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    • To examine the impact of cannabis use

    2018-11-07

    To examine the impact of cannabis use on Batimastat regions subserving emotional processing, we conducted an fMRI study on 14-year old cannabis users vs. controls using affective face stimuli. Angry and neutral faces provide a robust probe of activity within the amygdala and PFC in adults (Morris et al., 1996; Pessoa et al., 2002; Whalen et al., 1998), as well as children and adolescents (Baird et al., 1999; Thomas et al., 2001). The differential activity of the amygdala to angry versus neutral faces is an excellent index of emotional processing and may relate to psychopathology. However, in order to prevent ceiling effects, we used a set of stimuli that was only mildly negatively valenced on the basis that they may provide a sensitive test of enhanced amygdala reactivity (Grosbras and Paus, 2006). To date, few study have examined the relationship between cannabis and face processing. Phan and colleagues (2008) recruited healthy adults in a dual-session, double-blind, placebo-controlled study of THC intoxication and face processing using fMRI. Findings indicate THC attenuates the amygdala response to fearful faces. Similarly, Gruber and colleagues (2009) studied 15 chronic cannabis users vs. matched controls under fMRI during a masked affective face processing task. Results suggest chronic cannabis use is associated with decreased reactivity in the anterior cingulate and amygdala. While both Phan and Gruber\'s findings suggest anxiolytic effects in intoxicated adults, these studies do not address whether the effects would replicate in users not intoxicated during scanning, nor does it address whether the effects would generalize to adolescents. Nonetheless, these studies provide evidence that cannabis use is associated with differences in affective processing. In this relatively large fMRI study (N=140), we investigated the impact of previous cannabis use (n=70) compared to closely matched controls (n=70) in early adolescence using a face processing task during fMRI. To date, there has been no previous research directly studying history of cannabis use with face processing, especially not from a developmental affective neuroscience perspective.
    Methods
    Results
    ROI Correlations with Other Drugs To examine dosage–response effects, we investigated Pearson\'s correlation on frequency of cannabis use with the mean signal per face type within each region. Dosage effects within bilateral amygdalae and dlPFC were non-significant at p<.05. Interestingly, we detected a significant correlation within the right TPJ cluster with frequency of cannabis use. Both the mean signal related to angry faces (r=−.25, p<.05), and neutral faces (r=−.26, p<.05), was correlated with frequency of cannabis use, such that, more frequent cannabis use is associated with less processing by the right TPJ during presentation of both face types. We also investigated Pearson\'s correlation on age of onset of cannabis, alcohol, and cigarette use with the mean signal per face type within each ROI. However, we failed to detect any significant correlations at p<.05 between age of onset for any drugs of abuse with any of the ROIs.
    Discussion In renin study, we examined the functional neurobiology of angry and neutral face processing in a group of cannabis-experimenting adolescents vs. matched controls using fMRI. We found group-by-face type interaction effects in bilateral amygdala and three clusters of activation that span the right TPJ and bilateral dlPFC. Decomposing these results by face type, we found the cannabis-experimenting group exhibited increased activity to angry faces in the amygdala. Conversely, the control group exhibited increased activity to neutral faces in the cortical regions. Therefore, cannabis use during early adolescence is associated with hypersensitivity to negative affect in the amygdala. While we stress that this study does not permit us to conclude cannabis-experimentation caused the observed functional neurobiological differences, we are confident these differences are associated with the cannabis use status of the participants due to our relatively large sample size (N=140), carefully matched control group (who did not differ on sex, pubertal development, IQ, site, psychopathology, or alcohol and cigarette use), and a conservative criteria to meet statistical significance.