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Physical Activity Level Moderates Cannabis-Associated Reductions in Negative Affect in Anxious Individuals.

Jonathon K. Lisano, Luiza Rosa, Greg Giordano, Angela D Bryan, L Cinnamon Bidwell

Clinical Therapeutics September 2026 DOI: 10.1016/j.clinthera.2026.02.007 (opens in new tab)

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AI-extracted from the abstract
Characteristics Secondary analysis of a randomized controlled trial Peer reviewed
Sample size 178
Population Individuals with mild or greater anxiety who intended to use cannabis to reduce symptoms
Duration 4-week ad libitum use; actigraphy during the final 2 weeks
Measures Depression, Anxiety, and Stress Scale-21
Topics Anxiety Cannabis CBD
Keywords Δ-9-tetrahydrocannabinol
Registration NCT03491384
Key findings Negative affect decreased over time in all cannabis groups, but a three-way interaction indicated that in the THC-dominant group, higher daily moderate-to-vigorous physical activity was associated with a less steep decrease in negative affect (low vs high activity difference = -12.00). This moderating effect was not observed in the CBD-dominant or THC+CBD groups, suggesting the association depends on cannabinoid concentration.

Abstract

Emerging research indicates that the use of cannabis products, particularly those higher in cannabidiol (CBD), may be anxiolytic. Physical activity is another modality observed to have anxiolytic effects. Despite evidence of cannabis and physical activity being paired together, there is limited research on the possible synergistic effects of physical activity and cannabis use on reductions in negative affect. These secondary analyses included 178 individuals with mild or greater anxiety who intended to use cannabis to reduce symptoms. Participants were randomly assigned to use 1 of 3 cannabis chemovars (CBD-dominant, Δ-9-tetrahydrocannabinol (THC)-dominant, or THC+CBD) ad libitum for 4 weeks. The Depression, Anxiety, and Stress Scale-21 was used to measure changes in negative affect from baseline to week 4. Minutes of moderate to vigorous physical activity (MVPA) per day were measured via actigraphy during the final 2 weeks of the study. Although negative affect decreased over time in all cannabis groups (z = -3.47; P < 0.001), a significant 3-way group by time by physical activity interaction was observed (z = 2.55; P = 0.01). Negative affect significantly decreased over time in participants using THC-dominant products, and this was moderated by MVPA. As MVPA increased from low to high (low vs high MVPA: difference = -12.00; SE = 5.12; P = 0.02), the decrease in negative affect became less steep. This moderating effect was not observed in participants using CBD-dominant (low vs high MVPA: difference = -1.03; SE = 3.38; P = 0.76) or THC+CBD (low vs high MVPA: difference = 3.21; SE = 2.95; P = 0.28) products. This study is the first to describe cannabis associated reductions in negative affect being moderated by physical activity. These findings suggest that this association is dependent upon the cannabinoid concentration in the cannabis product being used. gov identifier: NCT03491384.

Comparable studies

Other randomized controlled trials on cannabis for anxiety, most cited first.

Study Year Design Participants
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... 2009 Double-blind, randomized, placebo-controlled crossover trial n = 15
Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... 2009 Randomized controlled trial n = 15
Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol Healthy subjects 2009 Randomized controlled trial n = 15
Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Healthy recreational cannabis users 2022 Randomized controlled trial, within-subjects n = 26
Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity Regular drug users 2015 Three-way crossover study n = 122

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