The metabolite kynurenine amplified THC-induced sensorimotor impairment and classic behavioral effects in mice, possibly by increasing THC blood levels.
Neuroscience researchers, psychiatrists, anyone interested in cannabis and psychosis risk
Kynurenine pretreatment increased both THC blood levels and its behavioral effects in mice
What the researchers found
Mice given kynurenine before THC showed significantly worse sensorimotor responses, greater motor impairment, and deeper hypothermia compared to THC alone. Kynurenine also increased blood levels of THC and its psychoactive metabolite 11-OH-THC.
Why it matters
The kynurenine pathway is dysregulated in schizophrenia, and THC can worsen psychotic symptoms. This study suggests a biological mechanism linking the two: elevated kynurenine may amplify THC's effects, potentially explaining why people with schizophrenia are especially vulnerable to cannabis-related harm.
The numbers in context
Brain kynurenic acid levels significantly increased 1 hour after kynurenine administration; THC and 11-OH-THC plasma levels were higher in kynurenine-pretreated mice; kynurenine amplified THC effects on motor tests (bar test, drag test, rotarod) and hypothermia but not pain response
How the study worked
Adult male mice received THC (30 mg/kg) and kynurenine (20 mg/kg) alone or combined. Researchers measured body temperature, pain responses, motor activity, sensorimotor function, brain kynurenic acid levels, and plasma THC concentrations.
What this study cannot tell us
Male mice only, high THC dose (30 mg/kg), kynurenine-THC interaction may be partly pharmacokinetic rather than pharmacodynamic, cannot confirm mechanism applies to humans
How to read the evidence
Single animal study with male mice only; first to demonstrate kynurenine-THC interaction on sensorimotor function
When this study was published
Published 2025
The bigger picture
Understanding why some people are more vulnerable to THC's negative effects is a major research priority. This study points to the kynurenine pathway as one biological factor that could amplify THC-related impairment, with particular relevance for people with schizophrenia.
Questions still open
- Do people with elevated kynurenine levels experience stronger THC effects? Could kynurenine pathway activity predict individual vulnerability to cannabis-induced psychosis? Would lower THC doses show the same interaction?
Common questions
What is kynurenine and why does it matter for cannabis?
Did kynurenine change how THC is processed in the body?
Read the original research
Kynurenine amplifies tetrahydrocannabinol-induced sensorimotor impairment and classic "tetrad" effects in mice.
Progress in neuro-psychopharmacology & biological psychiatry, 138, 111342
Citation
Bilel, Sabrine; Corli, Giorgia; Tiziani, Edoardo; Chirenti, Daniele; Dall'Acqua, Stefano; Comai, Stefano; Ferraro, Luca; Marti, Matteo; Beggiato, Sarah. (2025). Kynurenine amplifies tetrahydrocannabinol-induced sensorimotor impairment and classic "tetrad" effects in mice.. Progress in neuro-psychopharmacology & biological psychiatry, 138, 111342. https://doi.org/10.1016/j.pnpbp.2025.111342
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