Cannabinoid Modulation of Frontolimbic Activation and Connectivity During Volitional Regulation of Negative Affect

Abstract

Behavioral and brain research indicates that administration of Δ(9)-tetrahydrocannabinol (THC) alters threat perception and enhances the suppression of conditioned fear responses via modulation of the frontolimbic circuit. No prior studies, however, have examined whether THC also affects volitional forms of emotion processing such as cognitive reappraisal. The aim of the current study was therefore to examine the effects of THC on frontolimbic activation and functional connectivity during cognitive reappraisal in a sample of healthy adults. The study was a randomized, double-blind, placebo-controlled, between-subject design and all participants ingested either an oral dose of synthetic THC (n=41) or placebo (n=37) before completion of an emotion regulation task during functional magnetic resonance imaging (fMRI). Functional connectivity was assessed using generalized psychophysiological interaction (gPPI) analyses. Results indicated that although there were no group differences in self-reported attenuation of negative affect during cognitive reappraisal, relative to placebo, THC increased amygdala activation and reduced amygdala and dorsolateral prefrontal cortex (dlPFC) functional coupling during cognitive reappraisal of emotionally negative pictures. This suggests that in addition to automatic emotional processes, THC affects frontolimbic functioning during cognitive reappraisal.

A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis

“…Conversely, during fear processing, the parahippocampal gyrus and amygdala are known to activate in response to fear/threat-related environmental cues, particularly angry or fearful facial stimuli 45 – 47 . In the current study, both parahippocampal and amygdala activation were attenuated by CBD, suggesting that CBD may partially normalise (attenuate) the altered neurofunctional response to fear/threat-related stimuli in CHR patients, which is in line with the potential anxiolytic effects of CBD and the role of the endocannabinoid system as a regulator of subjective affective states, including anxiety, fear and aggression 62 – 64 . Indeed, previous work has shown that CBD attenuates limbic and paralimbic function in healthy individuals 13 , 65 and in patients with anxiety disorders 9 , and this is related to its anxiolytic effects 9 , 13 .…”

“…Our findings also agree with what is known about the opposite effects of THC and CBD on emotion-processing-related circuitry in healthy people. In the majority of (but not all 67 , 68 ) studies, THC appears to augment amygdala activation and increase anxiety during fearful face processing 14 , 62 and reduces amygdala–prefrontal connectivity during negative affect reappraisal 62 . Conversely, CBD increases fronto-striatal connectivity 69 and attenuates amygdala activation while concomitantly decreasing physiological anxiety 13 , 14 .…”

Emotion regulation deficits in regular marijuana users

“…Decreased emotion regulation‐associated dlPFC–amygdala coupling in the present sample of marijuana users may therefore be at the core of the deficiency in regulating negative affect. In line with a dense localization of CB(1) receptors in the fronto–limbic neural circuitry [Eggan and Lewis, ], acute THC administration reduces dlPFC–amygdala coupling during volitional regulation of emotions [Gorka et al, ], emphasizing the relevance of the CB(1) system for this functional domain and suggesting that alterations in the cannabinoid system due to regular marijuana use may specifically affect this regulatory system. However, downregulation of CB(1) receptor availability upon regular marijuana exposure [Hirvonen et al, ] normalizes after 2 days [D'Souza et al, ].…”

The Effectiveness of Cannabinoids in the Treatment of Posttraumatic Stress Disorder (PTSD): A Systematic Review

“…THC has also been shown to enhance amygdalaprefrontal connectivity, modulate subjective anxiety (dependent on dose), impair facial emotional processing, and increase fear extinction (Ballard, Bedi, & de Wit, 2012;D'Souza et al, 2004;Gorka, Fitzgerald, de Wit, & Phan, 2014;Hindocha et al, 2015;Rabinak et al, 2013). However, other research suggests that THC can increase amygdala reactivity to unpleasant images compared to neutral images, suggesting THC has a complex effect on amygdala reactivity and anxiety, where high doses can exacerbate anxiety (Gorka et al, 2015).…”