Metabolomic profiling of cannabis use and cannabis intoxication in humans.
Francisco Madrid-Gambin, Noemí Haro, Natasha L. Mason, Pablo Mallaroni, Eef L. Theunissen, Stefan W. Toennes, Óscar J. Pozo, Johannes G. Ramaekers
Neuropsychopharmacology May 1, 2025 DOI: 10.1038/s41386-025-02082-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Occasional and chronic cannabis users |
| Interventions | cannabis (300 μg/kg THC) placebo |
| Dose | 300 μg/kg THC |
| Duration | 70 min after treatment for blood sampling; attention and subjective high measured twice within 40 min after treatment |
| Topics | Cannabis |
| Citations | 4 |
| Key findings | Metabolomic fingerprints distinguished chronic from occasional cannabis users with 80% accuracy, and only occasional users showed attentional impairment and elevated subjective high during acute THC intoxication. |
Abstract
Acute intoxication from Δ9-tetrahydrocannabinol (THC, the primary active ingredient of cannabis) can lead to neurocognitive impairment and interference with day-to-day operations, such as driving. Present evaluations of THC-induced impairment in legal settings rely on biological drug tests that solely establish cannabis use, rather than cannabis impairment. The current study evaluated the metabolome in blood collected from occasional and chronic cannabis users (N = 35) at baseline and following treatments with cannabis (300 μg/kg THC) and placebo, with the aim to identify unique metabolic alterations that are associated with acute cannabis intoxication and cannabis use frequency. Blood samples were collected at baseline and repeatedly during 70 min after treatment. Sustained attention performance and ratings of subjective high were taken twice within 40 min after treatment. Metabolomic fingerprints of occasional and chronic cannabis users were distinctly different at baseline, when both groups were not intoxicated. A total of 14 metabolites, mainly related to endocannabinoid and amino acid metabolism, were identified that distinguished chronic from occasional cannabis users and that yielded a discriminant analysis model with an 80% classification rate (95% CI: 61-91%). Distinct metabolomic fingerprints were found for occasional cannabis users who, in contrast to chronic cannabis users, showed attentional impairment and elevated ratings of subjective high during cannabis intoxication. These included increments in organic acids, β-hydroxybutyrate and second messenger ceramides. The current study demonstrates the feasibility of the metabolomics approach to identify metabolic changes that are specific to the neurocognitive state of cannabis intoxication and to the history of cannabis use.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cited by 5
- Brain-body integromics of the ayahuasca experience. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2026
- Symmetrical Global Mental Health (Sym-GMH): Ayahuasca and shipibo traditional medicine for lasting changes in personality and quality of life Psychedelics April 20, 2026
- Regulation of neural connectivity and oscillations by cannabinoids: A review. Neuroscience & Biobehavioral Reviews September 7, 2026
- Chronic THC exposure modulates behavioral outcomes and endocannabinoid signaling in HIV-1 Tg26 mice in a sex-dependent manner. Brain Research Bulletin August 1, 2026
- Individual differences in the pharmacokinetic profiling of Δ9-THC may be associated with differential motivational effects of Δ9-THC on cognitive performance
Cites 9
- Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology November 1, 2020
- Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users Addiction Biology December 22, 2019
- Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience Biomedicine & Pharmacotherapy March 24, 2022
- Cannabis Use and Neuroadaptation: A Call for Δ9-Tetrahydrocannabinol Challenge Studies Frontiers in Psychiatry April 14, 2022
- The why behind the high: determinants of neurocognition during acute cannabis exposure. Nature Reviews Neuroscience July 1, 2021
and 4 more in the library