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Marijuana’s Effects on Brain Structure and Function: What Do We Know and What Should We Do? A Brief Review and Commentary

mmj in prescription pill bottle

The present epidemic of opioid addiction and the enthusiasm about marijuana use by advocates of its legalization may have diverted attention from its reported adverse health effects. These include clinical studies that demonstrate chronic marijuana use is associated with long-term deleterious effects on cognition.1 Neuroscientists have been carefully pairing neurodiagnostic tools with newer neuroimaging technologies to understand the relationships between the human brain endocannabinoid system and the effects on the system by exogenous cannabinoids, including the major psychoactive cannabinoid from marijuana, tetrahydrocannabinol (THC). Meta-analyses support observations that when compared with nonusers, regular users of marijuana have diminished executive function, attention, learning, memory, and motor skills that persist for varying times after abstinence occurs.2, 3 Combined structural and functional imaging show that morphological brain alterations in the medial temporal and frontal cortex and cerebellum are likely related to the degree of cannabis use. Even more troubling data suggest that when marijuana use begins prior to completion of brain maturation, changes in brain structure and function may persist. If substantiated, these findings have major medical and social implications.

Marijuana Use and Effects on Brain Maturation, Structure, and Function

Marijuana use starts early in Americans and is the most commonly used illicit drug in Americans 12 years of age and older.4, 5 Seven percent of 8th graders, 15% of 10th graders, and 21% of 12th graders report the use of marijuana in the last month.6 Of adolescent users, 2.7% meet criteria for addiction (cannabis use disorder), as compared with 4.9% of young adult users. Lifetime marijuana use reported in 2016 averaged 15% ages 12-17, 52% ages 18-25, 46% ages 26-65, and 22% ages 65 years and older.7 Few Americans believe that regular cannabis use is harmful to health, and legalization of marijuana in 29 states and the District of Columbia has increased the public’s interest in its possible benefits.8, 9

Regular use of marijuana is associated with a range of behavioral abnormalities.1, 10 Adolescents who use marijuana are twice as likely to smoke more marijuana and become addicted than those who begin smoking cannabis at a later age. The regular use of cannabis is associated with a decline in short-term memory and cognitive function, poor school or work performance, mood disorders, and psychosis.10, 11 Marijuana impairs the operation of airplanes, automobiles, motorcycles, and trains, and its effects appear to be dose-dependent.12, 13For instance, automobile accidents occur 2-7 times more frequently while using marijuana.14

Now there is evidence of permanent neurological changes associated with marijuana use that begins prior to the age of 21.15, 16, 17, 18 Investigators in New Zealand evaluated the association between regular cannabis use, the results of longitudinal neuropsychological testing, and whether or not functional neurologic decline was disproportionately greater in those who began cannabis use as adolescents than in those who begin use as adults.19 One thousand thirty-seven individuals in a prospective birth cohort were followed from birth to 38 years old. The presence of cannabis use was determined from interviews of the participants at ages 18, 21, 26, 32, and 38 years, and neuropsychological testing was conducted at age 13, prior to cannabis use, and again at age 38 after patterns of cannabis use had been established. Statistical methods corrected for possible confounders. Regular use was associated with decline across all neuropsychological domains as demonstrated by comprehensive neuropsychological testing. Adverse effects on executive function, memory, and verbal deficits were consistent among users across the cohort, but worse in those who began use of cannabis as adolescents when compared with adults, and greater functional decline was associated with more persistent use. Unfortunately, cessation of cannabis use did not fully restore the diminished neuropsychological functioning present in those who began use prior to age 21. Those findings persisted thereafter, with an average 6-point decrease in intelligence quotient from childhood to adulthood as compared with nonusers. The authors concluded that there is a “neurotoxic effect of cannabis on the adolescent brain” that demonstrates “the importance of prevention and policy efforts targeting adolescent use of marijuana.”19

A probable explanation for these neuropsychological findings exists in the biology of brain development. Neuroimaging and neurodiagnostic testing performed in tandem show that brain maturation persists throughout the adolescent and young adult years.20 Gray matter normally decreases in volume during brain maturation due to neuronal pruning, and white matter increases with myelination. Less frequently used neurons are pruned in the preteen years in order to build complex networks for the decision-making of adulthood. The limbic system below and posterior to the cortex matures prior to the gray matter of the prefrontal cortex that is responsible for logical thought and impulse regulation. This appears to explain problems with control of emotion-linked decision-making, risk-taking, and experimentation associated with immaturity.21, 22 Increased myelination in the brain may be visualized and quantitated on brain imaging as an increased volume of “white matter.”23 Myelin-coated nerve fibers distributed within the inner components of the brain facilitate rapid conduction of neuronal electrical potentials and thus, communication among regions of the cerebral cortex and between the brain and structures below it, including the midbrain and spinal cord. These cortico-cortical and cortico-subcortical pathways facilitate cognitive and motor functions.

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– Richard D. deShazo, MD, MACPa,b,e, Sara B. Parker, BAa, Daniel Williams, PhDc, John B. Ingram, MDb,d, Mahmoud Elsohly, PhDf, Kathryn Rodenmeyer, BAe, Kyle McCullouch, BBAa,f

-This article originally appeared in the March issue of The American Journal of Medicine.

-To watch a video commentary from Dr. Alpert on this topic, please follow this link.

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