Definitions

Types of Cannabinoids

Two numbering systems have been developed for cannabinoids. In the formal numbering system for pyran compounds (the dibenzopyran nomenclature), the main active ingredient is referred to as Δ9-THC. However, not all cannabinoids are pyran compounds; therefore, a second nomenclature was developed based on biogenetics (monoterpenoid nomenclature). In this older numbering system, Δ9-THC is actually referred to as Δ1-THC (which readers will find to be the case when looking at older literature).

Cannabis contains a total of 66 phytocannabinoids spanning several different subclasses of compounds, of which three are known to be psychoactive: Δ9-THC, Δ8-THC (67% of the potency of Δ9-THC as an isomer), and Δ9-tetrahydrocannabidivarin (25% of the potency of Δ9-THC as a propyl homolog). However, the latter two probably do not contribute greatly to the psychological or physiological effects of cannabis, representing considerably less than 10% of samples. The chemical structure of Δ9-THC was determined to be Δ1-3,4-trans-tetrahydrocannabinol (again, Δ1 is equivalent to Δ9). Over 483 natural components have been isolated (Table 8.3). Cannabis also frequently contains cannabinoid acids in various amounts relative to Δ9-THC, but many of these constituents are devoid of psychotropic effects. Cannabichromene has slight Δ9-THC-like effects. Cannabidiol appears to be largely inactive psychotropically. Cannabidiol does not bind to cannabinoid CB1 or CB2 receptors (for more on the receptor subtypes, see below), but it has been shown to have anti-arthritic properties in a mouse model of arthritis. It may also have anxiolytic-like and antipsychotic-like effects in animal models and may attenuate the effects of Δ9-THC (Table 8.4). Other cannabinoids, such as cannabinol, cannabigerol, cannabichromene, and cannabidiolic acid, appear to exert no major active or potentiating effects. The fiber type of the cannabis plant contains very little Δ9-THC. Dronabinol (Marinol) is the (−)trans-isomer of Δ9-THC, which is dissolved in sesame oil to create 2.5, 5.0, and 10 mg capsule formulations (Table 8.4).

TABLE 8.2

Average Cannabinoid Concentrations in Cannabis Preparations

Data from Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, Ross SA, Khan IA, ElSohly MA. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. Journal of Forensic Science, 2010, (55), 1209–1217.

TABLE 8.3

Cannabis Constituents

Chemical Class

Known Constituents in Cannabis

Cannabinoids

66

Nitrogenous compounds

27

Amino acids

18

Proteins, glycoproteins, and enzymes

11

Sugars and related compounds

34

Hydrocarbons

50

Simple alcohols

7

Simple aldehydes

12

Simple ketones

13

Simple acids

21

Fatty acids

22

Simple esters and lactones

13

Steroids

11

Terpenes

120

Noncannabinoid phenols

25

Flavonoids

21

Vitamins

1

Pigments

2

Elements

9

Total

483

Taken with permission from ElSohly MA. Chemical constituents of Cannabis. In: Grotenhermen F, Russo E (eds) Cannabis and Cannabinoids: Pharmacology, Toxicology and Therapeutic Potential. Haworth Integrative Healing Press, New York, 2002, pp. 27–36.

TABLE 8.4

Approved Medical Uses of Cannabinoids

Dronabinol (Marinol) is the pure isomer of Δ9-THC. It is available as a prescription drug in the United States and is approved by the Food and Drug Administration for nausea and vomiting in patients who undergo chemotherapy and anorexia in AIDS wasting syndrome. The pharmacokinetics of oral THC are far less conducive to psychotropic effects than those of smoked cannabis. The absorption of smoked THC is very rapid, with peak levels of intoxication reported after ∼30 min compared with 90 min or longer for oral administration.

Nabilone (Cesamet) is a synthetic analog of THC and was approved for use in the United States for nausea and vomiting in patients who undergo chemotherapy and anorexia in AIDS wasting syndrome. It is administered orally, so the same pharmacokinetic issues as dronabinol are relevant.

Nabiximols (Sativex) is a patented oromucosal mouth spray that is a cannabinoid-based medicine for multiple sclerosis. It is composed of the two main active ingredients of Cannabis sativa: a 1:1 mixture of Δ9-THC + cannabidiol. The psychotropic effects of Sativex are alleged to be less than smoked cannabinoids. Again, it is administered orally, so the same pharmacokinetic issues as dronabinol are relevant. The levels of THC in the blood are much less after oromucosal use of Sativex at equivalent doses (163 ng/ml smoked; 8.8 ng/ml Sativex spray; for further reading, see Stott et al., 2008). Sativex is being marketed in the United Kingdom, Canada, and a number of European countries for the treatment of spasticity associated with multiple sclerosis.

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