Cannabis use and glutamate across the psychosis spectrum: in vivo evidence from 7T proton magnetic resonance spectroscopy
David R. Roalf, Tyler M Moore, Jacquelyn Stifelman, Maggie Pecsok, Ally Atkins, Monica E. Calkins, Mariella de Biasi, Christian G. Kohler, Christina Mastracchio, Arianna Mordy, Heather Robinson, Ravinder Reddy, Ravi Prakash Reddy Nanga, Kosha Ruparel, Sage Rush‐Goebel, Daniel H. Wolf, Raquel E. Gur, J. Cobb Scott
Molecular Psychiatry June 27, 2026 DOI: 10.1038/s41380-026-03705-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional Longitudinal Peer reviewed |
|---|---|
| Sample size | 79 |
| Population | Typically developing controls, clinical high-risk individuals, and patients with psychosis |
| Topics | Cannabis |
| Keywords | Glutamatergic Psychosis Glutamate receptor Effects of cannabis Anterior cingulate cortex Concordance Schizophrenia object-oriented programming Clinical psychology Young adult |
| Key findings | Lower ACC glutamate levels were associated with higher positive symptoms in cannabis users, and ACC glutamatergic dysfunction is linked to symptom burden across the psychosis spectrum, especially in cannabis users with psychosis. |
Abstract
Abstract Cannabis use is linked to elevated psychosis risk, yet the neurobiological mechanisms that couple use to symptom expression remain unclear. Because glutamatergic dysregulation has been implicated in both cannabis effects and psychosis vulnerability, we examined whether brain glutamate relates to dimensional symptoms as a function of cannabis use across the psychosis spectrum. Seventy-nine participants—typically developing controls, clinical high-risk individuals, and patients with psychosis—completed dimensional clinical assessments, detailed cannabis surveys, urine toxicology, and ultra-high-field 7T 1 HMRS quantification of anterior cingulate cortex (ACC) glutamate levels. Linear models assessed the main and interactive effects of ACC glutamate and cannabis use on positive and negative symptoms. Self-reported cannabis use showed strong concordance with urine toxicology. Cannabis use was associated with higher positive and negative symptoms. Independently, higher ACC glutamate predicted greater positive and negative symptoms. Notably, lower glutamate levels were associated with higher positive symptoms in cannabis users. Exploratory analyses suggested interactions for depressive and manic symptoms, indicating that glutamatergic abnormalities may amplify the overall severity of cannabis-related symptoms. Sensitivity analyses revealed lower ACC glutamate in psychosis patients—especially cannabis users—highlighting diagnostic group differences and reinforcing the link between cannabis exposure and glutamatergic dysfunction. These findings implicate ACC glutamatergic dysfunction as a transdiagnostic correlate of symptom burden, particularly in those with psychosis who are cannabis users. Glutamate-targeted interventions and longitudinal designs will be needed to examine causal pathways linking cannabis exposure to psychosis-relevant outcomes.
Comparable studies
Other cross-sectional and survey studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... | 2011 | Observational cross-sectional study | n = 148 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents | 2020 | Cross-sectional survey | |
| User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire | 2010 | Cross-sectional survey | n = 600 |
| Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... | 2012 | Cross-sectional survey | n = 337 |
Citations in the library
Cites 15
- Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis World Psychiatry September 22, 2016
- Association Between Continued Cannabis Use and Risk of Relapse in First-Episode Psychosis JAMA Psychiatry September 28, 2016
- Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis Psychological Medicine March 24, 2022
- Rates and correlates of cannabis-associated psychotic symptoms in over 230,000 people who use cannabis Translational Psychiatry September 6, 2022
- Effects of Cannabis on Glutamatergic Neurotransmission: The Interplay between Cannabinoids and Glutamate. Cells June 29, 2024
and 10 more in the library