An investigation of the relationship between glutamate and resting state connectivity in chronic cannabis users
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ORIGINAL RESEARCH
An investigation of the relationship between glutamate and resting state connectivity in chronic cannabis users Sharlene D. Newman 1,2 & Hu Cheng 1,2 & Dae-Jin Kim 1 & Ashley Schnakenberg-Martin 1 & Ulrike Dydak 3,4 & Shalmali Dharmadhikari 3,4 & William Hetrick 1,2 & Brian O’Donnell 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Human and animal studies have shown that heavy cannabis (CB) use interacts with glutamatergic signaling. Additionally, recent studies have suggested that glutamate (Glu) may drive resting state functional connectivity (RSfc). The aims of the current preliminary study were to: 1) determine whether dorsal anterior cingulate cortex (dACC) Glu is related to RSfc between the dACC and two nodes of the reward network, the nucleus accumbens (NAc) and hippocampus (Hp); and 2) determine whether CB use interacts with the relationship between dACC Glu and RSfc. A group of 23 chronic CB users and 23 healthy controls participated in this multimodal MRI study. Glu levels were assessed in the dACC using magnetic resonance spectroscopy (MRS). Linear regression models were used to determine whether dACC Glu and CB use predicts RSfc between the dACC and the NAc and Hp. While the effect size is small, the results showed that the connectivity between the dACC and right NAc was predicted by the interaction between dACC Glu levels and monthly CB use. Additionally, while there is some suggestion that dACC Glu is correlated with dACC-hippocampal connectivity, unlike for dACC/NAc connectivity the relationship between them does not appear to be affected by CB use. These preliminary findings are significant in that they demonstrate the need for future studies with larger sample sizes to better characterize the relationship between resting state connectivity and neurochemistry as well as to characterize how CB use interacts with that relationship. Keywords Cannabis . MRS . Dorsal anterior cingulate . Resting state connectivity
Introduction The use of cannabis has increased over the past decade in the United States, and past-year prevalence of cannabis (CB) use exceeds 10% (Grucza et al. 2016) with few users seeking Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11682-019-00165-w) contains supplementary material, which is available to authorized users. * Sharlene D. Newman [email protected] 1
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA
2
Program in Neuroscience, Indiana University, Bloomington, IN, USA
3
School of Health Sciences, Purdue University, West Lafayette, IN, USA
4
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA
treatment (Brown et al. 2003). The primary psychoactive component of cannabis (CB) is Δ9-tetrahydrocannabinol (THC). THC has been found in animal models to modulate glutamatergic (Glu) neurotransmission and concentrations. The CB1 receptor is highly expressed in axons and termina
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