Although prior research suggests that this potential bias may be more pronounced in day level analyses covering periods longer than 60 days and that the TLFB may underestimate frequency and quantity of alcohol use , there is also evidence to suggest that the TLFB is not subject to reduced reliability with increased time intervals . In other words, reports are shown to be consistent with increased intervals from 30 or 60 days to 366 days or from 30 to 180 days . Second, we were also unable to establish temporal ordering of cannabis and alcohol use at the daily level. More detailed event-level ecological momentary assessment data would more directly address the question of whether or not cannabis use directly impacts alcohol consumption. Third, we relied on self-report data to determine user status . There is significant variability in the reported diagnoses for using cannabis, and often veterans reported more than one condition for using cannabis medicinally . More nuanced measurement at the event-level regarding whether cannabis is being used recreationally or medicinally, and if medicinally, what condition it is used for would provide important context for understanding the function of medicinal versus recreational cannabis use and its association with alcohol consumption. Ecological momentary assessment studies could examine these more nuanced associations in the moment to reduce recall bias and to more precisely examine related complex questions regarding the relative impact of medicinal versus recreational use on alcohol consumption. Fourth, vertical grow system we were unable to examine the effect of different cannabis products on these associations.
For instance, there is evidence that cannabis products with higher concentrations of cannabidiol , a non-psychoactive cannabinoid, compared to products higher in Δ9–tetrahydrocannabinol , may have unique medicinal and therapeutic benefits without the abuse potential and CBD may even have promise as a candidate AUD pharmacotherapy . Therefore, medicinal users may be more likely to use cannabis products with CBD, which may pose a reduced risk of alcohol misuse. Fifth, we were unable to examine the order of onset for those with CUD and AUD during the assessment period. As our previous work shows, AUD and CUD status does has an impact on daily co-use behaviors , therefore future research should examine how onset of these diagnoses would further explicate the nature of the association between daily cannabis and alcohol use for medicinal and recreational users. Sixth, we were also unable to assess substitution reasons among recreational users given this measure was specific to medicinal users. Future research should examine whether using cannabis for substitution reasons is also associated with reduced alcohol consumption among recreational cannabis users. Finally, confidence in the accuracy of the current pattern of findings, particularly the observed interactions, will be strengthened by replication in larger and more representative populations .While development of overall brain size is largely complete by age five, specific structural and functional changes continue during adolescence and contribute to more efficient cognitive functioning . During adolescence, the brain undergoes significant developmental changes, with the frontal lobe maturing in later adolescence and into early adulthood and both myelination and synaptic refinement continuing throughout adolescence . Studies in typically developing teens without heavy alcohol or drug use demonstrate that white matter volumes increase throughout the brain with continued myelination during adolescence.
Gray matter volumes peak around age 12 in males and age 11 in females and then decline as unnecessary neural connections are eliminated, resulting in a net volume loss during this time . Increases in myelination, detected as increases in white matter volumes, and in pruning of gray matter, detected as decreases in cortical gray matter, facilitate more effective communication among neurons in the brain. These changes allow specialized cognitive processing required for optimal cognition and performance . Neurotransmitter systems also mature during adolescence. Specific to marijuana, cannabinoid 1 receptors are widely distributed throughout the brain, with high levels of density in the hippocampus, cerebellum, basal ganglia, and prefrontal cortex . These CB1 receptors increase during adolescence, and, in doing so, both facilitate release of neurotransmitters and contribute to genetic expression of neural development . Healthy adolescent brain development therefore progresses with increases in white matter and in CB1 receptor density and decreases in grey matter volumes. Therefore, the potential neurotoxic effects of alcohol and marijuana include disruptions to grey matter macrostructure, white matter microstructure, neurochemical communication, and genetic expression of neural development, all of which have widespread implications for cognitive functioning and success in daily functioning.Most of what research has provided us in terms of understanding the impact of adolescent substance use on neuroanatomical and neurocognitive functioning has historically come from clinical populations of youth with substance use disorders and more recently from community samples of binge drinking and marijuana using youth. Understandably, many initial studies in this field utilized smaller, clinical samples of adolescents who frequently had comorbid conduct disorder, ADHD, depression, and substance use other than alcohol or marijuana.
Despite their methodological limitations, these earlier clinical samples provided informative findings that shaped the direction and methodology of later research. Recent research in this field typically recruits community youth with heavy drinking experiences or protracted marijuana use and compensates them financially for abstaining prior to neuropsychological assessments or brain scans. Ideally, researchers should continue the practice of monitored abstinence and consider carefully the impact of recent alcohol and marijuana use on results if teens are not abstinent prior to assessments or test positively for any substance at the time of testing. Studies seeking to understand the impact of alcohol and marijuana would also carefully consider potential confounding influences like gender, age, poor self regulation, family history of substance use, and comorbid Axis I disorders.Alcohol is the most commonly used illicit substance among adolescents. By the time students reach their senior year of high school, over 68% have consumed alcohol and over 54% have been drunk . According to national data, 39% of high school seniors drank alcohol in the past 30 days, and 23% of high school seniors reported heavy episodic drinking in the prior two weeks . The binge-type pattern of drinking prevalent among adolescents has been shown to be more harmful than the consumption of the same amount of alcohol consumed in moderation every day . This finding suggests that it is not the quantity of alcohol consumed that is concerning, but rather the combination of the quantity with the pattern of binge consumption common among teenagers. Imbibing greater quantities of alcohol in one sitting is concerning because heavy episodic alcohol consumption associates with high risk, life-threatening outcomes including motor vehicle accidents, alcohol poisoning, illegal activities, school failure, and risky sexual behavior . Such heavy episodic drinking appears to alter developmental trajectories and may interfere with normal neurocognitive and neuroanatomical development .Similar to alcohol, marijuana has consistently been a widely used illegal drug among adolescents in the United States . In 2013, 46% of high school seniors reported having tried marijuana, 22% used in the past month, and 7% endorsed daily use . Of individuals who initiated marijuana use before 15 years of age, 14% went on to meet criteria for drug abuse or dependence during adulthood . As mentioned previously, adolescence is a period of significant neurodevelopment , so the potential neurocognitive effects of alcohol and marijuana use are a concern.Because of its rigorous experimental control, animal research is amenable to the examination of the neurotoxic effects of alcohol and marijuana on a developing adolescent brain. Animal research provides the ability to control premorbid and environmental factors as well as to administer directly ethanol and cannabinoids during a rodent’s adolescence. In animals, postnatal days 28-49 correspond with human adolescent development, trim trays which can extend to days 21-59 to include early and late adolescence .
Animal studies involving exposure to ethanol and to cannabinoids during this postnatal time period evaluate cognitive functioning, behavior, emotions, and impact to specific brain structures. Overall, animal research suggests that adolescent animals are more vulnerable than adults to ethanol-induced decrements in functioning, especially following chronic, intermittent exposure to high levels of ethanol, which is considered the analog of ‘binge drinking’ in humans . A growing number of animal studies suggests that drinking alcohol during adolescence is particularly harmful to the brain and is associated with altered brain development and brain functioning . The effects of alcohol use in adolescence are similar to those in adulthood, except adolescents seem to experience lower initial brain sensitivity to ethanol than adults , abnormal development of sensitivity to alcohol-induced motor impairments that typically occur between adolescence and adulthood , and tolerance to alcohol’s sedating effects with slower onset of sedation following alcohol exposure and smaller magnitude of sedation . Adolescent rats also show more susceptibility to hippocampal injury and to frontal-anterior cortical damage . These decrements that first present during adolescence extend into later time periods with rats exposed to alcohol during their adolescent years continuing to show structural and functional abnormalities into adulthood. These adult rats show continued alcohol-induced spatial memory impairments , lasting decreases in sensitivity to the sedative effects of ethanol , and enduring neurophysiological effects in the cortex and hippocampus . On a physiological level, alcohol exposure in adolescence has also been linked to long-term alterations in brain signaling involving the neurotransmitter serotonin , to GABA-A receptors that alter sensitivity to ethanol’s aversive effects into adulthood , and to inhibition ordeactivation of NMDA receptors, which likely contributes to reduced long term potentiation seen following alcohol exposure . Similar to animal studies investigating the impact of ethanol, a large body of work can also be found on animal models with cannabis exposure. Of note, natural marijuana contains many cannabinoids. Although THC is the main active constituent in marijuana, it is possible THC interacts with other plant cannabinoids to produce unique effects in humans that cannot be replicated by isolated or synthetic cannabinoid used in rodent research. Despite this limitation, animal research offers evidence of unique cognitive effects of cannabinoid use in adolescents compared to adults. A series of studies has examined different aspects of learning after chronic administration of cannabinoids. Immature rats treated with the synthetic cannabinoid agonist WIN 55, 212-2, compared to mature rats , showed poorer performance on cognitive tasks including maze learning , which suggests learning dysfunction associated with chronic marijuana administration; more pronounced behavioral alterations and lasting deficits in social play and grooming behaviors ; and disrupted object recognition and reduced motivation . Chronic WIN treatment has been found to result in both acute and long term effects in spatial memory, object recognition, and long term potentiation in areas like the nucleus accumbens . Follow up investigations examining the influence of adolescent cannabinoid exposure on memory functioning revealed that THC-exposed adolescent rats showed object recognition memory deficits, and their THC exposure was associated with hippocampal protein expression abnormalities . In sum, animal research suggests that adolescents, compared to adults, experience heightened neuroanatomical and neurocognitive responses to alcohol and to marijuana. Specific to ethanol exposure, adolescents show reduced sensitivity to alcohol-induced motor impairing and sedative effects, which likely leads to greater alcohol intake and the attainment of higher blood alcohol concentrations with less sedation than would be expected in adulthood. The concurrence of reduced susceptibility to the sedating and motor impairing effects of alcohol with an enhanced vulnerability to alcohol-induced neuroanatomical and neurocognitive deficits presents a concerning effect during adolescence. Specific to cannabinoid exposure, rodent studies provide evidence of both structural and behavioral vulnerability to cannabinoid-induced impairments, particularly in the areas of learning and memory and working memory.Human studies utilizing magnetic resonance imaging, tomography, and post-mortem Thissue analyses demonstrate that adult alcoholics, particularly females, experience reduction in white and gray matter and enlarging of cerebral ventricles , which together suggest an overall reduction of adult alcoholics’ brain mass. Adults with histories of alcohol withdrawal related seizures showed greater loss of white matter volume in temporal brain regions, relative to controls and to alcohol dependent adults without histories of alcohol-related seizures . Animal studies have demonstrated that adolescent rats exposed to the same heavy dosage of ethanol as adult rats showed damage in the same olfactory mesocorticolimbic association and memory-consolidating brain regions as those found in adults; however, several regions that were spared in the adults were damaged in the adolescents, including the frontal cortical olfactory regions and the anterior perirhinal and piriform cortex .