World addiction medicine reports: formation of the International Society of Addiction Medicine Global Expert Network (ISAM-GEN) and its global surveys.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Impact of Early-Life Adversity on Cannabis Use: Exploring the Mediating and Moderating Effects of Chronic Pain.

Background: Although research suggests that early-life adversity (ELA) and cannabis use are linked, researchers have not established factors that mediate or modify this relationship. Identifying such factors could help in developing targeted interventions. We explored chronic pain as a potential mediator or moderator of this relationship. Methods: Using an online study, we collected cross-sectional data about ELA, cannabis use, and chronic pain to test whether ELA (adverse childhood experiences total score) is associated with cannabis use, and to examine pain as a potential mediator or moderator. Cannabis use was examined two ways: times used per day, and categorized as non-, some, or regular use. Chronic pain was measured as present/absent and as the number of painful body locations (0-8). Analyses used linear and multinomial regression. Results: ELA, chronic pain, and cannabis use were common among respondents. ELA was strongly associated with both measures of cannabis use. The number of painful body locations modestly mediated the association of ELA with cannabis use, reducing the magnitude of regression coefficients by about 1/7. The number of painful body locations modified the association between ELA and cannabis use (p≤0.006), while chronic pain presence/absence (a less-informative measure) had only a nonsignificant modification effect (p≥0.10). When either ELA or pain was high, the other was not associated with cannabis use; when either ELA or pain was low, more painful locations or higher ELA (respectively) was associated with more intense cannabis use. Conclusion: These exploratory findings suggest the importance of ELA and chronic pain as factors contributing to cannabis use, and of accounting for these factors in developing treatment and prevention strategies addressing cannabis use.

Biobehavioral and affective stress responses during nicotine withdrawal: Influence of regular cannabis co-use.

BACKGROUND: Co-use of cannabis is increasing in nicotine users and presents additional challenges in addressing nicotine dependence. This study examined the links between regular co-use of cannabis and nicotine with biobehavioral and affective changes in response to stress during nicotine withdrawal and ad libitum use. METHODS: Participants (N = 79) who regularly used nicotine-only, cannabis-only, both substances, or neither substance were invited to attend two laboratory stress assessment sessions. For nicotine users, one session occurred during ad libitum nicotine use and one occurred after abstinence from nicotine. During the stress sessions, participants provided saliva samples for cortisol assay and completed measures of subjective states. Cardiovascular measures were collected during resting baseline, exposure to acute stressors, and a recovery rest period. RESULTS: Nicotine-only users had higher average cortisol levels in the second lab session (nicotine withdrawal) relative to the first lab session (ad libitum nicotine use). Compared to nicotine non-users, nicotine users reported less positive affect and exhibited attenuated cortisol and systolic blood pressure (BP) stress responses. Cannabis users exhibited exaggerated diastolic BP responses to stress compared to cannabis non-users, and co-users of nicotine and cannabis had higher levels of cannabis craving than cannabis-only users (p < .01). CONCLUSIONS: This study partially replicated earlier findings on the effects of chronic nicotine use and provided novel results regarding the influence of cannabis co-use on physiological and affective responses to stress in nicotine users during nicotine withdrawal.

Barriers and facilitators of colorectal cancer screening among East African men in Minnesota: a qualitative investigation.

Objective: This study aimed to explore barriers and facilitators to colorectal cancer (CRC) screening among East African men in Minnesota.Design: Six focus groups were conducted in Minneapolis and St. Paul, MN, USA. Participants were asked to describe individual and structural barriers to CRC screening, and discuss strategies that would address individual and structural barriers to screening. Audio-recorded conversations were transcribed verbatim and translated to English. The transcriptions were analyzed using a thematic analysis. Major themes that emerged on individual barriers were lack of knowledge, fear, and privacy.Results: Themes that emerged on structural barriers were distrust in the medical system, lack of health care coverage, and access to the health care system. Education, client reminders, mass media, increased clarity in communication with the provider and translator, and increased access to health care were frequently mentioned strategies to increase CRC screening in the East African community. Participants expressed favorable views toward the concept of patient navigation.Conclusion: Our findings indicate the need to develop culturally appropriate, multi-faced, intervention programs that are aimed at eliminating personal, cultural, and structural barriers.

Early life adversity and substance use: The mediating role of mood and the moderating role of impulsivity.

INTRODUCTION: Early life adversity (ELA) is a risk factor for substance use and misuse, and multiple factors mediate and moderate this association. We examined whether moods mediate the relationships between ELA and nicotine use, cannabis use, and co-use, and whether these mediation effects varied as a function of delay discounting. METHODS: A total of 2555 adults completed a delay discounting task and responded to questions related to demographics, ELA, mood, and substance use. Data were analyzed using Pearson correlations and moderated mediation using Hayes' PROCESS macro (V3.4, Model 15). RESULTS: ELA was positively associated with cannabis use, nicotine use, co-use of both substances, depressed and stressed moods, and it was negatively associated with positive mood. While cannabis use was associated negatively with stressed and depressed moods and positively with positive mood, nicotine use was associated negatively with positive mood. Moderated mediation analyses indicated that positive mood mediated the relationship between ELA and cannabis use for those with average and above average delay discounting. Positive mood also mediated the relationship between ELA and co-use among those with above average delay discounting. CONCLUSION: The results suggest that ELA's associations with cannabis use and cannabis-nicotine co-use may be partially attributable to ELA's effects on positive mood among those who are predisposed to moderately to highly impulsive decision making.

Acculturation Style Is Associated with Stress and Tobacco Use among East African Immigrants.

While tobacco use rates are relatively high among East African immigrants in the U.S., factors contributing to this high rate are largely unknown. Acculturation is associated with stress and substance use. Whether acculturation styles are related to stress and current tobacco use has not been tested among this population. We conducted a cross-sectional study that included 376 East African adults who provided information on demographic background, acculturation style, acculturative stress, depressive symptoms, and tobacco use. Multivariate analysis indicated that individuals who were distant to both the culture of the host country and the culture of origin (marginalization style) had greater levels of acculturative stress than those who adopted both cultures (integration style; p < .001). Marginalized people were four to eight times and assimilated people were three to four times more likely than integration people to be a current tobacco user (p < .04). This relationship did not change after controlling for demographic information and stress. In this study, acculturation style was associated with perceived stress and current tobacco use among East African immigrants. Research focused on characterizing integrated individuals may guide efforts to develop culturally-relevant strategies to reduce tobacco-related disparities among East African individuals.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

INTRODUCTION: The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. AIMS AND METHODS: This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. RESULTS: CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). CONCLUSIONS: Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. IMPLICATIONS: The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

Smoking abstinence and cessation-related outcomes one month after an immediate versus gradual reduction in nicotine content of cigarettes.

The United States Food and Drug Administration has the authority to reduce the nicotine content in cigarettes to minimal or non-addictive levels and could do so immediately or gradually over time. A large clinical trial compared the two approaches. This secondary analysis assesses abstinence and cessation-related outcomes one month after the trial concluded, when participants no longer had access to very low nicotine content (VLNC) research cigarettes. Smokers not interested in quitting (N = 1250) were recruited for the parent trial from 2014 to 2016 across 10 sites throughout the US and randomized to a 20-week study period during which they immediately switched to VLNC cigarettes, gradually transitioned to VLNC cigarettes with five monthly dose reductions, or smoked normal nicotine research cigarettes (control). At the one-month follow-up, both immediate and gradual reduction resulted in greater mean cigarette-free days (4.7 and 4.6 respectively) than the control group (3.2, both p < .05). Immediate reduction resulted in fewer mean cigarettes per day (CPD = 10.3) and lower Fagerström Test for Cigarette Dependence (FTCD = 3.7) than the gradual (CPD = 11.7, p = .001; FTCD = 3.8, p = .039) and control (CPD = 13.5, p < .001; FTCD = 4.0, p < .001) groups. Compared to controls, gradual reduction resulted in reduced CPD (p = .012) but not FTCD (p = .13). Differences in CO-verified 7-day point-prevalence abstinence were not significant. Findings demonstrate that switching to VLNC cigarettes resulted in reduced smoking and nicotine dependence severity that was sustained for at least a month after the VLNC trial period in smokers who were not interested in cessation. The greatest harm reduction endpoints were observed in those who immediately transitioned to VLNC cigarettes.

Uncertainty and psychological distress during COVID-19: What about protective factors?

The present study examined the relationship between perceived uncertainty and depression/ anxiety symptoms during the COVID-19 pandemic and it tested the moderating roles of resilience and perceived social support in this relationship. A cross-sectional study was conducted between March 31st and May 15th, 2020, using an online, multi-language, international survey built within Qualtrics. We collected data on sociodemographic features, perceived uncertainty, perceived social support, depression and anxiety symptoms, and resilience. A moderation model was tested using model 2 of Hayes' PROCESS macro for SPSS. The study included 3786 respondents from 94 different countries, 47.7% of whom reported residence in the United States of America. Results demonstrated that higher perceived uncertainty was associated with more symptoms of depression and anxiety. Higher resilience levels and higher perceived social support were associated with fewer depression and anxiety symptoms. The moderation hypotheses were supported; the relationship between uncertainty and symptoms of depression and anxiety decreased as levels of resilience increased and as perceived social support increased. The results suggest that resilience and social support could be helpful targets to reduce the negative effects of uncertainty on depression and anxiety symptoms. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03244-2.

Circulating ghrelin changes as a biomarker of the stress response and craving in abstinent smokers.

RATIONALE: There has been growing interest in the role of ghrelin in stress and addiction. Ghrelin regulates central reward mechanisms by mediating the mesolimbic dopaminergic system. Stress also induces neurophysiological activations related to drug reward. However, the extent to which psychosocial stress is associated with changes in ghrelin levels has not been tested in individuals with nicotine dependency undergoing withdrawal, a condition known to induce stress-like symptoms. OBJECTIVES: We investigated the association of stress-induced ghrelin, craving, and smoking lapse. METHODS: Thirty-six smokers attended a laboratory session that included acute stress tasks during the initial phase of quitting. Self-report measures and biochemical samples were collected for the assessment of smoking status. Blood samples for the measurement of ghrelin and self-report measures of craving were collected multiple times throughout the session RESULTS: Multivariate analysis of variance controlling for gender found a significant main effect of sampling time and lapse group (p < 0.05). Ghrelin levels significantly increased over the pre-stress and post-stress periods (ps < 0.001), suggesting a delayed stress response. Those who lapsed during the study had higher ghrelin levels than those who were able to successfully abstain. A ghrelin stress response was calculated and a significant association was found between this response and craving, which changed across time points (ps < 0.008). CONCLUSIONS: The results of this study demonstrate that ghrelin is sensitive to acute manipulation of stress and that there is potential usefulness for ghrelin as a marker of stress, craving, and smoking lapse.

Effects of regular cannabis and nicotine use on acute stress responses: chronic nicotine, but not cannabis use, is associated with blunted adrenocortical and cardiovascular responses to stress.

RATIONALE: Cannabis is one of the most prevalent substances used by tobacco smokers and, in light of the growing list of states and territories legalizing cannabis, it is expected that co-use of cannabis and nicotine will escalate significantly and will lead to continuing challenges with tobacco use. OBJECTIVES: This study was conducted to examine the interactive effects of chronic cannabis and nicotine use on adrenocortical, cardiovascular, and psychological responses to stress and to explore sex differences in these effects. METHODS: Participants (N = 231) included cannabis-only users, nicotine-only users, co-users of both substances, and a non/light-user comparison group. After attending a medical screening session, participants completed a laboratory stress session during which they completed measures of subjective states, cardiovascular responses, and salivary cortisol during baseline (rest) and after exposure to acute stress challenges. RESULTS: Nicotine use, but not cannabis use, was associated with blunted cortisol and cardiovascular responses to stress across both men and women. Men exhibited larger cortisol responses to stress than women. Co-users had significantly larger stress-related increases in cannabis craving than cannabis-only users. Cannabis users reported smaller increases in anxiety during stress than cannabis non/light-users, and both male nicotine-only users and male cannabis-only users experienced significantly smaller increases in stress than their non/light-user control counterparts. CONCLUSIONS: This study replicates and extends earlier research on the impacts of sex and nicotine use on stress responses, and it provides novel findings suggesting that when co-used with nicotine, cannabis use may not confer additional alterations to physiological nor subjective responses to stress. Co-use, however, was associated with enhanced stress-related craving for cannabis.

Stress-induced analgesia: an evaluation of effects on temporal summation of pain and the role of endogenous opioid mechanisms.

INTRODUCTION: Acute stress reduces responses to static evoked pain stimuli (stress-induced analgesia [SIA]). Whether SIA inhibits temporal summation of pain, a dynamic evoked pain measure indexing central sensitization, has been little studied and mechanisms were not evaluated. OBJECTIVES: We tested whether acute laboratory stressors reduce temporal summation and whether endogenous opioid (EO) mechanisms contributed. METHODS: Participants were 72 healthy individuals who attended 2 laboratory sessions, receiving either oral naltrexone (50 mg; opioid antagonist) or placebo (randomized, counterbalanced order). In each session, participants underwent a temporal summation protocol with evoked heat pain stimuli, once after extended rest and once after experiencing 2 acute stressors (public speaking and mental arithmetic challenge). Reduced temporal summation in the stress/pain relative to rest/pain condition indexed SIA. RESULTS: Analyses in the placebo condition indicated significant SIA on initial pain ratings but not temporal summation slope (index of central sensitization). This SIA effect was moderated by stress reactivity, with SIA only observed in high stress responders. Analyses comparing SIA across the drug conditions did not reveal any evidence of stress-related EO inhibition of temporal summation outcomes. Moderation analyses revealed that high, but not low, stress responders exhibited paradoxical analgesic effects of naltrexone on initial pain ratings but not temporal summation slopes. Independent of stress effects, significant EO inhibition of temporal summation slopes was observed, but only in females. CONCLUSIONS: Results suggest that acute stress may reduce initial ratings in temporal summation protocols via nonopioid mechanisms but does not alter the temporal summation slope commonly used to index central sensitization.

Stress and COVID-19 related behaviours: The mediating role of delay discounting.

We examined stress as a predictor of behaviours related to Coronavirus Disease-2019 (COVID-19) through its effects on delay discounting. Adults (N = 3686) completed an online survey with a behavioural measure of delay discounting and questions regarding stress, physical distancing, and stockpiling of food and supplies. Stress was weakly, but positively, correlated with delay discounting (p < 0.01). Delay discounting was positively correlated with stockpiling (p < 0.01); and discounting was negatively correlated with physical distancing (p < 0.01). Mediation models indicated that discounting was a significant mediator of the relationship between stress and physical distancing (-0.003) and stockpiling (0.003); bootstrap 95% CIs (-0.006, -0.001) and (0.001, 0.005), respectively. After accounting for its indirect effects through discounting, stress continued to have a direct effect on these outcomes. This study indicates that delay discounting partially mediates the link between stress and behaviours related to COVID-19. Results suggest that interventions reducing stress and/or delay discounting may be profitable for increasing infection prevention and reducing stockpiling.

Psychosocial Correlates of Experience and Intention to Receive Colorectal Cancer Screening: A Cross-Sectional Study Among East African Men in the U.S.

Cancer screening is an important approach to reducing disease burden. The rate of colorectal cancer (CRC) screening among immigrants in the U.S. is very low. Our study's aim was to examine correlates of experience with, and intention to, receive CRC screening among East African men who were up-to-date (UTD) with CRC screening (n = 64, mean age 65) and those who had never been screened or were overdue for one (NOD; n = 47, mean age 60), compared on demographic characteristics, attitudes toward cancer, psychosocial stress, and health behaviors. UTD men had significantly less emotional concerns about cancer screening and experienced significantly greater distress and lower resiliency than NOD men. However, these results were attenuated after controlling for demographic confounders. Perceived risk, trust in the medical system, and PTSD symptoms were significantly associated with an intention to undertake CRC screening in the next 12 months. These results should be used to guide efforts toward increasing CRC screening rates among immigrant communities.

Stress and pain: modality-specific opioid mediation of stress-induced analgesia.

Preclinical research has demonstrated that exposure to acute stress is associated with attenuated pain perception, so called stress-induced analgesia (SIA). Mechanisms of SIA in humans have not been reliably demonstrated. This study examined the role of the endogenous opioid system in the impact of combined interpersonal and mental stressors on evoked pain responses in 84 participants (34 women). Using a within-subject, double-blinded, counterbalanced design, participants were administered either oral placebo or the opioid antagonist naltrexone (50 mg) across two testing sessions. In each session, they experienced two evoked pain stimuli (cold pressor test [CPT], heat pain) after an extended rest period (rest condition) and after exposure to an acute stressor (a combination of public speaking and mental arithmetic challenge; stress condition). Results showed that both stress and opioid blockade produced significant changes in hormonal and cardiovascular measures, consistent with successful induction of acute stress. Stress was associated with attenuated pain perception (SIA) as indicated by significantly increased CPT tolerance. These effects were particularly pronounced in individuals experiencing the stress condition first. More importantly, SIA effects on CPT tolerance were abolished by opioid blockade. There were no significant SIA effects on heat pain responses. This study demonstrates that the endogenous opioid system may mediate effects of acute stress on pain perception, although this effect seems to be qualified by the type of evoked pain stimuli experienced.

Impact of Acute and Chronic Cannabis Use on Stress Response Regulation: Challenging the Belief That Cannabis Is an Effective Method for Coping.

Although research has only recently started to examine the impact of cannabis use on stress response, there is some evidence that indicates acute and chronic impacts of cannabis on these processes. In this paper, we review processes involved in regulating the stress response and we review the influence of acute and chronic exposure to cannabis on patterns and regulation of the stress response. We also highlight the role of stress as a risk factor for initiation and maintenance of cannabis use. In this context, we examine moderating variables, including sex and life adversity. In light of recent observations indicating increasing prevalence of cannabis use during pregnancy, we provide additional focus on cannabis use in this vulnerable population, including how acute and chronic stress may predispose some individuals to use cannabis during pregnancy. While this line of research is in its infancy, we review available articles that focus on the perinatal period and that examined the association between cannabis use and various life stressors, including partner violence, job loss, and lack of housing. We also review psychiatric co-morbidities (e.g., post-traumatic stress disorder, anxiety). A better understanding of the way stress and cannabis use relate within the general population, as well as within certain subgroups that may be at a greater risk of using and/or at greater risk for adverse outcomes of use, may lead to the development of novel prevention and intervention approaches.

Impulsivity mediates the impact of early life adversity on high risk behaviors among Tunisian adolescents.

Adverse childhood experience (ACE) has become an alarming phenomenon exposing youth at a great risk of developing mental health issues. Several studies have examined the mechanism by which ACE affects adolescent's engagement in risky behaviors. However, little is known about these associations in the Tunisian/African context. We investigated the role of impulsivity in the link between ACE and health risk behaviors among schooled adolescents in Tunisia. We performed a cross sectional study among 1940 schooled adolescents in the city of Mahdia (Tunisia) from January to February 2020. To measure ACE, we used the validated Arabic version of the World Health Organization ACE questionnaire. The Barratt Impulsivity Scale and the Internet Addiction Test were used as screening tools for impulsivity and internet addiction. A total of 2520 adolescents were recruited. Of those, 1940 returned the questionnaires with an overall response rate of 77%. The majority (97.5%) reported experiencing at least one ACE. Emotional neglect (83.2%) and witnessing community violence (73.5%) were the most reported intra-familial ACEs. Males had higher rates of exposure to social violence than females. The most common risky behavior was internet addiction (50%, 95%CI = [47.9-52.3%]). Our survey revealed that ACEs score predict problematic behaviors through impulsiveness (% mediated = 16.7%). Specifically, we found a major mediating role of impulsivity between the exposure to ACE and the risk of internet addiction (% mediated = 37.5%). Our results indicate the role of impulsivity in translating the risk associated with ACE leading to engagement in high risk behaviors.

Tobacco withdrawal increases junk food intake: The role of the endogenous opioid system.

BACKGROUND: The aims of this study were to 1) determine whether acute nicotine withdrawal increases the intake of junk food (high in salt, fat, and sugar) and 2) assess whether the endogenous opioid system is involved in junk food intake during nicotine withdrawal using naltrexone as a pharmacological probe. METHODS: Smokers were randomly assigned to 24-hr withdrawal from tobacco products (n = 42) or smoking ad libitum (n = 34). A non-smoking group (n = 29) was included. Participants completed two laboratory sessions where a placebo or 50 mg of naltrexone was administered. At the end of each session, participants were given a tray of snack items that differed in high to low energy density and dimensions of salty, sweet, and fat. Self-reported mood and withdrawal measures were collected immediately before the snacks were offered. Generalized linear and logistic models were used to assess the effects of acute smoking withdrawal, drug, and sex on the intake of snack items and self-reported measures. RESULTS: Choice and consumption of food items were impacted by smoking condition (withdrawal > ad lib smoking and non-smokers; p < .05), the opioid blockade (naltrexone < placebo; p < .05), and sex (male > female; p < .05). The effects were evidenced in high sweet and high fat foods. No differences were found in low sweet and fat foods. CONCLUSIONS: These findings extend earlier studies indicating impact of tobacco use on appetite, and identify the regulatory influence of the endogenous opioid system on appetite during nicotine withdrawal.

Neurobiological mechanisms of early life adversity, blunted stress reactivity and risk for addiction.

Blunted stress reactivity resulting from early exposure to stress during childhood and adolescence may increase vulnerability to addiction. Early life adversity (ELA) affects brain structure and function and results in blunted stress axis reactivity. In this review, we focus on the underlying neurobiological mechanisms associated with a blunted response to stress, ELA, and risk for addictive disorders. ELA and blunted reactivity are accompanied by unstable mood regulation, impulsive behaviors, and reduced cognitive function. Neuroimaging studies reveal cortical and subcortical changes in persons exposed to ELA and those who have a genetic disposition for addiction. We propose a model in which blunted stress reactivity may be a marker of risk for addiction through an altered motivational and behavioral reactivity to stress that contribute to disinhibited behavioral reactivity and impulsivity leading in turn to increased vulnerability for substance use. Evidence supporting this hypothesis in the context of substance use initiation, maintenance, and risk for relapse is presented. The effects of ELA on persons at risk for addiction may lead to early experimentation with drugs of abuse. Early adoption of drug intake may alter neuroregulation in such vulnerable persons leading to a permanent dysregulation of motivational responses consistent with dependence. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.

Early life adversity and appetite hormones: The effects of smoking status, nicotine withdrawal, and relapse on ghrelin and peptide YY during smoking cessation.

There is evidence suggesting that ghrelin and peptide YY (PYY) modulate stress responses and the rewarding effects of drugs, although no research has examined the impact of exposure to early life stress on these hormones in smokers nor during smoking cessation. This study examined the relationships between early life adversity (ELA) and circulating ghrelin and PYY during ad libitum smoking and early withdrawal in tobacco smokers (N = 98) who were interested in cessation. We also included a comparison group of nonsmokers (N = 36). We prospectively compared levels of hormones between smokers who were successful in quitting within a 2-week period, smokers who relapsed during that period, and nonsmokers. Results showed that ELA was positively associated with elevated ghrelin in nonsmokers. Among those reporting no ELA, successful quitters had higher ghrelin levels than nonsmokers during ad libitum smoking, while relapsers had higher ghrelin levels than nonsmokers during withdrawal. In addition, having no ELA was associated with a decline in ghrelin from the ad libitum to abstinence sessions in successful quitters; this withdrawal-related decline was not found in relapsers. Although effects of ELA, smoking group, and time on PYY were not significant, greater PYY was associated with reduced urges to smoke during withdrawal. These findings suggest the importance of considering changes in appetite-related hormones in individuals who are dependent on tobacco. This research provides additional indications for effects of ELA on appetite-stimulating hormones.