Chapter 3 Pharmacology of Cannabis and the Cannabinoids

CHAPTER 3 PHARMACOLOGY OF CANNABIS AND THE CANNABINOIDS 3.1 The plant Cannabis sativa is also known as hemp; it is related to the nettle and the hop. It grows readily in a warm climate, and may be grown in more temperate regions. As a drug of abuse, it usually takes the form of herbal cannabis (marijuana), consisting of the dried leaves and female flower heads, or cannabis resin (hashish), the resin secreted by the leaves and flower heads, which may be compressed into blocks. 3.2 The family of chemically related 21­carbon alkaloids found uniquely in the cannabis plant are known as cannabinoids. There are more than 60 different cannabinoids; one of these, D 9 ­tetrahydrocannabi ol (THC), is the most abundant and accounts for the intoxicating properties of c nabis. Other ca nabin ids which occur in some abundance (e.g. cannabidiol and cannabinol) are not psychoactive, but it is thought that they may modify the effects of THC. The amounts and proportions of the various cannabinoids in each plant vary from strain to strain, and can be adjusted by breeding. By coincidence, the chemistry and pharmacology of cannabis were among the principal interests of the late Lord Todd, when he worked at Manchester University in the 1930s; he went on to become, among other things, the first Chairman of the House of Lords Select Committee on Science and Technology on its establishment in 1979. 3.3 THC and other cannabinoids dissolve readily in fat but not in water. This limits the possible formulations of cannabis and cannabinoid preparations, and slows down their absorption from the gut. On the other hand, when cannabis is smoked (in a "joint" or "reefer", or in a pipe), THC is absorbed very quickly into the bloodstream, through the large surface area of the pharynx and the lungs. After smoking, the psychoactive effects of THC are perceptible within seconds, and peak effects are achieved within minutes. When cannabis or cannabinoids are taken by mouth, peak effects may not occur for several hours, but they last longer. After smoking or oral ingestion, the drug persists in the brain longer than in the blood; so the psychological effects persist for some time after the level of THC in the blood has begun to decline. 3.4 Smoking delivers 30 per cent or more of the total THC in a cannabis cigarette to the blood stream. The proportion of THC absorbed after taking cannabis by mouth is 2-3 times less, because after absorption in the gut the drug is largely degraded by metabolism in the liver before it reaches the general circulation. Preliminary reports indicate that absorption into the circulation can be increased if THC is administered by rectal suppository, as this route delivers the drug directly into the circulation, avoiding the liver. 3.5 Once THC has entered the bloodstream, it is widely distributed in the body, especially in fatty tissues. The slow release of THC from these tissues produces low levels of drug in the blood for several days after a single dose, but there is little evidence that any significant pharmacological effects persist for more than 4-6 hours after smoking or 6-8 after oral ingestion. The persistence of the drug in the body, and the continuous excretion of degradation products in the urine, can however give rise to cannabis­positive forensic tests days or even weeks after the most recent dose. (The implications of this for roadside testing of drivers are considered below, at paragraph 4.9.) 3.6 According to Professor Trevor Robbins, speaking for the Medical Research Council (MRC), "Cannabinoid pharmacology has exploded in the last decade1⁄4, opening up1⁄4all sorts of exciting possibilities" (Q 628). These advances are reviewed in evidence to this Committee by the Royal Society and by Dr Roger Pertwee of the University of Aberdeen[ 5 ]. It is now recognised that THC int racts with a naturally oc urring system i the body, known as th cannabinoid system. THC t k s effect by acting up n cannabinoid receptors (see Box 1). Two types of cannabinoid receptor have been identified: the CB1 receptor and the CB2 receptor. CB1 rec ptors are pr sent on n rve cells in the brain and spinal cord as well as in some peripheral tissues (i.e. tissues outside the brain); CB2 receptors are found mainly on cells of the immune system and are not present in the brain. 3.7 The roles played by CB1 and CB2 receptors in determining the various effects of cannabis in the whole organism remain to be established. Among the effects of cannabinoids known from animal experiments to be mediated by CB1 receptors are pain relief, impairments in memory and in the control of movements, lowering of body temperature and reductions in the activity of the gut. As CB1 receptors are the only ones known to exist in the brain, it is assumed that they mediate the intoxicant effects of THC. Little is known about the physiological role of the more recently discovered CB2 receptor, but it seems to be involved in the modulation of the function of the immune system. BOX 1: CANNABIS PHARMACOLOGY—TERMINOLOGY