title: l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice.
abstract: l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine's stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980613, Richmond, VA 23298-0613, USA. lewise@vcu.edu
authors.forename: Laura E
authors.initials: LE
authors.lastname: Wise
authors.forename: Ishani D
authors.initials: ID
authors.lastname: Premaratne
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gamage
authors.forename: Aron H
authors.initials: AH
authors.lastname: Lichtman
authors.forename: Larry D
authors.initials: LD
authors.lastname: Hughes
authors.forename: Louis S
authors.initials: LS
authors.lastname: Harris
authors.forename: Mario D
authors.initials: MD
authors.lastname: Aceto
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D018782:Maze Learning; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
chemical_list: D005971:Glutamates; D009020:Morphine; C026166:theanine