Alcohol and cannabis co‐use and longitudinal gray matter volumetric changes in early and late adolescence

Abstract

Background Previous studies have characterized the impact of substance use on cerebral structure and function in adolescents. Yet, the great majority of prior studies employed a small sample, presented cross‐sectional findings, and omitted potential sex differences. Methods Using data based on 724 adolescents (370 females) curated from the NCANDA study, we investigated how gray matter volumes (GMVs) decline longitudinally as a result of alcohol and cannabis use. The impacts of alcohol and cannabis co‐use and how these vary across assigned sex at birth and age were examined. Brain imaging data comprised the GMVs of 34 regions of interest and the results were evaluated with a Bonferroni correction. Results Mixed‐effects modeling showed faster volumetric declines in the caudal middle frontal cortex, fusiform, inferior frontal, superior temporal (STG), and supramarginal (SMG) gyri, at −0.046 to −0.138 cm3/year in individuals with prior‐year alcohol and cannabis co‐use, but not those engaged in alcohol or cannabis use only. These findings cannot be explained by more severe alcohol use among co‐users. Further, alcohol and cannabis co‐use in early versus late adolescence predicted faster volumetric decline in the STG and SMG across assigned sex at birth. Conclusions Findings highlight the longitudinal impact of alcohol and cannabis co‐use on brain development, especially among youth reporting early adolescent onset of use. The volumetric decline was noted in cortical regions in support of attention, memory, executive control, and social cognition, suggesting the pervasive effect of alcohol and cannabis co‐use on brain development.

Consequences of adolescent drug use

“…There is mixed evidence in humans suggesting additive effects of ACE and AAE. One investigation reported decreases in GMV following poly use of alcohol and cannabis starting in early adolescence, but did not observe this in participants who had exclusively used alcohol or cannabis [234]. However, there is also evidence that the two do not have additive effects in some domains.…”

Acute alcohol induces greater dose-dependent increase in the lateral cortical network functional connectivity in adult than adolescent rats

“…One of the explanations concerning why early intoxication increases the risk of later alcohol problems is its interference with neurodevelopmental, hormonal and cognitive changes occurring at this age [ 6 ]. The frontal cortex undergoes substantial reorganization through adolescence [ 7 – 9 ], coinciding with ongoing puberty, improvement of executive functioning and top-down inhibitory control over behavior [ 10 – 12 ]. Several human imaging studies have suggested the frontal cortex may be particularly sensitive to alcohol [ 9 , 13 – 15 ].…”

“…The frontal cortex undergoes substantial reorganization through adolescence [ 7 – 9 ], coinciding with ongoing puberty, improvement of executive functioning and top-down inhibitory control over behavior [ 10 – 12 ]. Several human imaging studies have suggested the frontal cortex may be particularly sensitive to alcohol [ 9 , 13 – 15 ]. Studies using rodent models have likewise found that adolescent frontal cortex is sensitive to the effects of chronic alcohol as reflected in persistent neuronal [ 16 – 18 ] and cognitive deficits [ 19 , 20 ].…”

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats

“…This co-use, when heavy or associated with a substance use disorder, has been associated with persistent deficits in cognitive function and adverse psychosocial outcomes (Lees et al, 2021). A recent longitudinal imaging study in over 700 adolescents suggested faster declines in gray matter volume in multiple brain regions, including the frontal cortex, in participants that co-used alcohol and cannabis compared to those who used either drug alone (Luo et al, 2022). Published studies of co-exposure in laboratory rodents, which are relatively sparse despite the prevalence of co-use in adolescents, have thus far reported modest or no behavioral effects of co-exposure compared to alcohol or THC exposure alone (Liang, 2022).…”