TY  - JOUR
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 is associated with tolerance to cannabis impairment in chronic users
T2  - Addiction Biology
N2  - Cannabis is the most commonly used illicit drug in the world. However, because of 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 that 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 the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, 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 chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, 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, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations.
KW  - cannabis
KW  - glutamate
KW  - tolerance
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74725
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-747253
SN  - 1369-1600
VL  - 26.2021
IS  - 1, e12870
PB  - Wiley-Blackwell
CY  - Hoboken, NJ [u.a.]
ER  -