Cannabinol

Cannabinol, A -3,4-trans-tetrahydro-biological activity, 3, 877 Cannabinol, (—)-A -3,4- ran5-tetrahydro-as pharmaceutical, 1, 151 Cannabinolic acid synthesis, 3, 721 Cannabinolic acid, tetrahydro-photochemistry, 3, 721 Cannabis, citrylidene-, 3, 675 Cantharidin synthesis, 1, 440 Capillarin occurrence, 3, 677 ozonolysis, 3, 681... 

Frenkel aud Cserhis under the name ol cannabinol, but does not appear to be the same bodv as that described above under Ihe same name. 

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). 

Fig. 1 Concentrations reported for opiods and cannabinoids in surface water of different European countries. MOR morphine Nor-MOR nor-morphine 6ACM 6-monoacetyl morphine HER heroin MET methadone EDDP 2-ethylidene-l,5-dimethyl-3,3 diphenylpyrrolidine THC A9-tetrahydro-cannabinol THC-COOH 11-nor 9-carboxy-THC N/A Values not availabe, not measured...

Cannabinidiol (CBND, 2.18) and cannabinol (2.19) are oxidation products of CBD and A9-THC formed by aromatization of the terpenoid ring. For the dehydrogenation of THC a radical mechanism including polyhydroxylated intermediates is suggested [10,11]. CBN is not the sole oxidation product of A9-THC. Our own studies at THC-Pharm on the stability of A9-THC have shown that only about 15% of lost A9-THC is recovered as CBN. 

Oxidation of the phenol ring of cannabidiol (73) or cannabinol to a qui-none ring has been shown to afford compounds with anti-tumour activity. However, these compounds do not bind to the CBi receptor and their mechanism of action is unclear [128],... 

In this chapter, consideration will be given to two categories, which are well known CNS depressants (anticholinergics) and CNS stimulants (LSD). Although cannabinols and psylocibin, for instance, have been considered in the past, their effective dose is too high for these to be regarded as likely agents for use in the field. 

Solid extracts of (1) alfalfa and (2) red clover (used in food flavorings) were examined by GC/MS. 389 of 450 detected components were identified in (1), vs. 210 of 309 components detected in (2). In both extracts, predominant compounds identified were esters (1) 105, (2) 55 acids (1) 42, (2) 31 alcohols (1) 34, (2) 31 and hydrocarbons (1) 28, (2) 14. Many other compounds were also found, including cannabinol, caffeine, scopolamine, isocoumarin, phenylpentadienal, phenylhexadiene, and nepetalactone.25... 

Justinova, Z., Tanda, G., Redhi, G.H., and Goldberg, S.R., Self-administration of delta(9)-tetrahydro-cannabinol (THC) by drug naive squirrel monkeys, Psychopharmacology, 169, 135, 2003. 

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. 

Chesher GB and Jackson DM (1985). The quasi-morphine withdrawal syndrome Effect of cannabinol, cannabidiol and THC. Pharmacology, Biochemistry and Behaviour, 23, 13-15. 

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. 

HHC) (Tripathi 1987). Unless stated otherwise, THC will be used to refer to A9-THC throughout the remainder of this chapter. Other cannabinoids that are not psychoactive include cannabinol and cannabidiol. More recently, endogenous substances have been identified that activate these receptors, and are referred to collectively as endocannabinoids (table 10.2). 

Several additional useful publications demonstrating practical applications of CE/MS methods for neurotransmitter analysis and neuropharmaceutical studies are those of Larsson and Lutz (2000) (neuropeptides including substance P) Hettiarachchi et al. (2001) (synthetic opioid peptides) Varesio et al. (2002) (amyloid-beta peptide) Zamfir and Peter-Katalinic (2004) (gangliosides) Peterson et al. (2002) (catecholamines and metanephrines) Cherkaoui and Veuthey (2002) (fluoxetine) and Smyth and Brooks (2004) (various lower molecular weight molecules including benzodiazepines, steroids, and cannabinols). 

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. 

As shown in Table 2, cocaine concentrations are detected in almost all the studies targeting psychoactive substances or drugs of abuse in the literature, with the exception of Algiers and Serbia, where cannabinoids were found whilst cocaine was not (Tables 3 and 4). In the literature, cannabinoid concentrations are either expressed as A -tetrahydrocannbinol (THC) or as the sum of cannabinol, cannabidiol and THC (known as CBs). 

Fig. 2 Top Cocaine and CBs levels in the metropolitan region of Rome, detected during field campaigns in 2009-2010. COC cocaine, CBs cannabinol + cannabidiol + A -tetrahydrocannabi-nol). BEL Belloni Street, CIP Cipro Street, FRA Francia Boulevard, MLB Montelibretti, CIA Ciampino, CIV Civitavecchia, CEE Colleferro, GUI Guidonia. Bottom Heroin and THC levels in three Spanish cities, detected during field campaigns in 2008...

Fig. 3 Mean, maximum and minimum airborne concentrations of THC and cannabinoids (CBs) at urban and rural locations around the world. CBs sum of cannabinol, cannabidiol and THC...

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. 

Yamauchi et al demonstrated that the neutral cannabinoids and cannabinolic acid are artifacts produced from cannabinoid acids during the harvest and storage of cannabis. 

The first successful attempt to identify a typical cannabis constituent (today called cannabinoid) was achieved by Wood who isolated cannabinol... 

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. 

Several additional, non-psychotropic cannabinoids were also identified at that time. The best known are cannabigerol (CBG), cannabichromene (CBC) and cannabicyclol. Cannabinolic acid (CBNA) and cannabigerolic acid (CBGA) were also identified,followed by two... 

Mechoulam R, Gaoni Y, The isolation and structure of cannabinolic, cannabid-iolic and cannabigerolic acids. Tetrahedron 21 1223-1229, 1965. 

Yamauchi T, Shoyama Y, Aramald H, Azuma T, Nishioka I, Tetrahydro-cannabinolic acid a genuine substance of tetrahydrocannabinol, Chem Pharm Bull 15 1075-1076, 1967. 

---