Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users
Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten, Desmond H. Y. Tse, Stefan W. Toennes, Jacobus F.A. Jansen, Peter Stiers, Johannes G. Ramaekers
bioRxiv (Cold Spring Harbor Laboratory) July 19, 2019 preprint DOI: 10.1101/708677 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, cross-over study |
|---|---|
| Sample size | 24 |
| Population | Occasional and chronic cannabis users |
| Interventions | Cannabis (300 μg/kg THC) Placebo |
| Dose | 300 μg/kg THC |
| Topics | Cannabis CBD |
| Keywords | Effects of cannabis Dronabinol Placebo Drug tolerance Cannabinoid |
| Citations | 4 |
| Key points | Cannabis induced neurometabolic alterations in reward circuitry and impaired sustained attention in occasional users but not chronic users, indicating tolerance to cannabis effects. |
Abstract
Abstract 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.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cites 15
- Neurophysiological functioning of occasional and heavy cannabis users during THC intoxication Psychopharmacology October 5, 2011
- Cannabis and tolerance: acute drug impairment as a function of cannabis use history Scientific Reports May 26, 2016
- Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes Brain Imaging and Behavior December 14, 2015
- Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity. European Neuropsychopharmacology December 1, 2019
- Cannabis use and the development of tolerance: a systematic review of human evidence. Neuroscience & Biobehavioral Reviews October 2018
and 10 more in the library