Brain functioning during working memory task performance in young and long- term cannabis users

Introduction

Cannabis is the most widely consumed illicit psychoactive drug, with an estimated global prevalence of use of approximately 2.5% of the population. Its components interact with the brain’s endocannabinoid system, receptors for which are densely expressed in the frontal and anterior cingulate cortex and the hippocampus, among other areas. Functional neuroimaging studies evaluating memory and executive function have had positive, though sometimes inconsistent findings, and most studies have been in young adult users, with some evidence suggesting that altered brain activation may be more pronounced with greater duration and frequency of use; however, this relationship remains uncertain.

Aim

We aimed to evaluate the effect of cannabis on brain functioning during a working memory task in two groups of users differing in age, frequency and length of use.

Participants

Two samples of cannabis users were included: 38 long-term daily users (aged 26 to 49 years old) with at least 10 years of regular use and daily use for the last 5 years and 57 younger individuals (18 to 25 years old) reporting at least weekly use. Each group was matched by age, sex, and estimated IQ to a corresponding comparison group of non-users (n = 27 and n = 46, respectively). All participants were asked to maintain a minimum abstinence period of 24 hours prior to scanning.

Methods

Participants underwent functional magnetic resonance imaging (fMRI) while performing a working memory paradigm (the n-back task). This task required monitoring a sequence of letters and responding when the current stimulus matched either the immediately preceding item (control condition, 1-back) or the item presented two trials earlier (working memory condition, 2-back). Preprocessing and statistical analyses were conducted using the FEAT module implemented in the FSL software package, applying general linear Models. A significance threshold of p < 0.05 was applied, with a cluster-forming threshold of Z > 2.6.

Results

The mean duration of regular cannabis exposure was 11.08 years (range: 5–25) in the long-term group and 3.75 years (range: 1–9) in the younger group. Long-term individuals reported a mean daily intake of 1.07 g (range: 0.21–4), corresponding to approximately 7.5 g per week, whereas younger participants reported a mean weekly intake of 6 g (range: 1–26).During n-back task performance (2-back > 1-back contrast), the long-term users showed reduced activation compared to their controls in the bilateral hippocampus (left: x = −16, y = −24, z = −10; Z = 3.86, cluster size = 383 voxels, p = 0.002; right: x = 8, y = −8, z = −8; Z = 4.02, cluster size = 287 voxels, p = 0.01). No significant differences were observed between the younger group and their control group.

Conclusions

Individuals with prolonged cannabis exposure exhibited reduced hippocampal activation during working memory performance, whereas younger individuals with shorter exposure did not show detectable functional alterations. These findings provide preliminary evidence suggesting that long-term cannabis exposure may be associated with more pronounced alterations in brain function, particularly in regions critical for memory processing.

References

No references