Altered striatal reward processing in abstinent dependent cannabis users: Social context matters

Abstract

Public perception of cannabis as relatively harmless, alongside claimed medical benefits, have led to moves towards its legalization. Yet, long-term consequences of cannabis dependence, and whether they differ qualitatively from other drugs, are still poorly understood. A key feature of addictive drugs is that chronic use leads to adaptations in reward processing, blunting responsivity to the substance itself and other rewarding stimuli. Against this background, the present study investigated whether cannabis dependence is associated with reductions in hedonic representations by measuring behavioral and neural responses to social reward in 23 abstinent cannabis-dependent men and 24 matched non-using controls. In an interpersonal pleasant touch fMRI paradigm, participants were led to believe they were in physical closeness of or touched (CLOSE, TOUCH) by either a male or female experimenter (MALE, FEMALE), allowing the assessment of touch-and social context-dependent (i.e. female compared to male social interaction) reward dynamics.Upon female compared to male touch, dependent cannabis users displayed a significantly attenuated increase of reward experience compared to healthy controls. Controls responded to female as compared to male interaction with increased striatal activation whereas cannabis users displayed the opposite activation pattern, with stronger alterations being associated with a higher lifetime exposure to cannabis. Neural processing of pleasant touch in dependent cannabis users remained intact.These findings demonstrate that cannabis dependence in men is linked to similar lasting neuroadaptations in striatal responsivity to hedonic stimuli as observed for other drugs of abuse. However, reward processing deficits seem to depend on the social context. Clinical trial identifier: NCT02711371.

Common and separable neural alterations in substance use disorders: evidence from coordinate-based meta-analyses of functional neuroimaging studies in human

“…Based on early animal studies demonstrating that the acute reinforcing effects of all drugs of potential abuse increase dopamine in the terminal regions of the mesocorticostriatal system including the ventral striatum [11] -which with repeated use may drive dysregulations in incentive salience and habit formation [9], [12] -most research emphasizes the common neuropathological endpoints across substances and substance use disorders. In line with animal models demonstrating that neuroplastic changes in the striatum mediate exaggerated salience to drug cues at the expense of natural rewards and habitual responses to cues repeatedly paired with the drug [13], exaggerated striatal drug cue reactivity and blunted striatal processing of non-drug rewards has been demonstrated in functional MRI studies in human drug users with regular and addictive use of different substances [14]- [18]. However, despite convergent evidence for striatal maladaptation across different substance use disorders, substance-specific predisposing factors [19]- [22] and addiction-related alterations have been increasingly recognized, such that frontal regions have been found to be differentially impacted by stimulant or opioid use [23] and neurocognitive deficits in domains associated with striato-frontal circuits such as inhibitory control and cognitive flexibility have been found to be differentially impacted by alcohol, stimulants, and cannabis [24], [25].…”

Hypothalamic Responses to Cocaine and Food Cues in Individuals with Cocaine Dependence

“…Fourth, the whole-brain analyses did not reveal striatal responses to drug or food cues. The striatum has been implicated in cue-induced craving (Chase et al, 2011; Kühn and Gallinat, 2011) and reward-related processing (Filbey et al, 2016; Luijten et al, 2017; Zimmermann et al, 2019), whereas some studies of cue-induced craving did not demonstrate striatal activation (Garavan et al, 2000; Wexler et al, 2001; Duncan et al, 2007; Lee et al, 2013). Although not a primary aim of the current study, we conducted a ROI analysis focusing on the VS and dorsal striatum.…”

Common and separable neural alterations in substance use disorders: A coordinate‐based meta‐analyses of functional neuroimaging studies in humans

“…Based on early animal studies demonstrating that the acute reinforcing effects of all drugs of potential abuse increase dopamine in the terminal regions of the mesocortical‐striatal system including the ventral striatum (Di Chiara & Imperato, 1988)—which with repeated use may drive dysregulations in incentive salience and habit formation (Everitt & Robbins, 2016; Robinson & Berridge, 2001)—most research emphasizes the common neuropathological endpoints across substances and substance use disorders. In line with animal models demonstrating that neuroplastic changes in the striatum mediate exaggerated salience to drug cues at the expense of natural rewards and habitual responses to cues repeatedly paired with the drug (Robbins, Ersche, & Everitt, 2008), exaggerated striatal drug cue reactivity and blunted striatal processing of nondrug rewards has been demonstrated in functional MRI studies in human drug users with regular and addictive use of different substances (Chase, Eickhoff, Laird, & Hogarth, 2011; Kühn & Gallinat, 2011; Vollstädt‐Klein et al, 2010; Zhou et al, 2019; Zimmermann et al, 2019). However, despite convergent evidence for striatal maladaptations across different substance use disorders, substance‐specific predisposing factors (Becker et al, 2015; Cheng et al, 2019; Elsayed et al, 2018; Zilberman, Yadid, Efrati, & Rassovsky, 2019) and addiction‐related alterations have been increasingly recognized, such that frontal regions have been found to be differentially impacted by stimulant or opioid use (Badiani, Belin, Epstein, Calu, & Shaham, 2011) and neurocognitive deficits in domains associated with frontostriatal circuits such as inhibitory control and cognitive flexibility have been found to be differentially impacted by alcohol, stimulants, and cannabis (Fernández‐Serrano, Pérez‐García, & Verdejo‐García, 2011; Smith, Mattick, Jamadar, & Iredale, 2014).…”