Fourteen-year-olds who say they have smoked just one or two joints of marijuana in their lifetime demonstrate structural changes to multiple regions of their brains, according to the results of research by an international team of scientists across Europe and North America. “The implication is that this is potentially a consequence of cannabis use,” commented senior study author Hugh Garavan, PhD, a University of Vermont (UVM) professor of psychiatry. “You’re changing your brain with just one or two joints. Most people would likely assume that one or two joints would have no impact on the brain.”

The researchers said the findings, reported in The Journal of Neuroscience, warrant further study of cannabis use among adolescents. “Given the increasing levels of cannabis use amongst adolescents today, we suggest that studying the effects of recreational use early in life is an area of particular importance that should be addressed in the future by large scale, prospective studies,” they wrote in their published paper, which is titled, “Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence.”

The legal status of cannabis is changing in many territories, and young people are less mindful of the perceived risks of smoking cannabis, the authors suggested. Rates of cannabis use among adolescents are now high. Despite this high level of use among teenagers, little is understood about the earliest effects of cannabis use, as most studies are carried out in adults who have used the drug over extended periods. “Most neuroimaging research is conducted in adults with a heavy, chronic pattern of cannabis use, and does not reflect most people’s experience, which is recreational,” the authors stated. “Almost 35% of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects.” There is, however, a lack of studies on the recreational use of cannabis in young people, “especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabinol (THC) on brain structure.”

The researchers used a whole brain image analysis technique called Vox-based morphometry to compare the grey matter volume (GMV) in 46 14-year-old adolescents (both male and female) who reported having used cannabis on just one or two occasions, with matched controls who had never used THC. The teenagers were all participants in the long-term European IMAGEN study, and for some of the cannabis users there were data available at two years follow up to assess substance use, cognitive, and other psychological parameters. As well as measuring brain volume in this primary group of individuals, the researchers also calculated and compared brain volumes in a second group of teenagers who said they hadn’t used cannabis by the time the reached 14 years of age, but who had subsequently used the drug a limited number of times by the time they reached 16 years of age.

After controlling for a wide range of variables, the results indicated that even a very low level of prior cannabis use among the 14-year-olds was associated with changes to the GMV in areas of brain rich in cannabinoid receptors, including the hippocampus, amygdala, and striatum, and regions of the cerebellum and left medial temporal gyrus. The largest differences in GMV were in the amygdala, which is involved in fear and other emotion-related processes, and in the hippocampus, which is involved in memory development and spatial abilities. In contrast, there were no structural differences in the brains of the future cannabis users and their matched controls.

The analyses also found an association between changes to brain GMV in the 14-year-old cannabis users and assessments of anxiety and reasoning. “GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users,” the investigators stated.

Whilst acknowledging that the study does have a number of limitations, they further suggested that the findings are consistent with previous reports of a dose-response effect of cannabis on behavioral and brain measures following heavier use. Further research to asses the effects of recreational use on adolescents is mandated, they continued. “This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence … Some adolescents may be vulnerable to GMV effects at extremely low levels of cannabis use and it will be critical to identify those at risk as these structural brain changes may be associated with individual risk for psychopathology and deleterious effects on mood and cognition.”

One potential mechanism by which cannabis could lead to neurobiological changes is through the endogenous endocannabinoid system (eCB), the authors suggested. “Converging evidence suggests a role for the endocannabinoid system in these effects.” What the increased brain volume associated with cannabis use means in biological and clinical terms is less clear, but Garvan pointed out that during adolescence the brain undergoes a “pruning” process where it becomes thinner, rather than thicker, as synaptic connections are refined. “One possibility is that they’ve actually disrupted that pruning process,” he suggested.  “The eCB system mediates maturation-related neural reorganization, which may place adolescents at heightened vulnerability to structural brain effects of cannabis exposure as adolescence is a time of rapid neural maturation,” the authors concluded.

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