The Effect of a Novel Theanine Complex (JDS‐MT‐003) on Sleep in a Caffeine‐Induced Insomnia Mouse Model

Objective L‐theanine is an amino acid found in tea that is commonly used to improve relaxation, sleep quality, and cognitive function. L‐theanine exerts its effects by modulating alpha brain waves and neurotransmitters involved in the regulation of the sleep cycle. The following study was carried out to examine the effects of JDS‐MT‐003, a novel theanine complex, compared to L‐theanine on sleep duration and latency in a caffeine‐induced insomnia model in mice. Methods Twenty‐eight male BALB/c mice were randomized into one of the following groups: Control (saline followed by saline; SS), Caffeine Control (caffeine followed by saline; CS), Theanine (caffeine followed by L‐theanine; CT) or JDS‐MT‐003 (caffeine followed by JDS‐MT‐003; CmT). Caffeine (7.5 mg/kg), L‐theanine (20 mg/kg), and JDS‐MT‐003 (20 mg/kg) were dissolved in distilled water and injected intraperitoneally. Electrocorticography (ECoG) recordings were performed following caffeine injection, with ECoG spike frequency and spike amplitude analysis recorded with the Labchart 7.3.3 program. Animals were deeply anesthetized with 4% isoflurane (30% O 2 , remainder N 2 O) 120 minutes after the caffeine injection. Brain tissues were then removed and stored for analysis. Concentrations of receptor proteins were determined by Western blot analysis and neurotransmitter levels were measured by ELISA. Results ECoG frequencies were lower in the CmT group compared to all other groups throughout the recording duration, with frequencies significantly differing from the CS group during the 75–90 and 90–105 minute time intervals (p<0.05). Treatment with JDS‐MT‐003 resulted in the greatest increase in sleep duration and greatest decrease in sleep latency time compared to the CS and CT groups (p<0.05). Mean sleep durations (mean ± SD) in minutes were as follows: 61.9 ± 3.8 (SS), 28.8 ± 1.6 (CS), 41.8 ± 4.1 (CT), and 50.8 ± 2.8 (CmT). Mean sleep latency times (mean ± SD) in minutes were as follows: 0.92 ± 0.08 (SS), 1.95 ± 0.06 (CS), 1.49 ± 0.14 (CT) and 1.11 ± 0.06 (CmT). Brain serotonin, melatonin, and dopamine levels were highest in the CmT group compared to the CS and CT groups (p<0.05), with dopamine levels normalized to Control levels. Brain concentrations of GluA1, GluN1, GluN2A, GABA A receptor α2, GABA B receptor 1, GABA B receptor 2, and 5‐HT1A were highest in the CmT group compared to the CS and CT groups (p<0.05). No significant adverse events were observed. Conclusions A novel theanine complex, JDS‐MT‐003, demonstrated superior effects on sleep quality and neurotransmitter modulation compared to L‐theanine in a caffeine‐induced insomnia mouse model. JDS‐MT‐003 decreased the negative effects of caffeine on sleep latency and duration in mice significantly more than L‐theanine. These data support the use of JDS‐MT‐003 as a potential relaxation and sleep support supplement for individuals having trouble falling and staying asleep. Support or Funding Information This study was conducted at Istanbul Medipol University and funded by JDS Therapeutics LLC.