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.
Molecular structure (1)
Molecular formula: C21H30O2
Molecular weight: 314.4 g/mol
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 is usually smoked, often mixed with tobacco or in a smoking device (bong). Because THC has a low water solubility, ingestion of cannabis leads to poor absorption. The average ‘reefer’ cigarette contains around 200 mg of herbal cannabis or cannabis resin.
In many countries, herbal cannabis and cannabis resin are formally known as marijuana and hashish (or just ‘hash’) respectively. Cannabis cigarettes may be termed reefers, joints or spliffs.Street terms for cannabis/cannabis resin include bhang, charas, pot, dope, ganja, hemp, weed, blow, grass and many others.
Although the leaves of Cannabis sativa are reasonably characteristic, cannabis and cannabis resin can both be positively identified by low-power microscopy, where the appearance of glandular trichomes and cystolithic hairs is diagnostic. The Duquenois test is considered to be specific for cannabinols. It is based on the reaction of cannabis extracts with p-dimethylbenzaldehyde. This produces a violet blue coloration that is extractable into chloroform. The mass spectrum of THC shows major ions at m/z = 299, 231, 314, 43, 41, 295, 55 and 271. Using gas chromatography, the limit of detection of THC in blood is 0.3 μg/L.
In 2009, cannabis resin at retail level in Europe was reported to have an average THC content that varied from 2.9 % (Bulgaria) to 17.3% (Netherlands), while herbal cannabis potency ranged from 1.3 % (Hungary) to 15.1 % (Netherlands) (Table PPP-5 part (i), An overview of cannabis potency in Europe). Herbal cannabis produced by intensive indoor methods may have an average potency two or three times greater than that of imported herbal cannabis, although the two overlap. In some EU countries there is licensed cultivation of cannabis for fibre production (hemp), but the THC content of these plants is less than 0.3 %. Small amounts of cannabis resin are illicitly produced in the EU (e.g. nederhasj). Like cannabis oil, this product may have THC content in excess of 30 %.
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.
Population surveys conducted in Europe indicate that between 1.5 % (Romania, 2007) and 32.5 % (Denmark, 2010) of adults (aged 15–64 years) have tried the substance at least once, depending on the country (Table GPS-1 part (ii)). A rough European estimate would suggest that around 22 % of adults have ever tried cannabis, representing 74 million European adults. The fact that recent (last 12 months) or current (last 30 days) use is substantially lower than lifetime experience indicates that a substantial proportion of cannabis use is occasional, or discontinued after some time (Figure GPS-2). Information from most recent surveys shows a stabilisation of cannabis use in most countries.
In 2009, the retail price of cannabis resin in the EU was reported as varying from EUR 3 (Portugal) to EUR 19.2 (Estonia) per gram, while the price of herbal cannabis ranged from EUR 2.3 (Bulgaria) to EUR 70 (Malta) per gram, (Table PPP-1 part (i)). Average retail prices of cannabis resin, remained stable over the period 2004–09 in EU countries reporting sufficient data for trend analysis whereas average retail prices of herbal cannabis rose slightly over the same period (Figure PPP-1).
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.
EMCDDA (2007, in production), A cannabis reader. Global issues and local experiences: Perspectives on cannabis controversies, treatment and regulation in Europe, European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
King, L. A. and McDermott, S. (2004), ‘Drugs of abuse’, in: Moffat, A. C., Osselton, M. D. and Widdop, B. (eds.) Clarke's Analysis of Drugs and Poisons, 3rd edn, Vol. 1, pp. 37–52, Pharmaceutical Press, London.
King, L. A., Carpentier, C. and Griffiths, P. (2004), An Overview of Cannabis Potency in Europe, Insights no. 6. European Monitoring Centre for Drugs and Drug Addiction, Lisbon.
United Nations (2006), Multilingual Dictionary of Narcotic Drugs and Psychotropic Substances under International Control, United Nations, New York.
United Nations Office on Drugs and Crime (2004), World Drug Report 2004, Vol. 1: Analysis, United Nations Office on Drugs and Crime, Vienna (http://www.unodc.org/pdf/WDR_2004/volume_1.pdf).
The following publications have been proposed for further reading by Reitox national focal points. They represent a shortlist of key publications on the drug in each Member State*.
Ministry of Public Health of Belgium (2003), Cannabis 2002 report, Brussels.
Decorte, T., Muys, M. and Slock, S. (2003), Cannabis in Vlaanderen, Acco, Leuven.
Patesson, R., Steinberg, P. and Joris, L. (2003), Enquête jeunes et bien-être. Premiers résultats cannabis, ecstasy et autres substances, ULB, Rodin Foundation, V4.
Peuskens, J. (2003), Psychiatrische effecten van cannabisgebruik: een kritische analyse van wetenschappelijke resultaten en onderzoeksmethoden, Project DR/01/007, Universitair Centrum St.Jozef, Kortenberg.
Rysheuvels, S., Schotte, C. and Sabbe, B. (2005), Medicinale cannabis: meta-analyse van het onderzoek naar de doeltreffendheid en doelmatigheid van het medicinaal gebruik van cannabis, Academia Press, Gent.
Spruit, I. P. (2002), International Scientific Conference on Cannabis, Ministry of Public Health of Belgium, Brussels.
Van Tichelt, K., Canfyn, M., Govaerts, C., Lenaerts, K., Piette, V. and Parmentier, F. (2004), THC concentraties in cannabis in 2003 en 2004, FOD Volksgezondheid, Veiligheid van de Voedselketen en Leefmilieu - WIV - Afdeling Geneesmiddelenanalyse, Brussel.
Täschner, K.-L. (2005), Cannabis. Biologie, Konsum und Wirkung. Deutscher Ärzte-Verlag, Köln.
Bobes, J. and Calafat, A. (2000), Monografia Cannabis.
Choquet, M., Ledoux, S and Hassler, C. (2002), Alcool, tabac, cannabis et autres drogues illicites parmi les élèves de collège et de lycée. ESPAD, OFDT, Paris.
Beck, F., Legleye, S. and Peretti-Watel, P. (2002), Alcool, tabac, cannabis et autres drogues illicites parmi les élèves de collège et de lycée. ESPAD, OFDT, Paris.
INSERM (2001), Cannabis: quels effets sur le comportement et la santé?, Paris.
Ramström, J. (2004), Skador av hasch och marijuana: en genomgång av vetenskapliga studier publicerade till och med hösten 2003 [Adverse health consequences of cannabis use: a survey of scientific studies into the range of damage to health caused by cannabis], Statens folkhälsoinstitut, Stockholm.
Ramström, J. (2004), Adverse health consequences of cannabis use, National Institute of Public Health, Sweden.
* Please note that not all national focal points have provided references so the list above cannot be considered exhaustive. Moreover, inclusion in this list does not imply that the EMCDDA endorses these publications. The views expressed in these publications are those of the authors and do not necessarily reflect those of the EMCDDA.