2026 ECNP Congress

PS04-4205

Age-dependent effects of cannabis use on functional brain connectivity: evidence from a longitudinal resting-state fMRI study

Elizabeth Davies — N. Ertl, T.P. Freeman, M. Claire, H.V. Curran, W. Lawn, M.B. Wall · Perceptive, Discovery: Translational MRI, London, United Kingdom

2026 ECNP Congress

Adolescence is a critical period for brain development which coincides with the maturational peak of cannabinoid-1 receptor expression [1]. This may heighten vulnerability to the effects of repeated cannabis use. We aimed to investigate whether regular cannabis use is associated with differential changes of functional connectivity in resting state networks over a year interval in adolescents compared with adults.

Methods

Resting-state fMRI data from two time points, one year apart, were analysed from adolescents (n = 31; 16-17 years) and adults (n = 35; 26-29 years) who consistently used cannabis (>1 day/week; average ~3 days/week) and controls (non-users; < 11 lifetime use). Seed-based functional connectivity analyses were conducted across seven networks (default mode, executive control, salience, hippocampal and three striatal networks). Preprocessing used established best-practice procedures following previous similar work.

Seed-to-voxel analyses tested main effects of age group, user group, and an age x user group interaction on longitudinal change maps (timepoint 2 – timepoint 1). Clusters surviving a cluster-based correction for multiple comparisons (Z > 2.3; p < .05) were extracted and used to visualise the directionality of significant effects by 2 × 2 ANOVAs. Anticorrelations were determined by the sign of functional connectivity at each timepoint.

Results

Significant age × user group interactions were observed in regions anticorrelated to salience and default mode networks (DMN) across the one-year interval. Two bilateral dorsomedial prefrontal clusters (Left: Z = 4.13, p < .001; Right: Z = 3.32, p = .042) anticorrelated with the salience network, and one pre-supplementary motor area cluster (Z = 3.74, p = .049) anticorrelated with the DMN, strengthened in negative functional coupling in adolescent cannabis users and adult controls, over the year. This coupling decreased or became positively functionally connected in adolescent controls and adult cannabis users. The opposite pattern emerged in a salience network thalamic cluster (Z= 4.08, p = .024), and cerebellar cluster (lobule VI; Z = 3.94, p = .029). Main effects of user group revealed divergent effects in cognitive control networks. Anticorrelation between the associative striatum and occipital cortex strengthened in controls but reduced in cannabis users (calcarine sulcus: Z = 3.85, p < .001; temporo-occipital junction: Z = 3.59, p = .039). Functional connectivity between the executive control network and bilateral superior parietal lobules decreased in users and increased in controls (Left: Z = 3.85, p = .004; Right: Z = 3.69, p = .042). Main effects of age were present in associative striatal and hippocampal networks.

Conclusions

The observed age × user group interactions indicate that regular cannabis use is associated with divergent developmental trajectories of large-scale networks across adolescence and adulthood, potentially reflecting age-related differences in neurobiological sensitivity to cannabis exposure. Previous work has shown inconsistent results, possibly due to conflating different developmental stages [2]. However, the present data recapitulate cannabis use related connectivity alterations within cognitive control networks [3]. These results suggest that regular cannabis use interacts with ongoing brain maturation and executive control systems, underscoring the importance of such longitudinal investigations for understanding the developmental consequences of cannabis use.

References

  1. Bossong, M.G. and Niesink, R.J., 2010. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Progress in neurobiology, 92(3), pp.370-385.
  2. Thomson, H., Labuschagne, I., Greenwood, L.M., Robinson, E., Sehl, H., Suo, C. and Lorenzetti, V., 2022. Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature. Psychopharmacology, 239(5), pp.1191-1209.
  3. Ertl, N., Lawn, W., Mokrysz, C., Freeman, T.P., Alnagger, N., Borissova, A., Fernandez-Vinson, N., Lees, R., Ofori, S., Petrilli, K. and Trinci, K., 2023. Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults. Journal of Psychopharmacology, 37(9), pp.904-919.