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Inflammatory state moderates response to cannabis on negative affect and sleep quality in individuals with anxiety

Richard G. Hunter, Annelise Madison, Jonathon K. Lisano, Carillon J. Skrzynski, Gregory Giordano, Angela D Bryan, L. Bidwell

Frontiers in Behavioral Neuroscience July 1, 2025 DOI: 10.3389/fnbeh.2025.1549311 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 171
Population Participants with mild or greater anxiety
Interventions THC + CBD THC CBD
Duration 4-week intervention
Topics Anxiety Cannabis
Key findings Baseline inflammatory status moderated the relationship between cannabis use and both negative affect and sleep quality, with CBD-rich chemovars producing more consistent improvements.

Abstract

Introduction: Inflammation 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.

Methods: Participants 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.

Results: There 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.

Conclusion: These novel findings suggest that baseline inflammatory status influences the relationship between cannabis use, negative affect, and sleep quality in people with anxiety.

Comparable studies

Other observational and cohort studies on cannabis for anxiety, most cited first.

Study Year Design Participants
Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms Former chronic ecstasy users 2001 Observational cohort n = 29
Rates and correlates of cannabis-associated psychotic symptoms in over 230,000 people who use cannabis International sample of people who use cannabis (PWUC) 2022 Observational cohort n = 233,475
Who Turns to Amazonian Medicine for Treatment of Substance Use Disorder? Patient Characteristics at the Takiwasi Addiction Treatment Center Patients with substance use disorders seeking treatment 2020 Observational study
Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption. Adults with no prior exposure to ayahuasca participating in neo-shamanic ayahuasca... 2025 Prospective cohort study n = 66
Naturalistic use of psychedelics is associated with longitudinal improvements in anxiety and depression during global crisis times. Citizen science cohort recruited agnostically to an interest in drug use 2025 Observational cohort n = 242,260

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