Jin H. Yoon

EFFECTS OF D-CYCLOSERINE ON CUE-INDUCED CRAVING AND CIGARETTE SMOKING AMONG CONCURRENT COCAINE- AND NICOTINE-DEPENDENT VOLUNTEERS

Rates of cigarette smoking are 3- to 4-fold greater among those with cocaine-dependence, and compared to non-users, cocaine users are at greater risk of incurring smoking-related negative health effects and death. The current study examined D-cycloserines (0 or 50mg once weekly) effects on 1) extinction of cue-induced craving for cigarettes, 2) cigarette smoking in conjunction with cognitive-behavioral therapy, and 3) safety and tolerability in cocaine-dependent smokers. This was a double-blind, placebo-controlled, between groups, outpatient study. Participants (N=29) were concurrent cocaine- and nicotine-dependent volunteers seeking treatment for their cigarette smoking. Study visits were 3 times per week for 4 consecutive weeks. At each visit, participants received cognitive-behavioral therapy for smoking, were exposed to smoking cues. A subset of participants (N=22) returned for 6-month follow-up visits. While craving decreased, no significant effects of D-cycloserine treatment were observed. Likewise, significant decreases in smoking were observed at study days 6 (p<0.002) and 12 (p<0.0001) relative to baseline, although no participants achieved complete abstinence. However, there was no effect of D-cycloserine on cigarette smoking during treatment or at 6-mos follow-up. The treatment was safe and tolerable, with nearly 90% of treatment sessions attended based on an intent-to-treat analysis. While no effects of D-cycloserine on craving or smoking were observed in the current study, the results do suggest that smoking treatment is well accepted and may be effective for cocaine-dependent individuals.

Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition

ObjectiveA substantial body of evidence implicates TNF-alpha (TNFα) and TNFα-related signaling pathways in the pathophysiology of schizophrenia. The current study examined the relationship between TNFα serum levels and both psychopathological as well as cognitive symptoms in schizophrenia.Materials and methodsSerum TNFα levels were assessed in 89 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum TNFα levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA).ResultsTNFα levels were significantly lower in patients with chronic schizophrenia relative to healthy control subjects (p < 0.01). Correlation analysis revealed a significant negative correlation between the TNFα levels and the PANSS total score (p < 0.01). Additionally, TNFα levels were significantly negatively correlated with scores on general psychopathology (p < 0.01), positive (p < 0.05) and cognitive subscales (p < 0.05). Stepwise multiple regression analysis identified TNFα levels as a significant predictor of scores on the general psychopathology subscale of the PANSS.ConclusionThe significant relations observed in the current study between TNFα and the PANSS and its subscales suggest that immune disturbance may be involved in the psychopathology and cognitive deficits of schizophrenia.

Evaluation of the effects of rivastigmine on cigarette smoking by methamphetamine-dependent volunteers

Compared to smokers alone, smokers with co-morbid substance use disorders are at greater risk of suffering from smoking-related death. Despite this, relatively few studies have examined smoking cessation treatments for those with stimulant dependence. In the current study, we sought to evaluate the effects produced by short-term exposure to the cholinesterase inhibitor rivastigmine (0, 3 or 6 mg) on cigarette smoking in non-treatment-seeking, methamphetamine-dependent volunteers. This was a double-blind, placebo-controlled, crossover study that took place over 9 days. The data indicate that rivastigmine treatment did not alter Fagerström Test for Nicotine Dependence scores, carbon monoxide readings, or cigarettes smoked per day, but a trend toward reduced urges to smoke (p<0.09) was detected during treatment with rivastigmine 3mg. These data, while preliminary, indicate that cholinesterase inhibitors warrant consideration as treatments for nicotine dependence, including use in stimulant-dependent individuals who exhibit significantly higher rates of smoking than the general population.

Smoking, MATRICS consensus cognitive battery and P50 sensory gating in a Han Chinese population

BACKGROUND The effects of smoking on cognitive performance have long been studied, with mixed results. P50 sensory gating has been used as endophenotype for studying nicotinic systems genetics, and P50 gating deficits have been reported to be a sensitive biomarker for cognitive impairment in schizophrenia. This study examined the inter-relationship between P50 suppression, cognitive function, and smoking in a healthy Han Chinese population, which has not been reported before. METHODS We recruited 82 healthy male subjects, including 48 smokers and 34 non-smokers who were matched for age and education. The authors measured P50 sensory gating and administered the Chinese-language version of the MATRICS consensus cognitive battery (MCCB) and Stroop tests. RESULTS The results showed that the smokers scored lower than nonsmokers on the MCCB brief visuospatial memory test (BVMT) index and the STROOP test. Furthermore, the MCCB total score was negatively associated with number of cigarettes smoked per day in the smoker group. However, P50 sensory gating was not associated with either smoking status or any cognitive performance. CONCLUSIONS Our results show that smoking is associated with cognitive impairment, but not with P50 sensory gating.

Opioid Analgesics and Nicotine: More Than Blowing Smoke

ABSTRACT Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs—including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

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.

Virtual Reality Cue Reactivity Assessment A Comparison of Treatment- vs. Nontreatment-Seeking Smokers

Objectives: The cue-reactivity paradigm has been widely used to assess craving among cigarette smokers. Seeking to replicate and expand on previous virtual reality (VR) nicotine cue-reactivity research on nontreatment-seeking smokers, the current study compared subjective reports of craving for cigarettes when exposed to smoking (proximal and contextual) and neutral cues using VR in treatment-seeking and nontreatment-seeking cigarette smokers. Methods: Data from two previously published studies in nontreatment seekers from our group (Bordnick et al., 2004; Bordnick, Graap, Copp, Brooks, & Ferrer, 2005) were compared to results with 82 newly enrolled treatment-seeking smokers. Results: Overall, VR cues produced similar levels of craving for both treatment seekers and nontreatment seekers across the different cue environments. Specifically, craving was greater for both groups in smoking environments (paraphernalia and party) than those in the neutral environments. Conclusions: These findings provide strong evidence that VR is a useful tool that may be used by social workers and other clinical professionals to present smoking (proximal and contextual) cues for assessment and treatment and illustrate the utility of standardizing VR procedures to compare craving between different groups.

The impact of self-reported life stress on current impulsivity in cocaine dependent adults.

Current cocaine treatments may be enhanced with a better understanding of the underlying mechanisms that contribute to the onset and maintenance of the disease, such as life stress and impulsivity. Life stress and impulsivity have previously been studied independently as contributors to drug use, and the current study expands upon past research by examining how these factors interact with one another. The aim of the current study was to evaluate the role of life stress in predicting impulsivity in a non-treatment seeking cocaine-dependent sample (N = 112). Analyses revealed that trait impulsivity (as measured by the Barratt Impulsiveness Scale) was associated with education (r = −3.09, p < 0.01), as those who had higher educational attainment also reported lower rates of trait impulsivity. In addition, those over the age of 30 demonstrated lower impulsivity in decision-making (as measured by delay discounting) than those under 30 (t = 2.21, p = 0.03). Overall exposure to life stress was not significantly correlated to either aspect of impulsivity. However several specific life stressors were significantly related to greater impulsivity including having been put up for adoption or in foster care (t = −2.96, p < 0.01), and having a child taken away against their will (t = −2.68, p = 0.01). These findings suggest that age and education relate to impulsivity; and that while an overall compilation of life stress scores was not related to impulsivity, specific types of stress related to either being taken away from a parent or having a child taken away were. Future studies should assess these constructs longitudinally to restrict response bias.

Low dose, short-term rivastigmine administration does not affect neurocognition in methamphetamine dependent individuals

Neurocognitive impairment is a well-documented consequence of methamphetamine addiction. Not surprising, methamphetamine-associated neurocognitive impairment has been identified as an important target of treatment. Thus, this study sought to determine whether rivastigmine, an acetylcholinesterase inhibitor and cognition enhancing agent, could improve neurocognitive performance in a sample of long-term, high-dose methamphetamine addicts who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a daily dose 0, 3, or 6 mg of rivastigmine, administered over six consecutive days, would enhance performance on measures of attention/information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that rivastigmine did not alter neurocognition in this cohort. There are a number of factors that may have mitigated the effects of rivastigmine in this particular study, including especially the short-term, low-dose treatment regimen utilized. The negative findings notwithstanding, the study serves as a springboard for future investigations that will examine whether other medications can alter neurocognition in methamphetamine dependent study participants.

Remote physiological monitoring of acute cocaine exposure

Abstract Cocaine exposure results in predictable cardiovascular changes. The current study evaluated the utility of BioHarness for assessing cardiovascular and respiratory changes following cocaine exposure (0 and 40 mg, IV) under controlled laboratory conditions. Participants (n = 28) included non-treatment-seeking, cocaine-dependent volunteers. Results showed that BioHarness was able to detect a significant increase in heart rate following cocaine exposure, in comparison to placebo, (p < 0.0001). Additionally, heart rate values obtained using BioHarness were significantly correlated with those obtained from standard hospital equipment (p < 0.001). Significantly greater peak effects in breathing rate were also observed (p = 0.04). BioHarness is a promising remote physiological monitoring device that can accurately assess exposure to cocaine in the laboratory and may provide additional advantages when compared to standard hospital equipment.