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Bankole A Johnson

Publications and source records attributed to Bankole A Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Emerging biomarkers: new directions and clinical applications.

This article summarizes content proceedings of a symposium held at the 2004 Research Society on Alcoholism Scientific Annual Meeting in Vancouver, Canada. The chairs were Friedrich M. Wurst and Raye Litten. The presentations were (1) Introduction, by Raye Litten; (2) Direct Ethanol Metabolites--On the Threshold From Science to Routine Use, by Friedrich M. Wurst; (3) Sialic Acid Index of Plasma Apolipoprotein J (SIJ) as a Viable Marker for Chronic Alcohol Consumption, by Philippe Marmillot; (4) The Emergence of Ethyl Glucuronide (EtG) Testing as a Tool in Monitoring Healthcare Professionals, by Gregory E. Skipper; (5) Application of Biomarkers for Alcohol Use Disorders in Clinical Practice, by Tim Neumann; (6) Utility of Biomarkers in Assessing the Efficacy of Medications for Treating Alcoholism, by Marty Javors; and (7) Discussion, by Raye Litten.

Alcoholism↗
PubMed2005

Challenges and opportunities for medications development in alcoholism: an international perspective on collaborations between academia and industry.

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on September 30, 2004. The organizers and cochairs were Bankole A. Johnson, DSc, MD, PhD, and Karl Mann, MD. The presentations included the following: (1) A Perspective from Academia, by Bankole A. Johnson, DSc, MD, PhD; (2) A Perspective from NIAAA, by Mark L. Willenbring, MD; (3) A Perspective from US Clinical Practice, by Robert M. Swift, MD, PhD; (4) A European Perspective on Medications Development, by Otto M. Lesch, MD, PhD, and (5) A Scandinavian Perspective on Evidence-Based Addiction Treatment, by Mats Berglund, MD.

Academies and Institutes↗
PubMed2005

Comorbid alcohol and nicotine dependence: from the biomolecular basis to clinical consequences.

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on October 1, 2004. The organizers and cochairs were Nassima Ait-Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following:L (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol-Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfützer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol-Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD.

Alcohol Deterrents↗
PubMed2005

The COMBINE SAFTEE: a structured instrument for collecting adverse events adapted for clinical studies in the alcoholism field.

OBJECTIVE: In the many clinical studies conducted in the alcoholism field with psychotropic drugs--and throughout the drug development field in medicine, where evaluation of adverse events can be incomplete, arbitrary or misleading--few standardized methods have been developed for assessing adverse events, whereas defining standardized methods for evaluating clinical efficacy is typical. For the National Institute on Alcohol Abuse and Alcoholism COMBINE Study, testing the safety and efficacy of naltrexone and acamprosate, both alone and in combination, in the treatment of alcohol dependence, we adapted a standardized instrument--the Systematic Assessment for Treatment Emergent Events (SAFTEE)--for assessing adverse events in these Phase 2- to Phase 3-type studies. METHOD: We standardized use of the SAFTEE with training, supervision and clear guidelines for its implementation, including development of a nomenclature for the typical adverse events associated with these medications and a format for examining symptom severity. Data from the COMBINE SAFTEE include not only frequency of adverse events but also severity level and a composite index taking into account both the severity and duration of symptoms. RESULTS: The COMBINE SAFTEE was incorporated into the Medical Management therapy and showed high fidelity with its utility, consistency of deliverability and flexibility in measuring adverse events in both the human laboratory and clinical trial settings using intervals that varied from daily to weekly use. CONCLUSIONS: Due to its high standardization level, the COMBINE SAFTEE could be incorporated into other brief compliance enhancement strategies in clinical studies to assess the efficacy of putative therapeutic drugs.

Acamprosate↗
PubMed2005

Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function.

Neuroscientific developments have promulgated interest in developing efficacious medications for the treatment of substance dependence. Previous pharmacological strategies that involve the use of relatively specific medications to alter corticomesolimbic dopaminergic neuronal activity--the critical pathway for expression of the reinforcing effects of abused drugs--have yielded modest efficacy in the treatment of alcohol dependence, and no medication has been established as a treatment for cocaine dependence. Since corticomesolimbic dopaminergic neurons interact with other neurotransmitters that modulate the effects of dopamine in the nucleus accumbens, would it not be possible to control these dopaminergic effects more reliably with a medication that acts contemporaneously on more than one neuromodulator of dopaminergic function? Further, since the long-term use of either alcohol or cocaine results in neuronal adaptations as a result of sensitisation, would the chances of effective therapy not be bolstered by administering a medication that was also able to mitigate these chronic effects? Thus, a new conceptual approach is needed. My proposal is that a medication--in this case topiramate--that principally potentiates inhibitory GABA(A) receptor-mediated input and antagonises excitatory glutamatergic afferents to the corticomesolimbic dopaminergic system should have therapeutic potential in treating either alcohol or cocaine dependence or perhaps both. This is because the principal neurochemical effects of topiramate would not only serve to decrease the acute reinforcing effects of alcohol or cocaine, but might also facilitate cessation of their use following a period of long-term use by decreasing neuronal sensitisation. This overview highlights the scientific concepts and clinical evidence for the development of topiramate in the treatment of alcohol dependence and introduces preliminary evidence to indicate that it might also have utility in treating cocaine dependence. Finally, to place the material on topiramate in context, information has been included on the utility and development of other medications that modulate GABA- or glutamate-mediated neuronal systems for the treatment of alcohol or cocaine dependence.

Alcoholism↗
PubMed2004

Kinetic and cardiovascular comparison of immediate-release isradipine and sustained-release isradipine among non-treatment-seeking, cocaine-dependent individuals.

The authors sought to determine whether sustained-release (SR) isradipine provided comparable systemic availability to that of immediate-release (IR) isradipine in non-treatment-seeking, cocaine-dependent individuals. This information could be used to design a rational dosage regimen for additional isradipine clinical trials in the treatment of stimulant dependence and related neurovascular disorders. Eight male volunteers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a randomized, double-blind, crossover study. Subjects received a 15-mg dose of an IR isradipine formulation and a 30-mg dose of an SR isradipine formulation, separated by a 2-day interval. Vital signs and blood sampling for isradipine serum levels were performed before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, and 24 h after each isradipine dose administration. Neither the 15-mg dose of IR isradipine nor the 30-mg dose of SR isradipine produced significant adverse effects on cardiovascular parameters, but the IR formulation was more likely to produce marked short-term decreases in pressor response. Significant intersubject variability in serum concentrations and pharmacokinetic parameters occurred for both formulations. The relative bioavailability of the SR formulation was 55.5% of that of the IR formulation. Both formulations cumulatively may deliver about the same amount of drug, but IR isradipine achieves a higher peak concentration than SR isradipine. The more favorable cardiovascular profile of SR isradipine would, however, make it more appropriate as an investigational medication for the treatment of stimulant dependence and related neurovascular disorders.

Adult↗
PubMed2004

A prospective, open-label trial of ondansetron in adolescents with alcohol dependence.

Ondansetron has been shown to be effective in the treatment of early-onset adult alcohol dependence. To date, no studies have been conducted in adolescents with alcohol dependence to assess the feasibility, safety, tolerability, and potential utility of ondansetron treatment. We conducted an 8-week, prospective, open-label study of ondansetron (4 microg/kg b.i.d.) in 12 adolescents who had alcohol dependence. Oral ondansetron was safe and well tolerated in our sample. Adverse events were mild and resolved quickly without intervention. No subjects discontinued due to adverse events. Intent-to-treat analyses showed a significant within-group decrease (improvement) for drinks/drinking day (t=-3.10, df=11, p=0.01), as well as decreases in drinks/day (t=-2.01, df=11, p=0.06) and percentage of days abstinent (t=1.45, df=11, p=0.18). These preliminary data suggest that ondansetron is safe and well tolerated in adolescents with alcohol dependence. Findings of decreased drinking underscore the need for future double-blind, placebo-controlled studies in this adolescent population.

Adolescent↗
PubMed2004

Platelet serotonin uptake and paroxetine binding among allelic genotypes of the serotonin transporter in alcoholics.

Expression rates of long (L) and short (S) alleles of the serotonin (5-HT) transporter (5-HTT) gene have been shown to differ under various circumstances. We compared 5-HTT uptake (function) level and paroxetine binding (density) in platelets of alcoholics as indices of 5-HTT expression rate among LL, LS, and SS genotypes. Concentration curves of [3H]5-HT and [3H]paroxetine were used to quantify the equilibrium constant (Km) and maximum 5-HT uptake rate (Vmax) for 5-HTT uptake into intact platelets and the dissociation constant (Kd) and maximum specific binding density (Bmax) for paroxetine binding to platelet membranes, respectively. Genotypes were determined using electrophoresis with fluorescent markers. Vmax for 5-HTT uptake did not correlate with Bmax for paroxetine binding (r=-0.095, P=0.415). Means of Vmax and Bmax did not differ in a statistically significant manner among LL, LS, and SS genotypes in these alcoholic subjects. However, Vmax for LL and SS appeared to have a bimodal distribution, so the percentage of subjects with Vmax <200 fmol/min-10(7) platelets was statistically significantly higher in LL than in SS (51.5% vs. 22.7%, respectively), with an odds ratio of 3.6 (P<0.05). The percentage of Vmax <200 fmol/min-10(7) platelets for LS was 39.3% (not significant vs. LL or SS). Previous studies of healthy human controls have shown that 5-HTT density in raphe nuclei and 5-HTT uptake in platelets are higher in the LL genotype than in S carriers. Our findings in currently drinking alcoholics support the hypothesis that those with the LL genotype of the 5'-HTTLPR region of the 5-HTT gene have reduced 5-HTT function.

Adult↗
PubMed2004

Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition.

RATIONALE: While the effects of d-amphetamine in increasing performance have been established, there is a paucity of information on the effects of methamphetamine on cognition in drug-naive subjects, and no published information on the effects of intravenous methamphetamine administration in dependent individuals. The dihydropyridine-class calcium channel antagonist, isradipine, has been posited as a putative treatment to prevent methamphetamine-associated hypertensive crisis and its sequelae. Yet, isradipine's effects on cognitive performance in methamphetamine-dependent individuals are not known. OBJECTIVE: Since individuals whose dependence on methamphetamine is attributable to the need to enhance performance may be loath to take a cognition-impairing medication, even for the treatment of life-threatening hypertensive crisis, it would be important to determine isradipine's effects on performance. METHODS: We therefore examined in a blinded, placebo-controlled, crossover design the cognitive effects of low and high doses of intravenous methamphetamine (15 mg and 30 mg, respectively) in both the presence and absence of isradipine. RESULTS: Intravenous d-methamphetamine produced dose-dependent increases in attention, concentration, and psychomotor performance. Isradipine, both with and without methamphetamine, had a modest effect to decrease attention. CONCLUSION: Our results do not support the further testing of isradipine as a medication for improving the cognitive impairments that have been associated with chronic methamphetamine use.

Adult↗
PubMed2004

Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial.

BACKGROUND: Topiramate, a fructopyranose derivative, was superior to placebo at improving the drinking outcomes of alcohol-dependent individuals. OBJECTIVES: To determine whether topiramate, compared with placebo, improves psychosocial functioning in alcohol-dependent individuals and to discover how this improvement is related to heavy drinking behavior. DESIGN: Double-blind, randomized, controlled, 12-week clinical trial comparing topiramate vs placebo for treating alcohol dependence (1998-2001). PARTICIPANTS: One hundred fifty alcohol-dependent individuals, diagnosed using the DSM-IV. INTERVENTIONS: Seventy-five participants received topiramate (escalating dose of 25 mg/d to 300 mg/d), and 75 had placebo and weekly standardized medication compliance management. MAIN OUTCOME MEASURES: Three elements of psychosocial functioning were measured: clinical ratings of overall well-being and alcohol-dependence severity, quality of life, and harmful drinking consequences. Overall well-being and dependence severity and quality of life were analyzed as binary responses with a generalized estimating equation approach; harmful drinking consequences were analyzed as a continuous response using a mixed-effects, repeated-measures model. RESULTS: Averaged over the course of double-blind treatment, topiramate, compared with placebo, improved the odds of overall well-being (odds ratio [OR] = 2.17; 95% confidence interval [CI], 1.16-2.60; P =.01); reported abstinence and not seeking alcohol (OR = 2.63; 95% CI, 1.52-4.53; P =.001); overall life satisfaction (OR = 2.28; 95% CI, 1.21-4.29; P =.01); and reduced harmful drinking consequences (OR = -0.07; 95% CI, -0.12 to -0.02, P =.01). There was a significant shift from higher to lower drinking quartiles on percentage of heavy drinking days, which was associated with improvements on all measures of psychosocial functioning. CONCLUSIONS: As an adjunct to medication compliance enhancement treatment, topiramate (up to 300 mg/d) was superior to placebo at not only improving drinking outcomes but increasing overall well-being and quality of life and lessening dependence severity and its harmful consequences.

Administration, Oral↗
PubMed2004

Topiramate-induced neuromodulation of cortico-mesolimbic dopamine function: a new vista for the treatment of comorbid alcohol and nicotine dependence?

Alcohol and nicotine dependence are commonly occurring disorders that together represent the most important preventable causes of morbidity and mortality in the United States. While there have been differences of opinion as to which disorder to treat first when they occur, there is growing evidence that a management strategy addressing both conditions contemporaneously would be optimal. Advances in the neurosciences have demonstrated not only that the reinforcing effects of both alcohol and nicotine are mediated by similar mechanisms resulting in enhanced activity of the cortico-mesolimbic dopamine system, but that their neurochemical interactions can lead to an aggregation of these effects. Despite this striking neurobiological overlap between alcohol and nicotine consumption, few studies have sought to take advantage of this commonality by devising a pharmacological approach that serves to treat both disorders. The results of our proof-of-concept study showed that topiramate is a promising medication for the treatment of both alcohol and nicotine dependence, presumably by its ability to modulate cortico-mesolimbic dopamine function profoundly; however, other mechanisms might also contribute to this effect. Further studies are ongoing to establish and extend topiramate's efficacy in the treatment of each and both disorders.

Alcoholism↗
PubMed2004

Development of novel pharmacotherapies for the treatment of alcohol dependence: focus on antiepileptics.

This article represents the proceedings of a symposium, "Development of Novel Pharmacotherapies for the Treatment of Alcohol Dependence: Focus on Antiepileptics," presented at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers and cochairs were Bankole A. Johnson and Robert M. Swift. The presentations were (1) Development of topiramate in the treatment of alcoholism, by Bankole A. Johnson; (2) Craving as a predictor of treatment outcome in pharmacotherapy trials for the treatment of alcoholism, by Nassima Ait-Daoud; (3) Use of biomarkers as a predictor of treatment response in treating alcoholism, by Martin A. Javors; (4) Psychotherapy to enhance compliance with pharmacotherapy in treatment trials for alcohol dependence, by Carlo C. DiClemente; (5) Synopsis of promising medications to treat alcoholism, by Robert M. Swift; and (6) New knowledge on the development of antiepileptic medications for the treatment of alcoholism, by Robert J. Malcolm, Jr.

Alcoholism↗
PubMed2004

Serotonin-3 receptors in the actions of alcohol, alcohol reinforcement, and alcoholism.

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers and chairs were William J. McBride and David M. Lovinger. The presentations were (1) Mechanisms of alcohol potentiation of 5-HT3 receptor function, by David M. Lovinger and Tina Machu; (2) Chronic alcohol drinking alters 5-HT3 receptors regulating the mesolimbic dopamine system, by Richard J. Thielen; (3) 5-HT3 receptors in the VTA regulate alcohol drinking and the reinforcing effects of alcohol, by Zachary A. Rodd and James M. Murphy; and (4) Ondansetron as a treatment for "biological" alcoholism, by John D. Roache and Bankole A. Johnson.

Alcohol Drinking↗
PubMed2004

Progress in the development of topiramate for treating alcohol dependence: from a hypothesis to a proof-of-concept study.

Advances in neuroscientific knowledge have evoked interest in developing effective medications for the treatment of alcohol dependence. Pharmacological approaches that involve the use of relatively specific medications at a particular neuronal target to modulate corticomesolimbic dopamine neuronal activity, the critical pathway for expression of the reinforcing effects of abused drugs, have yielded modest efficacy in the treatment of alcohol dependence. A new approach is needed. Because corticomesolimbic dopamine neurons interact with a variety of neurotransmitters that modulate its effects in the nucleus accumbens, it might be possible to more reliably control these dopaminergic effects with a medication that acted contemporaneously on more than one neuromodulator of dopamine function. Additionally, because alcohol use results in neuronal adaptations due to sensitization, the chances of effective therapy might be bolstered by administering a medication that also has utility with mitigating its chronic effects. My proposed conceptual framework suggests that a medication that facilitates inhibitory gamma-aminobutyric acid-A input and antagonizes excitatory glutaminergic afferents to the nucleus accumbens would have pharmacotherapeutic potential in treating the alcohol dependence syndrome because these effects would act contemporaneously to suppress corticomesolimbic dopamine release. Through similar effects, topiramate might also aid chronic drinkers to wean themselves off alcohol and might ameliorate the symptoms of alcohol withdrawal. This commentary highlights the scientific concepts and clinical evidence for the development of topiramate in the treatment of alcohol dependence.

Alcoholism↗
PubMed2004

A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence.

BACKGROUND: : Oral naltrexone is currently used as part of a treatment regimen for alcohol-dependent patients, but its clinical utility is hampered by poor patient adherence. A long-acting injectable naltrexone formulation (Vivitrex) was designed to facilitate patient adherence by providing an extended duration of therapeutic naltrexone over 1 month, thereby eliminating the need for daily dosing. METHODS: : A multicenter, randomized, double-blind, placebo-controlled pilot study was conducted to evaluate the safety and tolerability of intramuscular repeat dose administration of this extended-release naltrexone formulation in DSM-IV alcohol-dependent patients. Thirty patients were randomized to treatment with injectable naltrexone (400 mg; n = 25) or a matching placebo injection (n = 5) and were dosed once every 28 days over 4 months. Psychosocial treatment was offered to patients in both treatment groups. Outcome measures related to drinking activity and trough plasma concentrations of naltrexone and its primary metabolite, 6-beta-naltrexol, were evaluated. RESULTS: : Injectable naltrexone was generally safe and well tolerated. Reported adverse events were mild to moderate and resolved without intervention; only two patients discontinued due to adverse events. The most common adverse events (nausea and headache) occurred at a similar rate for patients in both treatment groups. Pharmacokinetic analysis confirmed that therapeutic levels of naltrexone were delivered throughout the four 1-month treatment cycles. CONCLUSIONS: : The results of this pilot study provide the basis and methods for a larger, more definitive trial to determine the utility of this long-acting injectable naltrexone formulation in the treatment of alcohol-dependent patients.

Adult↗
PubMed2004

Effects of isradipine on cocaine-induced subjective mood.

We hypothesized that in humans, as in animals, isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.

Adolescent↗
PubMed2004

An overview of the development of medications including novel anticonvulsants for the treatment of alcohol dependence.

The development of treatments for alcohol dependence has been significantly complicated by the multiple actions of ethanol at the neurotransmitter level, heterogeneity among patients with alcohol dependence, the complexity of defining and measuring the phenomenon of craving, and the challenge of quantifying alcohol intake in patients. Increasingly, anticonvulsant medications are showing promise for the safe and effective amelioration of alcohol withdrawal symptoms. Furthermore, there is evidence that anticonvulsant medications are promising treatments for reducing drinking and preventing relapse among alcohol-dependent individuals. In recent years, many medications have been evaluated for the treatment of alcohol dependence, including those that interact with dopaminergic, serotonergic, opioid or glutamate and/or GABA systems. So far, naltrexone, acamprosate and, more recently, the anticonvulsant, topiramate, have shown some efficacy for the treatment of heterogeneous populations of individuals with alcohol dependence. Both ondansetron and sertraline appear to have some efficacy in treating different subgroups of alcoholic.

Alcohol Deterrents↗