TY  - INPR
A1  - Mason, Natasha L.
A1  - Theunissen, Eef L.
A1  - Hutten, Nadia R. P. W.
A1  - Tse, Desmond H. Y.
A1  - Tönnes, Stefan W.
A1  - Jansen, Jacobus F. A.
A1  - Stiers, Peter
A1  - Ramaekers, Johannes G.
T1  - Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users
T2  - bioRxiv
N2  - Cannabis is the most commonly used illicit drug in the world. However due to a changing legal landscape, and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly, cannabis impairment. Importantly, a growing body of evidence suggests regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo controlled, cross-over study assessed the acute influence of cannabis on brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional (OUs) and 12 chronic (CUs) cannabis users received acute doses of cannabis (300 μg/kg THC) and placebo, and underwent ultra-high field functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS). In OUs, cannabis induced significant neurometabolic alterations in reward circuitry, namely decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in CUs. The finding that cannabis altered circuitry and distorted behavior in OUs, but not CUs, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72585
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-725859
UR  - https://www.biorxiv.org/content/10.1101/708677v1
N1  - Now published in Addiction Biology doi: 10.1111/adb.12870
IS  - 708677 Version 1
PB  - bioRxiv
ER  -