Visualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mapping

• Published in: The international journal of neuropsychopharmacology Vol. 5; no. 3; pp. 199 - 215
• Main Authors: Saletu-Zyhlarz, Gerda M., Anderer, Peter, Linzmayer, Leopold, Semlitsch, Heribert V., Assandri, Alessandro, Prause, Wolfgang, Hassan Abu-Bakr, Manal, Lindeck-Pozza, Elisabeth, Saletu, Bernd
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.09.2002; Oxford University Press
• Subjects: Adult; Alpha Rhythm - drug effects; Antidepressants; Antidepressive Agents - pharmacology; Arousal - drug effects; Attention - drug effects; Beta Rhythm - drug effects; Blood Pressure - drug effects; Brain Mapping; Cross-Over Studies; Double-Blind Method; Drug dosages; Electroencephalography; Electroencephalography - drug effects; Female; Flicker Fusion - drug effects; Heart Rate - drug effects; Humans; Male; Psychometrics; Quantitative psychology; S-Adenosylmethionine - pharmacology; Time Factors; Ademetionine; pharmaco-EEG mapping; psychotropic effects; psychometry; encephalotropic effects; nutraceutical and pharmaceutical substance
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145702002924

In a double-blind, placebo-controlled, cross-over study, the central effects of the natural molecule S-adenosyl-L-methionine (SAMe), or ademetionine (ADE), used in low doses as a nutraceutical and in higher doses as a pharmaceutical, were investigated by means of EEG mapping and psychometry. Ten young, normal healthy volunteers of both sexes, with a mean age of 25.2+3.9 yr received, in random order, infusions of 800 mg ADE in 250 ml of isotonic solution, and placebo consisting of 250 ml of isotonic solution administered over 30 min for 7 d, with a wash-out period of 3 wk in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 h after drug administration on days 1 and 7. While there were no significant changes in psychometric findings, multivariate analyses of the EEG results based on MANOVA/Hotelling T2 tests demonstrated significant encephalotropic effects of ADE compared to placebo. ADE-induced changes were characterized by a decrease in total power, an increase in absolute δ power and a decrease in absolute α and β power, further by an increase in relative δ and β power and a decrease in relative α power, a slowing of the δ/θ centroid, an acceleration of the α centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. Time–efficacy calculations demonstrated a significant central effect of ADE in the first hour after the first infusion, declining slowly until the third hour and thereafter steeply until the sixth hour; a further significant effect was after 1 wk of daily infusions and in the third hour after one superimposed infusion on day 7 of subacute treatment. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects at the neurophysiological level, underlying the antidepressant properties well-documented in clinical trials.