Michael Mancino, M.D.
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
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
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.