Evaluating the Link Between Metabolic Syndrome and Cognitive Dysfunction in People Who Use Cannabis: A Critical Review of Mechanistic Pathways, Evidence Quality, and Future Research Directions

Authors

• Ghadah Alharbi, Qassim UniversityFollow
• Ahmad H. Alhowail, Qassim University
• Ashraf Mahmoud Emara, Qassim University

Keywords

Cannabis use disorder, Metabolic syndrome, Cognitive dysfunction, Endocannabinoid system, Neuroinflammation, Insulin resistance, THC potency

Document Type

Review Article

Abstract

Background: Cannabis is the most commonly used internationally controlled substance worldwide, with increasing rates of heavy use and cannabis use disorder (CUD) among adolescents and adults. While epidemiological evidence links cannabis exposure to both metabolic dysfunction and cognitive impairment, these outcomes have been examined predominantly in isolation. The mechanistic relationship between metabolic syndrome (MetS) and cannabis-related cognitive deficits remains poorly characterized. Objective: This review critically appraises the evidence linking cannabis use to metabolic dysfunction and cognitive impairment, proposes an integrative ``Cannabis–Metabolic–Cognitive Axis'' model, and identifies gaps limiting causal inference in the existing literature. Key Findings: Human studies frequently report lower body mass index among cannabis users, whereas findings regarding insulin sensitivity, dyslipidemia, metabolic syndrome, and inflammatory markers remain heterogeneous and are influenced by differences in exposure patterns, populations, and study design. Cognitive domains most consistently associated with impairment include working memory, attention, processing speed, and executive function, with recovery potential following sustained abstinence. Converging indirect and mechanistic evidence suggests that endocannabinoid-system dysregulation, neuroinflammation, oxidative stress, and metabolic alterations may provide biological links between cannabis exposure and neurocognitive dysfunction; however, direct evidence for metabolic mediation remains limited. Critical Insights: Methodological limitations characterize the existing evidence, including small sample sizes, cross-sectional designs, inadequate measurement standardization, incomplete control of confounding, and difficulty establishing causal direction. Recent advances in multi-omics, neuroimaging biomarkers, and Mendelian randomization approaches offer novel opportunities to clarify these relationships. Conclusion: The intersection of metabolic dysfunction and cognitive impairment in cannabis users represents an important but understudied clinical and public health concern. Future longitudinal and mechanistic studies integrating detailed cannabis-exposure characterization with concurrent metabolic and neurocognitive assessments are needed to clarify the direction, magnitude, and clinical significance of these relationships. Direct human evidence assessing cannabis exposure, metabolic abnormalities, and cognitive outcomes within the same participants remains scarce; accordingly, the proposed Cannabis–Metabolic–Cognitive Axis should be regarded as a hypothesis-generating framework requiring empirical validation rather than an established causal pathway.

Recommended Citation

Alharbi, Ghadah; Alhowail, Ahmad H.; and Emara, Ashraf Mahmoud (2026) "Evaluating the Link Between Metabolic Syndrome and Cognitive Dysfunction in People Who Use Cannabis: A Critical Review of Mechanistic Pathways, Evidence Quality, and Future Research Directions," Saudi Toxicology Journal: Vol. 3: Iss. 2, Article 4.
Available at: https://stj.researchcommons.org/journal/vol3/iss2/4

Subject Area

Clinical Toxicology

Data Availability Statement

All data supporting this study are included in the manuscript.

Ethical Approval

Ethical approval was not required for this study.

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