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A new systematic review published in Brain, Behavior, and Immunity suggests that using cannabinoids does not have a single, straightforward effect on the human immune system. Instead, regular use tends to be associated with concurrent increases in both pro-inflammatory and anti-inflammatory biological markers. These findings provide evidence that cannabis products might modulate the immune system in ways that require more nuance to fully understand.
Cannabis use is rising globally, driven by shifting legal policies and a changing public perception of its safety. At the same time, medical science views cannabis through a divided lens. Certain components are being explored as treatments for pain and epilepsy, while regular use is also linked to cognitive and psychiatric risks.
Preclinical studies in animals or isolated cells have often indicated that cannabinoids might reduce inflammation. In these laboratory settings, cannabinoids typically suppress immune cell activation. This early evidence led many to view cannabis as a broadly anti-inflammatory substance.
However, the translation of these laboratory findings to human biology has been incredibly inconsistent. Some previous human studies reported increases in specific immune markers, while others found no effect or only isolated reductions in inflammation. Prior statistical reviews of this topic were often limited because they focused on a very narrow set of biological markers.
To address this confusion, researchers set out to conduct a comprehensive analysis of the existing literature. They aimed to clarify the association between regular cannabinoid use and peripheral inflammatory biomarkers. These biomarkers are measurable proteins and cells found in the blood that indicate how actively the immune system is responding to threats.
Clarifying this relationship is highly relevant to public health. Long-term, low-grade inflammation tends to contribute to heart disease, metabolic conditions, and psychiatric disorders. The scientists wanted to know if cannabinoids push the immune system toward or away from this risky state.
“We were motivated by the fact that cannabinoids are often described as having anti-inflammatory properties, but the human evidence has been inconsistent and scattered across different biomarkers and populations. We wanted to examine this more systematically by focusing on studies of regular cannabinoid use in adults and, importantly, by excluding samples with physical illnesses or other conditions likely to directly alter inflammatory status. This allowed us to look more clearly at the association in non-medical and psychiatric populations,” said study author Martino Belvederi Murri, an associate professor at the University of Ferrara.
The scientists performed a systematic review and meta-analysis. This is a statistical method that combines data from multiple independent studies to identify overall trends. The team searched major scientific databases for research published up to late 2025 that compared inflammatory biomarkers between people who used cannabinoids and those who did not.
They included data from 46 studies, encompassing a massive total of 54,382 participants. The participants were a diverse mix of physically healthy individuals, people with psychiatric disorders like schizophrenia, and individuals with substance use disorders. The researchers extracted data on a wide variety of immune markers from blood, serum, and plasma samples.
These markers included pro-inflammatory proteins, which signal the body to increase immune activity and cause inflammation. Examples include C-reactive protein and various interleukins, which spike during infections or tissue damage. The researchers also looked at anti-inflammatory markers, which work to calm the immune response down and restore balance.
The included research featured 34 cross-sectional and case-control studies. These types of studies look at data at a single point in time to compare different groups. The scientists also included data from two prospective studies that followed people over time, as well as four randomized controlled trials.
They utilized a sophisticated statistical approach known as a Bayesian multilevel model to synthesize 190 different effect sizes. This advanced mathematical approach allowed them to account for the complex nature of the data. For instance, it helped adjust for the fact that multiple different biomarkers were often measured within the same single study group.
The analysis revealed that regular cannabinoid use in observational studies was associated with higher levels of both pro-inflammatory and anti-inflammatory biomarkers. For instance, cannabinoid users tended to show elevated counts of white blood cells and neutrophils, which are cells that rush to the site of an infection. At the same time, users displayed elevated levels of certain proteins specifically designed to suppress the immune system.
Rather than suppressing the immune system entirely or pushing it into a state of chronic inflammation, cannabinoids seem to exert a complex modulating effect. The researchers noted that the exact shifts in these biological markers varied systematically depending on the study design and the specific demographics of the participants. Case-control studies, which deliberately select patients with specific traits, yielded slightly different patterns of biomarker changes than broad cross-sectional surveys.
For example, recent cannabis use yielded higher levels of these biomarkers compared to past use. This suggests a direct, temporary relationship between active substance exposure and immune system fluctuation. The researchers also found that synthetic cannabinoids were associated with much larger inflammatory effects than natural cannabis products.
Demographic factors played a role as well, with the percentage of male participants and the age of the users influencing the magnitude of the immune changes. The research team highlighted that the context of the user matters immensely. They noted that when an overt medical illness is present, anti-inflammatory effects might be more likely to prevail, but in otherwise healthy populations, the biological response is much more mixed.
In the randomized controlled trials, the researchers found a slightly different pattern. These experimental studies primarily tested cannabidiol, commonly known as CBD, in healthy individuals over short periods. The pooled data from these trials suggested a small increase in pro-inflammatory markers following CBD administration.
This finding provides evidence that contrasts with the popular notion that CBD is strictly anti-inflammatory in humans without medical conditions. Most preclinical work demonstrating anti-inflammatory effects relied on animal models facing acute, severe inflammatory challenges. In healthy humans without an active infection or crisis, CBD appears to provoke a mild immune response rather than calm it down.
“What was striking was that the human evidence did not support a clear overall anti-inflammatory signal,” Belvederi Murri told PsyPost. “Instead, the pattern was mixed. One possible interpretation is that when an overt medical illness is present, anti-inflammatory effects may be more likely to prevail, whereas in otherwise non-medical populations the picture may be more mixed, with concurrent pro- and anti-inflammatory changes. That said, the evidence for anti-inflammatory biomarkers in our review was based on fewer studies, so that part of the picture remains more uncertain.”
Despite the large dataset, the scientists urge readers to be cautious about translating these biological shifts into everyday clinical meaning. A primary limitation is that most of the included studies were observational in nature. This means the research can only show an association and cannot prove that cannabinoid use directly causes the observed changes in immune markers. People who use cannabinoids often differ from non-users in several other ways that also influence the immune system.
“These findings should not be simplified into ‘cannabis causes inflammation’ or ‘cannabis reduces inflammation,'” Belvederi Murri explained. “Most of the included studies were observational, so causality remains uncertain, and cannabinoid users may differ from non-users in many ways that also affect inflammation, such as tobacco smoking, alcohol or other drug use, BMI, medications, and psychiatric comorbidity. Also, “cannabinoid use” is a broad category that includes very different compounds and patterns of exposure.”
“A key next step is to characterize exposure more precisely, distinguishing better between THC, CBD, synthetic cannabinoids, mixed products, dose, potency, and recency of use. We also need more longitudinal and experimental studies, especially in well-characterized samples, to understand when cannabinoid-related immune changes may be adaptive, neutral, or potentially harmful.”
These future studies would help determine whether cannabinoid-related immune changes are neutral, adaptive, or potentially harmful to long-term health. As cannabinoid use continues to become more prevalent in society, understanding its true immunological footprint will be highly important for anticipating downstream clinical outcomes.
The study, “Regular cannabinoid use and inflammatory biomarkers: Systematic review and hierarchical meta-analysis,” was authored by Martino Belvederi Murri, Riccardo Guglielmo, Alessio Zizzi, Angela Muscettola, Maria Giulia Nanni, Manuela Dall’Oro, Gianluca Serafini, Alberto Inuggi, Andrea Escelsior, Mario Amore, and Luigi Grassi.
