Download Cannabis Use and the Adolescent Brain

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Cannabis Use and the Adolescent Brain
Lucy Albertella and Jan Copeland
National Cannabis Prevention and Information Centre
Animal and human research suggests that adolescent exposure to cannabis carries a particularly
high risk for a range of negative outcomes, including psychosis-related symptoms, cognitive
impairment, and substance use problems1-5. Findings of heightened risk associated with
adolescent cannabis use, coupled with research pointing to a role of the endocannabinoid system
in regulating neurodevelopmental processes, have led to speculation that adolescent cannabis use
may disrupt the normal course of neurodevelopmental processes and result in long-term changes
in brain functioning6. Further, it appears there are a number of factors (e.g., female sex, early
trauma experience, genetics) that may moderate the effects of adolescent cannabis use on brain
development7.
This bulletin reviews the current research in this area, including endocannabinoid influences on
adolescent brain maturation and the types of impairments that have most been associated with
adolescent cannabis use. Further, this bulletin outlines various factors that have been found to
confer vulnerability to either early onset cannabis use and/or its adverse effects. Finally, the current
gaps in the literature and the need to better understand how various risk factors interact with
adolescent cannabis use to further increase the risk of developing a range of adverse outcomes,
including psychosis and substance use disorders, in adulthood are highlighted.
Adolescent brain development
The brain undergoes important structural and functional changes during adolescence and into
young adulthood. For instance, there are significant reductions in grey matter across adolescence,
which are primarily the result of synaptic pruning (to cull weak and/or unused synapses)8. Through
synaptic pruning, the speed and efficiency within regional brain circuits is enhanced. Areas that
undergo considerable synaptic pruning in adolescence are temporal and frontal regions and
striatal areas, with prefrontal cortical areas being especially late to mature. Importantly, circuits
involving the prefrontal cortex and the striatum are critical to higher order cognitive skills such as
decision making, risk and reward processing, and cognitive control9.
The endocannabinoid system plays an important role in guiding neurodevelopmental processes,
including that of synaptic pruning10. Thus, adolescent cannabis use might be associated with longterm changes in brain functioning in part through the disruption of synaptic pruning processes in
those areas that are concurrently maturing6, 7. Indeed, in line with adolescence being a particularly
important period for the maturation of prefrontal brain areas, recent animal studies have shown
that altering endocannabinoid neurotransmission in adolescent female rats causes long-lasting
changes in prefrontal brain areas reflective of disrupted synaptic pruning11. Such research supports
the idea that, at least in part, some of the cognitive and behavioural impairments associated with
early adolescent cannabis use in human studies might be related to the disruption of
endocannabinoid-mediated neurodevelopmental events by cannabis.
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Cognitive Impairment
Adolescents who use cannabis regularly typically display a number of non-acute cognitive deficits
compared to adolescents who do not use cannabis or use it occasionally. For instance, a recent
study12 found long-lasting deficits in selective attention in a group of adolescent heavy cannabis
users compared to a control group who had used cannabis less than 5 times in their lifetime.
Changes in verbal learning and memory among this group, however, improved following a period of
abstinence. Furthermore, a number of studies have shown that adults who started using cannabis
early in adolescence show greater cognitive impairment than adults who started using cannabis
latere.g., 5, 13.
Findings of non-acute cognitive deficits in adolescent cannabis users (and in adults who started
using cannabis early in adolescence) have been used to support the idea that adolescence may be
a particularly sensitive period for the adverse effects of cannabis. There is also research, however,
to suggest that pre-existing factors related to cognition (and/or related personality traits) may
account for some of the differences found between adolescent cannabis users and non-users. In
other words, some group differences in cognition may not be the result of cannabis use per se but
rather, may be due to pre-existing group differences leading to earlier onset of cannabis use. For
instance, measures of selective attention (which depend on successfully ignoring distracting and/
or irrelevant information) taken in early adolescence have been found to predict greater cannabis
use by late adolescence14. Similarly, impulsivity-related personality traits have also been shown to
predict regular adolescent cannabis use15.
Studies have also found differences in brain structure between those who commence cannabis use
in adolescence and non-users. These include differences in orbitofrontal cortex volume — a
prefrontal brain area related to impulsivity, reward processing, and cognitive control16, 17 — at age
13, which predicted subsequent onset of cannabis use by age 1618. Thus, some of the cognitive
deficits seen in adolescent cannabis userse.g., 12 may in fact have preceded cannabis use.
Animal research also supports the notion that adolescent cannabinoid exposure can result in longterm cognitive impairments, although findings are mixed. For instance, in one study, female rats
exposed to a cannabinoid in adolescence showed memory deficits when tested as adults
compared with female rats that were exposed to the cannabinoid as adults19. In another study,
both adolescent and adult male rats exposed to cannabinoids showed long-lasting memory
deficits20. In yet another study, neither male adolescent or adult rats showed long-lasting cognitive
impairments following chronic cannabinoid exposure21. Though male rats have not consistently
been shown to display cognitive performance deficits related to adolescent cannabinoid exposure,
studies have found that adolescent cannabinoid exposure may, nonetheless, induce lasting brain
changes in prefrontal areas22. This suggests that in some cases, the use of more sensitive
measures may have detected differences in performance. Overall, long-term effects of adolescent
cannabinoid exposure have been found on various measures of learning and memory, but these
effects have not been replicated consistently and appear to vary according to gender and the strain
of laboratory rats included in the study23, 24. In summary, animal studies do appear to indicate that
adolescent rats may be more susceptible than adult rats to the adverse long-term effects of chronic
cannabinoid exposure on cognition25. More consistently, adolescent rats have been shown to be
more sensitive than adult rats to the acute adverse effects of cannabis on cognitione.g., 21.
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Psychosis-related symptoms
Longitudinal studies indicate that adolescent cannabis use is associated with an increased risk of
psychosis-related symptoms in adulthood3. For instance, in a longitudinal cohort study3,
adolescents who had used cannabis by age 15 were found to be 6 times more likely to experience
psychotic symptoms at age 26 than adolescents who had not (after controlling for psychotic
symptoms at age 11). This risk is even higher for adolescents who are already experiencing some
sub-clinical symptoms26 or who carry a genetic predisposition27.
Consistent with these findings, animal research also appears to support the view that adolescence
may be a critical period for exposure to cannabis that results in an increased risk of psychosisrelated brain changes. A study of adult rats exposed to THC in adolescence showed significant
deficits on a measure of sensorimotor gating, known as prepulse inhibition (PPI), compared to rats
exposed equivalent amounts of THC in adulthood4. Importantly, because PPI deficits are typically
used in animal research to model the sensory processing deficits seen in people with
schizophrenia, this finding supports the idea that exposure to cannabis during critical
neurodevelopmental periods can increase the risk of developing psychosis or, at least, psychosisrelated sensory processing impairments.
Drug-related problems
Longitudinal studies suggest that early onset cannabis use may be associated with an increased
risk of other drug use2, 28 and an increased likelihood of developing more problematic use of
cannabis, alcohol, and other drugs2, 28, 29. The complexity of social, psychological, and
environmental interactions involved in the initiation and maintenance of cannabis and other drug
use in human epidemiology, however, makes it very difficult to address the question of causality in
this reported association. One method, such as twin studies has found that early onset cannabis
use was strongly associated with later illicit drug use as well as an increased likelihood of alcohol
dependence and other substance use disorders2.
Animal research suggests that exposure to cannabinoids in adolescence may result in long-term
brain changes in various reward-related brain areas, which in turn may increase addiction
vulnerability30. For instance, in a recent study, adult rats exposed to THC in adolescence selfadministered cannabinoids more quickly and in higher amounts than rats not given THC in
adolescence and showed lasting striatal dopamine receptor changes30. In another study, adult rats
exposed to THC in adolescence showed heightened sensitivity to opioids, as evidenced by greater
self-administration of heroin, and corresponding brain changes in striatal areas31. Further, rats
exposed to THC in adolescence have been found to be more vulnerable to stress-induced
reinstatement of heroin seeking32.
Individual differences in adolescent vulnerability
Research suggests there are individual differences in adolescent vulnerability to the long-term
negative effects of cannabis use7. The factors mediating this vulnerability remain largely unknown,
however, studies have pointed to early life trauma33 and genes27 as playing an important role. For
instance, Caspi et al (2005) found that participants who carried the COMT val/val genotype and
who used cannabis before the age of 17 were over ten times more likely to develop
schizophreniform disorder (when symptoms of psychosis are present for at least one month but
less than 6 months) than those who carried the met/met genotype. Animal research also supports
the role of individual differences in mediating the vulnerability to the long-term effects of
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adolescent exposure to cannabinoids. For instance, novelty-seeking in rats moderates the longterm effects of adolescent cannabinoid exposure on cocaine addiction vulnerability and brain
changes in areas related to reward processing34.
Conclusion
Adolescent exposure to cannabis is associated with a range of long-term adverse effects, such as
increased addiction vulnerability, cognitive impairment, and psychosis-related illness, which may
be related to cannabis-induced disruptions in neurodevelopmental processes. There are various
factors that appear to moderate these effects, with adolescents exposed to early life stress and/or
who possess certain genetic and personality predispositions being more likely to experience
adverse long term effects. Research is also pointing to the role of gender in moderating
vulnerability to different long-term consequences of adolescent cannabis use35, including
interactions with genetic risk36. Further research is needed to uncover exactly how various risk
factors interact with cannabis use and how such interactions may affect neurodevelopmental
processes in vulnerable individuals.
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