An investigation of the relationship between glutamate and resting state connectivity in chronic cannabis users

  • Sharlene D. NewmanEmail author
  • Hu Cheng
  • Dae-Jin Kim
  • Ashley Schnakenberg-Martin
  • Ulrike Dydak
  • Shalmali Dharmadhikari
  • William Hetrick
  • Brian O’Donnell
Original Research


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.


Cannabis MRS Dorsal anterior cingulate Resting state connectivity 



This study was supported by the National Institute on Drug Abuse (NIDA) Grant #5R21DA035493 (BFO/SDN), the National Institute of Mental Health (NIMH) Grant #2R01MH074983 (WPH), a National Science Foundation Graduate Research Fellowship Grant #1342962 (AMSM) as well as a NIDA T32 Predoctoral Fellowship Grant #T32DA024628 (AMSM). Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NIDA, NIMH, or the National Science Foundation.

Compliance with ethical standards

Conflict of interest

All authors reported no biomedical financial interests or potential conflicts of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

Supplementary material

11682_2019_165_MOESM1_ESM.docx (2.5 mb)
ESM 1 (DOCX 2586 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Psychological and Brain SciencesIndiana UniversityBloomingtonUSA
  2. 2.Program in NeuroscienceIndiana UniversityBloomingtonUSA
  3. 3.School of Health SciencesPurdue UniversityWest LafayetteUSA
  4. 4.Department of Radiology and Imaging SciencesIndiana University School of MedicineIndianapolisUSA

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