Tetrahydro-cannabinols

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...

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. 

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. 

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. 

Hively RL, Mosher WA, Hoffmann FW, Isolation of tn7 t-A -tetrahydro-cannabinol from marijuana,Chem Soc 88 1832—1833, 1966. 

Mechoulam R, Ben-Zvi Z, Yagnitinsky B, Shani A, A new tetrahydro-cannabinolic acid. Tetrahedron Lett 10 2339—2341, 1969. 

THC-Delta 9-tetrahydro-cannabinol (cannabis) Cannabinoid receptor Relaxation, euphoria, and enhancement of senses, increase in appetite, sense of time... 

El Sohly, M. A., J. H. Holley and C. E. Turner. Constituents of Cannabis sa tiva L. XXVI. The delta-9-tetrahydro-cannabinol content of confiscated marijuana, 1974-1983. Proc Oxford Symp Cannabis 1985 1984 37-42. Morita, M. and H. Ando. Analysis of hashish oil by gas chromatography / mass spectrometry. Kagaku Keisatsu Kenkyusho Hokoku Hokagaku Hen 1984 37(2) 137-140. 

Lai, S. D. and B. K. Yadav. Folk medicine of Kurushetra District (Haryana), India. EconBot 1983 37(3) 299-305. Me Phail, A. T., H. N. El Sohly, G. E. Turner and M. A. El Sohly. Stereochemical assignments for the two enantiomeric pairs of 9,10-dihydroxy-delta-6-alpha(10-alpha)-tetrahydro-cannabinols. X-ray crystal structure analysis of (DL)-trans-cannabitriol. Abstr 24th Annual Meeting American society of Pharmacognosy Univ Mississippi Oxford July 24-28 1983 ABSTR-50. 

Henry. The acute effects of tetrahydro-cannabinol on auditory threshold and CS377 frequency resolution in human sub jects. Hum Exp Toxicol 2002 21(6) ... 

CS463 Romero, J., L. Garcia, J. J. Fernandez-Ruiz, M. Cebeira, and J. A. Ramos. Changes in rat brain cannabinoid binding sites after acute or chronic exposure to their endogenous agonist, anandamide, or to delta 9-tetrahydro-cannabinol. Pharmacol Biochem... 

Tashkin, D.P., Shapiro, B.J., and Frank, I.M. Acute pulmonary physiologic effects of smoked marijuana and oral A -tetrahydro-cannabinol in healthy young men. N. Engl. J. Med. 289 336-341, 1973. 

N.A. Tetrahydro-cannabinols, thiamine protein. Seeds contain choline, inositol, xylose, phytosterols, trigonelline.100102 Induce euphoria and exhilaration, sedative, antispasmodic. 

Chen, Jianping, William Paredes, Joyce H. Lowinson, and Eliot L. Gardner. 1991. "Strain-Specific Facilitation of Dopamine Efflux by -Tetrahydro-cannabinol in the Nucleus Accumbens of the Rat In Vivo Microdialysis Study." Neuroscience Letters 129 136-40. 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

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. 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

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. 

Acidic and basic drugs (phenobarbital, diazepam, methaqualone, testosterone, cannabinol, testosterone propionate, 9-tetrahydro-cannabinol, 9-tetrahydrocannabinolic acid) CEC Hypersil C8 Acetonitrile-50 mAf phosphate buffer, pH 2.5 (60 40) with 2 pl/ml hexylamine for 1 min, then linear gradient to acetonitrile-25 mM phosphate buffer with 2 pl/ml hexylamine (75 25) 340 mm x 100 pm i.d. 250 mm to the detector, stepped gradient, comparison with MECC... 

Boucher AA, Arnold JC, Duffy L, Schofield PR, Micheau J, et al. 2007a. Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydro-cannabinol. Psychopharmacology 192 325-336. 

A -Tetrahydrocannabinol (= Dronabinol A l-Tetrahydro-cannabinol (—)-A -3,4-trans-Tetrahydrocannabinol (dibenzopyranol) globally 144 million cannabis users out of 180 million illicit drug users negligible mortality compared to that from use of alcohol, tobacco, heroin amphetamine-related drugs... 

Tetrahydro- cannabinol (bhang), smoked leaf (ganja)] hallucinogenic, intoxicant,... 

SP 104 (I)-ALtETRAHYDROCANNABINOL A -TETRAHYDROCANNABINOL (-)-AL3,4-trans-TETRA-HYDROCANNABINOL (-)-A -trans-TETRAHYDRO-CANNABINOL trans-A -TETRAHYDROCANNABINOL... 

Berdyshev EV, Boichot E, Germain N, AUain N, Anger J-P, Lagente V (1997) Influence of fatty acid ethanolamides and A -tetrahydro-cannabinol on cytokine and arachidonate release by mononuclear cells. Eur J Pharmacol 330 231-240. 

Fischer-Stenger K, Dove Pettit DA, Cabral GA (1993) A -tetrahydro-cannabinol inhibition of tumor necrosis factor-a Suppression of post-translational events. J Pharmacol Exp Ther 267 1558-1565. 

Narimatsu, S. Matsubara, K. Shimonishi, T. Watanabe, K. Yamamoto, I. and Yoshimura, H. Pharmacological activities in the mouse of delta-9-tetrahydro-cannabinol metabolites oxidized at the 8-position. Chem Pharm Bull 33 392-395,1985. 

In order to achieve this object firstly trans-delta-9-tetrahydro-cannabinol is produced as an intermediate, which may be readily purified by crystallization. This intermediate is then converted by ring condensation to the desired delta-9-THC. 

It has now been found that cannabidiol isomerizes upon treatment, for example, with a variety of reagents such as p-toluenesulfonic acid, sulfuric acid, hydrochloric acid and ethanol, hydrogen chloride in ether, pyridine hydrochloride, sulfamic acid, zinc chloride, ethanolic phosphoric acid, etc. and is converted to tetrahydro cannabinol which has marihuana activity and which may be represented by the following formula, with doubt merely in regard to the position of the double bond in the left-hand cycle. 

The tetrahydro cannabinols form acyl derivatives, such as the monoacetates, and ether-derivatives such as the monomethyl ether, with specific rotations corresponding to the rotation of the tetrahydro cannabinol from which each may be formed. 

When the tetrahydro cannabinols are reduced, regardless of the specific rotation of the initial material used, after absorption of one molecule of hydrogen a hexahydro cannabinol is produced. 

It will be obvious to those skilled in the art that the present invention is directed to the treatment of red oil (obtained from hemp and preferably American hemp) as well as the treatment of isolated cannabidiol. For example, a product of increased activity or potency may be obtained by treating purified red oil obtained from Minnesota wild hemp so as to isomerize the cannabidiol contained therein to tetrahydro cannabinol. It will also be understood by those skilled in the art that the present invention is not limited to any particular acid isomerizing agent or process. Source Adams 1947... 

Elsohly, M.A. Ross, S.A. Feng, S. Method of Preparing delta-9-Tetrahydro-cannabinol Esters 1999 US 6,008,383... 

Stoss, P. Merrath, P. Method for the Production of 6,12-dihydro-6-hydroxy-cannabidiol and the use Thereof for the Production of trans-delta-9-tetrahydro-cannabinol 1992 EP0494665... 

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