Kannabis ja nuorten kehittyvät aivot- tutkimus ei tue kannabiksen laillistamista
Albaugh M et al:
Association of Cannabis Use During Adolescence With Neurodevelopment
IMPORTANCE Animal studies have shown that the adolescent brain is sensitive to disruptions
in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral
effects. However, few studies have investigated ties between cannabis use and adolescent
brain development in humans.
OBJECTIVE To examine the degree to which magnetic resonance (MR) imaging–assessed
cerebral cortical thickness development is associated with cannabis use in a longitudinal
sample of adolescents.
DESIGN, SETTING, AND PARTICIPANTS Datawere obtained from the community-based
IMAGEN cohort study, conducted across 8 European sites. Baseline data used in the present
study were acquired from March 1, 2008, to December 31, 2011, and follow-up data were
acquired from January 1, 2013, to December 31, 2016. A total of 799 IMAGEN participants
were identified who reported being cannabis naive at study baseline and had behavioral
and neuroimaging data available at baseline and 5-year follow-up. Statistical analysis was
performed from October 1, 2019, to August 31, 2020.
MAIN OUTCOMES AND MEASURES Cannabis usewas assessed at baseline and 5-year follow-up
with the European School Survey Project on Alcohol and Other Drugs. Anatomical MR images
were acquired with a 3-dimensional T1-weighted magnetization prepared gradient echo
sequence. Quality-controlled nativeMR images were processed through the CIVET pipeline,
RESULTS The study evaluated 1598 MR images from 799 participants (450 female
participants [56.3%]; mean [SD] age, 14.4 [0.4] years at baseline and 19.0 [0.7] years at
follow-up). At 5-year follow-up, cannabis use (from 0 to >40 uses) was negatively associated
with thickness in left prefrontal (peak: t785 = –4.87, cluster size = 1558 vertices;
P = 1.10 × 10−6, random field theory cluster corrected) and right prefrontal (peak: t785 = –4.27,
cluster size = 1551 vertices; P = 2.81 × 10−5, random field theory cluster corrected) cortices.
There were no significant associations between lifetime cannabis use at 5-year follow-up and
baseline cortical thickness, suggesting that the observed neuroanatomical differences did not
precede initiation of cannabis use. Longitudinal analysis revealed that age-related cortical
thinning was qualified by cannabis use in a dose-dependent fashion such that greater use,
from baseline to follow-up, was associated with increased thinning in left prefrontal (peak:
t815.27 = –4.24, cluster size = 3643 vertices; P = 2.28 × 10−8, random field theory cluster
corrected) and right prefrontal (peak: t813.30 = –4.71, cluster size = 2675 vertices;
P = 3.72 × 10−8, random field theory cluster corrected) cortices. The spatial pattern of
cannabis-related thinning was associated with age-related thinning in this sample (r = 0.540;
P < .001), and a positron emission tomography–assessed cannabinoid 1 receptor–binding map
derived from a separate sample of participants (r = −0.189; P < .001). Analysis revealed that
thinning in right prefrontal cortices, from baseline to follow-up, was associated with
attentional impulsiveness at follow-up.
CONCLUSIONS AND RELEVANCE Results suggest that cannabis use during adolescence is
associated with altered neurodevelopment, particularly in cortices rich in cannabinoid 1 receptors
and undergoing the greatest age-related thickness change in middle to late adolescence.
Specifically, adolescent exposure to THC has been shown to decrease social behavior in adult rats as well as alter motivational processes. Rodent and primate studies have also demonstrated that adolescent exposure to THC results in working memory deficits in adulthood.Several rodent studies have also found that adolescent THC exposure results in lasting alterations in glutamatergic and γ-aminobutyric acidergic functioning.
To our knowledge, the present investigation represents the largest longitudinal neuroimaging study
of adolescent cannabis use to date. We report evidence of an association between adolescent cannabis use
and altered cortical thickness development in a longitudinal sample of youths.
The spatial pattern of cannabis-related thinning was associated with a PET-derived map of CB1 receptor
availability as well as a map of age-related thickness change. The findings underscore the importance of
further longitudinal studies of adolescent cannabis use, particularly given increasing trends
in the legalization of recreational cannabis use.
JAMA Psychiatry. doi:10.1001/jamapsychiatry.2021.1258
Published online June 16, 2021.