The Pharmacology of Cannabis

A detailed description of the pharmacological effects of Cannabis was already accessible to Greek and Roman physicians in the first century AD, when Dioscorides included the plant in his classic textbook of Materia Medica (Fig. 6.2). As expected from the wide distribution of Cannabis in the Far East, ancient Indian and Chinese medical writers were also familiar with its therapeutic usage and were indeed much more accurate than their European 

We know now that these central effects—which, from animal and human studies, are often epitomized as a combination of euphoria, analgesia, hypomotility and hypothermia—are principally caused by the dibenzopyrane derivative, A -tetrahydrocannabinol, 

A partial answer to this question, whose therapeutic significance should not be underestimated, came from the discovery of a second cannabinoid receptor restricted in its localization to macrophages resident in the marginal zone of spleen and, possibly, to peripheral mast cells.This receptor, called CB2, has only about 

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Dixon, W.E The Pharmacology of Cannabis Indica British Medical Journal (1899) 2 1354-1357 1517... 

The pharmacology of Cannabis, and, in the last 20 years, of A -THC, has been the object of thousands of publications and has been thoroughly reviewed. Most of the work has centered on the cannabimimetic effects in man as well as in various animal species. As the cannabimimetic effect has no medicinal value, we shall refrain from a detailed recapitulation of the well-reviewed material on this particular aspect. We would like to refer the reader to some recent reviews as well as to several older, critical, thoughtful and surprisingly topical reviews by Sir W.D.M. Paton and his colleagues from 1973 and 1975 [3-8, 52-61]. In the present review, we shall address ourselves to and summarize only four aspects related to cannabimimetic action (a) pharmacological test methods (b) structure-activity relationships (SAR) (c) stereochemical requirements and (d) recent approaches to the biochemical basis of cannabimimetic action. 

Paton, WD.M, and R.G. Pertwee 1973A. The pharmacology of Cannabis in animals In Mechoulam, R. (Ed.) Marijuana Chemistry, Pharmacology, Metabolism and ClinicalEjfcts. Academic Press, New rk. pp. 191-285. 

Cannabinoids were used in medicine in the form of their crude extracts many centuries ago. Lately the use of cannabis for so-called recreational purposes has become a national vice of substantial proportions. Several attempts have been made to focus the potentially useful pharmacological properties of marijuana into drug molecules with no abuse potential. 

In summary, research on the use of antidepressants to treat cannabis dependence, particularly among individuals with comorbid major depressive disorder, although limited, offers a promising avenue for the development of pharmacological aids to assist in the treatment of cannabis withdrawal. There are clear parallels between this literature and the existing research on the use of antidepressants in the treatment of alcohol dependence comorbid with major depressive disorder (see Chapter 1, Medications to Treat Co-occurring Psychiatric Symptoms or Disorders in Alcoholic Patients). 

An annotated bibliography (3045 references 1964—1974) of marihuana has been published " and the pharmacology of marihuana, " the analysis and biochemical aspects " of Cannabis, and the chemistry of cannabinoids have been reviewed. The analysis of THC and metabolites in physiological fluids has been discussed. ... 

Hardman, H.F., and Hosko, M.J. Autonomic effects An overview of the cardiovascular-autonomic actions of cannabis. In Braude, M.C., and Szara, S., editors. The Pharmacology of Marihuana. 

The use of cannabis is widespread and in all parts of society in long term and heavy use has been thought to cause various organic changes which have never been fully evaluated. In vulnerable individuals a cannabis induced psychosis can occur which can be long lasting and difficult to treat even in spite of intensive pharmacological treatment. 

The chief differences in the use of cannabis between the United States and Morocco are smoking technique, pharmacology, and formality. Although kif is more readily available and cheaper in Morocco, it appeared from sessions with the... 

Cannabis and some cannabinoids relieve pain. However, the therapeutic doses are essentially equivalent to the doses that cause CNS effects and, except in very specific conditions (possibly migraine) they are of limited use. Although several companies have produced a large number of derivatives, as previously reviewed in this series [1] and elsewhere [105,107] the situation has not changed. No practical separation of activity has been achieved, except with the synthetic cannabinoid HU-211 (see below) which does not bind to either CBi or CB2. Hence most of the work reported in the last decade deals mainly with the pharmacology of pain reduction by cannabinoids, rather than with drug discovery and development. 

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. 

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)). 

J.W. Fairbaim et al., The Stability of Cannabis and its Preparations on Storage, Journal of Pharmacy and Pharmacology 28 (1976) 1 C.E. Turner et al., Constituents of Cannabis Sativa L. IV Stability of Can-nabinoids in Stored Plant Material, Journal of Pharmaceutical Science 62(1973) 1601. 

Zeeuw, R.A. de et al. A -Tetrahydrocannabinolic Acid, an Important Component in the Evaluation of Cannabis Products. Journal of Pharmacy and Pharmacology 24 (1972) 1. 

The interest in Mechoulam s study extended very rapidly from the field of Cannabis pharmacology to that of arachidonic acid biochemistry. In fact, it had not escaped the attention of many readers of the Science report that the chemical structure of the endogenous cannabinoid isolated by the Jerusalem s group—called anandamide after ananda, the Sanskrit word for bliss —was that of a unique arachidonic acid derivative, N-arachidonoylethanol-amine. This structure, depicted in Figure 6.1, clearly showed that anandamide was not produced through any of the then known metabolic transformations of free arachidonate. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

Nabitan (39) is a cannabis-inspired analgesic whose nitrogen atom was introduced in order to improve water solubility and perhaps to affect the pharmacological profile as well. The phenolic hydroxyl of benzopyran synthon is esterified with 4-(l-piperidino)butyric acid under the influence of dicyclohexyl carbodi mi de. In addition to being hypotensive and... 

Based on the role of endocannabinoids and cannabinoid receptors in several pathological conditions, the pharmacological manipulation of their levels or action is being developed as a therapeutic strategy. Enhancement of endocannabinoid signalling when this plays uniquely a protective role can be effected in a safer way using (i) cannabis extracts in which the presence of non-psychotropic cannabinoids with therapeutic activity per... 

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