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The Association Between Cannabis Use and Reward Processing, and the Role of Adolescent Vulnerability


Type

Thesis

Change log

Authors

Skumlien, Martine 

Abstract

Cannabis is the third most commonly used controlled substance worldwide, after alcohol and nicotine. With its changing legal profile, a deeper understanding of how cannabis affects the brain and cognition is in urgent need. Cannabis use has historically been linked with the ‘amotivational syndrome’, implying that reward or motivational processes are dysfunctional in cannabis users. Maladapted reward processing, such as anhedonia and apathy, is a cross-diagnostic symptom in psychiatric disorders, including substance use disorders. Finally, adolescents may be particularly vulnerable to adverse effects of cannabis, due to the important socio-emotional, cognitive, and neuromaturation that takes place during this time. The aims of this thesis were twofold. First, to investigate whether acute and chronic cannabis exposure was associated with disrupted reward processing across psychological, behavioural, and neuroimaging outcomes. Second, to assess whether adolescents showed stronger reward processing disruption after acute or chronic cannabis exposure compared with adults. Firstly, a systematic review of the human literature examining the association between cannabis exposure and reward processing was conducted. Results were mixed, with the strongest evidence for a positive relationship between anhedonia and cannabis use in adolescents. A number of caveats prevented the distillation of clear conclusions, including highly variable operationalisation of cannabis use, lack of or only partial control of important confounders, and small, chiefly adult samples, with consequently low power. The subsequent empirical work expanded on previous research by directly comparing large samples of adult and adolescent cannabis users (1-7 days/week) and gender- and age-matched controls on several measures of reward processing, with rigorous assessment of cannabis use and control of important confounders. The primary source of data for this thesis was the CannTeen study, which is a large study of the effects of cannabis in adults and adolescents. The CannTeen study has an acute arm and a non-acute longitudinal arm, and includes both behavioural measures and neuroimaging. First, data from the CannTeen acute study was used to examine whether cannabis exposure was associated with altered neural responses to reward anticipation on the Monetary Incentive Delay task in adults and adolescents. Acute active cannabis attenuated neural reward anticipation responses in key reward regions, including the ventral striatum and insula, relative to placebo. No previous study has shown this effect in healthy participants or adolescents. Subsequently, adult and adolescent cannabis users and controls from the CannTeen non-acute study were compared on neural reward anticipation and feedback, using the same task. There were no significant differences between cannabis users and controls during reward anticipation or in pre-defined regions during feedback. However, cannabis users showed unhypothesised greater feedback activity in the frontopolar and inferior parietal cortex in an exploratory whole-brain analysis. Neither study found differential effects of cannabis exposure in adolescents and adults. Adult and adolescent cannabis users and controls from the CannTeen non-acute study were then compared on two novel, non-neuroimaging reward processing tasks. The Physical Effort task assessed effort-based decision-making for reward and the Real Reward Pleasure task assessed subjective reward wanting and liking. There were no significant differences between cannabis users and controls on any outcomes, and no interactions between user-group and age-group. Finally, two samples of adult and adolescent cannabis users and controls from the CannTeen non-acute study and a separate online survey study, respectively, were compared on anhedonia and apathy. There was tentative evidence of elevated anhedonia in adolescent cannabis users, but not adult users, and no overall differences between users and controls in levels of apathy. This work suggests that cannabis affects the brain’s reward system acutely, but is not associated with lasting disruptions to reward or motivation non-acutely. Adolescents may show greater vulnerability to cannabis-related anhedonia, but not other reward processing outcomes. Thus, reward processes appear to be largely spared in adolescents and adults with moderate cannabis use, and the cannabis-related ‘amotivational syndrome’ is not supported by scientific evidence.

Description

Date

2022-09-01

Advisors

Sahakian, Barbara J

Keywords

Cannabis, Marijuana, Reward processing, Adolescents, Anhedonia, Apathy, Effort, Monetary Incentive Delay task, THC, CBD

Qualification

Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Sponsorship
Aker Foundation