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Biomedical subjects

Thomas F Newton

Publications and source records attributed to Thomas F Newton.

14 recordsLinked to original sources
PubMed2006

MDMA use and neurocognition: a meta-analytic review.

RATIONALE: To determine the association between MDMA misuse and neurocognition using meta-analysis. OBJECTIVE: Separate analyses were conducted based on two sets of inclusion/exclusion criteria. A relatively stringent set required that the subjects be matched on important moderator variables, whereas the other did not. The study participants' performance in the following neurocognitive domains was reviewed: attention/concentration, verbal and nonverbal learning and memory, psychomotor speed and executive systems functioning. RESULTS: In the 11 studies meeting the relatively stringent inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Similarly, in the 23 studies meeting the relatively lenient inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Small to medium effect sizes were generally observed. A comparison of the effect sizes across the two sets of analyses did not reveal significant differences. CONCLUSIONS: The findings from this review reveal that MDMA use is associated with neurocognitive deficits. The implications of these findings are discussed.

Amphetamine-Related Disorders↗
PubMed2006

A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline.

Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor shown to be effective in the treatment of Parkinson's and Alzheimer's diseases. Recent evidence suggests that selegiline may also be useful in treating specific aspects of cocaine and nicotine dependence, generating interest in this compound for the treatment of methamphetamine addiction. To investigate this, we performed a randomized, single-blind, placebo-controlled study to evaluate the safety of selegiline treatment (as compared to placebo), concurrent with intravenous methamphetamine (15 or 30 mg). Secondary study objectives included determinations of plasma levels of selegiline and its metabolites, evaluating whether selegiline administration altered the pharmacokinetics of methamphetamine or its metabolites, and evaluating whether selegiline treatment alters the subjective responses to methamphetamine. Twenty-four methamphetamine-dependent participants were randomized to treatment, and 9 of these (N = 5 selegiline, N = 4 placebo) completed the entire protocol. The principal finding from this study was that intravenous administration of moderate doses of methamphetamine was safely tolerated during treatment with selegiline. No participants had electrocardiogram changes, and there were no meaningful differences in any laboratory values either between groups at screening or as a result of the study procedures. In general, adverse events were mild or moderate, and no subjects were discontinued due to adverse events or serious adverse events. Selegiline treatment did not enhance any of the cardiovascular changes (heart rate, blood pressure) produced by methamphetamine administration. Selegiline treatment slightly increased methamphetamine associated "bad effects" but did not alter any other subjective effects. The elimination half-life of methamphetamine was approximately 12 h, and selegiline did not alter clearance of methamphetamine. The available data suggest that selegiline is likely to be safe if used as a pharmacotherapy for methamphetamine dependence.

Adult↗
PubMed2005

Bupropion reduces methamphetamine-induced subjective effects and cue-induced craving.

Bupropion is an antidepressant with stimulant properties, which inhibits the reuptake of dopamine (DA) and norepinepherine, and is purported to enhance DA neurotransmission. Bupropion is considered an appealing candidate medication for the treatment of methamphetamine dependence. The current laboratory study was set forth to assess the impact of bupropion treatment on the subjective effects produced by methamphetamine in the laboratory. We also assessed the effects of bupropion treatment on craving elicited by exposure to videotaped methamphetamine cues. A total of 26 participants were enrolled and 20 completed the entire study (n=10 placebo and n=10 bupropion, parallel groups design). Bupropion treatment was associated with reduced ratings of 'any drug effect' (p<0.02), and 'high' (p<0.02) following methamphetamine administration. There was also a significant bupropion-by-cue exposure interaction on General Craving Scale total score (p<0.002), and on the Behavioral Intention subscale (p<0.001). Overall, the data reveal that bupropion reduced acute methamphetamine-induced subjective effects and reduced cue-induced craving. Importantly, these data provide a rationale for the evaluation of bupropion in the treatment of methamphetamine dependence.

Adolescent↗
PubMed2005

Safety of intravenous methamphetamine administration during treatment with bupropion.

RATIONALE: Methamphetamine dependence is a growing problem for which no medication treatments have proven effective. OBJECTIVES: We evaluated bupropion, an antidepressant with beneficial effects for the treatment of nicotine dependence, in patients with methamphetamine dependence, to assess the safety and tolerability of methamphetamine administration during bupropion treatment. METHODS: Twenty-six participants entered the study and 20 completed the protocol. Participants received intravenous methamphetamine (0, 15, and 30 mg) before and after randomization to twice-daily bupropion (150 mg SR) or matched placebo. Dependent measures included cardiovascular effects of methamphetamine, methamphetamine and amphetamine pharmacokinetics, and peak and trough plasma concentrations of bupropion and its metabolites. RESULTS: Bupropion treatment was well tolerated, with bupropion- and placebo-treated groups reporting similar rates of adverse events. Methamphetamine administration was associated with expected stimulant cardiovascular effects, and these were not accentuated by bupropion treatment. Instead, there was a trend for bupropion to reduce methamphetamine-associated increases in blood pressure and a statistically significant reduction in methamphetamine-associated increases in heart rate. Pharmacokinetic analysis revealed that bupropion treatment reduced the plasma clearance of methamphetamine and also reduced the appearance of amphetamine in the plasma. Methamphetamine administration did not alter the peak and trough plasma concentrations of bupropion or its metabolites. CONCLUSIONS: Methamphetamine administration was well tolerated during bupropion treatment. There was no evidence of additive cardiovascular effects when the drugs were coadministered. This study provides initial evidence for the safety of prescribing bupropion for the treatment of methamphetamine abuse and dependence. The impact of bupropion treatment in patients who abuse larger doses of methamphetamine remains undetermined.

Adolescent↗
PubMed2005

Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects.

The stimulant effects of cocaine and methamphetamine are mediated by changes in synaptic concentrations of brain monoamines; however, the drugs alter monoamine levels via different mechanisms. This study examined the subjective and cardiovascular responses produced by investigational administration of cocaine or methamphetamine, in order to examine the onset and patterns of subjective and cardiovascular responses. Subjects included 14 non-treatment seeking cocaine-dependent and 11 non-treatment seeking methamphetamine-dependent volunteers. As part of ongoing research studies, cocaine and methamphetamine subjects received cocaine (40 mg, IV) or methamphetamine (30 mg, IV), respectively. Subjective and cardiovascular responses were assessed for 30 min and 60 min, respectively. The data reveal significant within groups differences for all subjective effects and cardiovascular effects (p<0.05). Significant between group differences in subjective effects were observed for "Any Drug Effect" (p<.008 for group, and p<.029 for group x time), for "High" (p<.002 for group, and p<.0001 for group x time) and for "Stimulated" (p<.001 for group, and p<.006 for group x time). Significant between group differences in cardiovascular effects were observed for Systolic blood pressure (p<.0001 for group, and p<.002 for group x time), Diastolic blood pressure (p<.0001 for group, though p=NS for group x time), and for Heart Rate (p<.0001 for group, and p<.0001 for group x time). The only difference between the groups for placebo was for heart rate, where there was a significant group x time effect (p<.005). Taken together, the data reveal that the subjective effects of cocaine tended to peak and then decline more rapidly than those produced by methamphetamine. The subjective effects of methamphetamine tended to rise more slowly, and remain elevated longer. Cardiovascular effects of cocaine and methamphetamine had similar onset, but effects of cocaine tended to decline more rapidly. Overall, the results reveal differences in the onset, pattern, and duration of subjective and cardiovascular responses following cocaine or methamphetamine administration in stimulant addicted patients. We predict that these differences may impact drug use and relapse patterns, and may have implications in medications development for these addictive disorders.

Cardiovascular System↗
PubMed2005

Apathy predicts hedonic but not craving response to cocaine.

Cocaine-induced craving has been implicated in the maintenance of ongoing cocaine use and is presumed to be mediated by enhanced synaptic availability of monoamines, including dopamine. Apathy is a neuropsychiatric syndrome that is associated with hypodopaminergic functioning and is neurobiologically distinct from depression. Apathy has been observed to be prevalent during the initial phases of abstinence in cocaine-dependent individuals. In the current report, we sought to investigate the relationship between apathy, depression, and craving in response to an acute intravenous administration of cocaine. To this end, sixteen non-treatment seeking volunteers were evaluated. Following acute administration of cocaine (40 mg, IV), patients with low apathy scores exhibited increased craving, whereas patients with high apathy scores exhibited decreased craving. In addition, patients with high apathy scores exhibited increased ratings of the subjective measure of "High", suggesting that high apathy predicts a greater hedonic response in dependence. Self-reported ratings of depression did not account for the observed differences. The data reveal that cocaine-induced craving is not ubiquitous, and may not play a critical role in the maintenance of cocaine dependence. Overall, the findings suggest that apathy predicts hedonic but not craving response to cocaine.

Cocaine↗
PubMed2004

Association between quantitative EEG and neurocognition in methamphetamine-dependent volunteers.

OBJECTIVE: Exposure to methamphetamine is associated with long-lasting reductions in markers for dopaminergic neurons in preclinical models and in humans. These changes may be associated with alterations in brain electrical activity and in cognition. METHODS: The sample included 9 methamphetamine-dependent subjects and 10 non-drug-using volunteers. Methamphetamine-dependent subjects were hospitalized for 4 days to document abstinence; non-drug-using volunteers were studied as outpatients. EEGs were recorded in the eyes-closed resting state, and absolute EEG power in each frequency band (0.5-4 Hz, 4-8 Hz, 8-12 Hz, and 12-20 Hz) was measured using a fast Fourier transform. EEG power was log-transformed prior to analysis. Cognition was measured using computerized reaction time tasks. RESULTS: Within the methamphetamine-dependent group only, increased theta quantitative EEG (QEEG) power correlated significantly with reaction time on tasks that were more difficult or that were degraded by fatigue. Increased theta QEEG power also correlated with reduced accuracy on a working memory task. CONCLUSIONS: Increased QEEG power in the theta band is associated with worse performance on reaction time tasks in the methamphetamine-dependent sample but not in the non-drug-using volunteers. SIGNIFICANCE: Methamphetamine dependence is associated with pathological alterations in brain electrical activity and in cognitive performance. QEEG appears to provide a sensitive measure of methamphetamine-associated alterations in brain function.

Adult↗
PubMed2003

Irritability following abstinence from cocaine predicts euphoric effects of cocaine administration.

This study evaluated the association between negative affective symptoms during initial abstinence and euphorigenic response to experimentally administered cocaine. Cocaine-dependent individuals achieved 5 days of abstinence in a hospital setting. Forty milligrams of cocaine was given intravenously on the fifth day of abstinence, and participants were asked to rate the subjective effects produced by the drug. The associations between irritability, self-reported depression, and the subjective "high" produced by cocaine were evaluated. Increased levels of irritability and depression both correlated positively and statistically significantly with heightened response to experimentally administered cocaine as indexed by self-reported subjective "high." The positive association between irritability and subjective "high" remained after controlling for self-reported depressive symptoms. The opponent process model predicts that increased levels of negative affect should be associated with diminished euphoric response to cocaine; however, the opposite was observed. If these findings are replicated in a larger sample, then it may be necessary to reconsider the applicability of the opponent process model to cocaine addiction in humans.

Adult↗
PubMed2003

Quantitative EEG abnormalities in recently abstinent methamphetamine dependent individuals.

OBJECTIVE: Methamphetamine exposure is associated with long-lasting reductions in markers for dopaminergic neurons in preclinical models and probably in humans. Quantitative electroencephalography (EEG) has been used to characterize abnormalities in brain function in a number of disorders, including cocaine dependence, but this technique has not been used to characterize abnormalities associated with methamphetamine dependence. METHODS: The sample included 11 methamphetamine dependent subjects and 11 non-drug using volunteers. Methamphetamine dependent subjects were hospitalized for 4 days to document abstinence; non-drug using volunteers were studied as outpatients. EEGs were recorded in the eyes-closed resting state, and absolute EEG power in each frequency band (0.5-4, 4-8, 8-12, and 12-20 Hz) was quantitated using a fast Fourier transform. EEG power was log-transformed prior to analysis. Conventional, EEG tracings were interpreted by a qualified electroencephalographer who was blinded to the subjects' identity. RESULTS: Methamphetamine dependent volunteers with 4 days of abstinence had increased EEG power in the delta and theta bands. Power in the alpha and beta bands did not differ between the groups. Within the methamphetamine dependent group, a majority of the conventional EEGs were abnormal (64%), compared to 18% in the non-methamphetamine using group. CONCLUSIONS: Recently abstinent methamphetamine dependent subjects demonstrate QEEG abnormalities that are consistent with a generalized encephalopathy. SIGNIFICANCE: Encephalopathic changes in brain electrical activity, as found here in methamphetamine dependence, are frequently associated with a range of cognitive and psychiatric abnormalities, suggesting further avenues of investigation.

Adult↗
PubMed2003

Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence.

This study documented the association between neurocognitive impairment and methamphetamine dependence in a sample of 27 methamphetamine-dependent individuals who achieved 5 to 14 days of continuously monitored abstinence and in 18 control subjects. Methamphetamine-dependent individuals performed significantly worse than control subjects on neurocognitive measures sensitive to attention/psychomotor speed, on measures of verbal learning and memory, and on executive systems measures sensitive to fluency. These findings are the first to demonstrate that methamphetamine dependence is associated with impairments across a range of neurocognitive domains in a sample of users whose abstinence was continuously monitored with the use of urine screening.

Adult↗
PubMed2002

Apathy syndrome in cocaine dependence.

The cocaine abstinence syndrome has been associated with a range of symptoms, including apathy and depression. Although initial studies reported high prevalence rates of 'apathy/amotivation' and depression, validated rating scales of apathy were not then available. Using a validated measure of apathy, we hypothesized that newly abstinent cocaine-dependent subjects would report increased apathy compared with non-cocaine-using control subjects. Furthermore, because apathy and depression are dissociable in other neuropsychiatric syndromes, we examined whether they were dissociable in recently abstinent cocaine-dependent subjects. Following 4 days of monitored abstinence, cocaine-dependent subjects (n=11) and non-drug-using control subjects (n=19) were administered standardized tests of apathy and depression. Cocaine-dependent subjects had elevated scores on the apathy rating scale compared with the control group, but the groups did not differ in ratings of depression. These data suggest that apathy is present during the initial phases of abstinence for a subset of cocaine-dependent individuals. This group may benefit from targeted pharmacological intervention.

Adult↗
PubMedDate not supplied

Methamphetamine abstinence syndrome: preliminary findings.

Retrospective reports suggest that chronic use of methamphetamine is associated with a prolonged abstinence syndrome; however, there are no prospective studies confirming this. Nineteen non-treatment-seeking methamphetamine-dependent volunteers participated in a study of mood during initial abstinence. Moderate levels of depression were reported during the first several days of abstinence, with minimal levels reported thereafter. The most prominent symptoms were anhedonia, irritability, and poor concentration. The abstinence syndrome associated with methamphetamine dependence varied considerably in intensity and duration but generally was mild and resolved quickly for most individuals.

Adult↗