Daisy G. Thompson-Lake

Perceptions about e-cigarette safety may lead to e-smoking during pregnancy

Electronic cigarettes (e-cigarettes) are nicotine-delivery devices that are increasingly used, especially by young people. Because e-cigarettes lack many of the substances found in regular tobacco, they are often perceived as a safer smoking alternative, especially in high-risk situations such as pregnancy. However, studies suggest that it is exposure to nicotine that is most detrimental to prenatal development. The authors studied perceptions of tobacco and e-cigarette health risks using a multiple-choice survey. To study the perceived safety of e-cigarettes versus tobacco cigarettes, 184 modified Global Health Youth Surveys (WHO, http://www.who.int/tobacco/surveillance/gyts/en/ ) were completed electronically or on paper. Age range, smoking status, and perceptions about tobacco cigarettes and e-cigarettes were studied. The results verified that younger people use e-cigarettes more than older people. Tobacco cigarettes were perceived as more harmful than e-cigarettes to health in general, including lung cancer and pregnancy. Although more research is necessary, the authors postulate that the perception that e-cigarettes are safer during pregnancy may induce pregnant women to use these devices more freely. Given that nicotine is known to cause fetal harm, pregnant mothers who smoke e-cigarettes could cause even greater harm to the fetus because e-cigarettes are perceived as being safer than tobacco cigarettes. Until more data about the effects of nicotine during pregnancy are available, the authors advocate for labeling of e-cigarettes as potentially harmful, at least during pregnancy.

Characterizing white matter changes in cigarette smokers via diffusion tensor imaging.

BACKGROUND Tobacco use remains the most preventable cause of death; however, its effects on the brain, and particularly white matter, remain elusive. Previous diffusion tensor imaging (DTI) studies have failed to yield consistent findings, with some reporting elevated measures of fractional anisotropy (FA) and others reporting lowered FA. METHODS In our study, we sought to elucidate the effects of tobacco on white matter by using enhanced imaging acquisition parameters and multiple analysis methods, including tract-based spatial statistics (TBSS) with crossing fiber measures and probabilistic tractography. RESULTS Our TBSS results revealed that chronic cigarette smokers have decreased FA in corpus callosum and bilateral anterior internal capsule, as well as specific reduced anisotropy in the two major fiber directions in a crossing fiber model. Further, our tractography results indicated that smokers have decreased FA in tracts projecting to the frontal cortex from (1) nucleus accumbens, (2) habenula, and (3) motor cortex. We also observed that smokers have greater disruptions in those regions when they had recently smoked compared to when they abstained from smoking for 24h. Our results also support previous evidence showing hemispheric asymmetry, with greater damage to the left side compared to the right. CONCLUSIONS These findings provide more conclusive evidence of white matter disruptions caused by nicotine use. By better understanding the neural disruptions correlating with cigarette smoking we can elucidate the addictive course and explore targeted treatment regimens for nicotine dependence.

A comparison of impulsivity, depressive symptoms, lifetime stress and sensation seeking in healthy controls versus participants with cocaine or methamphetamine use disorders:

Previous research has focused on developing theories of addiction that may explain behavior in cocaine- and methamphetamine-dependent individuals. The primary goal of this report was to compare and contrast the prevalence of self-reported measures of impulsivity, depression, lifetime stress and sensation-seeking in healthy controls versus individuals with cocaine or methamphetamine use disorders. Twenty-nine individuals with cocaine use disorders and 31 individuals with methamphetamine use disorders were matched with 31 healthy control participants on several demographic variables. All participants were administered behavioral questionnaires including the Barrett Impulsiveness Scale (assessing impulsivity), Beck Depression Inventory II (assessing depression), Life Stressor Checklist–Revised (assessing lifetime stress) and the Impulsive Sensation Seeking Scale (assessing sensation-seeking). When compared to healthy controls, individuals with cocaine and methamphetamine use disorders had significantly higher levels of impulsivity and sensation-seeking. In addition, when compared to healthy controls, individuals with cocaine use disorders had significantly higher Beck Depression Inventory II scores, while individuals with methamphetamine use disorders had significantly higher Life Stressor Checklist–Revised scores. The results revealed that there were significantly higher levels of impulsivity, depression and sensation-seeking in cocaine users and significantly higher impulsivity, lifetime stress and sensation-seeking in methamphetamine users when compared to healthy controls.

Alterations in interhemispheric functional and anatomical connectivity are associated with tobacco smoking in humans

Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.e., cigarette smoking) is associated with altered interhemispheric connectivity. To that end, we examined resting state functional connectivity (RSFC) using magnetic resonance imaging (MRI) in short term tobacco deprived and smoking as usual tobacco smokers, and in non-smoker controls. Additionally, we compared diffusion tensor imaging (DTI) in the same subjects to study differences in white matter. The data reveal a significant increase in interhemispheric functional connectivity in sated tobacco smokers when compared to controls. This difference was larger in frontal regions, and was positively correlated with the average number of cigarettes smoked per day. In addition, we found a negative correlation between the number of DTI streamlines in the genual corpus callosum and the number of cigarettes smoked per day. Taken together, our results implicate changes in interhemispheric functional and anatomical connectivity in current cigarette smokers.

Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder.

Background: Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder. Methods: The current report describes results from a double-blind, placebo-controlled study in which participants (n=14–17/group) were randomized to huperzine A (0.4 or 0.8mg) or placebo. Participants received randomized infusions of cocaine (0 and 40mg, IV) on days 1 and 9. On day 10, participants received noncontingent, randomized infusions of cocaine (0 and 20mg, IV) before making 5 choices to receive additional infusions. Results: Huperzine A was safe and well-tolerated and compared with placebo, treatment with huperzine A did not cause significant changes in any cocaine pharmacokinetic parameters (all P>.05). Time-course and peak effects analyses show that treatment with 0.4mg of huperzine A significantly attenuated cocaine-induced increases of “Any Drug Effect,” “High,” “Stimulated,” “Willing to Pay,” and “Bad Effects” (all P>.05). Conclusions: The current study represents a significant contribution to the addiction field since it serves as the first published report on the safety and potential efficacy of huperzine A as a treatment for cocaine use disorder.

Choosing Money over Drugs: The Neural Underpinnings of Difficult Choice in Chronic Cocaine Users

Addiction is considered a disorder that drives individuals to choose drugs at the expense of healthier alternatives. However, chronic cocaine users (CCUs) who meet addiction criteria retain the ability to choose money in the presence of the opportunity to choose cocaine. The neural mechanisms that differentiate CCUs from non-cocaine using controls (Controls) while executing these preferred choices remain unknown. Thus, therapeutic strategies aimed at shifting preferences towards healthier alternatives remain somewhat uninformed. This study used BOLD neuroimaging to examine brain activity as fifty CCUs and Controls performed single- and cross-commodity intertemporal choice tasks for money and/or cocaine. Behavioral analyses revealed preferences for each commodity type. Imaging analyses revealed the brain activity that differentiated CCUs from Controls while choosing money over cocaine. We observed that CCUs devalued future commodities more than Controls. Choices for money as opposed to cocaine correlated with greater activity in dorsal striatum of CCUs, compared to Controls. In addition, choices for future money as opposed to immediate cocaine engaged the left dorsolateral prefrontal cortex (DLPFC) of CCUs more than Controls. These data suggest that the ability of CCUs to execute choices away from cocaine relies on activity in the dorsal striatum and left DLPFC.

Cocaine-dependent adults and recreational cocaine users are more likely than controls to choose immediate unsafe sex over delayed safer sex.

Cocaine users have a higher incidence of risky sexual behavior and HIV infection than nonusers. Our aim was to measure whether safer sex discount rates-a measure of the likelihood of having immediate unprotected sex versus waiting to have safer sex-differed between controls and cocaine users of varying severity. Of the 162 individuals included in the primary data analyses, 69 met the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria for cocaine dependence, 29 were recreational cocaine users who did not meet the dependence criteria, and 64 were controls. Participants completed the Sexual Discounting Task, which measures a persons likelihood of using a condom when one is immediately available and how that likelihood decreases as a function of delay to condom availability with regard to 4 images chosen by the participants of hypothetical sexual partners differing in perceived desirability and likelihood of having a sexually transmitted infection. When a condom was immediately available, the stated likelihood of condom use sometimes differed between cocaine users and controls, which depended on the image condition. Even after controlling for rates of condom use when one is immediately available, the cocaine-dependent and recreational users groups were more sensitive to delay to condom availability than controls. Safer sex discount rates were also related to intelligence scores. The Sexual Discounting Task identifies delay as a key variable that impacts the likelihood of using a condom among these groups and suggests that HIV prevention efforts may be differentially effective based on an individuals safer sex discount rate. (PsycINFO Database Record

Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial.

BACKGROUND Serotonin and norepinephrine reuptake inhibitors are effective first-line agents for the treatment of posttraumatic stress disorder (PTSD), but treatment is associated with a range of side effects that limit treatment adherence. Prazosin, an α1-noradrenergic antagonist with a half-life of roughly 2-3 hours, has shown promise in the treatment of sleep disturbance and nightmares. Doxazosin extended release (XL) is also an α1-noradrenergic antagonist but with a half-life of approximately 15-19 hours. METHODS We conducted a double-blind, placebo-controlled, within-subjects trial to characterize the impact of doxazosin XL on PTSD symptoms. Participants (N = 8) were diagnosed using DSM-IV criteria. They completed the study twice, once during treatment with doxazosin XL and once during treatment with matched placebo, with a 2-week washout separating the 2 episodes. Doxazosin XL was titrated from 4 mg/d to 16 mg/d over 12 days. After 4 days of treatment at 16 mg/d or the equivalent number of placebo capsules, PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS17) and the PTSD Checklist-Military version (PCL-M). Repeated measures analysis of variance were used to evaluate effects of treatment, time, and treatment × time. This study was run from November 20, 2013, to June 31, 2014. RESULTS Doxazosin XL treatment was associated with a nonsignificant treatment × time reduction in ratings on the CAPS hyperarousal subscale (P < .10) (but not on the CAPS Total score) and with significant treatment × time reductions in PCL-M ratings (P = .002). CONCLUSIONS Doxazosin XL may be an effective alternative to prazosin for the treatment of some PTSD symptoms. TRIAL REGISTRATION ClinicalTrials.gov Identifier:NCT02308202.

Anterior cingulum white matter is altered in tobacco smokers.

BACKGROUND AND OBJECTIVES The anterior cingulate cortex (ACC) is hypothesized to be involved in decision making and emotion regulation. Previous observations of drug dependent individuals indicate that substance dependence may be associated with cingulum white matter abnormalities. The present study evaluated cingulum white matter in cigarette smokers. METHODS Diffusion tensor imaging (DTI) in adult tobacco smokers and healthy non-smoker controls (total N = 70) was performed in a 3T Siemens Trio MRI scanner. RESULTS Analyses of DTI tractography of the cingulum in tobacco-smoking individuals and controls indicated that tobacco abusers have significantly reduced fractional anisotropy (FA) in the right cingulum. In addition, FA in the left cingulum white matter was negatively associated with the number of cigarettes smoked per day and the Fagerstrom test for nicotine dependence, a self-report measure of tobacco dependence severity. CONCLUSIONS The white matter of the cingulum is altered in a non-symmetrical way in tobacco smokers. An inverse relationship between FA and reported number of cigarettes per day was observed. Previous studies have also noted altered neural connectivity in cigarette smokers using similar methods. Similar white matter differences in the cingulum have been observed in methamphetamine dependent individuals and patients with dementia, which suggests that the cingulum may be altered by mechanisms not specific to tobacco exposure. SCIENTIFIC SIGNIFICANCE By better understanding the effects of tobacco abuse on the brain, we hope to gain insight into how drug dependence influences the neurological foundations of behavior.

Treadmill exercise improves fitness and reduces craving and use of cocaine in individuals with concurrent cocaine and tobacco-use disorder

Exercise may be a useful treatment for substance use disorders. Participants (N=24) included treatment-seeking individuals with concurrent cocaine and tobacco-use disorder (cigarette smokers). Participants were randomized to either running or walking (30min per session, 3 times per week) or sitting (control condition) for 4 consecutive weeks. Several metrics indicated significant differences among runners, walkers, and sitters during sessions, including mean distance covered and calories burned. In addition, remote physiological monitoring showed that the groups differed significantly according to mean maximum heart rate (HR), respiration, and locomotor activity. Across the 4-week study, exercise improved fitness measures including significantly decreasing resting HR. Though not statistically significant, exercise improved abstinence from cocaine and increased self-reports of no cocaine use in last 24h. In general, reductions in tobacco use and craving were not as robust. To our knowledge, this is the first study to evaluate the effects of a multi-week exercise program in individuals with concurrent cocaine and tobacco-use disorder. The data clearly show significant improvements in basic fitness measures and several indices reveal that exercise improved both self-report and biochemically verified reports of cocaine abstinence. Taken together, the data from this study provide preliminary evidence for the efficacy of exercise for improving fitness and reducing cocaine use.