Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.

BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine. METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38). RESULTS: Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study. DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling. SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.

The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.

Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development. This review details the past ten years of research on pregnenolone, progesterone, allopregnanolone, pregnanolone, estradiol, testosterone and dehydroepiandrosterone/dehydroepiandrosterone-sulfate (DHEA/DHEA-S) in the context of PTSD and AUD, including examination of trauma/alcohol-related variables, such as stress-reactivity. Emerging evidence that exogenous pregnenolone, progesterone, and allopregnanolone may be promising, novel interventions is also discussed. Specific emphasis is placed on examining the application of sex as a biological variable in this body of literature, given that women are more susceptible to both PTSD diagnoses and stress-related alcohol consumption.

Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder - A Pilot Study.

OBJECTIVE: Evidence from laboratory studies suggests that progesterone may be effective in reducing stress and craving, and may improve cognitive performance in smokers and individuals with cocaine dependence. The objective of this study was to examine if progesterone would attenuate stress-induced craving, anxiety, affect and physiological measures, as well as improve stress-induced cognitive performance (processing speed and selective attention) in individuals diagnosed with alcohol use disorder (AUD) and post traumatic stress disorder (PTSD). METHODS: This laboratory study included (n = 13) participants who were diagnosed with current AUD and PTSD who were randomly assigned to recive either progesterone (200mg bid) or placebo in identical looking capsules for 3 days. On the fourth day they completed a laboratory session. In the morning of the test session, they received the last dose of medication and completed the rest of the laboratory procedures. The procedures included presentation in random order of personalized trauma and neutral scripts with relaxation in between. Main outcomes included measure of craving, anxiety, affect and cognitive performance. RESULTS: Consistent with other research, trauma scripts produced significantly greater increases in craving, anxiety and negative affect when compared with neutral scripts. Progesterone significantly reduced stress-induced symptoms of craving, anxiety, fear, anger and sadness but had no effect on positive emotions (joy, relaxation). Progesterone was effective in ameliorating stress-induced decreases in cognitive performance. CONCLUSIONS: The findings from this study demonstrate that progesterone can be effective in reducing stress-induced craving, anxiety and negative affect in a laboratory setting in individuals with comorbid AUD and PTSD. Interestingly, progesterone also improved cognitive performance. These findings require replication in a larger clinical trial and may have implications for treatment among individuals with AUD and PTSD.This study was registered as NCT02187224, at www.clinicaltrials.gov.

Ghrelin Predicts Stimulant and Sedative Effects of Alcohol in Heavy Drinkers.

AIM: The aim of this study was to examine the relationship between ghrelin levels and the subjective effects of alcohol in heavy drinkers, and to compare them to healthy controls. METHODS: Ghrelin levels were collected as part of two laboratory studies. Both groups received either IV infusion of saline or high dose of alcohol (100 mg%). In the study of heavy drinkers, ghrelin was gathered on all subjects, but data was analyzed only for participants who received placebo (N=12). Healthy controls (N=20) came from another study that collected data on family history. Ghrelin levels and measures of alcohol effects (BAES, VAS, NDS, YCS [see manuscript for details]) were collected at 4 timepoints: baseline, before infusion, during infusion and after infusion. RESULTS: IV alcohol significantly reduced ghrelin levels and higher fasting ghrelin levels were associated with more intense subjective alcohol effects. There were no differences in fasting ghrelin levels or subjective effects between heavy drinkers and controls. However, while both groups showed similar decline in ghrelin levels following alcohol infusion, on the placebo day, ghrelin levels in the healthy subjects increased significantly and exponentially over time while for the heavy drinkers ghrelin levels remained flat. CONCLUSIONS: Our findings support the role of ghrelin in reward mechanisms for alcohol. Contrary to others, we found no differences in fasting ghrelin levels or subjective experiences of alcohol between heavy drinkers and healthy controls. However, the group differences on the IV placebo day may be a possible indication of ghrelin abnormalities in heavy drinkers.

Rationale, design and methods of VA-BRAVE: a randomized comparative effectiveness trial of two formulations of buprenorphine for treatment of opioid use disorder in veterans.

BACKGROUND: To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges. METHODS: This 52-week, parallel group, open-label, randomized controlled trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952). The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness trial with this population and during COVID-19 pandemic were also included. DISCUSSION: The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost. Trial registration Registered at Clinicaltrials.gov NCT04375033.

Depression and/or PTSD Comorbidity Affects Response to Antidepressants in Those With Alcohol Use Disorder.

Objective: Depression and post-traumatic stress disorder (PTSD) highly co-occur with alcohol use disorder (AUD). The comparative effects of noradrenergic vs. serotonergic antidepressants on drinking and depressive outcomes for those with AUD and co-occurring depression and/or PTSD are not well known. Methods: This study was an analysis of a randomized control trial of 128 patients with AUD who had co-occurring depression and/or PTSD. They were randomized to treatment with paroxetine vs. desipramine and naltrexone vs. placebo leading to four groups: paroxetine plus naltrexone, paroxetine plus placebo, desipramine plus naltrexone, and desipramine plus placebo. Outcomes were percent of drinking days, percent heavy drinking days, drinks per drinking day (Time Line Follow-back Method), and depressive symptoms (Hamilton Depression Scale). Groups compared were (1) depression without PTSD (depression group; n = 35), (2) PTSD without depression (PTSD group; n = 33), and (3) both depression and PTSD (comorbid group; n = 60). Results: There were no overall significant differences in drinking outcomes by medication in the entire sample, and no significant interaction when diagnostic groups were not considered. However, when diagnostic groups were included in the model, the interactions between time, diagnostic group, and medication (desipramine vs. paroxetine) were significant for percent drinking days (p = 0.042), and percent heavy drinking days (p = 0.036); paroxetine showed better drinking outcomes within the depression group, whereas desipramine showed better drinking outcomes in the PTSD and comorbid groups. Regarding depressive symptoms, paroxetine was statistically superior to desipramine in the total sample (p = 0.007), but there was no significant interaction of diagnostic group and medication. Naltrexone led to a decrease in craving but no change in drinking outcomes. Conclusions: The results of this study suggest that drinking outcomes may respond differently to desipramine and paroxetine depending on comorbid MDD and/or PTSD.

Zonisamide as an Adjunctive Treatment to Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder and Comorbid Alcohol Use Disorder: A Pilot Study.

BACKGROUND AND OBJECTIVES: There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT). METHODS: This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior. RESULTS: Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).

Thiopental Does Not Produce Hyperalgesia: A Laboratory Study Using Two Human Experimental Pain Models.

OBJECTIVE: Past investigations assessing the effects of thiopental on pain are conflicting. Although several studies demonstrate hyperalgesia as a result of barbiturate administration, others show analgesia. Our objective was to assess the effects of an infusion of the GABAA agonist thiopental, compared with placebo, in healthy participants on two subjective experimental pain paradigms: noxious electrical stimulation and intradermal capsaicin. METHODS: For electrical stimulation, the milliamps required to achieve pain threshold and tolerance were recorded, and the percent change from baseline was determined for each infusion condition. In the intradermal capsaicin condition, the area of hyperalgesia was determined by von Frey technique pre- and postinfusion, and the percent change in the area of hyperalgesia was calculated. RESULTS: Though thiopental infusion resulted in an increase in the electrical stimulation current required to elicit pain threshold or reach pain tolerance when compared with baseline, this finding was not statistically significant. In the intradermal capsaicin condition, there was a statistically significant difference in overall pre- and postinfusion pain interpretation, as measured by the McGill Pain Questionnaire (P < 0.05), but there was no significant difference in area of hyperalgesia. CONCLUSIONS: In this human study of thiopental's effects on two experimental pain models, our results show that thiopental does not induce hyperalgesia.

Trauma- and Stress-Induced Craving for Alcohol in Individuals Without PTSD.

AIMS: The main objective of the study was to compare the differences in craving following trauma and stress scripts in individuals with alcohol dependence (AD) who have experienced trauma but did not meet criteria for post-traumatic stress disorder (PTSD). METHODS: Twenty-eight men and women who participated in a treatment trial were included in this study before starting treatment. All had to meet criteria for AD and had experienced trauma at some point of their lives but were never diagnosed with PTSD. All participants had one laboratory session and were exposed to stress, trauma and neutral scripts randomly assigned. Main measures of craving, anxiety and mood were administered before, during and after each script. RESULTS: Stress and trauma scripts induced significantly more craving and anxiety than the neutral scripts. Interestingly, stress scripts produced stronger craving and anxiety than the trauma scripts but only with some measures. Stress and trauma scripts produced significantly more fear, anger and sadness and significantly lower ratings of joy and relaxation than the neutral script. Again, there were no differences between stress and trauma scripts for any of the emotional subscales. CONCLUSIONS: Trauma scripts did not result in stronger craving than stress scripts. These findings suggest that trauma in the absence of PTSD diagnosis does not lead to stronger craving for alcohol.

Targeting neuroinflammation with minocycline in heavy drinkers.

RATIONALE: Alcohol has both acute and chronic effects on neuroimmune signaling, including triggering pro-inflammatory cytokine release by microglia. Minocycline, a second-generation tetracycline antibiotic, inhibits microglial activation and reduces neuroinflammation in preclinical studies. In mice, minocycline also reduces ethanol intake, attenuates ethanol-induced conditioned place preference, and inhibits ethanol-induced microglial activation and pro-inflammatory cytokine release. OBJECTIVE: Here, for the first time, we tested the effects of minocycline on subjective response to ethanol and acute ethanol-induced inflammation in humans. METHODS: Forty-eight heavy drinkers participated in a double-blind, placebo-controlled trial in which they were randomized to receive placebo, 100 mg, or 200 mg of minocycline for 10 days. Each subject then underwent two experimental sessions in which they were given a fixed dose of intravenous ethanol using a "clamp" procedure (100 mg%) or placebo (normal saline) on days 8 and 10 of treatment. RESULTS: Minocycline was well tolerated, but there was no effect of either dose of minocycline on subjective response to ethanol or ethanol-induced craving; minocycline effects on cognitive function seem to interact with age. Minocycline treatment did not alter serum cytokine levels at baseline or during ethanol-exposure, although certain baseline cytokine levels predict sedative response to ethanol. CONCLUSION: These findings indicate that a short-term treatment with minocycline may not alter ethanol-related inflammation or subjective response to ethanol in humans. Further research is needed to identify pharmacological agents with robust effects on ethanol-induced inflammation to determine whether neuroimmune modulation represents a viable treatment strategy for alcohol use disorder.

A Pilot Randomized, Placebo-Controlled Trial of Glycine for Treatment of Schizophrenia and Alcohol Dependence.

Objectives: The hypofunctioning of N-methyl-D-aspartate (NMDA) receptors are thought to play an important role in the pathophysiology of schizophrenia. The augmentation of the glutamatergic system through the NMDA receptor may attenuate alcohol craving and use. This study was designed to evaluate the efficacy of glycine, an agonist of the glycine B co-agonist site of the NMDA receptor on alcohol consumption and cravings as well as on negative symptoms in schizophrenia. Methods: Participants (N = 20) were given 0.8 g/kg glycine or matching placebo (provided in bottles with mixed in solution) each week for the duration of the 12-week trial. Primary outcome measures included drinking, craving for alcohol, and symptoms of schizophrenia. Cognitive functioning (attention, concentration, and memory) was also evaluated. Results: Glycine showed no benefit over placebo in the reduction of heavy drinking days or craving for alcohol over a 12-week treatment period. Nor was there an effect on negative symptoms of schizophrenia or on cognitive functioning. Conclusions: Although our study showed no beneficial effect of glycine over placebo, our results are consistent with the largest trial of glycine treatment in schizophrenia. Diagnosed schizophrenia and alcohol dependence might be more difficult to treat because of more severe psychopathology. This is the first study to date to examine an innovative treatment approach with an amino acid, glycine, as potentially acting on both alcohol intake and negative symptoms of schizophrenia.

Alcohol Abstainer Status and Prazosin Treatment in Association with Changes in Posttraumatic Stress Disorder Symptoms in Veterans with Comorbid Alcohol Use Disorder and Posttraumatic Stress Disorder.

BACKGROUND: The noradrenergic system has been implicated in alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD), with adrenergic agents reducing drinking in individuals with AUD and improving sleep disturbances in individuals with PTSD. In a recent clinical trial, prazosin, an α1-adrenergic antagonist, was not superior to placebo in reducing PTSD symptoms, sleep problems, or alcohol consumption in a comorbid population; however, patients in both treatment conditions improved in all symptom domains over the course of treatment. It remains unknown whether alcohol abstinence is related to changes in PTSD symptoms and medication effects in individuals with this comorbidity. METHODS: Veterans with comorbid alcohol dependence and PTSD (n = 96) were randomized to prazosin (16 mg) or placebo in a 12-week outpatient, double-blind clinical trial. In this secondary data analysis, we examined main effects of alcohol abstainer status (abstainer vs. nonabstainer), treatment, and their interaction on changes in PTSD symptoms over time using linear mixed models. RESULTS: There was a main effect of alcohol abstainer status on symptoms of PTSD (p = 0.03), such that nonabstainers had lower total Clinician-Administered PTSD Scale (CAPS) scores than abstainers. There was a significant treatment by alcohol abstainer status interaction (p = 0.01); specifically, among placebo-treated individuals, those who did not abstain from alcohol had lower total CAPS scores compared to alcohol abstainers. Within the prazosin-treated group, abstainers and nonabstainers did not differ on total CAPS scores. Results were similar for the avoidance (p = 0.02), reexperiencing (p = 0.01), and hyperarousal (p = 0.04) subscales, such that placebo-treated nonabstainers had lower CAPS scores overall. CONCLUSIONS: Overall, prazosin treatment was not significantly related to changes in PTSD symptoms over the course of the 12-week clinical trial in a comorbid population. Interestingly, placebo-treated alcohol nonabstainers had a significant reduction in PTSD symptoms. Whether placebo-treated individuals continued to use alcohol because of ongoing symptoms of PTSD is not known.

Heart rate variability in alcohol use: A review.

BACKGROUND: Prior studies have shown that resting heart rate variability (HRV) is reduced in those with alcohol use disorders (AUD). However, HRV following an acute stressful stimulus (reactive HRV), and the relationship between resting or reactive HRV and drinking, craving and relapse in AUD have received less attention. METHODS: Studies using HRV in relationship to acute or chronic alcohol consumption were included in this review. Manuscripts that related to alcohol in the context of cardiovascular disease were excluded. RESULTS: Thirty-three articles were included and findings are presented in healthy social drinkers, moderate/heavy drinkers without AUD and individuals with AUD. Results on resting and reactive HRV were presented separately. Acute alcohol reduced resting HRV in healthy subjects but healthy controls had higher resting HRV then AUD subjects and moderate/heavy drinkers (in some studies). Resting HRV improved in AUD subjects only after at least 4 months of abstinence. AUD subjects had higher reactive HRV scores when compared to controls. In AUD subjects increased reactivity was related to more craving, faster relapse and more negative mood. Reactive HRV showed slower improvement with abstinence in AUD subjects. CONCLUSIONS: Chronic, heavy alcohol has a negative effect on the autonomic nervous system and may be a sensitive biomarker of craving and relapse.

Tobacco use during a clinical trial of mecamylamine for alcohol dependence: Medication effects on smoking and associations with reductions in drinking.

Mecamylamine is a nicotinic acetylcholine receptor (nAChR) antagonist that was recently used in a clinical trial to treat alcohol use disorder (AUD) in both smokers and non-smokers. The current manuscript reports a reanalysis of data from this clinical trial in which we examine changes in smoking that occurred over the course of the trial. We focused on examining the effects of mecamylamine on smoking and the association between reductions in alcohol use and smoking. Participants were the subgroup of smokers who participated in the clinical trial of mecamylamine (10 mg/day) to treat their AUD (n = 76). Smoking was assessed prior to randomization and tracked throughout the course of the 12-week medication treatment phase. Participants were categorized as treatment responders or non-responders based on their changes in drinking over the course of the clinical trial. Participants showed a reduction in smoking over the course of the clinical trial, but there were no significant differences in smoking outcomes between the mecamylamine and placebo groups. Among moderate/high dependence smokers, those who successfully reduced drinking showed a significant reduction in cigarettes smoked per day over the clinical trial. Mecamylamine had no detectable effect on smoking outcomes. Reductions in alcohol use predicted more favorable smoking outcomes among moderate/high tobacco dependence smokers irrespective of medication condition. The reduction in smoking among patients who decreased their alcohol use responders highlights an opportunity for patients being treated for AUD to reduce their smoking.

Suicidal ideation in military veterans with alcohol dependence and PTSD: The role of hostility.

BACKGROUND AND OBJECTIVES: Suicide is a significant public health problem among US military Veterans with rates exceeding civilian samples. Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) are both associated with increases in suicidality. Given that risk of suicide is higher among those with both disorders, the study of relevant risk factors among those in this group is important. The current investigation focused on one such factor, hostility, and examined both overt hostility (ie, hostility that is more behavioral in nature and directed outwardly) and covert hostility (ie, hostility that is cognitive in nature and introspective) and their relationships to suicidal ideation. METHODS: Ninety-three Veterans participating in a randomized, double-blind, placebo-controlled treatment study evaluating the efficacy of the alpha-adrenergic agonist prazosin completed measures assessing overt hostility, covert hostility, and suicidal ideation at baseline. Depression symptoms and PTSD symptom severity also were assessed. RESULTS: Of the total sample, 60 participants (63.8%) indicated that they experienced suicidal ideation at some point in their lives. Covert hostility, in addition to PTSD symptom severity were found to be associated with the presence of lifetime suicidal ideation. Furthermore, depression symptoms were found to be associated with greater intensity of that ideation. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Findings highlight the importance of covert hostility as it relates to suicidal ideation among those with comorbid PTSD and AD and provides information which may help inform treatment approaches for high-risk military Veterans. (Am J Addict 2018;27:124-130).

Negative Affect Intensity and Hostility in Individuals With Alcohol Use Disorder With or Without Posttraumatic Stress Disorder.

OBJECTIVE: Negative affect intensity and hostility have both been implicated in alcohol use disorders (AUD) and posttraumatic stress disorder (PTSD) when they occur separately, but neither have been compared or explored among those with comorbid AUD and PTSD. This study is a secondary analysis designed to compare levels of negative affect intensity and hostility among those with AUD to those with comorbid AUD and PTSD. METHODS: Participants (n = 113) were recruited from the placebo-controlled groups of two distinct 12-week clinical trials (NCT00342563 and NCT00744055). The Short Affect Intensity Scale and Buss-Durkee Hostility Inventory were administered at weeks 0, 4, 8, and 12 to all study participants to assess negative affect intensity and hostility levels, respectively. RESULTS: Individuals with comorbid AUD and PTSD showed significantly higher levels of negative affect intensity and hostility than individuals with AUD only. These levels remained relatively stable over the course of the study in spite of all study participants showing clinically significant improvements in AUD severity and PTSD symptomatology (for those with dual diagnosis). CONCLUSIONS: Our results indicate that individuals with comorbid AUD and PTSD have higher levels of negative affect and higher levels of hostility compared to individuals with AUD alone. In addition, these heightened levels of negative affect intensity and hostility appear to function somewhat independently of diagnosis severity and symptomatology improvement. To our knowledge, this is the first study to compare negative affect intensity and hostility levels between individuals with AUD alone and those with comorbid AUD and PTSD.

Ghrelin is Related to Personality Differences in Reward Sensitivity and Impulsivity.

AIMS: Ghrelin, a feeding-related peptide mainly produced in the stomach, has been linked to reward mechanisms for food and drugs of abuse in addition to traits of impulsivity. This study is a secondary analysis of an existing data set designed to examine the direct relationships between fasting ghrelin levels and reward sensitivity/impulsivity in healthy social drinkers. METHODS: Participants (n = 20) were recruited from an original study examining the subjective effects of alcohol among social drinkers. Fasting ghrelin levels were collected at baseline. Personality measures (Behavioral Inhibition, Behavioral Activation, and Affective Response to Impending Reward and Punishment and Barratt Impulsiveness Scale) were administered at baseline to evaluate sensitivity to reward and punishment, and measure traits of impulsivity, respectively. RESULTS: Fasting ghrelin levels were significantly related to reward sensitivity and impulsivity traits. Specifically, those with higher ghrelin levels were more sensitive to reward and were more impulsive (have lower self-control). CONCLUSIONS: The results indicate that individuals with higher levels of ghrelin are more sensitive to reward. In addition, they are less able to exercise self-control and to an extent more likely to act without thinking. This is the first study to report on the direct relationship between fasting ghrelin levels and personality characteristics such as reward sensitivity and aspects of impulsivity among healthy social drinkers. SHORT SUMMARY: Individuals with higher levels of fasting ghrelin are more sensitive to reward, but less sensitive to punishment. Higher ghrelin levels are also related to some aspects of impulsivity such as decreased self-control and increased likelihood of acting without thinking.

Mecamylamine treatment for alcohol dependence: a randomized controlled trial.

BACKGROUND AND AIMS: The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects. DESIGN: Out-patient, randomized, double-blind clinical trial for 12 weeks of treatment with mecamylamine (10 mg) (n = 65) versus placebo (n = 63). SETTING: Connecticut, USA. PARTICIPANTS: Individuals had current alcohol dependence (n = 128), had an average age of 48.5 [standard deviation (SD) = 9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non-smokers (42.2%). Participants were randomized to mecamylamine 10 mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel. MEASUREMENTS: Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects. FINDINGS: There were no significant differences in the percentage of heavy drinking days at 3 months between the mecamylamine (mean = 18.4, SD = 29.0) and placebo treatment groups (mean = 20.4, SD = 29.2) [F1, 100  = 1.3, P = 0.25; effect size d = 0.07; mean difference = 2.06, 95% confidence interval (CI) = -8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions. CONCLUSIONS: Mecamylamine 10 mg per day did not reduce alcohol consumption significantly in treatment-seeking smokers and non-smokers with alcohol use disorder.

Ghrelin is Supressed by Intravenous Alcohol and is Related to Stimulant and Sedative Effects of Alcohol.

AIMS: Evidence indicates that feeding-related peptides, such as ghrelin, have a role in the rewarding properties of addictive substances like alcohol. Oral alcohol administration significantly suppresses ghrelin. This study was designed to evaluate the effects of two doses of alcohol on ghrelin and examine if ghrelin levels predict the subjective effects of alcohol. METHODS: Healthy social drinkers (N = 20) participated in three, randomly assigned, and counterbalanced laboratory sessions. During each session they received a continuous IV infusion of either placebo (saline), low dose (40 mg%) or high dose (100 mg%) of alcohol. Participants were given a standardized, light breakfast 90 min before the start of the infusion. Ghrelin levels [acyl ghrelin (AG) and total ghrelin (TG)] were collected at four time points before, during and after the infusion. Subjective effects of alcohol, using the BAES, were evaluated before, during and after alcohol infusion. RESULTS: IV alcohol significantly reduced AG but not TG levels with no difference between the two doses of alcohol. The percent change (%∆) in AG suppression was substantial in both high dose (43.4%∆), and low dose (39.5%∆) of alcohol. Also, fasting AG and TG levels were significant predictors of alcohol stimulant and sedative effects. Higher fasting ghrelin levels were associated with longer and more intense subjective effects. CONCLUSIONS: The results provide evidence that IV alcohol suppresses ghrelin levels similarly to oral alcohol. This study is the first to show that ghrelin predicts subjective effects of alcohol, suggesting that ghrelin may have a role in the rewarding mechanisms for alcohol. SHORT SUMMARY: Intravenous alcohol infusion (low dose and high dose of alcohol) when compared to placebo (saline) significantly suppresses ghrelin in healthy social drinkers. Fasting ghrelin levels also predict subjective behavioral effects of alcohol. Those with higher fasting ghrelin levels tend to experience alcohol effects longer and more intensely.