Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

Abstract

There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.

Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks

“…Preclinical models could also benefit research assessing how CBD may moderate THC-induced decision-making impairments. As discussed in section 2.2, ratios of THC/CBD in cannabis can vary widely (Swift et al, 2013; Syed et al, 2014), CBD can attenuate THC-induced memory and attentional impairments (Morgan et al, 2010a; Morgan et al, 2010b), and both agents differentially influence brain activity when performing cognitive or emotional processing tasks (Bhattacharyya et al, 2015; Bhattacharyya et al, 2010; Borgwardt et al, 2008; Fusar-Poli et al, 2009). However, only one human study has attempted to relate decision-making impairments to CBD concentrations in hair (Hermann et al, 2009), and no studies have assessed how it might modulate THC’s effects.…”

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

“…This raises the possibility that the amygdala plays a role in mediating CBD regulation of fear memory. CBD also reduces mPFC-hippocampus functional connectivity during cognitive processing (Bhattacharyya et al, 2015). This suggests that the hippocampus, which is crucial for contextual processing in particular, may also be involved in CBD regulation of certain aspects of learned fear.…”

A Model for Classification Based on the Functional Connectivity Pattern Dynamics of the Brain

“…The cannabis network identified by the LASSO algorithm can be also interesting from the clinical point of view. The pattern of selected functional ROIs include several cognitive control and sensory processing related areas that have been reported to be associated with cannabis use [12], [21], [22], including connections which were found to be stronger in addicted subjects, resulting in both lower DTW distance and shorter path-length values due to some compensatory mechanisms [22], and connections that were shown to be weaker due to the general neural desynchronization reported in cannabis use [23] increasing the length of the warping path.…”