HormonesMelatonin

Co-administration of cannabidiol and L-theanine 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. The combination also elevated serum serotonin and melatonin levels by more than 40% and increased cortical GABA levels relative to caffeine-treated controls.

Last updated: Jul 8, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score24/100
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.

observational

Kim J, Yu YJ, Kim HK, Ullah A, Bappi MH, Shim HJ, Cheong J, Compomayor NB, Kim HJ, Chae HJ · 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:

PubMed: 42375087DOI: 10.4062/biomolther.2025.160

Mechanism Graph

CBD increases serotonin levels in a dose-dependent manner
↓
L-theanine elevates serotonin at lower doses
↓
Combination treatment elevates serum serotonin and melatonin by >40%
↓
Combination treatment elevates cortical GABA levels
↓
Result: Improved sleep onset latency and total sleep duration

Limitations

  • ⚠Animal model, not directly generalizable to humans
  • ⚠Precise mechanisms remain to be determined
  • ⚠Synergistic interaction only observed at lower doses under normal conditions, not at higher doses

Frequently Asked Questions

What were the specific ratios of CBD to L-theanine tested?▼

The study tested ratios of 1:1, 2:1, and 1:2 (CBD:L-theanine).

Did the combination show synergy at all doses?▼

No, combination index analysis indicated a synergistic interaction only at lower doses under sleep-disturbed conditions; this was not observed at higher doses under normal conditions.

What neurochemical changes were associated with the combination treatment?▼

The combination treatment increased serum serotonin and melatonin levels by more than 40% relative to the caffeine-treated group, and also elevated cortical GABA levels.

Is this study applicable to humans?▼

No, this was a mouse model study, so results are preliminary and not directly applicable to humans without further clinical research.

Products

Affiliate links coming soon. We only recommend products that match the doses and forms used in the cited research.

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.