Human adolescent studies have found similar results both for subclinical, binge drinking teens who do not meet criteria for alcohol abuse or dependence and for clinical populations of teens with alcohol use disorders . Results suggest reduced white matter integrity in frontal and parietal regions in subclinical teens , smaller prefrontal cortex white matter volumes in adolescents with comorbid alcohol use disorders and Axis I disorders compared to controls , and a unique gender effect with female adolescents with AUDs having smaller PFC volumes and male adolescents with AUDs having greater PFC volumes, relative to demographically-matched controls . The findings of Medina and colleagues do conflict with those of De Bellis and colleagues as the De Bellis group found smaller PFC volumes in both genders. However, the De Bellis study utilized a slightly older population and one with a higher frequency of comorbidity with conduct disorder, ADHD, depression, and other substance use. These methodological inconsistencies could have impacted the findings about PFC volume in adolescent drinkers. Specific to marijuana use, adolescent cannabis users were found to have decreased right medial orbital prefrontal cortex volume compared to non-using youth . It appears that both alcohol and marijuana use during this time of development impact the volume and white matter integrity of the prefrontal cortex. Animal research also suggests that the hippocampus is especially sensitive both to acute and to chronic alcohol and marijuana exposure during adolescence.
Acute alcohol exposure, even at low doses, trimming tray has been shown to inhibit long term potentiation in the rat hippocampus . Nixon and Crews showed that ethanol inhibits neural progenitor cell proliferation and survival in the rat hippocampus, which they believe contribute to alcohol-induced neuropathology and cognitive deficits. Compared to adult rodents, adolescent rodents were found to be more susceptible to hippocampal injury and were found to have increased activation of microglia in the hippocampus following binge-type alcohol exposure . A follow-up study found consistent findings and reported enhanced activation of excitatory amino acid glutamate and other phagocytic cells in the hippocampus of binge drinking adolescent mice, which could be an early indication of neurodegeneration in this brain region . Similarly, adolescent cannabis exposure has been associated with hippocampal protein expression abnormalities in adolescent rats . Consistent with animal research, human studies have also shown heightened sensitivity in the hippocampus. Both the left and right hippocampi were found to be significantly smaller in adolescent AUD subjects than in control subjects . These findings were replicated in studies of adolescents with AUDs without significant histories of other substance use or psychiatric conditions.
Specifically, left hippocampal volumes were smaller in teens with AUDs than in demographically matched controls, and youth with greater severity of AUDs had the smallest left hippocampi . In adolescent cannabis users, those abstinent for a month still showed smaller bilateral hippocampal volumes compared to controls, whereas no group effects were identified in amygdala volume . Furthermore, disruptions in hippocampal white matter integrity have also been identified with decreased fractional anisotropy in hippocampal projections of cannabis using youth . The heavy drinking and marijuana use during adolescence that are linked to smaller hippocampi are concerning as the hippocampus is a brain structure critical for learning and memory function . Human research about the effects of alcohol on the corpus callosum has demonstrated both macrostructural and microstructural abnormalities. While one study found that the corpus callosum is smaller in alcoholic women compared to non-alcoholic women of the same age , another study found that gross area measures of the corpus callosum and its components were equivalent between groups; however more sensitive measurements by diffusion tensor imaging of fractional anisotropy and intervoxel coherence showed alcohol related disruption of white matter fiber integrity in the genu of the corpus callosum and in the centrum semiovale . Consistent with adult research, white matter microstructure abnormalities in the corpus callosum have also been shown in human adolescents with histories of alcohol abuse and dependence .
Increased mean diffusivity of white matter tracts has also been identified in the prefrontal bundle fibers of the corpus callosum in heavy cannabis using adults . The adolescent literature therefore suggests that both alcohol and marijuana use impact white matter integrity in the corpus callosum of substance using adolescents.In addition to possibly impairing the growth and integrity of certain brain structures, heavy drinking and marijuana use in adolescence has also been linked to poorer neuropsychological and academic performance. Neuropsychological studies of demographically matched, non-drinking teens and adolescents with AUDs or with subclinical, heavy drinking have consistently reported group differences in executive functioning, visuospatial abilities, learning and memory, processing speed and attention, and academic achievement. Further, heavy drinking during adolescence is associated with poorer neurocognitive functioning into adulthood, particularly in visuospatial abilities and attention . Protracted marijuana use among adolescents has been linked to group differences across neuropsychological domains in executive functioning, attention, and processing speed, and most notably in learning and memory. Studies on adolescents with AUDs have consistently found deficits in tests of planning and executive functioning . Adolescents with comorbid alcohol and substance use disorders committed commission errors twice as often when responding impulsively to a non-target stimulus . Binge drinkers also showed less advantageous decision making on the Iowa Gambling Task , and female, binge-drinking young adults were less able to inhibit their response to an alerting stimulus during a vigilance task, suggesting that binge drinking may associate with deficits in inhibitory control . Deficits in executive functioning and inhibition are particularly concerning given the slow rate of neurocognitive recovery in the frontal lobe from ethanol exposure . Executive functioning scores also predict age at first drink, with those students using alcohol prior to sixth grade having less well-developed decision making skills . Studies on teens with marijuana use histories found worse performance on perseverative responding and flexible thinking compared to controls . Poorer performance on executive functioning among adolescent marijuana users was related to more days of cannabis use in the prior month . In a recent, large-scale, longitudinal investigation, individuals with persistent cannabis dependence showed decline in their intelligence quotient with time, particularly in executive functioning . Animal research suggests that the acquisition of spatial memory is impaired more in adolescent animals exposed to ethanol than in adult animals with the same quantity of exposure . In general, adolescent rats exposed to alcohol experience heightened vulnerability to spatial impairments later in life . Adolescent and young adult heavy drinkers perform more poorly on spatial operation assessments and block design tasks . A study comparing detoxified, alcohol-dependent adolescents to control teens found that aspects of visuospatial cognition were poor in the AUD adolescents . Binge drinking teens and young adults were found to perform worse than non-binge drinkers on spatial working memory and pattern recognition tasks . Among female adolescents , trimming trays increased drinking predicted greater reductions in visuospatial performance on a complex figure delay . Worse visuospatial ability continues in the decade following treatment for AUD youth , with frequent drinkers performing more poorly on delayed recall complex figure tasks . Similar to the adolescent literature, a study of male adults found deficits in spatial imagination among the alcoholics .
One study of 18- to 35-year-old alcoholics, with an average of six years of excessive alcohol consumption, found their cognitive functioning to be within normal limits; however, the study did not utilize a control group for comparison and it did find that greater lifetime consumption and shorter periods of abstinence predicted lower scores .Verbal and spatial working memory abilities improve throughout adolescence, with older teens responding more accurately and more quickly , and alcohol use and marijuana use during this time appear to interfere with those improvements. Animal literature suggests that adolescence is a time of enhanced sensitivity to memory attenuation by ethanol and cannabis, and studies on heavily drinking and marijuana using adolescent humans are largely consistent with these findings. Animal research suggests that adolescent rats show greater impairment than adult rats in acquisition of memory tasks following acute ethanol exposure . Longer lasting and heavier patterns of alcohol and marijuana use among adolescents are linked to disruptions in the hippocampus, a brain structure critical for learning and memory. As discussed previously, adolescent drinking and marijuana use are linked to smaller hippocampal volumes and disturbed hippocampal white matter integrity. Hence, it is not surprising that many studies have found impaired learning and memory function among adolescents with either protracted alcohol or marijuana exposure. Neuropsychological studies of adolescents with AUDs demonstrate deficits in verbal and non-verbal memory . Poorer verbal learning and recognition discriminability were identified among detoxified 15- to 16- year-old teens with protracted alcohol exposure , and female young adult participants with greater withdrawal history performed worse on verbal working memory tasks . Another study among 13- to 18-year-old adolescents presented consistent findings and identified that heavy use of alcohol was related to impaired learning of verbal material and to poorer free recall after a short delay . Studies have also found that alcohol dependent youth underutilized semantic learning strategies, which likely led to the poorer retention rates after a short delay . AUD youth made more perseveration errors when recalling recently learned words on the CVLT, a verbal learning task . Consistent with adolescent memory literature, male adult drinkers’ auditory verbal learning scores were worse than those of controls after six weeks of abstinence, and detoxified female adults were shown to have deficits in verbal working memory . Non-verbal memory deficits have also been identified among AUD youth . A study of detoxified teens with AUD showed a ten percent deficit of AUD teens’ ability to recall nonverbal information that had previously been presented to them: visual reproduction rates were significantly lower in the alcohol dependent teens than in the controls . Female young adults with greater withdrawal history performed worse on non-verbal, working memory tasks . Interestingly, more self-reported alcohol withdrawal symptoms predicted poorer performance on learning and memory in a sample of teens with histories of heavy drinking . Similar to studies examining the impact of alcohol on learning and memory, multiple studies have shown similar deficits among cannabis using youth. In one of the earliest investigations of the impact of marijuana on adolescent cognition, Schwartz and colleagues identified that short-term memory impairment persisted even after six weeks of abstinence in cannabis-dependent adolescents compared to matched controls . Studies in the past two decades have consistently identified deficits in immediate and delayed recall among adolescent and young adult cannabis users . In a study of adolescent marijuana users ages 16-18, marijuana users demonstrated poorer verbal learning and memory, even after one month of abstinence . Memory deficits identified among young adult cannabis users with recent use showed improvement with abstinence over the course of eight years . Importantly, impaired performance on learning and recall among adolescent cannabis users has been linked to severity, frequency, and age of initiation of cannabis use .Neuropsychological studies of adolescents with either alcohol use disorders or protracted marijuana exposure have consistently reported deficits in processing speed and attention. Alcohol dependent first year college undergraduates were found to have more impaired motor speed than alcohol abusing youth of a similar age, and both alcohol abusing and alcohol dependent youth showed worse attention scores than controls . In a longitudinal study of youth treated for alcohol and substance use disorders during adolescence, participants with continued alcohol use were found to develop deficits in attention in the decade following treatment . Male adolescents were found to have slower completion times on the DigitVigilance Test while not showing impairments on DVT accuracy . Similar to those found in adolescent literature, decrements among male adult alcoholics were found in completion time of the DVT but not on other tasks for processing speed . This finding suggests alcohol-induced deficits in sustained attention and not simply in processing speed . In the marijuana literature, deficits in attention and processing speed have also been consistently identified. Adolescent marijuana users who smoke more than once per week were found to have worse performance on attention tasks . In a longitudinal study examining neuropsychological performance among heavy marijuana using youth compared to non-using youth, between-group differences in attention were identified at baseline and across 3 weeks of monitored abstinence, with attention differences persisting with time .