Peter Jatlow's research while affiliated with Yale University and other places

Publications (205)

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Introduction Menthol cigarette use remains a serious public health problem, prompting the consideration of tobacco regulatory efforts to ban menthol cigarettes. The current study uses a novel empirical design to model the potential effects of a ban of menthol cigarettes on smoking behaviour among current menthol smokers. Methods 29 non-treatment-s...
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Background: Acute alcohol triggers release of cytokines, which are immune signaling molecules. Dysregulated cytokine levels are associated with impaired immune function, and peripheral cytokine levels may communicate with the brain to propagate drinking-related behaviors. This exploratory study aims to characterize the peripheral cytokine response...
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Introduction: Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products' reinforcing or aversive actions. Palatable flavors (e.g., fruit) may increase appeal through primary rein...
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Objective: This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers. Methods: A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the s...
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Objectives: Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconju...
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Importance Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking. Objectives To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment,...
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Objective: Compared to the general U.S. population, smokers with comorbid psychiatric and/or substance use disorders (SUD) have lower quit rates after evidence-based treatments, and disproportionately high smoking-related deaths. Improved modalities for reducing tobacco-related harm in this subpopulation are needed. Because electronic cigarettes (e...
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Background: Tobacco products containing menthol are widely used by youth. We used e-cigarettes to conduct an experimental evaluation of the independent and interactive effects of menthol and nicotine among youth. Procedures: Pilot chemosensory experiments with fourteen e-cigarette users identified low (barely perceptible, 0.5%) and high (similar...
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Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify a...
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Background: Electronic cigarettes (ECs) can influence nicotine addiction by delivering aerosolized nicotine. We investigated if nicotine from ECs is delivered to the brain β2*-nicotinic-acetylcholine receptors (β2*-nAChR) and how this relates to the behavioral effects and nicotine delivery from cigarettes. Methods: Seven nicotine users participa...
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Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern, comparatively less research has evaluated exposure to alcohol vapor. Inhaled alcohol initially bypasses first-pass metabolism and rapidly reaches the arterial circulation and the b...
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Background: The liquids (e-liquids) used in an electronic cigarette (e-cigarette) contain myriad chemicals without adequate human inhalation safety data. Furthermore, the absence of e-liquid labeling requirements poses a formidable challenge to understanding how e-liquid constituents may promote nicotine addiction and/or have independent or synerg...
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The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3'-hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, incl...
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Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortal...
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Lower concentrations of serum bilirubin, an endogenous antioxidant, have been associated with risk of many smoking-related diseases, including lung cancer and cardiovascular disease, and current smokers are reported to have lower bilirubin levels than nonsmokers and past smokers. This study evaluates the effects of smoking cessation on bilirubin le...
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Background The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results...
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The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction. This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers. Overnight ab...
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The uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, ketamine, induces a range of symptoms resembling those seen in schizophrenia. Enhancement of nicotinic acetylcholine receptor (nAChR) function may have potential as a treatment for the cognitive deficits and negative symptoms of schizophrenia. Accordingly, we examined the modulator...
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The ratio of nicotine metabolites (trans-3'-hydroxycotinine (3HC) to cotinine) correlates with nicotine clearance. In previous studies, high nicotine metabolite ratio (NMR) predicted poor outcomes for smoking cessation treatment with nicotine patch. The underlying mechanisms that associate NMR with treatment outcomes have not been fully elucidated....
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In a series of exploratory analyses, we examined the roles of gender, reproductive status and negative affect on smoking abstinence in subjects participating in a large (n=385) 6-week randomized clinical trial (RCT) of nicotine patch therapy, with varying doses of oral naltrexone (0mg, 25mg, 50mg, 100mg) treatment. Negative affect was assessed dail...
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Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit ou...
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Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor metabolites of ethanol. Multiple studies have documented that, depending upon the amount of alcohol consumed, they can be measured in biological fluids for hours to days after the parent compound can no longer be detected. Testing for the presence of EtG, in a manner analogous to urinary dru...
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Chronic cocaine use has been shown to significantly decrease buprenorphine concentrations in the blood with potential for adverse events and poor treatment response. In this study, we investigated whether a similar drug interaction occurred between cocaine and methadone. In a retrospective analysis, methadone pharmacokinetics were compared for thos...
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Aim: The primary aim of this study was to determine the safety and efficacy of the monoamine oxidase-B (MAO-B) inhibitor selegiline hydrochloride (SEL, l-Deprenyl; Eldepryl) as an aid for smoking cessation in cigarette smokers. Methods: One hundred and one nicotine-dependent adult cigarette smokers without current psychiatric or substance use di...
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Understanding the drug interactions between antiretrovirals and opioid therapies may decrease toxicities and enhance adherence with improved HIV outcomes in opioid-dependent individuals. The authors report the results of a clinical pharmacology study designed to determine whether significant pharmacokinetic and/or pharmacodynamic interactions occur...
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Understanding drug interactions between antiretrovirals and opiate therapies may decrease toxicities and enhance adherence, with improved HIV outcomes in injection drug users. We report results of a clinical pharmacology study designed to examine the interaction of the protease inhibitor, nelfinavir, with methadone and LAAM (N = 48). Nelfinavir dec...
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The clinical pharmacology of biochemical measures of nicotine exposure has been thoroughly reviewed with regard to usefulness and limitations in detecting abstinence from cigarette smoking. While plasma nicotine concentration measures only acute nicotine exposure, plasma, salivary, and urine cotinine concentrations reflect exposure over an extended...
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Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H3 receptor inverse agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice. We investigated whether...
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Contingency management (CM) is a powerful behavioral intervention shown to reduce the use of a variety of substances including tobacco. Use of CM techniques for smoking cessation has been restricted by the use of multiple daily measurements of breath CO as the objective indicator to reinforce abstinence. Cotinine, with its longer half-life, may be...
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Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizoph...
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Prospect theory suggests that because smoking cessation is a prevention behavior with a fairly certain outcome, gain-framed messages will be more persuasive than loss-framed messages when attempting to encourage smoking cessation. To test this hypothesis, the authors randomly assigned participants (N=258) in a clinical trial to either a gain- or lo...
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The Medication Adherence Questionnaire (MAQ) is a scale used to evaluate adherence to medications. The present study assessed the factor structure and validity of the MAQ with cigarette smokers. A principal components analysis was conducted on MAQ scores from a sample of smokers presenting for treatment in a clinical trial of naltrexone and nicotin...
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Disulfiram has been studied as a treatment for cocaine dependence. We report results of a randomized, double-blind, placebo-controlled, within-subject study to examine the interaction of disulfiram with intravenous cocaine. Non-treatment-seeking, cocaine-dependent, volunteers participated in serial experiments in which they received disulfiram plac...
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Schizophrenics have higher rates of smoking than the general population, and more difficulty with smoking cessation. However, there has been little study of differences between schizophrenics and controls with respect to biochemical and behavioral indices of smoking. We compared smokers with schizophrenia (SS; n=27) and control smokers (CS; n=26) o...
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We report results of a randomized, double-blind, placebo-controlled, within-subject study (n = 8) to determine the ability of cocaethylene to modulate acute responses to cocaine and identify significant pharmacokinetic interactions between cocaine and cocaethylene. Stable plasma cocaethylene concentrations (0, 50, or 200 ng/ml) were maintained for...
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We examined drug interactions between buprenorphine, an opioid partial agonist available by prescription for treatment of opioid dependence, and the protease inhibitors (PIs) nelfinavir (NFV), ritonavir (RTV), and lopinavir/ritonavir (LPV/R). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers...
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This study examined drug interactions between buprenorphine, an opioid partial agonist medication used in the treatment of opioid dependence, and the nonnucleoside reverse-transcriptase inhibitors (NNRTIs) efavirenz (EFV) and delavirdine (DLV). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative voluntee...
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Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs). In particular, nAChRs containing beta2-subunits (beta2*-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine. We hypothesized that abnormal numbers of beta2*-nAChRs during early abstinen...
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Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose. Six-week...
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We demonstrated that neonatal isolation (ISO) increases acquisition of cocaine self-administration and alters psychostimulant-induced ventral striatal dopamine and serotonin levels in female rats. Both dopamine and serotonin modulate the behavioral effects of cocaine and these effects can vary across estrous stages. We now test whether ISO modifies...
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Adaptations in gamma-aminobutyric acid type A (GABA(A))-benzodiazepine receptors contribute to the neurobiology of human alcohol dependence and withdrawal. To study GABA(A)-benzodiazepine receptor adaptations in subjects with alcohol dependence over the first month of sobriety. Inpatients who were not receiving medication, were either smokers or no...
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Current laboratory paradigms of human cocaine administration generally dictate the timing of drug access in ways that may limit assessing aspects of cocaine-taking behavior. Patient-controlled analgesia (PCA) methods, which allow individuals less restricted access to narcotic (i.e., opiate) analgesics, have proven safe and clinically effective for...
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Cigarette smoking rates in schizophrenia are higher than in the general population. To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive enhancement. Neuropsychological assessments were performed at...
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Use of cocaine, alcohol, and the two drugs simultaneously is common and the risk of morbidity and mortality associated with these drugs is widely reported. This double-blind, placebo-controlled, randomized study examined gender differences in response to administration of these drugs alone and in combination. Current users of cocaine and alcohol (n...
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Given that nicotine modulates amino acid neurotransmission, we sought to examine the impact of nicotine on cortical gamma-aminobutyric acid (GABA) levels in male and female smokers. Healthy nicotine-dependent men (n = 10) and women (n = 6) underwent proton magnetic resonance spectroscopy (1H-MRS) to measure occipital cortex GABA concentrations. A s...
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A family history of alcoholism is a risk factor for the development of ethanol dependence. Ethanol is an antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, and alterations in NMDA receptor function are thought to be involved in ethanol abuse and dependence. The purpose of this study was to determine in healthy individuals with no eth...
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Although several antidepressants are now available, all have limited efficacy and a delayed onset of action. The current study was undertaken as a proof of the concept that combining norepinephrine and serotonin reuptake inhibition would be more effective and act more rapidly than either drug alone. Inpatients with nonpsychotic unipolar major depre...
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Disulfiram (DS; Antabuse) inhibits dopamine-beta-hydroxylase leading to increased brain dopamine levels and shows treatment efficacy for cocaine addiction. Yet few preclinical studies have been performed. This study establishes the effects of DS on locomotor sensitization to cocaine in rats. Rats were administered vehicle, cocaine (10 mg/kg; intrap...
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Postpartum major depression, a frequently (10%) occurring complication of childbirth, adversely affects the mother's functioning, the mother-infant relationship, and the child's subsequent development and propensity for later psychopathology. Although selective serotonin reuptake inhibitors (SSRIs) are effective in treating postpartum depression, c...
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This study examines the pharmacokinetic/pharmacodynamic interactions between (1) lopinavir-ritonavir (L/R), a fixed combination of protease inhibitors used for the treatment of HIV disease, and (2) ritonavir alone at the same dosage as that in the L/R formulation, with methadone, an opiate frequently used in substance abuse pharmacotherapy for opio...
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Since dopaminergic mechanisms appear to be involved in nicotine dependence, we studied the safety and efficacy of the monoamine oxidase B inhibitor selegiline hydrochloride compared with placebo for smoking cessation in nicotine-dependent cigarette smokers. Forty subjects with DSM-IV nicotine dependence were randomized to: 1) selegiline hydrochlori...
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Functional magnetic resonance imaging (fMRI) is increasingly being applied in the study of brain effects of nicotine. In addition, because tobacco smoking is common, many subjects studied with fMRI for other reasons may have appreciable levels of nicotine in plasma and brain during scanning. However, there is concern that the vascular effects of ni...
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Injection drug use is an important factor in the spread of HIV infection, and strategies to enhance adherence to HIV therapeutics are critically important to controlling viral transmission and improving clinical outcomes. To this end, the authors sought (1) to enhance adherence to highly active antiretroviral therapy (HAART) among methadone-maintai...
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Methadone pharmacokinetics were determined in an open-label, within subject study in 16 methadone-maintained, non-HIV-infected subjects prior to and following administration of one lamivudine 150-mg/zidovudine 300-mg combination tablet to determine whether this antiretroviral therapy alters methadone serum concentrations. No significant differences...
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Pharmacological treatment of postpartum depression is frequently complicated by the mother's desire to breast-feed. Although breast milk levels of several selective serotonin reuptake inhibitors (SSRIs) have been reported to be relatively low, a critical question is whether SSRI exposure during nursing results in clinically significant blockade of...
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Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in...
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: For opiate-dependent injection drug users infected with HIV, methadone therapy may facilitate adherence to complex highly active antiretroviral therapy (HAART) regimens. Current HAART regimens include one or more nucleoside analogues. We investigated the effects of methadone on the pharmacokinetics of the tablet formulation of didanosine (ddI) an...
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Objectives: To examine the association of prescribed zidovudine (ZDV) during pregnancy with congenital anomalies in a population-based cohort. Methods: Medicaid claims were used to assess prescribed ZDV and children's major congenital anomalies in 1932 liveborn deliveries from 1993 to 1996 to HIV-infected women in the state of New York (NYS), U.S.A...
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Because clozapine may be prescribed to cocaine abusing patients with schizophrenia, we studied cocaine-clozapine interactions in a controlled setting. Eight male cocaine addicts underwent four oral challenges with ascending doses of clozapine (12.5, 25 and 50 mg) and placebo followed 2 h later by a 2-mg/kg dose of intranasal cocaine. Subjective and...
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We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On eac...
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Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hy...
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Tolerance to abused drugs may impact on patterns of abuse, and in the case of agonist therapies, may be beneficial in that it reduces the reward value of a given dose of abused drug. Cocaethylene, a psychoactive metabolite resulting from concurrent alcohol and cocaine consumption, was examined because of its use in human research studies of drug re...
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Disulfiram (Antabuse) is being used in outpatient clinical trials to determine its efficacy as a treatment for cocaine dependence. This inpatient randomized, double-blind, placebo-controlled, within-subjects study was conducted to determine whether disulfiram (placebo, 250 or 500 mg/day) alters responses to acute intranasal cocaine (placebo, 1 or 2...
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Large numbers of injection drug users (IDUs) are infected with HIV and receive both methadone and zidovudine (ZDV) therapy. Pharmacokinetic interactions between these agents may effect drug efficacy, toxicity, and compliance. To confirm and expand previous studies that identified a potential interaction between ZDV and methadone, we performed a wit...
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Simultaneous abuse of cocaine and alcohol is widespread and increasingly detected in patients seeking emergent care. This double-blind, randomized, within-subjects study used a paradigm more closely approximating practices of drug abusers to better understand the pathogenesis of cocaine-alcohol abuse. Subjects meeting DSM-IV criteria for cocaine de...
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Passive exposure to crack/cocaine and the associated clinical symptoms may present a significant health risk to very young infants and children. This study was designed to determine the incidence of cocaine exposure, presumed to be passive, in ill infants younger than 1 year of age, using a threshold of detection for cocaine and/or its major metabo...
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Simultaneous abuse of cocaine and alcohol is common. Alcohol decreases negative stimulant effects and potentiates "high." Disulfiram (Antabuse) is being studied in outpatient trials as a cocaine pharmacotherapy with the rationale that inability to modulate cocaine effects with alcohol may decrease cocaine use. We examined the interaction of disulfi...
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Low doses of neuroleptics are the standard for treating psychosis in elderly patients because of concern about inducing adverse effects. The authors found that fixed, low-dose neuroleptic treatment (0.15 mg/kg/day) for 10 days resulted in low perphenazine levels and low rates of acute response (25%) in elderly patients with primary psychotic illnes...
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Lewis and Fischer inbred rat strains differ in behavioral and biochemical responses to psychoactive drugs: Lewis rats show greater behavioral responses to psychoactive drugs than Fischer rats and they fail to show biochemical adaptations in the mesolimbic dopamine system after chronic drug exposure, in contrast to Fischer and outbred rats. This sug...
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The impact of endogenous dopamine on in vivo measurement of D2 receptors in humans was evaluated with single photon emission computerized tomography (SPECT), by comparing the binding potential (BP) of the selective D2 radiotracer [123I]IBZM before and after acute dopamine depletion. Dopamine depletion was achieved by administration of the tyrosine...
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This study evaluated the effect of an acute reduction in catecholamine synthesis produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to intranasal administration of 2 mg...
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This study determined whether the development of delayed ischemic sequelae due to cocaine use-after the return of arterial blood pressure (BP) and heart rate to near-baseline values-may be attributable to regional vasoconstriction which persists beyond the acute systemic hemodynamic response. Five cocaine-using volunteers received intravenous infus...