Adverse effects of chronic cannabis use

In Europe, according to the European Monitoring Centre (EMCDDA, 2013)¹, 22% (70 million) of those aged between 15 and 64 years have used cannabis preparations (mainly marijuana) for recreational purposes at least once in their lifetime, 7% (23 million) within the last year, and 4% (14 million) within the last month. These percentages increase (17%) when considering use in the last year, in the age range 15-24 years. Cannabis use begins in adolescence and its prevalence is highest between 15 and 24 years of age (late teens-early adulthood), the period corresponding to secondary school and college, drastically reducing the uptake of work, family and social responsibilities. In general, the risk and severity of adverse effects associated with long-term daily use of cannabis are higher in adolescence, a critical developmental stage in which the brain undergoes final maturation, with the training and pruning of excess synapses.^2.3

Dependency

Cannabis use is associated with addiction in 9% of those who have used it at least once in their life (lifetime prevalence), in 17% of adolescents and in 25-50% of daily users.⁴ Although cannabis use is associated with a risk of developing addiction about three times lower than that for harder drugs (e.g. heroin), the prevalence of cannabis use is such that addiction to cannabis is now a social problem that is no less serious than heroin addiction. In fact, over the last decade the nature of the soft drug cannabis has been changing, mainly due to the introduction of new techniques for cultivating traditional varieties (Sensimilla) and genetically modified cultivars containing higher concentrations of tetrahydrocannabinol (THC). For this reason, the titration of marijuana preparations has gradually increased, rising from 4% in 1995 to 12%.^3,4 Perhaps partly because of these developments, the profile of cannabis addiction has become increasingly similar to that for hard drugs, with clear identification and coding as a body of symptoms (DSM-V), and of a withdrawal syndrome characterized by strong desire to consume the drug (craving), irritability, aggression, dysphoria, depression, anorexia, sleep disturbances, strange dreams and motor agitation. On abstaining from cannabis, the physical symptoms are less intense than those for alcohol and heroin abstinence, but not the craving.⁵ Abstinence has a motivational role in cannabis use, as evidenced by the fact that subjects in withdrawal consume cannabis in order to mitigate the effects, and abstinence makes it hard to stop using it.

Gateway hypothesis

One of the most controversial aspects of cannabis epidemiology is the possibility that its use in adolescence smoothes the transition towards using illegal drugs with a higher potential for abuse. Various mechanisms have been proposed to explain this association.
Although not explicitly, the gateway hypothesis suggests that the relationship between cannabis and drugs with a high potential for abuse is a causal one, which is due to the properties of cannabis.
Alternatively, the association between the use of cannabis and other drugs could derive from a combination of individual factors, of genetic or environmental origin (common liability). For example, a lower impulse control, or a greater tendency to seek gratification (reward seeking) in which genetic factors could lead to greater individual vulnerability towards using cannabis and other illicit drugs. Another possibility is that people who use cannabis have a greater opportunity of being exposed to the other drugs they share the illegal market with.⁵
The hypothesis of a causal relationship between the use of cannabis and hard drugs cannot be proved using epidemiological methods; experimental preclinical studies, however, have shown that repeated exposure to THC, the active ingredient of cannabis, during adolescence is associated with an increase in the gratifying properties and reinforcement with heroin in rats with a genetic vulnerability to drugs.⁵ Therefore, in genetically predisposed subjects, exposure to cannabis increases the risk of using hard drugs (heroin).

Cognitive disturbances

Daily use of cannabis in adolescence is associated with impaired development of cognitive brain areas like the precuneus and the hippocampus, with a reduction of cognitive function in adulthood, an overall reduction in IQ, reduced school performance and an increase in the frequency of interruption to studies.
Metabolic and local oxygenation studies using brain imaging (functional magnetic resonance imaging, positron emission tomography), combined with the neuropsychological study of cognitive function have shown that in daily adult consumers, normal cognitive performance is achieved via the recruitment of other brain areas, the function of which compensates for malfunctioning of the areas normally delegated to these functions.
Therefore, the lack of detectable cognitive impairment using neuropsychological testing does not exclude the existence of functional deficits associated with heavy cannabis use. Longitudinal studies exclude the possibility that the long-term cognitive impairments associated with cannabis use are the same as those before use, even if they cannot prove the causal relationship.³

Schizophrenia

Regular use of cannabis doubles the risk of developing a schizophrenic psychosis (from 7/1,000 to 14/1,000). This risk is doubled (from 10 to 20%) in the case of individuals who have a first-degree relative affected by psychosis.⁶
Using cannabis anticipates the emergence of psychotic symptoms in susceptible individuals within 2-6 years, depending on the frequency of use, the potency of cannabis preparations and early systemic exposure. If there was a causal relationship between cannabis use and the onset of schizophrenia, the increased prevalence of cannabis use that occurred in the 80s and 90s should correspond to an increased incidence of schizophrenia relative to previous years. Two studies have confirmed this prediction, but another two were negative, and a fifth study in 2008 concluded it was too early to draw conclusions. Unfortunately, no more recent studies are available.^4,7

Other adverse effects

Cannabis is considered to be a drug with an acute mortality index close to zero. The heavy use of cannabis is nevertheless associated with cardiovascular and respiratory disorders. There have been reports of sudden deaths in people smoking marijuana who suffer from heart disease, in which the cause of death was attributed to the cardio-stimulant effects of cannabis.⁸
Heavy cannabis smoking is associated with an increased risk of chronic bronchitis, and an increased risk of lung infections and lung cancer. However, in these studies, the use of tobacco is a key confounding element hence no conclusions can be drawn on the actual role of cannabis smoking in these conditions.