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Elizabeth KC Schwartz,1,2 Noah R Wolkowicz,1,2 Joao P De Aquino,1,2 R Ross MacLean,1,2 Mehmet Sofuoglu1,2 1Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 2Department of Psychiatry, VA Connecticut Healthcare System, West Haven, CT, USACorrespondence: Elizabeth KC Schwartz, Tel +1-203-932-5711, Fax +1-203-937-3472, Email Elizabeth.schwartz@yale.eduAbstract: Cocaine use disorder (CUD) is a devastating disorder, impacting both individuals and society. Individuals with CUD face many barriers in accessing treatment for CUD, and most individuals with CUD never receive treatment. In this review, we provide an overview of CUD, including risk factors for CUD, common co-occurring disorders, acute and chronic effects of cocaine use, and currently available pharmacological and behavioral treatments. There are no FDA-approved pharmacological treatments for CUD. Future studies with larger sample sizes and testing treatment combinations are warranted. However, individuals with CUD and co-occurring disorders (eg, a mood or anxiety disorder) may benefit from medication treatments. There are behavioral interventions that have demonstrated efficacy in treating CUD – contingency management (CM) and cognitive-behavioral therapy for substance use disorders (CBT-SUD) in particular – however many barriers remain in delivering these treatments to patients. Following the discussion of current treatments, we highlight some promising emerging treatments, as well as offer a framework that can be used in building a treatment plan for individuals with CUD.Keywords: cocaine, cocaine use disorder, treatment, pharmacotherapy, behavioral interventions

Introduction: Avoidance is a well-documented risk factor for poor mental and physical health outcomes. However, limited research has explored this relationship specifically among trauma-exposed veterans, a population known to be particularly prone to avoidance behavior. Conceptually, avoidance is often divided into two distinct but overlapping constructs - experiential avoidance (resisting distressing internal states) and behavioral avoidance (avoiding or changing experiences that elicit distress). In this exploratory survey study, we examined associations between behavioral and experiential avoidance and mental, physical, and cognitive functioning, as well as quality of life., Methods: Veterans with a trauma history (N = 89) completed a 121-item survey containing validated assessments to examine several mental and physical health and wellness-related variables. Correlations between experiential avoidance and outcome measures, and behavioral avoidance and outcome measures, were explored. Multivariable linear regression analyses were conducted to explore the association between experiential and behavioral avoidance on mental health outcomes. In addition, we conducted exploratory analyses in which we investigated these correlations in those who screened positive for PTSD versus those who did not, and between different types of behavioral avoidance and major outcomes., Results: Experiential avoidance was moderately correlated with distress from depressive symptoms, distress related to past trauma, and health-related and cognitive dysfunction. Experiential Avoidance was weakly correlated with distress from anxiety symptoms and poorer quality of life. Behavioral avoidance was moderately correlated with distress from depressive and anxiety symptoms, distress related to past trauma, and cognitive dysfunction, and was weakly correlated with health-related dysfunction and poorer quality of life. Results from multivariable analyses revealed that experiential avoidance was associated with greater distress related to depressive symptoms and past trauma, and behavioral avoidance was associated with greater distress related to anxiety symptoms, depressive symptoms, and past trauma., Conclusions: Results suggest that avoidance negatively influences major domains of mental and physical health as well as functioning and health-related quality of life in trauma-exposed veterans. They further indicate that behavioral and experiential avoidance may be differentially linked to mental health outcomes. The results support the idea that avoidance may be an important marker for psychosocial functioning and may serve as a treatment target in trauma-exposed veterans., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Chronic pain and opioid use disorder (OUD) are major public health problems, with rising opioid-related overdose deaths linked to increased opioid prescriptions for pain management. Novel treatment approaches for these commonly comorbid disorders are needed. Growing evidence supports a role for glial activation for both chronic pain and substance use disorders, including OUD. This review provides an overview of glial modulators as a novel treatment approach for comorbid pain and OUD. We aim to synthesize clinical studies investigating the efficacy of glial modulators in treating these comorbid disorders. We conducted a literature search of PubMed and Google Scholar databases in October 2023 to identify relevant clinical trials. The included studies varied in terms of patient population, study methodology and outcomes assessed, and were often limited by small sample sizes and other methodological issues. Additionally, several glial modulators have yet to be studied for chronic pain and OUD. Despite these limitations, these studies yielded positive signals that merit further investigation. Both chronic pain and OUD remain significant public health problems, with many treatment challenges. Glial modulators continue to hold promise as novel therapeutics for comorbid pain and OUD, given positive indications that they can improve pain measures, and reduce addiction-related outcomes. As our understanding of the mechanisms underlying the contributions of glial modulators to pain and addiction behaviours deepens, we will be better equipped to identify more specific therapeutic targets for chronic pain and OUD., (© 2024 British Pharmacological Society.)

Introduction: Childhood trauma is known to be associated with nicotine dependence, yet limited smoking outcomes have been examined and few studies have assessed associations between specific trauma subscales and smoking. Additionally, sex differences in trauma-smoking relations are understudied. This study examined associations between childhood trauma and several smoking-related outcomes in adults who smoke after overnight abstinence., Aims and Methods: People who smoke (N = 205) completed self-report and biochemical assessments evaluating childhood trauma, affect, nicotine dependence, smoking urges, withdrawal, and plasma cortisol and cotinine levels. Smoking outcomes were compared between those with and without a history of moderate to severe childhood trauma among the total sample and by sex., Results: Relative to those with no to minimal abuse, those with moderate to severe abuse had higher negative affect, withdrawal severity, and plasma cotinine levels. Exploratory analyses revealed that women were more likely than men to have urges to smoke for negative reinforcement and have higher withdrawal severity, but no interactions between abuse group and sex were observed. Examining specific trauma subscales, the moderate to severe emotional abuse group had more severe nicotine dependence, negative affect, and withdrawal compared to the no to minimal group. The moderate to severe sexual abuse group had more severe nicotine dependence and withdrawal compared to the no to minimal group., Conclusions: Exposure to childhood trauma is associated with more severe nicotine dependence, negative affect, withdrawal, and higher plasma cotinine levels. Findings also indicate that different types of trauma may differentially affect smoking behaviors., Implications: This study of adults who smoke finds that childhood trauma history may be a marker for smoking susceptibility and suggests that individuals with experiences of emotional and sexual abuse may require targeted forms of smoking cessation interventions. Moreover, findings suggest that smoking risks may differ for men and women. Findings inform public health interventions intended to reduce cigarette use in individuals with exposure to childhood trauma., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Large racial disparities exist in the prevention and treatment of smoking-related diseases, and minoritized populations carry a heavier burden of smoking-related morbidity and mortality. To date, most studies investigating smoking-related illnesses have been conducted in samples in which the majority, or totality, self-identified as White or Caucasian. While Black individuals who smoke tend to have a lower rate of nicotine clearance, in part due to the use of mentholated cigarettes, less is known about how slower clearance affects their acute subjective and physiologic responses in response to either overnight abstinence or subsequent nicotine administration. This study aimed to investigate differences between the experiences of Black and White individuals who smoke across these outcomes after a period of short-term abstinence and after IV nicotine infusion., Methods: The study included 206 smokers (N = 103 Black, N = 103 White, by self-report). The study investigated self-report, physiological, and biochemical smoking-related outcomes following confirmed overnight abstinence followed by IV nicotine infusion. The outcome measures were separately analyzed with repeated-measures mixed-models., Results: Black individuals had lower rates of nicotine clearance and were more likely to smoke mentholated cigarettes than White individuals. Despite these differences, no differences in withdrawal, cravings, or physiological outcomes were observed between the two groups. There were some trends toward differences in subjective experiences, in that an interaction with trend level significance between race and dose was observed for negative subjective drug effects, with White smokers trending towards endorsing higher levels of negative affect after abstinence and nicotine infusion. We also observed that Black individuals trended towards experiencing more negative drug effects in response to initial nicotine delivery than to saline, whereas White individuals had no differences in negative drug effects across saline or nicotine doses., Conclusions: Despite slower nicotine clearance, Black participants exhibited withdrawal and urges to smoke as severe as White participants, and did not have blunted physiological responses to overnight abstinence or administration of nicotine, which were contrary to our hypotheses. Our findings suggest minimal differences across races in the acute pharmacologic effects of nicotine. We observed trend-level differences in subjective and affective responses to nicotine. Greater insight into these differences may lead to improved prevention and treatment strategies for smoking-related illnesses for Black individuals who smoke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This secondary analysis sought to determine if plasma menthol glucuronide (MG) concentrations predict changes in three outcomes, subjective drug effects, urges to smoke, and heart rate, following concurrent inhaled menthol and intravenous nicotine. A total of 45 menthol and non-menthol cigarettes smokers (36 male, nine female, 20 Black, and 23 White) were included in this double-blind, placebo-controlled study. Across three test sessions, participants were assigned to a different flavor condition for each session: 0% (no menthol), 0.5%, or 3.2% menthol. In each test session, participants received in a random order one intravenous delivery of saline and two intravenous deliveries of nicotine (0.25 mg/70 kg and 0.5 mg/70 kg), each 1 h apart, concurrent with menthol delivery by e-cigarettes. The main outcomes were subjective drug effects, urges to smoke, and heart rate. The results showed that following e-cigarette inhalation, changes in plasma MG concentrations or "menthol boost" increased proportionally to the menthol concentration in the e-liquids. While changes in plasma MG concentrations were not predictive of increases in heart rate or subjective drug effects that are reflective of acute effects from nicotine (i.e., feel good effects, stimulated, aversive effects ), they were predictive of cooling effect , a typical effect of menthol, but only in menthol smokers in the absence of concurrent active nicotine infusion. These findings demonstrate the utility of plasma MG as a biomarker both for acute menthol exposure by e-cigarette inhalation and for the examination of the concentration-dependent behavioral and physiological effects of menthol in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gueorguieva, Schwartz, MacLean, DeVito, Eid, Wu, O’Malley and Sofuoglu.)

Food produces powerful reinforcement that can lead to overconsumption and likely contributes to the obesity epidemic. The present studies examined molecular mechanisms mediating food-induced reinforcement in the model system C. elegans . After a 1-h training session during which food (bacteria) is paired with the odorant butanone, odor preference for butanone robustly increased. Glucose mimicked this effect of bacteria. Glucose-induced odor preference was enhanced similarly by prior food withdrawal or blocking glucose metabolism in the presence of food. Food- and glucose-induced odor preference was mimicked by serotonin signaling through the serotonin type-4 (5-HT4) receptor. Dopamine (thought to act primarily through a D1-like receptor) facilitated, whereas the D2 agonist bromocriptine blocked, food- and glucose-induced odor preference. Furthermore, prior food withdrawal similarly influenced reward produced by serotonin, dopamine, or food, implying post-synaptic enhancement of sensitivity to serotonin and dopamine. These results suggest that glucose metabolism plays a key role in mediating both food-induced reinforcement and enhancement of that reinforcement by prior food withdrawal and implicate serotonergic signaling through 5-HT4 receptor in the re-enforcing properties of food., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schwartz, Sosner, Desmond, Lum, Sze and Mobbs.)