Using marijuana even once or twice can significantly alter the grey matter volume (GMV) in several parts of the developing brains of teens, new research suggests. After analyzing data from a large research program assessing adolescent brain development and mental health, investigators found that brain regions rich in cannabinoid receptors are significantly affected in teens who reported very little cannabis use. "We were motivated to study the effects of low cannabis exposure because, while people have looked at the effect of heavy cannabis or other drug use on the brain, the effect of light use is very understudied," coinvestigator Hugh Garavan, PhD, professor of psychiatry at the University of Vermont, Burlington, told Medscape Medical News. The findings were published online January 14 in the Journal of Neuroscience. Homogenous Sample Although previous studies have shown both increases and decreases in human brain volume because of cannabis use, most of this research involved individuals who were chronic, heavy users who also smoked and drank, Garavan said. "There is some research on animal models showing that even a single administration might actually have an effect on abilities, on brain, and then we had this very large sample so we were able to search for kids who were reporting this very light use," he said. Using data from the IMAGEN research project, which included 2400 participants, the investigators identified those who reported only one or two instances of marijuana use. They were then matched with control participants using a variety of variables. Both groups were matched by age; sex; handedness; pubertal development; IQ, as measured by verbal comprehension and perceptual reasoning index scores; socioeconomic status; total GMV; alcohol use; and nicotine use. All participants denied using any other illicit substances and none reported using a fictional control substance, relevin, which supported the integrity of the self-report metrics. Adolescents for whom all four grandparents were the same nationality as the participant were recruited, making the sample racially and ethnically homogenous. Brain Imaging MRI scanning was conducted at all eight of the IMAGEN study sites, and voxel-based morphometry (VBM) was used to compare GMV among the use groups. Raw, T1-weighted images were inspected for the presence of anatomical abnormalities or artifacts, including head motion or reconstruction errors. After VBM 239 processing, the images were inspected again for errors in tissue segmentation or normalization into MNI space. Any images that failed quality control for any reason were excluded. Data were available for a subset of the 14-year-old cannabis-using participants at 2-year follow-up for substance use, cognitive ability, and psychopathology at age 16. This allowed for the assessment of cannabis-related GMV differences for future functioning in these domains. Of 47 adolescents who reported using cannabis only once or twice, one was excluded because of poor quality scans. This left 46 cannabis-using adolescent participants for the analysis. Researchers also identified 69 participants who had never used cannabis at age 14 but reported at least 10 instances of use at follow-up 2 years later. This allowed investigators to determine if group differences between cannabis users and matched controls may have preceded cannabis use. Substance use was assessed at baseline (age 14) and follow-up (age 16) using the European School Survey Project on Alcohol and Other Drugs, a self-report questionnaire that measures use of alcohol, nicotine, cannabis, a broad range of illicit substances, and the fictional control measure called relevin. Participants indicated how frequently they had used each of the substances in their lifetime, in the past 12 months, in the past 30 days, and in the past 7 days using a 7-point scale. They also indicated the age at which they first tried each substance. Provocative Finding Adolescents who reported using marijuana only once or twice displayed greater GMV in several brain regions that are rich in cannabinoid receptors than nonusers. Regions with greater GMV included the bilateral medial temporal lobes, bilateral posterior cingulate, lingual gyri, and cerebellum. "We don't really know for sure why. We also don't know for sure if the GMV differences themselves are because of cannabis use," Garavan said. "It may even be plausible that those GMV differences could have preceded cannabis use. Maybe it's not the case that the GMV differences are a consequence of cannabis use, but that the GMV differences are what caused kids to show more cannabis use," he added. Cannabis users also scored higher in sensation seeking and some anxiety measures than non-users. However, the investigators are unsure whether this was a result of the GMV differences or because of some other unknown factor. "I think we definitely need to investigate further," he said. "With any finding, especially something like this which is provocative, we want to replicate it. We want to see if this is consequential and we need to be very cautious about this." Counterintuitive Findings Commenting on the findings for Medscape Medical News, William Chow, MD, neurologist and assistant clinical professor at the University of California, Los Angeles, said that some other studies have suggested "brain shrinkage in the temporal lobes for individuals who have used cannabis." "However, I think this just means there is some variability in the imaging studies," Chow said. "We don't really understand the effects of cannabis on the brain at this stage." Also commenting on the study, Alex Dimitriu, MD, a psychiatrist and sleep doctor in Menlo Park, California, told Medscape Medical News that "the findings seem counterintuitive." "It's surprising to see such minimal cannabis use yield any measurable changes in brain structures or volumes," said Dimitriu, who was not associated with the study "Whether more grey matter is better or worse for a developing adolescent brain is yet to be determined, but the fact persists that even low level use causes changes," he added. Source
