Cannabis is the preferred designation of the plant Cannabis sativa, Cannabis indica, and of minor significance, Cannabis ruderalis. According to the 1961 United Nations Single Convention on Narcotic Drugs, 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 means “separated resin, whether crude or purified, obtained from the cannabis plant’’.
These definitions are narrower than the botanical definition and as a consequence, certain parts of the plant are not under international control. The term cannabis will be used instead of marijuana, or other names indigenous to local cultures, unless there is a need to refer to a specific phrase, e.g. medical marijuana ballot initiatives. Its use for medicinal, ritual or recreational purposes results from the actions of cannabinoids in the cannabis plant. These compounds also produce the unintended adverse consequences of cannabis.
Cannabinoids are basically derived from three sources: (a) Phytocannabinoids are cannabinoid compounds produced by plants Cannabis sativa or Cannabis indica; (b) Endocannabinoids are neurotransmitters produced in the brain or in peripheral tissues, and act on cannabinoid receptors; (c) Synthetic cannabinoids, synthesized in the laboratory, are structurally analogous to phytocannabinoids or endocannabinoids and act by similar biological mechanisms.
Cannabis, produced from the Cannabis sativa plant, is used in three forms: herbal cannabis, the dried leaves and flowering tops, also known as ‘cannabis,’ ganja,’ or ‘weed,’ among others; cannabis resin, the pressed secretions of the plant, known as ‘hashish’ or ‘charash;’ and cannabis oil, a mixture resulting from distillation or extraction of active ingredients of the plant.
Herbal cannabis is the cannabis product used most frequently in much of the world, while cannabis resin is primarily used in Europe. Cannabis oil is less widely used, accounting for only 0.05% of cannabis seizures in 2009 ( UNODC, Cannabis in Africa: An Overview, 2007)
Cannabis and Addiction
Long-term cannabis use can lead to tolerance to the effects of THC, as well as addiction. Cannabis dependence is the most common type of drug dependence in many parts of the world, including the United States, Canada, and Australia, after tobacco and alcohol.
It is estimated that 1 in 9 cannabis users overall will become dependent. Those who begin using the drug in their teens have approximately a one in six risk of developing dependence. (Wagner, F.A. & Anthony, J.C. From first drug use to drug dependence; developmental periods of risk for dependence upon cannabis, cocaine, and alcohol. Neuropsychopharmacology 26, 479‐488 (2002)).
Users who try to quit experience withdrawal symptoms that include irritability, anxiety, insomnia, appetite disturbance, and depression. A United States study that dissected the National Longitudinal Alcohol Epidemiologic Survey (conducted from 1991 to 1992 with 42,862 participants) and the National Epidemiologic Survey on Alcohol and Related Conditions (conducted from 2001 through 2002 with more than 43,000 participants) found that the number of cannabis users stayed the same while the number dependent on the drug rose 20 percent ‐ from 2.2 million to 3 million. (Compton, W., Grant, B., Colliver, J., Glantz, M., Stinson, F. Prevalence of Cannabis Use Disorders in the United States: 1991‐1992 and 2001‐2002 Journal of the American Medical Association. 291:21142121.)
Young people are especially susceptible to cannabis addiction. Research from treatment centers in the United States indicates that the earlier drug use is initiated, the higher the risk for abuse and dependence. In 2006, 10 percent of adults 21 and older who first tried cannabis at age 14 or younger were classified with illicit drug abuse or dependence compared to 2 percent of adults who had first used cannabis at age 18 or older.
The early use of more potent cannabis may be driving admissions for treatment of cannabis abuse. In 2006, 82 percent of admissions in individuals under age 18 reported cannabis use at the time of admission. This is with 56 percent of those under age 18 who were admitted for alcohol use (Substance Abuse and Mental Health Services Administration. (2009). Office of Applied Studies. (Treatment Episode Data Set (TEDS): 2009 Discharges from Substance Abuse Treatment Services, DASIS.)
Cognition and coordination
Crean, Crane & Mason (2011) reviewed a broad spectrum of cognitive functions, designated as executive functions, and identified studies that reported that attention, concentration, decision-making, impulsivity, inhibition (self-control of responses), reaction time, risk taking, verbal fluency and working memory were impaired acutely in a dose-dependent manner, although these effects were not consistently observed.
Cannabis acutely impairs several components of cognitive function, with the most robust effects on shortterm episodic and working memory, planning and decision-making, response speed, accuracy and latency (Ranganathan & D’Souza, 2006). Some studies also report increased risk-taking and impulsivity (Crean, Crane & Mason, 2011). Less experienced cannabis users undergo stronger intoxicating effects on attention and concentration than those with established drug tolerance.
Cannabis also acutely impairs motor coordination, interferes with driving skills and increases the risk of injuries. Evidence suggests that recent cannabis smoking is associated with substantial driving impairment, particularly in occasional smokers, with implications for work in safety-sensitive positions or when operating a means of transportation, including aircraft (Hartman & Huestis, 2013). Complex human/machine performance can be impaired as long as 24 hours after smoking a moderate dose of cannabis and the user may be unaware of the drug’s influence (Leirer, Yesavage & Morrow, 1991).
Anxiety and psychotic symptoms
A minority of first-time cannabis users become very anxious, have panic attacks, experience hallucinations and vomit. These symptoms may be sufficiently distressing to prompt affected users to seek medical care (Smith, 1968; Thomas, 1993; Weil, 1970). Long-term users may also have negative experiences if they use more potent cannabis products than usual, or use cannabis by an unfamiliar route (e.g. oral ingestion) that does not permit them to achieve their usual dose of THC.
Hallucinations may occur after using very high doses of THC, and may occur at lower doses in individuals with a pre-existing vulnerability to psychosis (e.g. having experienced psychotic symptoms or having a first-degree relative with a psychotic disorder). These distressing experiences are often time-limited and can usually be managed by reassurance and mild sedation in a safe environment (Dines et al., 2015).
The risk of a fatal cannabis overdose is extremely small compared to the risks of opioid and stimulant drug overdoses (Gable, 2004). The dose of THC that reliably kills rodents is extremely high and the equivalent fatal dose in humans extrapolated from animal studies is between 15 g (Gable, 2004) and 70 g (Iversen, 2007; Lachenmeier & Rehm, 2015). This is much greater than the amount of cannabis that a very heavy user would consume in a day (Gable, 2004). There are no reports of fatal overdoses in the epidemiological literature (Calabria et al., 2010b). The lack of respiratory overdoses is consistent with the absence of cannabinoid receptors in brain stem areas that control respiration (Iversen, 2012).
Acute cardiovascular effects
Acute exposure to cannabis increases heart rate and blood pressure and can in some cases cause orthostatic hypotension (Pacher & Kunos, 2013; Schmid et al., 2010). There have been case reports of serious cardiovascular complications, including acute coronary syndromes and strokes, in cannabis users (Jouanjus, 2014). Mittleman and colleagues found that the risk of myocardial infarction was four times higher in patients with a recent myocardial infarction in the hour after smoking cannabis compared to cannabis users without a history of myocardial infarction (Mittleman et al., 2001). The risk then declined rapidly.
Acute effects on lungs and airways
The acute bronchial effects of smoking tobacco and smoking cannabis differ; tobacco smoking produces acute bronchial constriction, while cannabis smoking causes acute bronchial dilation in proportion to the dose of THC (Tashkin, 2015).This effect has been reported in cannabis users in the United States where cannabis used to be smoked alone. Users in many parts of the world frequently smoke cannabis and tobacco together (especially when cannabis resin is used), and this combination is likely to produce different acute bronchial effects.
Psychosis and schizophrenia
In discussing relationships between cannabis use, psychosis and schizophrenia, it is necessary to define psychosis and schizophrenia clearly. Schizophrenia is a mental and behavioural disorder classified in the ICD10. Schizophrenia is characterized by distortions in thinking, perception, emotions, language, sense of self and behaviour. Common experiences include hearing voices and delusions (WHO, 1992). Regular cannabis use has been reported to be more common among persons with schizophrenia (Myles, Myles & Large, 2015). The regular use of cannabis with a higher THC content and a lower CBD concentration may increase the risk for schizophrenia and lower the age of onset of the disease (Di Forti et al., 2014, 2015)
Suicide risk, ideation and attempts
Bagge and Borges (Bagge & Borges, 2015) conducted a case-crossover study of 363 persons who had recently attempted suicide and were treated in a trauma hospital for a suicide attempt within the previous 24 hours in the state of Mississippi, USA. The researchers compared rates of cannabis use in the 24 hours leading up to the suicide (case period) to that in the 24 hours of the day before the suicide (control period). They found that 10.2% of suicide attempters had used cannabis in the case period while 13.2% used cannabis in the control period.
The USA’s Drug Abuse Warning Network (DAWN) estimated rates of cannabis use among drug-related visits to hospital emergency departments for suicide in 2011 (SAMHSA, 2013). Cannabis was coded as positive if hospital staff perceived it to be the cause or a contributor to the emergency visit. Cannabis was involved in an estimated 6.5% of drug-related suicide attempts, and in 46% of attempts the person also used alcohol. In the 23% of drug-related suicide attempts with toxicology reports, 16.8% tested positive for cannabis, although this cannabis use could have occurred days or even up to one week earlier. In general, 9.5% of all toxicology reports for deaths by suicide (Borges, Bagge & Orozco, 2016) show the presence of cannabis.
In recent decades, the incidence of stroke in young adults has increased, as have case reports of stroke in cannabis smokers (Wolff et al., 2013). In 2013, Wolff found only 59 cases of cannabis-associated strokes in the literature. These were ischaemic strokes or transient ischaemic attacks that occurred in persons with a mean age of 33 years.
By 2015, around 100 cases of cannabis-related ischaemic stroke had been reported (Wolff et al., 2013; Desbois & Cacoub, 2013; Hackam, 2015; Wolff et al., 2015). Some case-control studies also suggested that cannabis smoking was a risk factor for stroke in young adults (Barber et al., 2013), and at least five cases of ischaemic stroke have been reported in persons using synthetic cannabinoids (Benson-Leung, Leung & Kumar, 2013; Freeman et al., 2013; Takematsu et al., 2014).
THC and other cannabinoids are not carcinogens in microbial assays (MacPhee, 1999; Marselos & Karamanakos, 1999) or tests using rats and mice (Chan, 1996). However, cannabis smoke is carcinogenic in these assays (MacPhee, 1999; Marselos & Karamanakos, 1999; Leuchtenberger, 1983). This suggests that cannabis smoking could, like cigarette smoking, be a cause of cancers of the lung, the upper aerodigestive tract (mouth, tongue, oesophagus) and bladder (MacPhee, 1999).
This could be true because there is a strong qualitative similarity between the carcinogens found in cannabis and tobacco smoke (Institute of Medicine, 1999; Van Hoozen & Cross, 1997). The existing case reports raise a suspicion, but provide limited support for the hypothesis, that cannabis use can cause upper respiratory tract cancers. The quality of the case reports is insufficient as they do not compare rates of cannabis use in cases and controls; rather, they assess cannabis exposure retrospectively, in the knowledge that the user has cancer, and they do not control for confounding factors such as alcohol and tobacco use (Hall et al., 2002).