Frontiers in Behavioral Neuroscience (Jul 2025)
Inflammatory state moderates response to cannabis on negative affect and sleep quality in individuals with anxiety
Abstract
IntroductionInflammation has been implicated as an underlying pathology in negative affect and sleep disruption. Cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have demonstrated anti-inflammatory properties. This study aimed to assess if cannabis use altered cytokine concentration and whether inflammatory status moderated the influence of 4 weeks of cannabis use on negative affect and sleep quality in anxious individuals.MethodsParticipants with mild or greater anxiety (n = 147) were assigned to one of three cannabis chemovars (THC + CBD, THC, CBD), asked to consume their products ad libitum for 4 weeks, and were compared to a group of participants with anxiety who did not use cannabis (n = 24). Measures of negative affect (Depression Anxiety and Stress Scale-21: DASS-21), sleep quality (Pittsburgh Sleep Quality Index: PSQI), and plasma cytokine concentrations were measured at Baseline and Week-4. Multilevel modeling assessed if there were group-dependent changes in cytokine concentrations over time, and whether baseline inflammation moderated the association between cannabis use and both negative affect and sleep quality.ResultsThere were no group-dependent changes in cytokine concentrations throughout the study (p = 0.12). It was observed that baseline inflammatory state moderated the group-by-time relationship for DASS-21 (p < 0.001) and PSQI (p = 0.04). In both models, chemovars higher in CBD produced more consistent improvements, while THC-associated improvements varied by baseline inflammatory state.ConclusionThese novel findings suggest that baseline inflammatory status influences the relationship between cannabis use, negative affect, and sleep quality in people with anxiety.
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