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Effect on Brain Development

ADVERSE EFFECTS

Risk of Addiction

Despite some contentious discussions regarding the addictiveness of marijuana, the evidence clearly indicates that long-term marijuana use can lead to addiction. Indeed, approximately 9% of those who experiment with marijuana will become addicted (according to the criteria for dependence in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV]). The number goes up to about 1 in 6 among those who start using marijuana as teenagers and to 25 to 50% among those who smoke marijuana daily. According to the 2012 National Survey on Drug Use and Health, an estimated 2.7 million people 12 years of age and older met the DSM-IV criteria for dependence on marijuana, and 5.1 million people met the criteria for dependence on any illicit drug (8.6 million met the criteria for dependence on alcohol). There is also recognition of a bona fide cannabis withdrawal syndrome (with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxiety), which makes cessation difficult and contributes to relapse. Marijuana use by adolescents is particularly troublesome. Adolescents' increased vulnerability to adverse long-term outcomes from marijuana use is probably related to the fact that the brain, including the endocannabinoid system, undergoes active development during adolescence. Indeed, early and regular marijuana use predicts an increased risk of marijuana addiction, which in turn predicts an increased risk of the use of other illicit drugs. As compared with persons who begin to use marijuana in adulthood, those who begin in adolescence are approximately 2 to 4 times as likely to have symptoms of cannabis dependence within 2 years after first use.

Effect on Brain Development

The brain remains in a state of active, experience-guided development from the prenatal period through childhood and adolescence until the age of approximately 21 years. During these developmental periods, it is intrinsically more vulnerable than a mature brain to the adverse long-term effects of environmental insults, such as exposure to tetrahydrocannabinol, or THC, the primary active ingredient in marijuana. This view has received considerable support from studies in animals, which have shown, for example, that prenatal or adolescent exposure to THC can recalibrate the sensitivity of the reward system to other drugs and that prenatal exposure interferes with cytoskeletal dynamics, which are critical for the establishment of axonal connections between neurons.

As compared with unexposed controls, adults who smoked marijuana regularly during adolescence have impaired neural connectivity (fewer fibers) in specific brain regions. These include the precuneus, a key node that is involved in functions that require a high degree of integration (e.g., alertness and self-conscious awareness), and the fimbria, an area of the hippocampus that is important in learning and memory. Reduced functional connectivity has also been reported in the prefrontal networks responsible for executive function (including inhibitory control) and the subcortical networks, which process habits and routines. In addition, imaging studies in persons who use cannabis have revealed decreased activity in prefrontal regions and reduced volumes in the hippocampus. Thus, certain brain regions may be more vulnerable than others to the long-term effects of marijuana. One study showed that selective down-regulation of cannabinoid-1 (CB1) receptors in several cortical brain regions in long-term marijuana smokers was correlated with years of cannabis smoking and was reversible after 4 weeks of abstinence. Changes in CB1 receptors were not seen in subcortical regions.



The negative effect of marijuana use on the functional connectivity of the brain is particularly prominent if use starts in adolescence or young adulthood, which may help to explain the finding of an association between frequent use of marijuana from adolescence into adulthood and significant declines in IQ. The impairments in brain connectivity associated with exposure to marijuana in adolescence are consistent with preclinical findings indicating that the cannabinoid system plays a prominent role in synapse formation during brain development.


Date: 2015-12-17; view: 896


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