Future research might better characterize the legislative goals of the cannabis industry using additional review of campaign expenditures, legislative testimony, and using key informant interviews. According to the 2011 Monitoring the Future Study, marijuana remains the most commonly used illicit drug in adolescence in the United States, one of few increasing in prevalence. In fact, marijuana has been the most commonly used illicit substance for almost 40 years, and presently 23% of 12th graders in the U.S. report using marijuana in the past month. Marijuana use in adolescence could have implications for academic functioning, as well as social and occupational functioning extending into later life. Maturational brain changes, particularly myelination and synaptic pruning, are occurring throughout adolescence, well into early adulthood. These remodeling processes are purportedly linked to efficient neural processing, and believed to underlie specialized cognitive processing necessary for optimal neurocognitive performance. Cannabinoid receptors are widely distributed throughout the brain , and play a role in neurotransmitter release and concentrations across neural systems . It has been suggested that these receptors increase during adolescence, have a role in genetic expression of neural development, and that alteration of the endocannabinoid system during adolescence may results in a cascade of neurochemical and neurostructural aberrations, thus leading to poorer cognitive and emotional outcomes in adulthood. Disruptions in brain development related to neurotoxic effects of regular marijuana use could significantly alter neurodevelopmental trajectories by not only changing neurochemical communication and genetic expression of neural development, but causing a toxic effect on brain tissue. Such a marijuana-related effect on white matter and gray matter structures could have widespread implications for healthy brain development from childhood to young adulthood on subtle cognitive functioning and success in daily functioning.
Studies exploring the neurocognitive consequences and structural and functional neuroimaging changes related to marijuana use in adolescence will be discussed, along with recommendations for future work. Adult studies of marijuana use often find subtle decreases in performance compared to controls in cognitive domains such as attention, memory,indoor cannabis grow system and processing speed; such effects have been discussed as transient in the literature given limited group differences after prolonged abstinence from marijuana. It is unclear if findings translate to adolescent populations. Ongoing cognitive development in the domains of memory and executive functioning, and particularly in specialized functions like cognitive control, is not only tightly associated with adolescence and neocortical tissue maturation, but is likely to have implications for school performance and engagement in risk/reward behaviors. One of the earliest studies on the effects of marijuana on adolescent neurocognitive development evaluated verbal and nonverbal memory performance in cannabis-dependent adolescents compared to matched controls. Schwartz and colleagues found that short term memory impairment persisted after six weeks of monitored abstinence. In contrast, Teichner and colleagues found no relationship between marijuana use severity and cognitive performance among cognitively impaired and unimpaired adolescents referred for drug treatment. There have been considerable additions to the literature over the last decade, yet the degree of impairment related to marijuana use in adolescence remains inconclusive. A pattern of subtle yet potentially detrimental effects in cognitive domains related to attention, learning, and memory are most often described. A prospective study conducted in 2005 examined neurocognitive performance among 17–21 year olds with history of soft drug exposure in utero compared to prior performance at 9–12 years old. Current heavy cannabis users performed significantly worse on measures of processing speed and memory, controlling for pre-drug performance. Notably, former heavy users had similar scores to non-marijuana using controls.
In regard to higher-order cognitive functioning, Lane and colleagues found adolescents with histories of heavy marijuana use performed worse on perseverative responding and flexible thinking compared to controls with limited histories of use. This same research group also found evidence of reduced motivation among marijuana users compared to controls. In 2007, Harvey and colleagues found adolescent marijuana users performed worse on tests of attention, learning, and memory; furthermore, poorer performance on executive functioning in this sample was related to more days of cannabis use in the past month. Studies from our laboratory have largely found differences in similar domains following four weeks of monitored abstinence. Our first prospective investigation found that cumulative marijuana use over the course of eight years was related to poorer performance on measures of attentional functioning. In a subsequent cross-sectional study of adolescent marijuana users ages 16–18, we found that marijuana users demonstrated slower processing speed, poorer verbal learning and memory, and sequencing abilities. In order to better understand acute changes with abstinence, we examined neurocognitive performance over 3 weeks of monitored abstinence in marijuana users ages 15–19. Between-group differences in attention, learning, and memory were identified at baseline, however while learning and memory performance reached similar levels of performance to controls after 3 weeks of abstinence, attention differences persisted. Group differences in our studies generally persist despite controlling for alcohol use present in both controls and marijuana users; but to further understand differential contributions of marijuana and alcohol to neurocognitive functioning in our sample, we examined unique associations between alcohol use severity and cognitive functioning in both marijuana users as well as controls. In a recent investigation, we found that more self-reported alcohol withdrawal symptoms predicted poorer performance on learning and memory in a sample of non-marijuana using teens with histories of episodic alcohol use, despite no relationship in our marijuana users with similar and/or heavier self-reported history of alcohol use. This suggests differential relationships between marijuana, alcohol, and cognitive outcomes in our sample.
We have observed similar relationships in magnetic resonance imaging studies examining structural and functional brain alterations, which will be discussed in greater detail below. In recent work, Tait and colleagues looked at young adult cannabis users and found memory deficits, however cessation of cannabis use was associated with improved performance with abstinence over the course of eight years. Takagi and colleagues found that cannabis users performed worse on measures of immediate and delayed verbal memory compared to community controls. In a similar study by this team of investigators, no differences between cannabis users and community controls were found on measures of executive functioning. Similarly Gonzalez and colleagues found differences on immediate and delayed recall among young adult cannabis users compared to nonusing controls, however no differences were observed on measures of impulsivity. Despite no group differences on impulsivity, the authors found that worse performance on a decision making task was related to more cannabis use disorder symptoms. Solowij and colleagues looked at 181 adolescents and found that cannabis users performed worse on learning and recall, and poorer performance was related to severity, frequency, and age of initiation of cannabis use. A study on prospective memory evaluated undergraduates between the ages of 18 and 24 years old, while no differences in self-reported prospective memory was identified, cannabis users did recall fewer location-action combinations during the objective video based prospective memory task. A large-scale longitudinal investigation from New Zealand evaluating individuals from birth to age 38 recently found a decline in intelligence quotient, particularly executive functioning and processing speed, with persistent cannabis grow equipment dependence. Notably, those individuals with weekly use before age 18 demonstrated greater decline in cognitive performance. Studies evaluating early- and late-onset marijuana users have provided considerable insight into the effects of cannabis use on adolescent neuro development. For example, Ehrenreich and colleagues found that initiation of marijuana use prior to age 16 predicted impaired reaction time on a task of sustained attentional processing.
In 2003, Pope and colleagues also found that early-onset was related to poorer performance on verbal memory and fluency tasks, as well as verbal IQ. Focusing on executive functioning, Fontes and colleagues examined 104 chronic cannabis users ages 18–55. All participants met criteria for DSM-IV cannabis abuse or dependence. The authors found that adolescent cannabis users reporting initiation prior to age 15 demonstrated poorer performance on tasks of sustained attention, impulse control, and executive functioning. Overall, the majority of data support poorer cognitive performance on measures of attention and learning, and memory in adolescent users of cannabis, however frequency and severity of use is likely to play a role, particularly in those reporting younger age of initiation. Further, some evidence suggests that many of the subtle cognitive effects are likely to resolve after longer-term abstinence. A large body of literature has shown dynamic changes in gray matter structures that are ongoing over adolescent development . For instance, dendritic pruning and elimination of synapses likely results in cortical thinning and decreased cerebral volume to some degree, whereas some sub-cortical structures such as the hippocampus and amygdala have been shown to increase with age. Studies show a high density of CB1 cannabinoid receptors in neocortex, hippocampus, amygdala, hypothalamus, basal ganglia, and cerebellum; therefore the degree to which cannabis use alters cortical and sub-cortical gray matter tissue development is being increasingly explored in the literature. While some alterations in gray matter macro-structure have been suggested, there has been inconsistent evidence of morphological changes as evaluated by structural MRI. For instance, Block and colleagues as well as DeLisi and colleagues found no differences in gray matter tissue volume between adolescent cannabis users and matched controls. In 2010, adolescent cannabis abusers were found to have decreased right medial orbital prefrontal cortex volume compared to non-using counterparts; volume was also found to be positively correlated with age of initiation of marijuana use in the sample. A second study published in 2010 found that while age was associated with changes in brain morphometry among non-users, there was no relationship between age and cortical gyrification in adolescent and young adult cannabis users.
Cannabis users did show decreased concavity of the sulci and sulci thinning in frontal, temporal, and parietal lobes compared to non-users, highlighting the potential for cannabis to disrupt normal brain developmental trajectories. Ashtari and colleagues found that heavy adolescent cannabis users abstinent for a minimum of 30 days had smaller bilateral hippo-campal volumes compared to controls, and smaller right hippo-campal volume was correlated with more self-reported cannabis use among users; no between group differences were observed in amygdala volume. Several studies from our laboratory evaluating abstinent adolescent cannabis users have found similar outcomes in regard to gray matter macrostructural changes. Medina and colleagues found no difference in hippo-campal volumes or prefrontal cortex volume in adolescent cannabis users compared to matched controls, despite observed differences in both hippocampus and prefrontal cortex in adolescent alcohol users compared to matched controls. We did observe a subtle gender interaction, as female cannabis users had a slightly larger prefrontal cortex compared to non-using female controls; while this trend did not reach statistical significance, it may suggest that female marijuana users are more vulnerable to macrostructural alterations . Similarly, in 2011, amygdala volumes were compared between adolescent cannabis users and non-users. Increased amygdala volume was associated with more self-reported depression and anxiety symptoms. In a study investigating differences in cerebellum volumes, we found that adolescent marijuana users demonstrated larger inferior posterior vermis volume compared to controls; larger cerebellar volume was associated with poorer executive functioning. In recent investigation of temporal lobe structures, Cousijn and colleagues found that amygdala and hippo-campal volume in a sample of young adults ages 18–25 correlated negatively with amount of cannabis use. Specifically, more weekly cannabis use in grams was related to smaller hippocampus volume in heavy users and increased severity of cannabis use was associated with smaller amygdala volume. The authors also found that anterior cerebellum volume was larger in adolescent heavy cannabis users compared to nonusers. A prospective study looking at gray matter volume at 12 years of age, prior to initiation of marijuana, found that smaller orbitofrontal cortex volume predicted initiation of cannabis use by 16 years of age, suggesting pre-existing structural abnormalities may play a role in both behavioral differences that lead to cannabis use as well as continued differences in the course of development. There have been limited studies evaluating cortical thickness exclusively, however, LopezLarson evaluated 18 adolescents with histories of heavy marijuana use compared to non-using controls. Decreased cortical thickness was reported in the right caudal middle frontal and bilateral superior frontal cortices; decreased thickness was also found in the bilateral insula. Marijuana users demonstrated increased cortical thickness in the bilateral lingual, right superior temporal, right parietal and left paracentral regions. Alterations of cortical thickness were related to severity of cannabis use and younger age of initiation of use in several brain regions.