Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity.
Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten, Desmond H. Y. Tse, Stefan W. Toennes, Peter Stiers, Johannes G. Ramaekers
European Neuropsychopharmacology December 1, 2019 DOI: 10.1016/j.euroneuro.2018.12.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Occasional cannabis users |
| Intervention | THC |
| Dose | 300 µg/kg THC |
| Duration | Two separate testing days |
| Measures | magnetic resonance spectroscopy, functional magnetic resonance imaging |
| Topics | Cannabis |
| Keywords | Dopamine Functional connectivity Glutamate |
| Key points | THC increases striatal glutamate concentrations and reduces functional connectivity between the nucleus accumbens and cortical areas, with dose-dependent effects that correlate with subjective high and attention task performance. |
Abstract
Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Δ9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding effects of cannabis. Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release. This double-blind, placebo-controlled study assessed the acute influence of two doses of THC on brain kinetics of glutamate, GABA, and dopamine, in relation to behavioral outcomes, by using magnetic resonance spectroscopy and functional magnetic resonance imaging. Twenty occasional cannabis users received acute doses of cannabis (300 µg/kg THC) and placebo, in one of two dose regimes (full dose and divided dose), during two separate testing days. Administration of THC increased striatal glutamate concentrations, and dopamine as indicated by a reduction in functional connectivity (FC) between the nucleus accumbens (NAc) and cortical areas. Alterations in glutamate and FC were dose dependent and evident in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with FC alterations. Additionally, THC induced changes in FC correlated with feelings of subjective high and decreased performance on an attention task. Taken together, this suggests that THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, which is associated with an increase in striatal glutamate.
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
Cited by 31
- Spontaneous and deliberate creative cognition during and after psilocybin exposure Translational Psychiatry April 8, 2021
- Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users Addiction Biology December 22, 2019
- Multimodal MRI data fusion reveals distinct structural, functional and neurochemical correlates of heavy cannabis use Addiction Biology November 22, 2021
- Functional brain connectomes reflect acute and chronic cannabis use Scientific Reports February 14, 2022
- Individual and combined effects of cannabidiol and Δ 9 -tetrahydrocannabinol on striato-cortical connectivity in the human brain Journal of Psychopharmacology May 20, 2022
and 26 more in the library
Cites 21
- Psychiatric effects of cannabis The British Journal of Psychiatry February 1, 2001
- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities The International Journal of Neuropsychopharmacology May 17, 2017
- 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
and 16 more in the library