The Effect of a Novel Theanine Complex (JDS‐MT‐003) on Sleep in a Pentobarbital‐Induced Sleep Model in Mice

Objective JDS‐MT‐003 is a novel theanine complex that is hypothesized to have superior effects compared to L‐theanine, an amino acid found naturally in tea. L‐theanine has been clinically shown to positively affect sleep quality, mood, and cognitive performance. Structurally similar to the excitatory transmitter glutamate, L‐theanine induces its calming effects by decreasing the binding of glutamate and increasing production of the inhibitory neurotransmitter GABA. The purpose of the following preclinical study was to examine the effects of JDS‐MT‐003 compared to L‐theanine on sleep quality in a pentobarbital‐induced sleep model in mice. Methods Thirty‐five male BALB/c mice were randomized to receive one of the following treatments: Pentobarbital (42 mg/kg), Pentobarbital + Theanine (20 mg/kg) or Pentobarbital + JDS‐MT‐003 (20 mg/kg). L‐theanine and JDS‐MT‐003 samples were resuspended in physiological saline for oral administration. Forty‐five minutes following oral treatment with L‐theanine or JDS‐MT‐003 mice were injected with a hypotonic dose of pentobarbital (42 mg/kg) into the left side of the abdomen. Pentobarbital is a hypnotic drug prescribed for insomnia that can induce sleep but also impair sleep architecture. Mice were then placed in individual cages and subjected to measurements of sleep latency and duration. Sleep latency was measured as the period between pentobarbital injection and sleep onset. Sleep duration was measured as the time elapsed between reflex loss and recovery. Mice that failed to fall asleep within 10 minutes after pentobarbital injection were excluded from the experiments. Results Animals in the JDS‐MT‐003 group showed the greatest sleep duration and the lowest sleep latency times compared to all other groups (p < 0.05). Mean sleep duration times (mean ± SD) in minutes were as follows: 51.01 ± 2.32 (Pentobarbital), 61.64 ± 2.18 (Pentobarbital + Theanine), and 86.41 ± 4.45 (Pentobarbital + JDS‐MT‐003). Mean sleep latency times (mean ± SD) in minutes were as follows: 3.86 ± 0.07 (Pentobarbital), 3.64 ± 0.09 (Pentobarbital + Theanine), and 3.11 ± 0.17 (Pentobarbital + JDS‐MT‐003). Overall, a greater percentage of animals fell asleep in the Pentobarbital + JDS‐MT‐003 group compared to the Pentobarbital + Theanine group (62.5% vs. 37.5%, respectively). No significant adverse events were observed. Conclusions These results demonstrate that JDS‐MT‐003, a novel theanine complex, prolongs sleep duration and decreases sleep latency significantly more than L‐theanine when combined with pentobarbital. These data suggest that JDS‐MT‐003 can counteract the negative effects of pentobarbital and other hypnotic sleep drugs on sleep quality. Moreover, these data support the use of JDS‐MT‐003 as a potential treatment option to improve overall sleep quality in individuals having trouble falling and staying asleep. Support or Funding Information This study was conducted at Firat University and funded by JDS Therapeutics LLC