Perceived reward from using cigarettes with alcohol or cannabis and concurrent use: A smartphone-based daily diary study.

INTRODUCTION: Smoking cigarettes under the influence of alcohol or cannabis is associated with perceived pleasure. However, it is unclear whether these changes in perceived reward impact the extent of concurrent use of cigarettes with alcohol or cannabis. The current study investigated if self-reported changes in perceived reward from concurrent use of cigarettes with alcohol or cannabis are related to the extent of concurrent use in real-world contexts using a smartphone-based Ecological Momentary Assessment (EMA) study. METHODS: The sample included 126 diverse young adult smokers in the San Francisco Bay Area who reported current alcohol or cannabis use at baseline (M = 22.8 years, 50.8% male, 40.5% sexual minority, 39.7% Non-Hispanic White). Participants completed an online baseline survey and 30 days of smartphone-based daily EMA surveys of cigarette, alcohol, and cannabis use. The baseline assessed self-reported changes in perceived pleasure of smoking cigarettes while using alcohol or cannabis separately. EMA surveys included detailed questions about concurrent use (i.e., the extent of smoking while using another substance) covering the previous day. A total of 2,600 daily assessments were analyzed using mixed models. RESULTS: Higher perceived pleasure from smoking cigarettes while drinking alcohol or using cannabis at baseline were both associated with a greater extent of concurrent use of cigarettes with alcohol (b = 0.140; SE = 0.066; t = 2.1; p = .035) and cannabis (b = 0.136; SE = 0.058; t = 2.4; p = .019) on a given day. CONCLUSIONS: Results suggest that perceived reward from concurrently using cigarettes with alcohol or cannabis is associated with the extent of concurrent use. Findings can inform tailored smoking cessation interventions.

Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.

BACKGROUND: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. METHODS: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis. RESULTS: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. CONCLUSIONS: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. IMPACT: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease.

Sleep Management Among Patients with Substance Use Disorders.

Sleep and substance use disorders commonly co-occur. Insomnia is commonly associated with use and withdrawal from substances. Circadian rhythm abnormalities are being increasingly linked with psychoactive substance use. Other sleep disorders, such as sleep-related breathing disorder, should be considered in the differential diagnosis of insomnia, especially in those with opioid use or alcohol use disorder. Insomnia that is brief or occurs in the context of active substance use is best treated by promoting abstinence. A referral to a sleep medicine clinic should be considered for those with chronic insomnia or when another intrinsic sleep disorder is suspected.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

BACKGROUND: Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. METHODS: In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. RESULTS: There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. CONCLUSIONS: In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Assessing the Validity of Online Drug Forums as a Source for Estimating Demographic and Temporal Trends in Drug Use.

OBJECTIVES: Addiction researchers have begun monitoring online forums to uncover self-reported details about use and effects of emerging drugs. The use of such online data sources has not been validated against data from large epidemiological surveys. This study aimed to characterize and compare the demographic and temporal trends associated with drug use as reported in online forums and in a large epidemiological survey. METHODS: Data were collected from the Web site, drugs-forum.com, from January 2007 through August 2012 (143,416 messages posted by 8087 members) and from the US National Survey on Drug Use and Health (NSDUH) from 2007 to 2012. Measures of forum participation levels were compared with and validated against 2 measures from the NSDUH survey data: percentage of people using the drug in past 30 days and percentage using the drug more than 100 times in the past year. RESULTS: For established drugs (eg, cannabis), significant correlations were found across demographic groups between drugs-forum.com and the NSDUH survey data, whereas weaker, nonsignificant correlations were found with temporal trends. Emerging drugs (eg, Salvia divinorum) were strongly associated with male users in the forum, in agreement with survey-derived data, and had temporal patterns that increased in synchrony with poison control reports. CONCLUSIONS: These results offer the first assessment of online drug forums as a valid source for estimating demographic and temporal trends in drug use. The analyses suggest that online forums are a reliable source for estimation of demographic associations and early identification of emerging drugs, but a less reliable source for measurement of long-term temporal trends.

Randomized Trial of Reduced-Nicotine Standards for Cigarettes.

BACKGROUND: The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS: We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS: A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).

Cigarette Smoking During Substance Use Disorder Treatment: Secondary Outcomes from a National Drug Abuse Treatment Clinical Trials Network study.

INTRODUCTION: The majority of patients enrolled in treatment for substance use disorders (SUDs) also use tobacco. Many will continue to use tobacco even during abstinence from other drugs and alcohol, often leading to smoking-related illnesses. Despite this, little research has been conducted to assess the influence of being a smoker on SUD treatment outcomes and changes in smoking during a treatment episode. METHODS: In this secondary analysis, cigarette smoking was evaluated in participants completing outpatient SUD treatment as part of a multi-site study conducted by the National Drug Abuse Treatment Clinical Trials Network. Analyses included the assessment of changes in smoking and nicotine dependence via the Fagerström Test for Nicotine Dependence during the 12-week study among all smokers (aim #1), specifically among those in the experimental treatment group (aim #2), and the moderating effect of being a smoker on treatment outcomes (aim #3). RESULTS: Participants generally did not reduce or quit smoking throughout the course of the study. Among a sub-set of participants with higher baseline nicotine dependence scores randomized to the control arm, scores at the end of treatment were lower compared to the experimental arm, though measures of smoking quantity did not appear to decrease. Further, being a smoker was associated with poorer treatment outcomes compared to non-smokers enrolled in the trial. CONCLUSIONS: This study provides evidence that patients enrolled in community-based SUD treatment continue to smoke, even when abstaining from drugs and alcohol. These results add to the growing literature encouraging the implementation of targeted, evidence-based interventions to promote abstinence from tobacco among SUD treatment patients.

Effects of methadone plus alcohol on cognitive performance in methadone-maintained volunteers.

BACKGROUND: Methadone maintenance patients (MMP) often abuse other drugs, including alcohol. The combined use of methadone and alcohol could impair performance and daily functioning. OBJECTIVE: To examine the effects of methadone in combination with alcohol, as well as acute increases in methadone, on performance outcomes. METHODS: This double-blind, double-dummy, crossover study included eight opioid-dependent participants stabilized on methadone. Participants completed six inpatient sessions corresponding to methadone (100% or 150% of daily dose) and beverage (placebo, 0.25 or 0.50 g/kg alcohol). Performance tasks were completed before and after drug administration. Area under the time-course values were analyzed by a 2 (methadone dose) by 3 (alcohol dose) repeated measures analysis of variance. RESULTS: Main effects of methadone were observed for two attention outcomes, suggesting reduced accuracy and slowed responding at an elevated methadone dose. In addition, main effects of alcohol were observed for episodic memory (false alarms and response bias) suggesting more impulsive responding as alcohol dose increased. No robust interactions of methadone and alcohol were observed for any outcome. CONCLUSIONS: Study findings indicate that an acute increase in methadone (150%) and a moderate dose of alcohol (2-3 drinks) can impair distinct aspects of performance, although no significant interactive effect between methadone and alcohol was found. Future studies with larger sample sizes, larger doses, and more clinically informative tasks could expand on the present findings and further explore the cognitive consequences of concurrent opioid and alcohol use.

Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.

Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18-50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders.

Cognitive performance in methadone maintenance patients: effects of time relative to dosing and maintenance dose level.

Given the long-term nature of methadone maintenance treatment, it is important to assess the extent of cognitive side effects. This study investigated cognitive and psychomotor performance in 51 methadone maintenance patients (MMP) as a function of time since last methadone dose and maintenance dose level. MMP maintained on doses ranging from 40 to 200 mg (mean = 97 mg) completed a battery of psychomotor and cognitive measures across 2 sessions, during peak and trough states, in a double-blind crossover design. Peak sessions were associated with worse performance on measures of sensory processing, psychomotor speed, divided attention, and working memory, compared with trough sessions. The effects of maintenance dose were mixed, with higher dose resulting in worse performance on aspects of attention and working memory, improved performance on executive function, and no effects on several measures. Longer treatment duration was associated with better performance on some measures, but was also associated with increased sensitivity to time since last dose (i.e., worse performance at peak vs. trough) on some measures. The results suggest that cognitive functioning can fluctuate as a function of time since last dose even in MMP who have been maintained on stable doses for an extended time (mean duration in treatment = 4 years), but worsened performance at peak is limited to a subset of functions and may not be clinically significant at these modest levels of behavioral effect. For patients on stable methadone maintenance doses, maintenance at higher doses may not significantly increase the risk of performance impairment.

Effects of varenicline on abstinence and smoking reward following a programmed lapse.

INTRODUCTION: Varenicline (Chantix®) is an efficacious first-line medication for smoking cessation. Studies suggest that one mechanism by which varenicline facilitates sustained smoking abstinence is by reducing the likelihood of relapse to smoking when a lapse, or slip, occurs during a quit attempt. The present study extends this line of research by conducting a prospective laboratory study to examine the relapse prevention effects of varenicline following a programmed lapse. METHODS: Daily smokers (N = 47) completed a 5-week outpatient study in which they were randomized to receive varenicline or placebo. The first week was a medication induction period that was immediately followed by a 4-week quit attempt. A programmed lapse (2 cigarettes smoked in the laboratory) occurred on the second day of the quit attempt. RESULTS: Participants receiving varenicline were slower to relapse and had greater total abstinence rates following lapse exposure. Participants in the varenicline group rated lapse cigarettes lower on measures of reward and intoxication and showed increased behavioral economic demand elasticity for cigarettes (reduced cigarette purchasing at higher prices) compared with those receiving placebo. CONCLUSIONS: These results demonstrate a relapse prevention effect of varenicline following smoking lapse exposure and suggest that an attenuation of reward from smoking and the blunting of subjective effects of smoking may underlie and/or contribute to this effect.

[Pharmacological and psychosocial interventions for cannabis use disorders]. / Intervenções farmacológica e psicossocial para os distúrbios por uso da cannabis.

OBJECTIVE: Cannabis remains the most widely used illicit substance in most developed countries. Its addictive potential has been established and the need for interventions for cannabis-related problems has become apparent. This article provides a review of the research evaluating potential treatments for cannabis use disorders. METHOD: A search of publication databases identified research studies and reviews of the scientific literature on psychosocial and pharmacological interventions for cannabis use disorders. RESULTS: For adults, behaviorally-based interventions engender significant positive effects on abstinence and reductions in cannabis use. With adolescents, similar treatments and family-based interventions have demonstrated efficacy. Across studies, response rates appear modest even with the most potent psychosocial treatments. Evaluations of pharmacological approaches to cannabis use disorders have yet to provide clinical efficacy data for any specific medication. Agonist and antagonist approaches appear to offer the most promise. Advances in understanding of the neurobiology of the cannabinoid system provide optimism that the synthesis of compounds that alter CB(1) receptor site functioning may produce promising medications. CONCLUSION: Clinical research has identified effective psychosocial treatments, but has yet to yield effective pharmacotherapies. Much work remains to enhance the potency of and access to interventions for those seeking treatment for cannabis use disorders.

Intervenções farmacológica e psicossocial para os distúrbios por uso da cannabis / Pharmacological and psychosocial interventions for cannabisuse disorders

OBJETIVO: A cannabis continua sendo a substância ilegal mais amplamente utilizada na maioria dos países desenvolvidos. Seu potencial aditivo foi estabelecido e a necessidade de intervenções em problemas relacionados à cannabis se tornou clara. Este artigo faz uma revisão sobre as pesquisas que avaliam os tratamentos potenciais para transtornos por uso de cannabis. MÉTODO: Uma busca nos bancos de dados de publicações identificou os estudos e revisões na literatura científica sobre as intervenções psicossociais e farmacológicas nos transtornos por uso de cannabis. RESULTADOS: Para adultos, as intervenções com base comportamental geram efeitos positivos significativos na abstinência e nas reduções no uso de cannabis. Em adolescentes, tratamentos similares e intervenções com base na família demonstraram eficácia. Entre os estudos, os índices de resposta parecem ser modestos mesmo com os mais potentes tratamentos psicossociais. As avaliações das abordagens farmacológicas para os transtornos por uso de cannabis têm ainda que fornecer dados sobre a eficácia clínica de qualquer medicação específica. Enfoques baseados em agonistas e antagonistas parecem ser os mais promissores. Os avanços na compreensão da neurobiologia do sistema canabinoide são fonte de otimismo no sentido de que a síntese de compostos que alteram o funcionamento do sítio receptor CB1 possa produzir medicações promissoras. CONCLUSÃO: As pesquisas clínicas identificaram tratamentos psicossociais eficazes, mas ainda não produziram farmacoterapias eficazes. Muitos estudos ainda têm que ser feitos para aumentar a potência e o acesso às intervenções para aqueles que buscam o tratamento para transtornos por uso de cannabis.

OBJECTIVE: Cannabis remains the most widely used illicit substance in most developed countries. Its addictive potential has been established and the need for interventions for cannabis-related problems has become apparent. This article provides a review of the research evaluating potential treatments for cannabis use disorders. METHOD: A search of publication databases identified research studies and reviews of the scientific literature on psychosocial and pharmacological interventions for cannabis use disorders. RESULTS: For adults, behaviorally-based interventions engender significant positive effects on abstinence and reductions in cannabis use. With adolescents, similar treatments and family-based interventions have demonstrated efficacy. Across studies, response rates appear modest even with the most potent psychosocial treatments. Evaluations of pharmacological approaches to cannabis use disorders have yet to provide clinical efficacy data for any specific medication. Agonist and antagonist approaches appear to offer the most promise. Advances in understanding of the neurobiology of the cannabinoid system provide optimism that the synthesis of compounds that alter CB1 receptor site functioning may produce promising medications. CONCLUSION: Clinical research has identified effective psychosocial treatments, but has yet to yield effective pharmacotherapies. Much work remains to enhance the potency of and access to interventions for those seeking treatment for cannabis use disorders.

Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse.

This naturalistic telephone survey study compared perceptions of withdrawal severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist assessed the severity of abstinence symptoms and a Likert scale assessed perceived relations between abstinence symptoms and relapse. A composite Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0 for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were also of similar magnitude, except craving and sweating were slightly higher for tobacco. Both groups reported that withdrawal contributed substantially to relapse, and the strength of these ratings was similar across groups. The diverse convenience sample examined in this study adds external validity and generalizability to prior studies that included only users not planning to quit or excluded many common types of cannabis users. The comparable withdrawal experience from these heterogeneous cannabis and tobacco users supports previous findings from controlled laboratory studies and indicates that real-world, frequent cannabis users perceive that withdrawal symptoms negatively affect their desire and ability to quit.

Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms.

BACKGROUND: This study assessed whether oral administration of delta-9-tetrahydrocannbinol (THC) effectively suppressed cannabis withdrawal in an outpatient environment. The primary aims were to establish the pharmacological specificity of the withdrawal syndrome and to obtain information relevant to determining the potential use of THC to assist in the treatment of cannabis dependence. METHOD: Eight adult, daily cannabis users who were not seeking treatment participated in a 40-day, within-subject ABACAD study. Participants administered daily doses of placebo, 30 mg (10 mg/tid), or 90 mg (30 mg/tid) oral THC during three, 5-day periods of abstinence from cannabis use separated by 7-9 periods of smoking cannabis as usual. RESULTS: Comparison of withdrawal symptoms across conditions indicated that (1) the lower dose of THC reduced withdrawal discomfort, and (2) the higher dose produced additional suppression in withdrawal symptoms such that symptom ratings did not differ from the smoking-as-usual conditions. Minimal adverse effects were associated with either active dose of THC. CONCLUSIONS: This demonstration of dose-responsivity replicates and extends prior findings of the pharmacological specificity of the cannabis withdrawal syndrome. The efficacy of these doses for suppressing cannabis withdrawal suggests oral THC might be used as an intervention to aid cannabis cessation attempts.

A cross-study comparison of cannabis and tobacco withdrawal.

A valid cannabis withdrawal syndrome has recently been established, but its clinical importance remains unclear. One method to assess the importance of cannabis withdrawal is to compare it with an established withdrawal syndrome. Cannabis and tobacco withdrawal studies that employed similar methods were used to compare six participant-rated and four observer-rated symptoms. Descriptive and graphic comparisons indicate that the magnitude and time course of withdrawal effects are similar across the two syndromes. These findings are consistent with other evidence supporting the clinical importance of the cannabis withdrawal syndrome. There remains a need for prospective experimental studies to replicate these findings.

The time course and significance of cannabis withdrawal.

Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, decreased appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset typically occurred between Days 1-3, peak effects between Days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these effects appeared comparable to tobacco and other withdrawal syndromes. These effects likely contribute to the development of dependence and difficulty stopping use. Criteria for cannabis withdrawal are proposed.