HormonesMelatonin
Co-administration of cannabidiol and L-theanine synergistically improves sleep-related outcomes in a caffeine-induced sleep disturbance mouse model
In a mouse model of caffeine-induced sleep disturbance, combined administration of CBD and L-theanine at ratios of 1:1, 2:1, or 1:2 significantly reduced sleep onset latency and increased total sleep duration compared to single treatments. Combination index analysis indicated a synergistic interaction at lower doses, and combination treatment was associated with over 40% increases in serum serotonin and melatonin levels, as well as elevated cortical GABA levels.
Evidence Score
Evidence Score26/100
Human RCT
Meta-analysis
Mechanism
Safety
Confidencelow
Study Evidence
Study 1. Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model.
observationalKim J, Yu YJ, Kim HK, Ullah A, Bappi MH, Shim HJ, Cheong J, Compomayor NB, Kim HJ, Chae HJ ยท Biomolecules & therapeutics (2026)
Participants: N/A
Duration: Not specified in abstract
Intervention: Oral co-administration of cannabidiol and L-theanine at ratios of 1:1, 2:1, or 1:2
Outcome: Sleep onset latency, total sleep duration, serum serotonin and melatonin levels, cortical GABA levels
Effect Size: N/A
Population: Caffeine-induced sleep disturbance mouse model
Result:
Mechanism Graph
CBD increases serotonin levels in a dose-dependent manner
โ
L-theanine elevates serotonin at lower doses
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Combination treatment elevates serum serotonin and melatonin by >40%
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Combination treatment elevates cortical GABA levels
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Result: Improved sleep onset latency and total sleep duration
Limitations
- โ Animal model (mice) limits direct translation to humans
- โ Precise mechanisms remain to be determined
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References
- 1.Kim J, Yu YJ, Kim HK, Ullah A, Bappi MH, Shim HJ, Cheong J, Compomayor NB, Kim HJ, Chae HJ. "Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model.." Biomolecules & therapeutics, 2026. PMID: 42375087 DOI: 10.4062/biomolther.2025.160
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.