Mustafa al’Absi

Khat use and neurobehavioral functions: Suggestions for future studies

Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures.

Sex Differences in Hormonal Responses to Stress and Smoking Relapse: A Prospective Examination

INTRODUCTION Dysregulation in the hypothalamic-pituitary-adrenal axis has been shown to be associated with smoking relapse. No study has directly examined the role of sex differences in this relationship. METHODS Nicotine dependent men (n = 52) and women (n = 46) interested in cessation completed 2 laboratory stress sessions during ad libitum smoking and after 48 hr of abstinence. The laboratory session included baseline, stress, and recovery periods. Blood and saliva samples were collected at the end of each period for the measurement of cortisol and adrenocorticotropic hormone. Self-report measures of craving and withdrawal symptoms were also collected. Participants attended 4 weekly follow-up sessions for counseling where they provided biological samples and self-report measures including smoking status. Relapse was defined by smoking cigarettes for 7 consecutive days post-cessation. RESULTS Results showed that 60 participants relapsed during the 4-week period. Cox regression models from the abstinence session showed that cortisol levels regardless of source were predictive of relapse but the direction of prediction was sex dependent (Sex × Hormone, all ps < .05). Follow-up analyses further revealed that lower cortisol levels predicted relapse in men whereas greater cortisol levels predicted relapse in women (ps < .05). Enhanced craving predicted early smoking relapse in men but not in women (ps < .05). Data from the ad libitum session showed no differences in predicting relapse. CONCLUSION These findings highlight that sex differences in the hormonal response to stress and subjective craving during nicotine withdrawal are critical predictors of risk for understanding early relapse.

Gender differences in patterns and correlates of khat and tobacco use.

INTRODUCTION Although research suggests gender differences in patterns of tobacco use, whether gender moderates concurrent use of tobacco and other substances remains unclear. In some parts of Africa and the Middle East, tobacco is often accompanied with khat (Catha edulis), a widely used substance in these regions. The concurrent use of tobacco and khat may represent a public health burden spreading to other countries in Europe and North America. METHOD A total of 189 participants (69 women) khat users and smokers in Yemen were asked to complete questionnaires that focused on patterns of khat and tobacco use. Chi-square tests, analyses of variance, and correlational analyses were conducted. RESULTS Reported frequency and intensity of khat and tobacco use were greater among men than in women. Also, reported number of cigarettes smoked during a khat session was higher among men than among women, whereas frequency of waterpipe use during the session was greater among women than among men. Smoking status (daily or occasional) was positively associated with khat use in women only. Age of onset of khat use was inversely related to the number of cigarettes smoked during a khat session and with intensity of khat chewing. The majority of participants reported that they had thought about and have attempted to quit khat and tobacco use. CONCLUSIONS The results provide evidence for gender differences in patterns of concurrent use of tobacco and khat. Identifying determinants of tobacco and khat use may be useful in reducing the risk of their negative health outcomes.

Peptide YY and ghrelin predict craving and risk for relapse in abstinent smokers

Appetite hormones are directly involved in regulating satiety, energy expenditure, and food intake, and accumulating evidence suggests their involvement in regulating reward and craving for drugs. This study investigated the ability of peptide YY (PYY) and ghrelin during the initial 24-48 h of a smoking cessation attempt to predict smoking relapse at 4 weeks. Multiple regression analysis indicated that increased PYY was associated with decreased reported craving and increased positive affect. Cox proportional hazard models showed that higher ghrelin levels predicted increased risk of smoking relapse (hazard ratio=2.06, 95% CI=1.30-3.27). These results indicate that circulating PYY may have buffering effects during the early stages of cessation while ghrelin may confer increased risk of smoking relapse. Further investigation of the links between these hormones and nicotine dependence is warranted.

Effect of Stress and Bupropion on Craving, Withdrawal Symptoms, and Mood in Smokers

INTRODUCTION Studies suggest that in smokers attempting to quit smoking, the occurrence of stressful events is associated with smoking relapse. The purpose of this study was to determine the effect of bupropion (an agent known to increase smoking cessation rates) on the craving, withdrawal, and mood response to stressful tasks administered in a laboratory setting. METHODS Response to three tasks (a speech, math, and cold pressor task) was measured in 65 smokers during ad libitum smoking. Smokers were then randomized to either bupropion or placebo. Fourteen days after starting medication, 43 subjects (28 receiving bupropion and 15 receiving placebo) quit smoking and laboratory procedures were repeated on the third day of abstinence. RESULTS Prior to cessation, stressors presented in a laboratory setting increased craving, nicotine withdrawal symptoms, and subjective distress but decreased positive affect. Thirty minutes of relaxation after the stressors did not result in these measures returning to prestress levels. During the nicotine withdrawal period, stress-induced responses were generally smaller than during the precessation period. Bupropion (relative to placebo) reduced overall levels of craving and withdrawal symptoms but did not have significant effects on response to stress during the nicotine withdrawal period. CONCLUSIONS This study demonstrates that stress results in sustained increases in craving and withdrawal symptoms and changes in mood symptoms and that bupropion affects overall levels of these symptoms. Further research is needed to determine if modifying response to stress is predictive of an effective treatment for facilitating smoking cessation.

Changes in circulating leptin levels during acute stress and associations with craving in abstinent smokers: A preliminary investigation

Recent research suggests a role for the appetite hormone leptin in cigarette smoking. This study examined patterns of change in leptin in response to stress and associations with craving during the initial phase of a quit attempt. Thirty-six smokers (average age±SEM, 33.4±2.4) interested in smoking cessation set a quit day and were required to be abstinent for 24h. After, they completed a laboratory session including public speaking and cognitive challenges, and attended 4 weekly post-cessation assessments. Blood samples and self-report measures were collected throughout the laboratory session. The results indicated that leptin levels significantly increased following exposure to acute stress. We also found positive correlations between leptin and craving for cigarettes. No differences were observed in leptin levels between smokers who maintained abstinence for 4 weeks and those who relapsed during this period. These findings suggest that leptin levels may change in response to stress and that leptin could be a useful marker of craving for smoking.

Caffeine, extended stress, and blood pressure in borderline hypertensive men

Caffeine increases blood pressure (BP), and its pressor effects are larger in borderline hypertensive (BH) men than in controls. This article extends findings of larger caffeine effects on BP at rest and to brief mental stress in BH to a new analysis of caffeine and prolonged mental stress in BH. In a double-blind, crossover study, 24 male BH (140/90 mmHg < BP < 160/95 mmHg) and 23 normotensive controls who were habitual caffeine consumers (NT; BP < 135/85 mmHg; negative parental history) worked on alternating mental stressors for 35 min after placebo or caffeine (3.3 mg/kg). Caffeine raised systolic blood pressure (SBP) and diastolic blood pressure (DBP) alone and during the extended tasks (all ps < .00001/.00001). BH had larger SBP and DBP increases over all postcaffeine periods (ps < .04/04) and larger DBP rises to the extended tasks after caffeine (p = .007). These combined effects led to undesirably high BPs (> 140/82 mmHg) relative to controls (< 130/75) during the 100 min after caffeine intake. Caffeine taken by BH at times of extended behavioral stress may elevate BP to a clinically meaningful degree.

Subjective response to nicotine by menstrual phase

INTRODUCTION The luteal menstrual phase might be a favorable time for smoking cessation when non-nicotine interventions (e.g. counseling, bupropion) are used, whereas the follicular menstrual phase appears favorable when nicotine interventions are used. Thus, there may be an interaction between menstrual phase and response to nicotine. We sought to examine the role of menstrual phase on response to nicotine during acute smoking abstinence. METHODS In this controlled cross-over trial, women completed two identical experimental sessions (follicular [F] vs. luteal [L] phase) after four days of biochemically-verified smoking abstinence. During the sessions, nicotine nasal spray was administered, and participants provided a series of subjective assessments. RESULTS Participants (n=140) were 29.7±6.6years old and smoked 12.6±5.8 cigarettes per day. Compared to the F phase, the L phase was associated with a greater increase in stimulation (7.2±2.2 vs. 14.4±2.3, p=0.01, respectively) and greater decrease in urge to smoke (-13.6±2.3 vs. -21.1±2.5, p=0.02, respectively) after the first dose of nicotine. No other significant differences were observed. CONCLUSIONS Out of 13 total measures examined at two different time points, we observed only two significant menstrual phase differences in the subjective response to nicotine. Therefore, these data do not provide strong evidence for a menstrual phase difference in the subjective response to nicotine. Additional research is needed to confirm this relationship and explore how non-nicotine smoking reinforcements (such as sensory sensations) may vary by menstrual phase.

Changes in circulating peptide YY and ghrelin are associated with early smoking relapse

Ghrelin and peptide YY (PYY) during ad libitum smoking have been associated with decreased reported craving (ghrelin) and increased positive affect (PYY), and higher baseline ghrelin levels predicted subsequent increased risk of smoking relapse. The current study assessed PYY and ghrelin during ad libitum smoking and again after the initial 48h of a smoking cessation attempt. The data compared smokers who abstained for 28days (n=37), smokers who relapsed (n=54), and nonsmokers (n=37). Plasma samples and subjective measures assessing craving and mood were collected at the beginning of each session. Results showed that relapsers experienced greater levels of distress (ps <0.01). While nonsmokers and abstainers showed no change in ghrelin across the initial 48h, relapsers declined (p <0.01). With PYY, relapsers increased (p <0.05) across the early abstinent phase. PYY and ghrelin may be useful predictors of relapse, specifically in reference to early withdrawal.

Khat use and appetite: An overview and comparison of amphetamine, khat and cathinone

ETHNOPHARMACOLOGICAL RELEVANCE To understand the role of khat (Catha edulis) use on the aberrations in appetite and weight which are common comorbidities for khat and other amphetamine users. MATERIALS AND METHODS We provide a comprehensive overview and conceptual summary of the historical cultural use of khat as a natural stimulant and describe the similarities and differences between cathinone (the main psychoactive constituent of khat) and amphetamine highlighting the limited literature on the neurophysiology of appetite and subsequent weight effects of khat. RESULTS Animal and some human studies indicate that khat produces appetite suppression, although little is known about mechanisms of this effect. Both direct and indirect effects of khat stem from multiple factors including behavioral, chemical and neurophysiological effects on appetite and metabolism. Classic and newly identified appetite hormones have not been explored sufficiently in the study of appetite and khat use. Unique methodological challenges and opportunities are encountered when examining effects of khat and cathinone including khat-specific medical comorbidities, unique route of administration, differential patterns of behavioral effects relative to amphetamines and the nascent state of our understanding of the neurobiology of this drug. CONCLUSION A considerable amount of work remains in the study of the appetite effects of khat chewing and outline a program of research that could inform our understanding of this natural amphetamine׳s appetite effects and help prepare health care workers for the unique health effects of this drug.