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Research

Michael Mancino, M.D.  MancinoMichaelJ@uams.edu

   Methamphetamine dependence has become a significant problem, but methamphetamine withdrawal symptoms have not been well studied. Therefore we designed an observational pilot study to examine withdrawal symptoms, mood, anxiety, cognitive function and subjective measures of sleep over a 4-week period in patients entering residential treatment for methamphetamine dependence. Our results demonstrate that methamphetamine withdrawal symptoms, mood and anxiety symptoms all resolve fairly quickly within two weeks of cessation of methamphetamine. However, sleep continued to be disrupted over the course of the 4 week study. No clinically significant alterations in blood pressure or heart rate were identified. This study did not demonstrate any alterations in cognitive function over the 4 weeks of the residential stay.


Figure 1: Methamphetamine Withdrawal and Mood Rating Scores over Time. X-axis: study week; y-axis: assessment score. MAWA: Methamphetamine Withdrawal Assessment. MSSA: Methamphetamine Selective Severity Assessment. HAM-A: Hamilton Anxiety scale. HAM-D: Hamilton Depression scale. Each data point represents the mean ± S.E. a-significant difference from week 0. b-significant difference between weeks.

   The findings from this pilot study led to the design of a double-blind, placebo-controlled amphetamine withdrawal paradigm in humans. Thirty methamphetamine dependent participants (ages 20-65 yrs) are being entered into a 4-week residential study. Intake assessments include cognitive testing, standardized assessment of depression and anxiety, profile of mood states, methamphetamine selective severity assessment, methamphetamine withdrawal assessment, sleep quality and quantity, a pre-attentional measure (P50 potential amplitude assesses level of arousal in brainstem-thalamic processes, and habituation to paired stimulation determines sensory gating capacity) and attentional measure (performance on psychomotor vigilance task-PVT, a prototypical measure of thalamocortical attentional systems). Upon admission to the residential facility, all study participants are stabilized on 60mg d-amphetamine over the first 5 days. After stabilization participants are randomized based on sex and methamphetamine selective severity assessment score to either continued treatment with d-amphetamine or placebo for 2 weeks. All subjects are placed on placebo for the last 7 days. Intake assessments are repeated at least thrice weekly, except for pre-attentional and attentional measures that are repeated weekly. The primary outcomes of interest include retention in treatment, measures of methamphetamine withdrawal, cognitive assessments, and performance on quantitative pre-attentional and attentional neurophysiological measures. This project is currently underway and data collection is in progress.

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Selected Publications

Mancino, M.J., Gentry, W.B., Feldman, Z., Mendelson, J.E., and Oliveto, A. Characterizing methamphetamine withdrawal in recently abstinent methamphetamine users: A pilot field study. The American Journal of Drug and Alcohol Abuse. In review.

McGaugh, J., Mancino, M.J., Feldman, Z., Chopra, M.P., Gentry, W.B., Cargile, C., Oliveto, A.O. Open Label Pilot Study of Modafinil for Methamphetamine Dependence. The Journal of Clinical Psychopharmacology. 2009, Oct; 29(5): 488-91.