Roache JD, Substance Abuse-Medications
Development Research Center, Department of Psychiatry & Behavioral Sciences,
School of Medicine, University of Texas Mental Sciences Institute, Houston, USA.
roache
Two experiments examined the effects of
methylphenidate in male and female patients enrolled in an outpatient treatment
program for primary cocaine dependence.
The first study was a component of a
double-blind efficacy trial wherein 57 patients were first tested in a human
laboratory for their initial responsiveness to medication. Patients were
randomly assigned to receive either placebo or methylphenidate treatment and
received their first dose in the human laboratory environment before continuing
in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release
dose (twice daily) plus an additional 5-mg immediate-release dose combined with
the morning dose. Methylphenidate increased heart rate and subjective ratings;
however, the subjective effects were primarily of a "dysphoric" nature, and
significant effects were limited to increases in anxiety, depression, and anger
on the Profile of Mood States; shaky/jittery ratings on a visual analog scale;
and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction
Research Center Inventory. Methylphenidate did not increase cocaine craving nor
ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or
drug-liking scores, etc.). None of the drug effects observed in the human
laboratory was of clinical concern, and no subject was precluded from continuing
in the outpatient study. After outpatient treatment completion, 12 patients were
brought back into a second double-blind human laboratory study in which three
doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered
in an ascending series preceded and followed by placebo. Methylphenidate
produced dose-related increases in heart rate, subjective ratings of
shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving
or stimulant euphoria ratings. These results suggest that stimulant
substitution-type approaches to the treatment of cocaine dependence are not
necessarily contraindicated because of cardiovascular toxicity or medication
abuse potential. However, they also suggest that the subjective effects of
methylphenidate may not be positive enough for an adequate replacement approach.
TITLE: Lethal seizures predicted after aminophylline therapy in
cocaine abusers.
Eur J Pharmacol 2000 Jan
10;387(2):R15-R16 (ISSN: 0014-2999)
Gasior M, Drug Development Group,
Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, NIH,
5500 Nathan Shock Drive, Baltimore, MD, USA.
Mice with a history of chronic (10
days), but not acute, treatment with a non-convulsant dose of cocaine showed
increased sensitivity (P<0.001) to the toxic effects of aminophylline (seizures,
lethality) relative to controls even days after the cessation of cocaine
treatment. The present finding suggests that individuals with a history of
cocaine use may be at increased risk for convulsive and lethal complications
associated with the therapeutic use of aminophylline.
TITLE:
Effects of prenatal Cocaine/Crack and other drug exposure on
electroencephalographic sleep studies at birth and one year.
Scher MS, Division of Pediatric
Neurology, Rainbow Babies and Children's Hospital of University Hospitals of
Cleveland, Cleveland, Ohio.
OBJECTIVE
Little is known about the
neurophysiologic effects of prenatal cocaine/crack use. The aim of this study,
designed to overcome methodologic limitations of
previous research, was to investigate
the effects of prenatal cocaine use on electroencephalographic (EEG) sleep
patterns, a marker of central nervous system
development.
METHODS
In a longitudinal study of prenatal
cocaine/crack exposure, women were interviewed at the end of each trimester
about cocaine, crack, alcohol, tobacco, marijuana, and other drug use. Two-hour
paper- and computer-generated EEG sleep recordings were obtained on a sample of
the full-term infants on the second day of life and at 1 year postpartum.
Eligible newborns were full-term, had received no general anesthesia, and had a
5-minute Apgar score >5. All infants whose mothers used one or more lines of
cocaine during their first trimester or any crack (n = 37) were selected. A
comparison group was chosen randomly from the group of women who did not use
cocaine or crack during their pregnancy (n = 34).
RESULTS
Women who used cocaine/crack during the
first trimester were older, less educated, less likely to be working, and used
more tobacco, alcohol, marijuana, and other illicit drugs than women who did not
use cocaine/crack during the first trimester. There were no differences in
infant birth weight, length, head circumference, or gestational age between the
two exposure groups. After controlling for the significant covariates, prenatal
cocaine exposure was associated with less well developed spectral correlations
between homologous brain regions at birth, and with lower spectral EEG power
values at 1 year of age. Prenatal alcohol, marijuana, and tobacco use were found
to affect state regulation and cortical activities.
CONCLUSIONS
These results indicate that the
neurotoxic effects of prenatal cocaine/crack use can be detected with
quantitative EEG measures.
TITLE:
Cocaine administration decreases functional connectivity in human primary visual
and motor cortex as detected by functional MRI.
Magn Reson Med 2000 Jan;43(1):45-51 (ISSN: 0740-3194)
Li SJ, Biophysics Research Institute,
Medical College of Wisconsin, Milwaukee 53226, USA. sjli
Functional magnetic resonance imaging (fMRI)
was conducted to observe the effects of cocaine administration on the
physiological fluctuations of fMRI signal in two brain regions. Seven long-term
cocaine users with an average age of 32 years and 8 years of cocaine use history
were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI)
pulse sequence was employed at 1.5 T to acquire three sets of brain images for
each subject under three conditions (at rest, after saline injection, and after
cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using
the synchronous, low frequency signal from voxel time courses after filtering
respiratory, cardiac, and other physiological noise. A quantitative evaluation
of the changes in functional connectivity was made using spatial correlation
coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region
of primary visual cortex and 43% reduction in SCC values in the region of
primary motor cortex were observed after cocaine administration. This
significant reduction in SCC values in these cortical regions is a reflection of
changes in neuronal activity. It is suggested that the observed changes in low
frequency components after acute cocaine administration during a resting,
no-task situation may be used as a baseline reference source when assessing the
effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.
