THC disrupted brain connectivity by boosting striatal glutamate and dopamine in occasional users
THC increased glutamate in the striatum and reduced functional connectivity between the nucleus accumbens and cortex, with these neurochemical changes correlated with feeling high and impaired attention.
Quick Facts
What This Study Found
THC increased striatal glutamate concentrations and reduced functional connectivity (FC) between the nucleus accumbens and cortical areas, indicating increased dopamine activity. Glutamate changes correlated strongly with FC alterations. FC changes correlated with subjective high and decreased attention task performance. Effects were dose-dependent, appearing when THC blood levels exceeded 2 ng/ml.
Key Numbers
20 occasional users; 300 ug/kg THC dose; effects dose-dependent above 2 ng/ml blood THC; glutamate changes strongly correlated with connectivity loss; connectivity changes correlated with subjective high and attention deficits.
How They Did This
Double-blind, placebo-controlled study in 20 occasional cannabis users receiving 300 ug/kg THC or placebo in two dose regimes (full and divided dose). Magnetic resonance spectroscopy measured glutamate, GABA, and dopamine proxies; fMRI measured functional connectivity.
Why This Research Matters
This is one of the first human studies to show the neurochemical cascade through which THC produces its subjective and cognitive effects: THC boosts glutamate, which enhances dopamine, which disconnects reward circuits from cortical control.
The Bigger Picture
Understanding the glutamate-dopamine cascade explains why THC simultaneously produces reward (dopamine), cognitive impairment (cortical disconnection), and subjective intoxication, all through a single neurochemical pathway.
What This Study Doesn't Tell Us
Small sample (20 participants). Occasional users may respond differently than chronic users. Two dose regimes with 10 participants each limits statistical power. Single-session acute dosing only.
Questions This Raises
- ?Do chronic cannabis users show blunted glutamate responses to THC?
- ?Could glutamate-modulating medications reduce THC-induced cognitive impairment?
Trust & Context
- Key Stat:
- Glutamate-dopamine cascade identified
- Evidence Grade:
- Moderate: double-blind, placebo-controlled with advanced neuroimaging, but small sample.
- Study Age:
- Published in 2019.
- Original Title:
- Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity.
- Published In:
- European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(2), 247-256 (2019)
- Authors:
- Mason, Natasha L(4), Theunissen, Eef L(8), Hutten, Nadia R P W(5), Tse, Desmond H Y, Toennes, Stefan W, Stiers, Peter, Ramaekers, Johannes G
- Database ID:
- RTHC-02165
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
How does THC make you feel high?
This study found THC increases glutamate in the striatum, which enhances dopamine signaling and disconnects the brain's reward center from cortical control. These neurochemical changes directly correlated with feeling high.
At what blood THC level do brain effects begin?
Significant neurochemical and connectivity changes appeared when blood THC exceeded 2 ng/ml, a threshold that may be relevant for impairment-based regulation.
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Cite This Study
https://rethinkthc.com/research/RTHC-02165APA
Mason, Natasha L; Theunissen, Eef L; Hutten, Nadia R P W; Tse, Desmond H Y; Toennes, Stefan W; Stiers, Peter; Ramaekers, Johannes G. (2019). Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(2), 247-256. https://doi.org/10.1016/j.euroneuro.2018.12.003
MLA
Mason, Natasha L, et al. "Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity.." European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2019. https://doi.org/10.1016/j.euroneuro.2018.12.003
RethinkTHC
RethinkTHC Research Database. "Cannabis induced increase in striatal glutamate associated w..." RTHC-02165. Retrieved from https://rethinkthc.com/research/mason-2019-cannabis-induced-increase-in
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.