RESUMEN
Oral naltrexone reduces heavy drinking, but is less consistent as an abstinence promoter, whereas once-monthly extended-release naltrexone (XR-NTX) also maintains abstinence. The present study sought to determine if alcohol cue reactivity is attenuated by XR-NTX. Twenty-eight detoxified alcohol-dependent adult male and female volunteers received a single i.m. injection of either XR-NTX or placebo under double-blind conditions. An fMRI/cue reactivity procedure was conducted immediately before and two weeks after injection. At baseline, alcohol-related visual and olfactory cues elicited significant increases in orbital and cingulate gyri, inferior frontal and middle frontal gyri. Subsequently, brain activation was significantly altered in XR-NTX-treated individuals. These affected brain regions are associated with the integration of emotion, cognition, reward, punishment, and learning/memory, suggesting that XR-NTX attenuates the salience of alcohol-related cues. Such an effect on brain function may interrupt the processes associated with "slips" and relapse, which may account for XR-NTX's ability to maintain abstinence.
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Alcoholismo/tratamiento farmacológico , Mapeo Encefálico , Encéfalo/efectos de los fármacos , Imagen por Resonancia Magnética , Naltrexona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Adulto , Alcoholismo/fisiopatología , Encéfalo/fisiopatología , Señales (Psicología) , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , VoluntariosRESUMEN
In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent ³¹P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, ³¹P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain ß-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.
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Encéfalo/metabolismo , Encéfalo/fisiopatología , Trastornos Relacionados con Cocaína/metabolismo , Trastornos Relacionados con Cocaína/fisiopatología , Cognición , Metabolismo Energético , Privación de Sueño , Sueño , Adulto , Afecto , Estudios de Casos y Controles , Cocaína/administración & dosificación , Femenino , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Polisomnografía , Desempeño PsicomotorRESUMEN
BACKGROUND: Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol's effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis. METHODS: Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double-blinded, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. RESULTS: Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants' subjective responses to the alcohol challenge or to alcohol's effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. CONCLUSIONS: These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences, and furthermore the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol's subjective or psychomotor effects.
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Consumo de Bebidas Alcohólicas , Intoxicación Alcohólica , Depresores del Sistema Nervioso Central/sangre , Medicamentos Herbarios Chinos/farmacología , Etanol/sangre , Fitoterapia , Pueraria , Adulto , Cognición/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Etanol/farmacología , Femenino , Humanos , Isoflavonas/efectos adversos , Isoflavonas/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Raíces de Plantas , Escalas de Valoración PsiquiátricaRESUMEN
Zolpidem has abuse potential, particularly among individuals with histories of drug abuse. This double-blind, placebo-controlled, cross over pilot study investigated the subjective effects of zolpidem (10 mg) in drug-naïve females. Over the course of a 5-h period vital signs were monitored and a series of computerized questionnaires was administered. Results indicate that zolpidem engendered subjective effects characteristic of hypnotic drugs, but reduced ratings of drug liking, willing to take again, and willing to pay for, relative to placebo. Thus, a therapeutic dose of zolpidem may have limited potential for misuse among females who have no experience with drugs of abuse.
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Hipnóticos y Sedantes/farmacología , Piridinas/farmacología , Trastornos Relacionados con Sustancias/psicología , Adulto , Antipsicóticos/farmacología , Presión Sanguínea/efectos de los fármacos , Clorpromazina/farmacología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Pentobarbital/farmacología , Proyectos Piloto , Temperatura Cutánea/efectos de los fármacos , Adulto Joven , ZolpidemRESUMEN
How blood samples are processed and stored before being analyzed for alcohol levels is of concern in the forensic and toxicological fields, and is important in the standardization of research methods. This experiment explored for systematic differences in ethanol levels among several methods of processing and storing blood samples. Five adults consumed a standard alcoholic drink (0.7 g/kg) over a 15-min period, and blood samples were taken 5 times during a 3-h period following drinking onset. Samples for plasma and whole blood were drawn into Vacutainers containing either an anticoagulant or an anticoagulant plus preservative. Samples for serum were drawn into Vacutainers containing no additives or a preservative only. Separate sets of samples were analyzed on the day of the study, after storage at room temperature (25 degrees C) for 24 h, after storage at room temperature for 10 days, or after 10 days of refrigerated storage. Neither processing condition (i.e., type of additive) nor storage condition significantly affected ethanol levels. Consistent with the literature, plasma and serum samples had significantly higher concentrations of ethanol than whole blood. This study shows that blood samples containing ethanol at levels ranging from 60 to 90 mg/dL (0.06 to 0.09 mg%) are not significantly altered by the type of collection tube used or storage condition during a 10-day period.
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Depresores del Sistema Nervioso Central/sangre , Etanol/sangre , Adulto , Anticoagulantes/análisis , Cromatografía de Gases , Interpretación Estadística de Datos , Femenino , Humanos , Indicadores y Reactivos , Masculino , Plasma/química , Suero/química , Manejo de EspecímenesRESUMEN
BACKGROUND: Previous studies employing retrospective assessments methods found that regular ecstasy users frequently use alcohol, marihuana and other drugs in combination with ecstasy. METHODS: Twenty-two participants (13 males, 9 females) wore a wrist actigraph/data recorder to record real-time drug use and ecstasy craving for 6 weeks. Rates of alcohol and drug use on ecstasy use versus non-use nights, and before, during, and after ecstasy use were analyzed with generalized estimation equations (GEE). Craving was modeled with GEE and linear mixed models. RESULTS: Approximately 70% of ecstasy uses occurred on Friday or Saturday nights. No drug was significantly more likely to be used on ecstasy use nights than comparison Friday and Saturday nights. On nights ecstasy was used, in general across all drugs assessed, use was more likely before and during than after ecstasy intoxication, while alcohol use was also more likely before than during ecstasy intoxication. Though low overall, craving for ecstasy increased over 24 h before use and was higher on Friday nights of weeks ecstasy was used on weekends than weeks it was not used. CONCLUSIONS: Use of ecstasy on a particular night may not be associated with any greater likelihood of using any other intoxicating drug, and use of other drugs on nights involving ecstasy use may simply reflect a "natural history" of drug-use nights that begins with alcohol, progresses to more intoxicating drugs, and ends with little drug use. Confirmation of these findings awaits further advances in the application of ecological momentary assessment methodologies.
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Alcoholismo/epidemiología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Alucinógenos , Abuso de Marihuana/epidemiología , N-Metil-3,4-metilenodioxianfetamina , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Alcoholismo/diagnóstico , Comorbilidad , Demografía , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos Disruptivos, del Control de Impulso y de la Conducta/diagnóstico , Femenino , Humanos , Masculino , Abuso de Marihuana/diagnóstico , Prevalencia , Trastornos Relacionados con Sustancias/diagnósticoRESUMEN
OBJECTIVES: This study was undertaken to assess the pharmacokinetic profile of puerarin, the major isoflavone found in a kudzu (Pueraria lobata) extract after acute and repeated administration. METHODS: Participants were given either single or repeated doses of kudzu extract, and blood samples were collected for either 8 or 72 hours for subsequent pharmacokinetic analyses of puerarin. RESULTS: Using WinNonlin pharmacokinetic data analysis software, puerarin was found to be rapidly absorbed via the oral route, reach peak levels at 2 hours, and have a half-life of approximately 4.3 hours. The elimination half-life was not significantly altered after repeated administration. CONCLUSIONS: A formulation of kudzu extract delivers a large amount of the principal isoflavone in a rapid manner. The elimination rate constants and the mono-exponential decline in blood levels suggest that a one compartment model adequately explains how puerarin is handled by the body. Three times a day dosing is recommended as accumulation will not occur, and plasma levels remain at levels that are biologically active, even 8 hours after the last steady-state dose.
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Isoflavonas/administración & dosificación , Isoflavonas/farmacocinética , Pueraria , Vasodilatadores/farmacocinética , Administración Oral , Adulto , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Humanos , Isoflavonas/sangre , Masculino , Valores de Referencia , Reproducibilidad de los Resultados , Vasodilatadores/sangreRESUMEN
Despite the fact that tobacco and marihuana are often used together, relatively little is known about the effects of this combination. In order to investigate the effects of the principal psychoactive component in tobacco smoke, nicotine, on marihuana-induced intoxication, we conducted a double blind, cross-over experiment using nicotine transdermal patches. Ten male and 10 female participants received either placebo or a 21 mg transdermal nicotine patch 4 h before smoking one of two marihuana cigarettes (1.99 or 3.51% delta-9-tetrahydrocannabinol (Delta(9) THC) content). Measurements of physiological activity (heart rate, blood pressure, and skin temperature) and subjective effects (self-reports of drug effects on visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI)) were made periodically before and for 3h after smoking. Nicotine pre-treatment enhanced several responses to marihuana, in particular, heart rate, reports of "stimulated" on the visual analog scales, and scores on the Amphetamine scale of the ARCI. Male participants reported a more pronounced effect of marihuana that persisted longer than that of the female participants. Compared to the male participants, female participants experienced an attenuated response to marihuana and were less affected by the drug combination. The results of this study show that nicotine can have an important influence on the subjective and physiological effects of smoked marihuana. These effects have implications for the safety and efficacy of marihuana smokers who are self-medicating with the nicotine transdermal patch to manage their tobacco dependence.
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Cannabis/efectos de los fármacos , Nicotina/administración & dosificación , Administración Cutánea , Adulto , Presión Sanguínea/fisiología , Estudios Cruzados , Método Doble Ciego , Sinergismo Farmacológico , Emociones/efectos de los fármacos , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Fumar Marihuana , Temperatura Cutánea/fisiologíaRESUMEN
BACKGROUND: Overconsumption of alcohol has significant negative effects on an individual's health and contributes to an enormous economic impact on society as a whole. Pharmacotherapies to curb excessive drinking are important for treating alcohol use disorders. METHODS: Twenty (20) men participated in a placebo-controlled, double-blind, between subjects design experiment (n=10/group) that tested the effects of kudzu extract (Alkontrol-Herbal™) for its ability to alter alcohol consumption in a natural settings laboratory. A single dose of kudzu extract (2g total with an active isoflavone content of 520mg) or placebo was administered 2.5h before the onset of a 90min afternoon drinking session during which participants had the opportunity to drink up to 6 beers ad libitum; water and juice were always available as alternative beverages. RESULTS: During the baseline session, the placebo-randomized group consumed 2.7±0.78 beers before treatment and increased consumption to 3.4±1.1 beers after treatment. The kudzu group significantly reduced consumption from 3.0±1.7 at baseline to 1.9±1.3 beers after treatment. The placebo-treated group opened 33 beers during baseline conditions and 38 following treatment whereas the kudzu-treated group opened 32 beers during baseline conditions and only 21 following treatment. Additionally, kudzu-treated participants drank slower. CONCLUSION: This is the first demonstration that a single dose of kudzu extract quickly reduces alcohol consumption in a binge drinking paradigm. These data add to the mounting clinical evidence that kudzu extract may be a safe and effective adjunctive pharmacotherapy for alcohol abuse and dependence.
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Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Consumo Excesivo de Bebidas Alcohólicas/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/administración & dosificación , Pueraria/química , Adulto , Cerveza , Método Doble Ciego , Humanos , Isoflavonas/uso terapéutico , Masculino , Adulto JovenRESUMEN
OBJECTIVE: Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo. METHOD: The current study tested this hypothesis by examining the effects of citicoline in treatment-seeking chronic MJ smokers. In an 8-week double-blind, placebo-controlled study, 19 MJ smokers were randomly assigned via a double-blind procedure to the citicoline (8 Males, 2 Females) or placebo group (9 Males, 0 Females). All participants completed fMRI scanning at baseline and after 8 weeks of treatment during two cognitive measures of inhibitory processing, the Multi Source Interference Test (MSIT) and Stroop Color Word Test, and also completed the Barratt Impulsiveness Scale (BIS-11), a self-report measure of impulsivity. RESULTS: Following the 8 week trial, MJ smokers treated with citicoline demonstrated significantly lower levels of behavioral impulsivity, improved task accuracy on both the MSIT and Stroop tasks, and exhibited significantly different patterns of brain activation relative to baseline levels and relative to those who received placebo. CONCLUSIONS: Findings suggest that citicoline may facilitate the treatment of MJ use disorders by improving the cognitive skills necessary to fully engage in comprehensive treatment programs.
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BACKGROUND: Many cannabinoid medications are approved in North America or in phase III trials, such as dronabinol, nabilone, or nabiximols. Little is known about their subjective psychoactive effects when used for pain management. We hypothesized that when used for pain, dronabinol has psychoactive effects in a dose-response relationship, whose peak effects are comparable with smoking marijuana. METHODS: This was a randomized controlled trial of single dose placebo, 10 or 20 mg dronabinol in 30 chronic noncancer pain patients taking opioids and not using marijuana. Participants completed the Addiction Research Center Inventory (ARCI) hourly for 8 hours during 3 monitored sessions. Comparison sample was the ARCI ratings in participants with no pain (N=20), monitored every 30 minutes after smoking a 1.99% THC (low) and a 3.51% (high strength) marijuana cigarette. RESULTS: The 10 and 20 mg dronabinol doses had significantly elevated scores over time on 4/5 subscales versus placebo (P<0.05). Average daily morphine use, total pain relief (TOTPAR), age, sex, and baseline pain level were not significant covariates. ARCI peak effects at 2 hours were similar to peak effects of smoked marijuana at 30 minutes (P=0.80, 10 mg=low strength, 20 mg=high strength). CONCLUSIONS: In pain patients, oral dronabinol has similar psychoactive effects to smoking marijuana. This risk must be considered in any decision to prescribe cannabinoid medications for pain.
Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Dronabinol/uso terapéutico , Psicotrópicos/uso terapéutico , Administración Oral , Adulto , Anciano , Analgésicos Opioides/uso terapéutico , Dolor Crónico/fisiopatología , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Fumar Marihuana/fisiopatología , Marihuana Medicinal/uso terapéutico , Persona de Mediana Edad , Morfina/uso terapéutico , Dimensión del Dolor , Fitoterapia , Resultado del Tratamiento , Adulto JovenRESUMEN
STUDY OBJECTIVES: A principal function of sleep may be restoration of brain energy metabolism caused by the energetic demands of wakefulness. Because energetic demands in the brain are greater in gray than white matter, this study used linear mixed-effects models to examine tissue-type specific changes in high-energy phosphates derived using 31P magnetic resonance spectroscopy (MRS) after sleep deprivation and recovery sleep. DESIGN: Experimental laboratory study. SETTING: Outpatient neuroimaging center at a private psychiatric hospital. PARTICIPANTS: A total of 32 MRS scans performed in eight healthy individuals (mean age 35 y; range 23-51 y). INTERVENTIONS: Phosphocreatine (PCr) and ß-nucleoside triphosphate (NTP) were measured using 31P MRS three dimensional-chemical shift imaging at high field (4 Tesla) after a baseline night of sleep, acute sleep deprivation (SD), and 2 nights of recovery sleep. Novel linear mixed-effects models were constructed using spectral and tissue segmentation data to examine changes in bioenergetics in gray and white matter. MEASUREMENTS AND RESULTS: PCr increased in gray matter after 2 nights of recovery sleep relative to SD with no significant changes in white matter. Exploratory analyses also demonstrated that increases in PCr were associated with increases in electroencephalographic slow wave activity during recovery sleep. No significant changes in ß-NTP were observed. CONCLUSIONS: These results demonstrate that sleep deprivation and subsequent recovery-induced changes in high-energy phosphates primarily occur in gray matter, and increases in PCr after recovery sleep may be related to sleep homeostasis.
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Metabolismo Energético , Sustancia Gris/metabolismo , Privación de Sueño/metabolismo , Adulto , Electroencefalografía , Femenino , Sustancia Gris/fisiopatología , Voluntarios Sanos , Homeostasis , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Nucleótidos/metabolismo , Fosfocreatina/metabolismo , Metabolismo Secundario , Sueño/fisiología , Privación de Sueño/fisiopatología , Sustancia Blanca/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: We previously demonstrated that short-term treatment with a standardized kudzu extract (NPI-031) reduced alcohol drinking by men and women in a natural setting. The present study was conducted in nontreatment-seeking heavy drinkers to assess the safety and efficacy of 4 weeks of kudzu extract in an outpatient setting. METHOD: This randomized between-subject, double-blind, placebo-controlled study involved 2 weeks of baseline, 4 weeks of treatment, and 2 weeks of follow-up. Seventeen men (21-33 years) who reported drinking 27.6 ± 6.5 drinks/week with a diagnosis of alcohol abuse/dependence took either kudzu extract (250 mg isoflavones, t.i.d.) or matched placebo on a daily basis. They reported alcohol consumption and desire to use alcohol using a wrist actigraphy device; twice weekly laboratory visits were scheduled to monitor medication adherence and adverse events. RESULTS: Medication adherence was excellent and there were no adverse events and changes in vital signs, blood chemistry, and renal or liver function. There was no effect on alcohol craving, but kudzu extract significantly reduced the number of drinks consumed each week by 34-57 %, reduced the number of heavy drinking days, and significantly increased the percent of days abstinent and the number of consecutive days of abstinence. CONCLUSIONS: A standardized formulation of kudzu extract produced minimal side effects, was well-tolerated, and resulted in a modest reduction in alcohol consumption in young nontreatment-seeking heavy drinkers. Additional studies using treatment-seeking alcohol-dependent persons will be necessary to determine the usefulness of this herbal preparation in reducing alcohol use in other populations.
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Disuasivos de Alcohol/uso terapéutico , Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Alcoholismo/tratamiento farmacológico , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Pueraria/química , Adulto , Disuasivos de Alcohol/efectos adversos , Disuasivos de Alcohol/aislamiento & purificación , Disuasivos de Alcohol/normas , Consumo de Bebidas Alcohólicas/sangre , Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/sangre , Alcoholismo/psicología , Método Doble Ciego , Etanol/efectos adversos , Etanol/sangre , Humanos , Masculino , Cumplimiento de la Medicación , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/normas , Adulto JovenRESUMEN
BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) avoids the use of needles, and instead delivers a mild electric current at traditional acupoints. This technique has been used for treating heroin addiction, but has not been systematically tested for other drugs of abuse. This study aims to investigate the effects of TEAS on drug addiction. METHODS: Volunteers who were either cocaine-dependent (n = 9) or cannabis-dependent (n = 11) but were not seeking treatment for their dependence participated in a within-subject, single-blind study. Treatment consisted of twice daily 30-minute sessions of TEAS or sham stimulation for 3.5 days. The active TEAS levels were individually adjusted to produce a distinct twitching response in the fingers, while the sham stimulation involved 2 minutes of stimulation at threshold levels followed by 28 minutes of stimulation below the detection levels. The participants recorded their drug use and drug cravings daily. At 1 hour after the last morning session of TEAS or sham stimulation, a cue-induced craving EEG evaluation was conducted. Event-related P300 potentials (ERPs) were recorded, sorted, and analyzed for specific image types (neutral objects, non-drug-related arousing images, or drug-related images). RESULTS: TEAS treatment did not significantly reduce the drug use or drug cravings, or significantly alter the ERP peak voltage or latency to peak response. However, the TEAS treatment did significantly modulate several self-reported measures of mood and anxiety. CONCLUSION: The results of this pilot study with a limited sample size suggest that the acupoint stimulation techniques and protocol used in this trial alone do not significantly reduce cravings for or use of cocaine or cannabis. The findings that TEAS modulates mood and anxiety suggest that TEAS could be used as an adjunct in a multimodal therapy program to treat cocaine and cannabis dependence if confirmed in a full randomized controlled clinical trial.
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BACKGROUND: Isoflavone compounds naturally occurring in the root of the kudzu plant have been used historically to treat alcohol-related problems. A pilot study was conducted to assess the effects of one primary isoflavone--puerarin--for its ability to modify alcohol intake in humans. METHODS: Ten (10) healthy adult volunteers were administered puerarin (1200 mg daily) in a double-blind, placebo-controlled, crossover design experiment for one week prior to an afternoon drinking session lasting 1.5h. Participants had access to up to six bottles of their preferred brand of beer in addition to juice and water. A time course of drinking, sip volumes, and total amount consumed were recorded. RESULTS: Participants consumed on average 3.5 (±0.55) beers when treated with placebo and 2.4 (±0.41) beers when treated with puerarin. In contrast to drinking following placebo treatment when 3 participants drank 5 beers and 1 participant drank all 6 beers, none drank 5 or 6 beers when treated with puerarin. Drinking topography also changed. When treated with puerarin, participants decreased sip size, took more sips to finish a beer, and took longer to consume each beer. Additionally, after finishing a beer, latency to opening the next beer was increased. CONCLUSIONS: This study is the first demonstration that a single isoflavone found in the kudzu root can alter alcohol drinking in humans. These results suggest that alcohol consumption patterns are influenced by puerarin administration and this botanical medication may be a useful adjunct in the treatment of excessive alcohol intake.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Alcoholismo/tratamiento farmacológico , Isoflavonas/uso terapéutico , Antagonistas Adrenérgicos beta/efectos adversos , Adulto , Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/psicología , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Isoflavonas/efectos adversos , Masculino , Cumplimiento de la Medicación , Proyectos Piloto , Pueraria/química , Adulto JovenRESUMEN
OBJECTIVE: Assessment of the subjective and physiological effects of smoking cigarettes with different machine-smoked nicotine yields. METHODS: Eight volunteers rated the characteristics of cigarettes with varying levels of nicotine (Quest®). At 30 minute intervals, participants smoked one of three different Quest® brand cigarettes in a counterbalanced order (reported machine-smoked nicotine yield: 0.6 mg, 0.3 mg, or 0.05 mg). Smoking satisfaction and sensations were measured on a cigarette evaluation questionnaire. A mood questionnaire measured self-reported subjective changes in 'happy', 'stimulated', 'anxious', 'desire to smoke', and 'desire not to smoke'. Heart rate and skin temperature were recorded continuously. RESULTS: As nicotine yield decreased, cigarettes produced smaller changes in subjective ratings on the evaluation questionnaire with the placebo nicotine cigarette always rated lower or less potent than the other two cigarettes evaluated. Heart rate was significantly increased by the reduced nicotine cigarettes, but was not affected by the nicotine-free cigarette. CONCLUSION: These results indicate that machine-smoked yield is an important determinant of both the subjective and physiological effects of smoking. The use of reduced and nicotine free cigarettes in smoking cessation programs remains to be evaluated.
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Bupropion's (Zyban(®) SR) effectiveness to treat symptoms experienced in marihuana withdrawal was tested in a double-blind, placebo-controlled study with chronic, heavy marihuana users. Participants maintained their usual marihuana intake until Quit Day after which they were required to cease intake of THC products for 14 days. A Withdrawal Discomfort Score revealed that for 7 days immediately following cessation, placebo-treated subjects reported more symptoms than bupropion-treated subjects. Self-reported craving for marihuana increased for the placebo-treated group but not for those treated with bupropion. Measures of sleep and cognitive performance were not different between the two groups. Participants in the bupropion treatment arm were more likely to complete the study than those randomized to the placebo arm (50% completion for bupropion vs. 33% completion for placebo). These results suggest that bupropion may be useful for alleviating marihuana withdrawal symptoms and be useful in subject retention during long-term cessation programs.
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OBJECTIVES: According to ancient Chinese medicine, kudzu root has been used as an ingredient to treat alcohol intoxication for centuries. Kudzu root extract is effective at reducing alcohol intake in animals and in humans, both in a natural-settings laboratory environment and on an outpatient basis. In dependent populations, withdrawal from alcohol is associated with disturbed sleep. These disturbances to the quantity and quality of sleep likely impact relapse to drinking. Many medications used to treat alcohol dependence also affect sleep. Therefore, as a possible treatment for alcohol dependence, the impact of kudzu root extract on the sleep/wake cycle is an important aspect of its effectiveness. DESIGN: This double-blind, placebo-controlled, crossover trial tested the effects of kudzu root extract on the sleep/wake cycles of moderate drinkers. RESULTS: Kudzu extract had no effect on any of the sleep parameters measured, including sleep efficiency, sleep latency, total time asleep per night, number of waking episodes, time awake per episode, number of moving minutes, number of sleep episodes, time asleep per episode, and number of immobile minutes. CONCLUSIONS: These data suggest that the administration of kudzu root extract does not disturb sleep/wake cycles of moderate drinkers, and as such its utility as an adjunct treatment for alcohol dependence remains free of any potential side-effects on sleep.
Asunto(s)
Alcoholismo/fisiopatología , Fitoterapia , Extractos Vegetales/farmacología , Pueraria , Trastornos del Sueño-Vigilia , Sueño/efectos de los fármacos , Adulto , Alcoholismo/tratamiento farmacológico , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Recurrencia , Síndrome de Abstinencia a Sustancias , Adulto JovenRESUMEN
BACKGROUND: Citicoline (cytidine-5'-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy. METHOD: In this double-blind, placebo-controlled trial, the effects of citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants. RESULTS: In this non-abstinent, cocaine-dependent population, citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile. CONCLUSIONS: These data suggest that eight weeks of citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals.
Asunto(s)
Trastornos Relacionados con Cocaína/tratamiento farmacológico , Trastornos Relacionados con Cocaína/fisiopatología , Citidina Difosfato Colina/administración & dosificación , Citidina Difosfato Colina/efectos adversos , Sueño/efectos de los fármacos , Adulto , Trastornos Relacionados con Cocaína/psicología , Cognición/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Masculino , Nootrópicos/administración & dosificación , Nootrópicos/efectos adversos , Sueño/fisiología , Trastornos del Sueño-Vigilia/fisiopatología , Síndrome de Abstinencia a Sustancias/fisiopatología , Factores de TiempoRESUMEN
UNLABELLED: Many pharmacotherapies for treating cocaine dependence are aimed at reducing drug effects, alleviating craving, and preventing relapse. We demonstrated previously that citicoline, a compound used to repair neuronal damage in stroke and brain injury, is safe in cocaine-abusing volunteers. OBJECTIVES: This study assessed the effectiveness of an 8-week citicoline treatment period and 4-week follow-up in cocaine-dependent individuals. METHODS: Twenty-nine healthy nontreatment-seeking, cocaine-dependent male and female volunteers were randomized in this double-blind, placebo-controlled study, 18 of whom completed the treatment period of the study. Participants took citicoline (500 mg twice daily) or matched placebo each day and recorded the measures of craving and drug use. Participants visited the laboratory twice a week for urine screens and to attend weekly group therapy sessions. RESULTS: Citicoline had no effect on cocaine craving or total use. CONCLUSIONS: Although the current preliminary results from this small trial suggest that citicoline is not an effective treatment for heavy cocaine users, further investigation on efficacy citicoline as a treatment for substance dependence in other settings may be warranted.