Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users

Abstract

Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts structural and functional changes in the human brain. These changes have profound implications for our understanding of the neuropharmacology of cannabis and its effects on cognition, mental health and the brain.

Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis‐dependent males

“…Patterns of functional connectivity associated with a significant group (control vs user) by seed (VS vs. DS) interaction. As such, the present findings are in accordance with recent quantitative and qualitative reviews suggesting alterations in networks engaged in cognitive control and reward processing in chronic cannabis users(Weinstein et al, 2016;Wrege et al, 2014;Yanes et al, 2018). Error bars reflect the SEM.…”

“…Red color indicated stronger functional connectivity with VS than DS and blue color indicated stronger functional connectivity with DS than VS. All images were thresholded at p < .05, TFCE corrected (Weinstein et al, 2016;Wrege et al, 2014;Yanes et al, 2018) and social decision making (Gilman, 2017). In line with animal and human data that emphasize the specific contributions of the VS and DS, subregion-specific differences between cannabis users and controls mapped to the nucleus accumbens and the caudate nucleus.…”

“…Despite the important contributions of these studies to characterize mechanisms of cannabis dependence, the task-based approach does not allow direct evaluation of the ventral to dorsal striatal shift due to: (a) limitation of task-based fMRI to regions engaged by the experimental paradigm (Weinstein et al, 2016) and (b) stimulus and context dependences of striatal alterations in cannabis dependence (Gilman, 2017;. Resting state fMRI functional connectivity (rsfMRI-FC) approaches allow a more holistic assessment of functional alterations in the absence of task or contextual modulation.…”

Mechanisms Underlying Sex Differences in Cannabis Use

“…Several groups have investigated structural brain changes related to cannabis use [130, 131], yet as with the adolescent literature, few studies include women or analyze gender differences, as discussed and reviewed by Ketcherside and colleagues [132]. In mixed-gender populations, cannabis users have exhibited more grey matter volume in cerebellum [133], left putamen, and right precentral gyrus [134], and less thalamic [134] grey matter volume compared to healthy controls.…”

Positive and Negative Effects of Cannabis and Cannabinoids on Health

“…Impaired cognitive function following cannabis consumption was associated with an increased risk of having a road accident …”