If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

News and social media coverage is associated with more downloads and citations of manuscripts that focus on substance use.

BACKGROUND: A variety of substance use-related topics are discussed in the public discourse; however, it is unknown how public discussion of published substance-related findings relates to manuscript downloads and citations. This manuscript examines how traditional and social media coverage of published findings about substance use affects downloads and scientific citations. METHODS: Altmetric and bibliographic information was obtained for manuscripts published in Drug and Alcohol Dependence between 2018 and 2019 (n = 943). Associations were examined between news and social media coverage (i.e., Twitter, Facebook) in relation to number of manuscript downloads and number of citations. This was done in a bivariable manner and in a multivariable manner examining correlates of being in the top 10th percentile of downloads and citations. RESULTS: 73.3 % of articles were shared on Twitter, 23.6 % were shared on Facebook, and 13.9 % were covered in news sources (with 4.0 % receiving major media coverage). Epidemiology papers were among the most covered in the news, and e-cigarette review papers were among the most downloaded. News and social media coverage were positively associated with number of downloads and citations in bivariable models and with achieving the top 10 % of downloads and citations in multivariable models (ps < .001). Publishing a press release was associated with higher likelihood of receiving additional news coverage (aPR = 7.85, 95 % CI: 5.15-11.97). CONCLUSIONS: Traditional and social media coverage of manuscripts focusing on substance use are associated with more downloads and citations. Researchers should consider sharing findings not only to increase downloads and citations but also to educate the general public.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

BACKGROUND: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). METHODS: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. RESULTS: The GE-XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications. CONCLUSIONS: Overall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.

Patterns of concurrent substance use among adolescent nonmedical ADHD stimulant users.

OBJECTIVES: There are growing concerns about nonmedical use of ADHD stimulants among adolescents; yet, little is known whether there exist heterogeneous subgroups among adolescents with nonmedical ADHD stimulant use according to their concurrent substance use. METHODS: We used latent class analysis (LCA) to examine patterns of past-year problematic substance use (meeting any criteria for abuse or dependence) in a sample of 2203 adolescent participants from the National Surveys on Drug Use and Health 2006-2011 who reported past-year nonmedical use of ADHD stimulants. Multivariable latent regression was used to assess the association of socio-demographic characteristics, mental health and behavioral problems with the latent classes. RESULTS: The model fit indices favored a four-class model, including a large class with frequent concurrent use of alcohol and marijuana (Alcohol/marijuana class; 41.2%), a second large class with infrequent use of other substances (Low substance class, 36.3%), a third class characterized by more frequent misuse of prescription drugs as well as other substances (Prescription drug+class; 14.8%), and finally a class characterized by problematic use of multiple substances (Multiple substance class; 7.7%). Compared with individuals in Low substance class, those in the other three classes were all more likely to report mental health problems, deviant behaviors and substance abuse service use. CONCLUSIONS: Adolescent nonmedical ADHD stimulants users are a heterogeneous group with distinct classes with regard to concurrent substance use, mental health and behavioral problems. The findings have implications for planning of tailored prevention and treatment programs to curb stimulant use for this age group.

Patterns of concurrent substance use among nonmedical ADHD stimulant users: results from the National Survey on Drug Use and Health.

AIMS: To examine patterns of concurrent substance use among adults with nonmedical ADHD stimulant use. METHODS: We used latent class analysis (LCA) to examine patterns of past-year problematic substance use (meeting any criteria for abuse or dependence) in a sample of 6103 adult participants from the National Surveys on Drug Use and Health 2006-2011 who reported past-year nonmedical use of ADHD stimulants. Multivariable latent regression was used to assess the association of socio-demographic characteristics, mental health and behavioral problems with the latent classes. RESULTS: A four-class model had the best model fit, including (1) participants with low probabilities for any problematic substance use (Low substance class, 53.3%); (2) problematic users of all types of prescription drugs (Prescription drug class, 13.3%); (3) participants with high probabilities of problematic alcohol and marijuana use (Alcohol-marijuana class, 28.8%); and (4) those with high probabilities of problematic use of multiple drugs and alcohol (Multiple substance class, 4.6%). Participants in the 4 classes had distinct socio-demographic, mental health and service use profiles with those in the Multiple substance class being more likely to report mental health and behavioral problems and service use. CONCLUSION: Nonmedical users of ADHD stimulants are a heterogeneous group with a large subgroup with low prevalence of problematic use of other substances. These subgroups have distinct patterns of mental health comorbidity, behavior problems and service use, with implications for prevention and treatment of nonmedical stimulant use.

A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence.

OBJECTIVES: To assess the efficacy and safety of varenicline (Chantix) for the treatment of alcohol dependence. Varenicline is a partial α4ß2 nicotinic acetylcholine agonist approved by the Food and Drug Administration for smoking cessation. It has reduced drinking in animal studies and in small studies of humans who were both heavy drinkers and smokers. This is the first multisite clinical trial of varenicline in a population of smokers and nonsmokers with alcohol dependence. METHODS: Men and women (n = 200) meeting the criteria for alcohol dependence were recruited across 5 clinical sites. Patients received double-blind varenicline or placebo and a computerized behavioral intervention. Varenicline was titrated during the first week to 2 mg/d, which was maintained during weeks 2 to 13. RESULTS: The varenicline group had significantly lower weekly percent heavy drinking days (primary outcome) (adjusted mean difference = 10.4), drinks per day, drinks per drinking day, and alcohol craving compared with the placebo group (P < 0.05). The average treatment effect on alcohol use was similar for smokers and nonsmokers. Varenicline was well-tolerated; adverse events were expected and mild. CONCLUSIONS: Varenicline significantly reduced alcohol consumption and craving, making it a potentially viable option for the treatment of alcohol dependence.

Comparison of cognitive performance in methadone maintenance patients with and without current cocaine dependence.

BACKGROUND: There is evidence for psychomotor and cognitive performance impairment in methadone maintenance patients (MMP), as well as in individuals with current cocaine dependence. It is unknown whether MMP with concurrent cocaine dependence perform worse on tests of cognitive function than MMP without cocaine dependence. METHODS: Performance was compared between MMP with and without current cocaine dependence (MMP/CD+; N = 53 and MMP/CD-; N = 24) on a standard battery of tasks designed to measure psychomotor performance, attention, episodic and working memory, and executive function. RESULTS: Participant characteristics were mostly similar across groups. However, the MMP/CD+ group had a shorter duration of methadone treatment, and a larger percentage of participants with self-reported 30-day poly-substance abuse and positive urine drug tests on the day of cognitive testing. There were no differences between the groups on measures of balance, psychomotor coordination, divided attention, working memory, most measures of episodic memory, or executive function. Relative to MMP/CD-, MMP/CD+ showed significant impairment on select measures of psychomotor performance/attention (simple reaction time and trail-making test A) and episodic memory (higher false alarm rates on recognition memory). CONCLUSIONS: The absence of differences between MMP/CD+ and MMP/CD- on measures of higher order cognitive functions, and the relatively small magnitude between-group differences on other measures suggest that current cocaine dependence, in the absence of cocaine intoxication, is unlikely to be associated with clinically meaningful increases in performance impairment in MMP.

Effects of oral caffeine pretreatment on response to intravenous nicotine and cocaine.

Previous research suggests that under conditions of chronic daily caffeine administration, caffeine increases the effects of nicotine. Little is known about the effects of caffeine pretreatment on response to nicotine under infrequent caffeine administration conditions. The present study examined whether infrequent (not on consecutive days) acute oral caffeine administration alters subject-rated, physiological, and monetary value effects of intravenous nicotine in regular users of caffeine, tobacco, and cocaine. To determine the specificity of effects of caffeine on response to nicotine, the effects of caffeine administration on response to intravenous cocaine (another short-acting stimulant) were also studied. Fourteen (1 woman) volunteers participated in this 3-4 week, double-blind, inpatient study. Volunteers participated in 10 experimental conditions in pseudo-randomized order, in which oral caffeine (250 mg/70 kg) or placebo was administered 1 hr before an intravenous injection, consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline. Infrequent acute caffeine pretreatment attenuated the increase resulting from 2 mg/70 kg nicotine administration on ratings of "rush," "good effects," "liking," "high," and "drowsy/sleepy." Caffeine had no significant effect on physiological response to nicotine. Caffeine had no significant effect on subject-rated and physiological response to cocaine, with the exception that caffeine significantly augmented blood pressure response to cocaine. In contrast to the previous research using chronic caffeine maintenance, these data suggest that infrequent acute caffeine administration may attenuate nicotine effects.

Cigarette smoking knowledge, attitudes, and practices of patients and staff at a perinatal substance abuse treatment center.

This study compares cigarette smoking knowledge, attitudes, and practices (S-KAP) of opioid- and other substance-dependent patients and their multidisciplinary staff at an outpatient perinatal substance abuse treatment center. Consenting patients (n = 95) and staff (n = 41) concurrently completed a modified form of the S-KAP survey instrument. Ninety-five percent of patients reported currently smoking, and half endorsed wanting "to quit smoking now." This patient desire to quit smoking was significantly underrated by staff compared to the patients themselves (p = .028). Both patients and staff demonstrated suboptimal knowledge of smoking health risks, but 73% of patients reported trying to quit with past pregnancies to avoid harm to the fetus/baby. Although results show that patients could benefit from smoking cessation strategies centered on smoking's fetal/neonatal health risks, organizational interventions that focus on changing staff attitudes about patient desire to quit smoking may first need to be implemented.

The relationship between antidepressant use and smoking cessation in pregnant women in treatment for substance abuse.

BACKGROUND: Bupropion's efficacy for smoking cessation in pregnant women is unknown. OBJECTIVES: To determine if substance-dependent women prescribed bupropion smoked fewer cigarettes/day than those prescribed citalopram/escitalopram or no antidepressant medication. METHODS: Comparison of smoking in bupropion (n = 11), citalopram/escitalopram (n = 17), and no antidepressant (n = 28) groups. RESULTS AND CONCLUSIONS: Trend for greater decrease in smoking for the bupropion vs. citalopram/escitalopram group [-6.4 vs. -.4 cigarettes/day (p = .276)], although the bupropion decrease was similar to that seen in the no antidepressant group [-5.3 cigarettes/day]. SCIENTIFIC SIGNIFICANCE: Data support continued study of bupropion in depressed pregnant substance-dependent smokers.

Relationship between cigarette use and mood/anxiety disorders among pregnant methadone-maintained patients.

This study investigates the association between cigarette use and current mood/anxiety disorders among pregnant opioid-dependent patients. Pregnant methadone-maintained women (N = 122) completed the Addiction Severity Index and Structured Clinical Interview for DSM-IV. Participants were categorized based on past 30 days cigarette use: no (n = 15) and any smoking (n = 107); this latter group was then subdivided into light (one to ten cigarettes/day; n = 55), and heavy smokers (11+ cigarettes/day; n = 52). Any smoking was significantly associated with any current mood/anxiety disorder (p < 0.001), any current mood disorder (p = 0.007), and any current anxiety disorder (p < 0.001). No significant association was found between specific level of cigarette use and mood/anxiety disorders. This association between smoking and psychiatric disorders has implications for the mental and physical health of methadone-maintained women and their children, and may contribute to the understanding of the physiological mechanisms underlying smoking and nicotine dependence.

Experimentally-induced spontaneous opiate withdrawal: relationship to cigarette craving and expired air carbon monoxide.

Smoking often increases after opioid use among those addicted to both opioids and nicotine, but the relationship between smoking and experimentally induced spontaneous opioid withdrawal (OW) has not been characterized. Six inpatient opioid-dependent smokers were stabilized on morphine 15 mg SC QID. Expired air carbon monoxide levels and smoking craving were measured for each participant on ten days when spontaneous OW was experimentally induced and on ten separate days in the absence of OW. Spontaneous OW was associated with significantly reduced carbon monoxide levels and smoking craving. Interestingly, craving was only reduced for items related to the positive reinforcing effects of smoking. These preliminary results suggest that OW may be a favorable context to initiate smoking cessation treatment interventions.

Diretrizes para o tratamento de pacientes com síndrome de dependência de opióides no Brasil / Brazilian guideline for the treatment of patients with opioids dependence syndrome

Existe uma prevalência relativamente baixa do uso de ópioides no Brasil, em particular envolvendo o uso não médico da codeína e de xaropes que contêm opióides. No entanto, a síndrome de dependência apresenta um significativo impacto total na mortalidade e morbidade. Nos últimos 20 anos, o avanço científico tem modificado nosso entendimento sobre a natureza da adição aos opióides e os variados tratamentos possíveis. A adição é uma doença crônica tratável se o tratamento for realizado e adaptado tendo em vista as necessidades do paciente específico. Há, de um fato, um conjunto de tratamentos que podem efetivamente reduzir o uso da droga, ajudar a gerenciar a fissura pela droga, prevenir recaídas e recuperar as pessoas para o funcionamento social produtivo. O tratamento da dependência de drogas será parte de perspectivas de longo prazo do ponto de vista médico, psicológico e social. Esta diretriz almeja fornecer um guia para os psiquiatras e outros profissionais de saúde que tratam de pacientes com Síndrome de Dependência de Opióides. Ela tece comentários sobre o tratamento somático e psicossocial que é utilizado nesses pacientes e revisa as evidências científicas e seu poder. Da mesma forma, os aspectos históricos, epidemiológicos e neurobiológicos da dependência de opióides são revisados.