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.

Last updated: Jul 7, 2026โ€ข0 RCTsโ€ข๐Ÿ“– Read as article โ†’

Evidence Score

Evidence Score26/100
Human RCTโ˜†โ˜†โ˜†โ˜†โ˜†
Meta-analysisโ˜†โ˜†โ˜†โ˜†โ˜†
Mechanismโ˜†โ˜†โ˜†โ˜†โ˜†
Safetyโ˜†โ˜†โ˜†โ˜†โ˜†
Confidencelow

Study Evidence

Study 1. Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model.

observational

Kim 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
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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

  • โš Animal model (mice) limits direct translation to humans
  • โš Precise mechanisms remain to be determined

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References

  1. 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.