Cannabis is a natural product, the main psychoactive constituent of which is tetrahydrocannabinol (Δ9-THC). The cannabis plant (Cannabis sativa L.) is broadly distributed and grows in temperate and tropical areas. Together with tobacco, alcohol and caffeine, it is one of the most widely consumed drugs throughout the world, and has been used as a drug and a source of fibre since historical times. Herbal cannabis consists of the dried flowering tops and leaves. Cannabis resin is a compressed solid made from the resinous parts of the plant, and cannabis (hash) oil is a solvent extract of cannabis. Cannabis is almost always smoked, often mixed with tobacco. Almost all consumption of herbal cannabis and resin is of illicit material. Some therapeutic benefit as an analgesic has been claimed for cannabis, and dronabinol is a licensed medicine in some countries for the treatment of nausea in cancer chemotherapy. Cannabis products and Δ9-THC are under international control.
The major active principle in all cannabis products is Δ9- tetrahydrocannabinol (Δ9-THC or simply THC), also known by its International Non-Proprietary Name (INN) as dronabinol. The unsaturated bond in the cyclohexene ring is located between C-9 and C-10 in the more common dibenzopyran ring numbering system. There are four stereoisomers of THC, but only the (–)-trans isomer occurs naturally (CAS-1972-08-03). The fully systematic name for this THC isomer is (−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol. Two related substances, Δ9- tetrahydrocannabinol-2-oic acid and Δ9-tetrahydrocannabinol-4-oic acid (THCA), are also present in cannabis, sometimes in large amounts. During smoking, THCA is partly converted to THC. The active isomer Δ8-THC, in which the unsaturated bond in the cyclohexene ring is located between C-8 and C-9, is found in much smaller amounts.
Other closely related substances that occur in cannabis include cannabidiol (CBD) and, in aged samples, cannabinol (CBN), both of which have quite different pharmacological effects to THC. Other compounds include the cannabivarins and cannabichromenes; they are all collectively known as cannabinoids. Unlike many psychoactive substances, cannabinoids are not nitrogenous bases.
(1) Δ9-tetrahydrocannabinol, the major psychoactive principle of cannabis, showing the partial ring numbering system in the more common dibenzofuran system.
Cannabis sativa is dioecious: there are separate male and female plants. The THC is largely concentrated around the flowering parts of the female plant. The leaves and male plants have less THC, while the stalks and seeds contain almost none. Plants have characteristic compound leaves with up to 11 separate serrated lobes. Imported herbal cannabis occurs as compressed blocks of dried brown vegetable matter comprising the flowering tops, leaves, stalks and seeds of Cannabis sativa. Cannabis resin is usually produced in 250-g blocks, many of which carry a brandmark impression. Cannabis oil is a dark viscous liquid.
The pharmacology of cannabis is complicated by the presence of a wide range of cannabinoids. At small doses, cannabis produces euphoria, relief of anxiety, sedation and drowsiness. In some respects, the effects are similar to those caused by alcohol. Anandamide has been identified as the endogenous ligand for the cannabinoid receptor and has pharmacological properties similar to those of THC. When cannabis is smoked, THC can be detected in plasma within seconds of inhalation; it has a half-life of 2 hours. Following smoking of the equivalent of 10–15 mg over a period of 5–7 minutes, peak plasma levels of Δ9-THC are around 100 μg/L. It is highly lipophilic and widely distributed in the body. Two active metabolites are formed: 11-hydroxy-Δ9-THC and 8β-hydroxy-Δ9-THC. The first is further metabolised to Δ9-THC-11-oic acid. Two inactive substances are also formed — 8α-hydroxy-Δ9-THC and 8α,11-dihydroxy-Δ9-THC — and many other minor metabolites, most of which appear in the urine and faeces as glucuronide conjugates. Some metabolites can be detected in the urine for up to 2 weeks following smoking or ingestion. There is little evidence for damage to organ systems among moderate users, but consumption with tobacco carries all of the risks of that substance. Most interest in the adverse properties of cannabis has centred on its association with schizophrenia, although it is still unclear if there is a causative relation between mental health and cannabis. Fatalities directly attributable to cannabis are rare.
Herbal cannabis imported into Europe may originate from West Africa, the Caribbean or South-East Asia, but cannabis resin derives largely from either North Africa or Afghanistan. Cannabis oil (hash oil) is often produced locally from cannabis or cannabis resin by means of solvent extraction. Intensive indoor cultivation has become widespread in Europe and elsewhere. This is based on improved seed varieties and procedures such as artificial heating and lighting, hydroponic cultivation in nutrient solutions and propagation of cuttings of female plants. It leads to a high production of flowering material (sometimes known as ‘skunk’). As with other naturally occurring drugs of misuse (e.g. heroin and cocaine), total synthesis is not currently an economic proposition. No precursors to THC are listed in the United Nations 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.
Cannabis and cannabis resin are listed in Schedules I and IV of the United Nations 1961 Single Convention on Narcotic Drugs. In Article 1, Paragraph 1, of that Convention, cannabis is defined as: ‘The flowering or fruiting tops of the cannabis plant (excluding the seeds and leaves when not accompanied by the tops) from which the resin has not been extracted, by whatever name they may be designated.’ Cannabis resin is defined as: ‘The separated resin, whether crude or purified, obtained from the cannabis plant.’ Along with a number of its isomers and stereochemical variants, Δ9-THC is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.
Tinctures of cannabis (ethanolic extracts) were once common, but were removed from pharmacopoeias many years ago. Herbal cannabis (known as ‘cannabis flos’), with a nominal THC content of 18 %, is available as a prescription medicine in The Netherlands. It is indicated for multiple sclerosis, certain types of pain and other neurological conditions. An extract of cannabis (Sativex) has been licensed in Canada.