahydrocannabinol (A-9-THC). The other three important natural cannabinoids are A-8-THC, cannabinol and cannabidiol (Kumar et al., 2001). In addition, some of the metabolites of THC, such as 11-hydroxy-A-9-THC, are also psychoactive. As a consequence and contrary to many other drugs, the metabolism of THC in the liver does not decrease intoxication, rather it prolongs it. 

Chiu P, Olsen DM, Borys HK, Karler R, Turkanis SA. (1979). The influence of cannabidiol and delta 9-tetrahydrocannabinol on cotelt epilepsy in rats. Epilepsia. 20(4) 365-75. 

Hampson AJ, Grimaldi M, Axelrod J, Wink D. (1998). Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA. 95(14) 8268-73. 

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. ... 

Adams R, Loewe S, Pease DC, Cain CK, Wearn RB, Baker BR, Wolff H, Structure of cannabidiol. VIII. Position of the double bonds in cannabidiol. Marihuana activity of tetrahydrocannabinols, J Amer Chem Soc 62 2566—2567, 1940. 

Adams R, Baker BR, Structure of Cannabidiol. VII. A Method of Synthesis of a Tetrahydrocannabinol which Possesses Marihuana Activity, J Amer Chem Soc 62 2405-2408, 1940. 

Adams R,Pease DC, Cain CK, Clark JH, Structure of cannabinol. VI. Isomerization of cannabidiol to tetrahydrocannabinol, a physiologically active product. Conversion of cannabidiol to cannabinol, J Amer Chem Soc 62 2402—2405, 1940. 

Stone, and P. ]. Robson. Effect of Delta-9 tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J Clin Psychopharmacol 2004 24(3) 305-313. 

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. 

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

Lander N. et al., Total synthesis of cannabidiol and deltal-tetrahydrocannabinol metabolites, J. Chem. Soc. (Perkin 1), 1, 8-16, 1976. 

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). 

Cannabinoids (cannabigerol, cannabidiol, cannabinol, A-9-tetrahydrocannabinol, A-8-tetrahydrocannabinol, cannabichromene, A-9-tetra-hydrocannabinolic acid)... 

A8 -tetrahydrocannabinol were quantitatively separated with respective retention volumes of 6.37 and 6.62 ml (the dead volume between the UV detector and the collection point was 0.46 ml as determined by the iodoform test). Cannabidiol in the same system had a retention volume of 6.06 ml. 

Another solvent system was also used to resolve tetrahydrocannabinol, cannabinol and cannabidiol by the normal phase HPLC (column y-PorasilR eluent 20% chloroform in heptane at 2.5 ml/min). However, the chosen collection range would also collect cannabinol and cannabidiol if 98% of the tetrahydrocannabinol were to be collected. The retention volumes of cannabidiol and cannabinol relative to 1 significantly diverged with increasing percentages of increased percent of chloroform in heptane to give better separation. 

This was challenged by subjecting HPLC purified cannabidiol 0 (with a A9-tetrahydrocannabinol content less than 0.3%) to degradation under the same conditions and assaying the resultant products by GLC (Table 3). The appearance of , and was confirmatory. 

By the beginning of the 1940s, Roger Adams and coworkers at the University of Illinois—commissioned by the LaGuardia Commission—were able to demonstrate a simpler method for synthesizing cannabinol and isolated the second important member of this family cannabidiol. From their work, and that of A.R. Todd at about the same time, it became clear that these first two molecules are barely psychoactive and that the important components are produced by tetrahydrocannabinols (THCs). 

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. 

These authors reported high efficiency separations of heroin, heroin impurities, degradation products, and adulterants (Fig. 8.1). Also discriminated were acidic and neutral impurities present in heroin seized by law enforcement agencies, as well as in illicit cocaine samples, with resolution of benzoylecgon-ine, cocaine, cis- and frans-cinnamoylcocaine. MEKC was also used with a broad spectrum of other compounds of forensic interest, including psilocybin, morphine, phenobarbital, psilocin, codeine, methaqualone, lysergic acid diethylamide (LSD), amphetamine, chlordiazepoxide, methamphetamine, lora-zepam, diazepam, fentanyl, phencyclidine hydrochloride (PCP), cannabidiol, and tetrahydrocannabinol (THC), which were all separated with baseline resolution. 

Fast blue B solution. Cannabidiol gives an orange colour, cannabinol gives a violet colour, and A -tetrahydrocannabinol gives a red colour. The colours may be intensified by overspraying with M sodium hydroxide or by exposing the plate to ammonia fiimes. 

Fig. 4. Chromatogram of cannabis resin using System HL. Resin extracted with methanol chloroform (4 1). A, cannabidiolic acid B, cannabinol C, A -tetrahydrocannabinol D, A -tetra-hydrocannabinolic acid.

Despite years of study, not until 1964 was the principal psychoactive agent in cannabis isolated. This substance has been labeled delta-9-tetrahydrocannabinol but is more commonly known as A-9-THC, or simply THC. The THC compound w as first reported by Gaoni and Mechoulam (1964), two researchers w orking in Israel. Research since 1964 has shown that the A-9-THC cannabinoid accounts for the vast majority of the known specific pharmacological actions of marijuana. Although THC is the prime psychoactive agent in cannabis, other cannabinoids, such as cannabidiol and cannabinol, can be biologically active and can modify THC effects. However, they tend not to be psychoactive in and of themselves. 

Cannabinoids are aryl-substituted meroterpenes unique to the plant genus Cannabis. The pharmacology of most of the cannabinoids is largely unknown but the most potent psychoactive agent, [Delta] -tetrahydrocannabinol ([Delta] -THC, or THC), has been isolated, synthesized, and much studied. Other plant cannabinoids include [Delta] -THC, cannabinol, and cannabidiol. 

C]MVA, [l- H]geraniol, and [l- H]nerol were all incorporated into can-nabichromenic acid (120) and tetrahydrocannabinolic acid (121) by Cannabis sativa, and [car oxy- CJcannabigerolic acid (122) labelled these two compounds and also cannabidiolic acid (123). The results probably show that cannabigerolic... 

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