Mindfulness impairments in individuals seeking treatment for substance use disorders

Background: Mindfulness training may be an effective treatment for substance use disorders (SUDs). Little research has been done, however, on baseline levels of mindfulness in the substance using population. Objectives/Methods: We investigated mindfulness levels using the Mindful Attention Awareness Scale (MAAS) in individuals presenting for substance use treatment, and compared polydrug vs. monodrug users, as well as investigated for differences between groups based on substance used, predicting that group means would fall below the mean obtained from a large national adult sample, that the different drug groups would have comparable scores, and that the polydrug users would have a significantly lower score than do monodrug users. Results: We found that the means of most drug groups were below the national mean, and that the polydrug users had a lower score on the MAAS than did monodrug users (4 vs. 3.6, p = 0.04). We were also surprised to find that opiate users had a significantly higher score (4.31) than did users of other substances (p = 0.02). Conclusion/Significance: These results suggest that mindfulness deficits may be common in the substance using population, that there may be sub-groups in which these deficits are more pronounced, and that they may be a suitable focus of SUD treatment. These findings lend support to the ongoing development of mindfulness-based treatments for SUDs, and suggest that particular sub-groups may benefit more than others. Future research can aim at clarifying these deficits, and at elucidating their clinical relevance.     

The use of bupropion SR in cigarette smoking cessation

Cigarette smoking remains the largest preventable cause of premature death in developed countries. Until recently nicotine replacement therapy (NRT) has been the only recognised form of treatment for smoking cessation. Bupropion, the first non-nicotine based drug for smoking cessation was licensed in the United States of America (US) in 1997 and in the United Kingdom (UK) in 2000 for smoking cessation in people aged 18 years and over. Bupropion exerts its effect primarily through the inhibition of dopamine reuptake into neuronal synaptic vesicles. It is also a weak noradrenalin reuptake inhibitor and has no effect on the serotonin system. Bupropion has proven efficacy for smoking cessation in a number of clinical trials, helping approximately one in five smokers to stop smoking. Up to a half of patients taking bupropion experience side effects, mainly insomnia and a dry mouth, which are closely linked to the nicotine withdrawal syndrome. Bupropion is rarely associated with seizures however care must be taken when co-prescribing with drugs that can lower seizure threshold. Also, bupropion is a potent enzyme inhibitor and can raise plasma levels of some drugs including antidepressants, antiarrhythmics and antipsychotics. Bupropion has been shown to be a safe and cost effective smoking cessation agent. Despite this, NRT remains the dominant pharmacotherapy to aid smoking cessation.     

Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates

Benzodiazepines exert their effects by binding to multiple subtypes of the GABAA receptor, the predominant subtypes in the brain being those that contain alpha1-, alpha2-, alpha3-, and alpha5-subunits. To understand the potentially different roles of these subtypes in the therapeutic and side effects of benzodiazepines, we evaluated GABAA receptor subtype-preferring compounds in nonhuman primate models predictive of anxiolytic, sedative, motor, subjective, and reinforcing effects of benzodiazepine-type drugs. These compounds included zolpidem, which shows preferential binding to GABAA receptors containing alpha1-subunits (alpha1GABAA receptors); L-838,417, which shows functional selectivity for alpha2GABAA, alpha3GABAA, and alpha5GABAA receptors; and nonselective conventional benzodiazepines. The results provide evidence in nonhuman primates that alpha1GABAA receptors do not play a key role in the anxiolytic and muscle-relaxant properties of benzodiazepine-type drugs; instead, these effects involve alpha2GABAA, alpha3GABAA, and/or alpha5GABAA subtypes. Our results also suggest that the alpha1GABAA receptor subtype might be critically involved in the subjective, sedative, and motor effects of benzodiazepine-type drugs. In contrast, stimulation of alpha1GABAA receptors is sufficient, but not necessary, for mediation of the abuse potential of these drugs.     

Brain tract structure predicts relapse to stimulant drug use

Diffusion tractography allows identification and measurement of structural tracts in the human brain previously associated with motivated behavior in animal models. Recent findings indicate that the structural properties of a tract connecting the midbrain to nucleus accumbens (NAcc) are associated with a diagnosis of stimulant use disorder (SUD), but not relapse. In this preregistered study, we used diffusion tractography in a sample of patients treated for SUD (n = 60) to determine whether qualities of tracts projecting from medial prefrontal, anterior insular, and amygdalar cortices to NAcc might instead foreshadow relapse. As predicted, reduced diffusion metrics of a tract projecting from the right anterior insula to the NAcc were associated with subsequent relapse to stimulant use, but not with previous diagnosis. These findings highlight a structural target for predicting relapse to stimulant use and further suggest that distinct connections to the NAcc may confer risk for relapse versus diagnosis.

Around the world during the year 2020, over 250 million people reported using drugs for nonmedical purposes, with 35.6 million conceding problematic use of drugs (1). Problematic drug use imposes a significant burden on individuals and societies alike by exacting substantial and lasting physical, psychological, economic, and social costs (2). Successful treatments are elusive and relapse remains prevalent (3, 4). Relapse rates vary as a function of substance type (5) but are particularly problematic in the case of stimulant use disorder (SUD) (6) (including [meth]amphetamine and [crack] cocaine). For instance, estimates indicate that ∼50% of methamphetamine users relapse within 6 mo and over 60% relapse within 12 mo after release from treatment (7). Consistent with these estimates, we previously found that 36% of SUD patients relapsed within 3 mo after release from treatment (8). Recent trends in drug use increase the urgency of addressing SUD. While cocaine remains a default choice of drug in the United States, use of stimulants like amphetamines increased by 40% from 2016 to 2018, coinciding with a surge in drug treatment admissions with amphetamine-type stimulants being the primary drug of concern (1). Research into key factors that contribute to relapse to stimulant use might reveal novel targets for prediction, intervention, and treatment.Predicting drug relapse represents an important first step toward developing better interventions for prevention, but very few measures reliably predict relapse to stimulant use (9). While many physiological, psychological, social, and clinical factors have been associated with the risk of relapse across a broad range of substances (3, 5), the role of these factors in relapse to stimulant use is less clear. Since addiction has been associated with alterations in neural circuits (10, 11), new neuroimaging methods offer the hope that neural markers related to addiction can be noninvasively measured in humans (12).Research on animal models has centrally implicated dopaminergic projections from the midbrain in addiction (13, 14). Specifically, dopamine release and activation of receptors in the nucleus accumbens (NAcc) plays a critical role in supporting drug self-administration (15, 16). Structurally, through its white-matter connections, NAcc projections then propagate signals through ascending prefrontal-striatal loops thought to convert affective impulses into motivated action (17–19). Functionally, NAcc activity in response to drug cues may predict relapse to stimulant use in human patients after leaving treatment (8). If NAcc activity can promote relapse in nonhuman as well as human models, then structural connections to the NAcc might modulate that activity. Specifically, both retrograde and anterograde tracer studies of nonhuman primates indicate that the NAcc receives glutamatergic projections from anterior aspects of the insula (18, 20, 21). The NAcc also receives glutamatergic projections from several amygdalar nuclei [including the basolateral, basal, basal accessory, central, and periamygdaloid nuclei (21–23)]. Finally, the striatum receives glutamatergic projections from prefrontal cortex (PFC) along a ventromedial to dorsolateral gradient. Specifically, ventromedial aspects of the striatum (including the NAcc) receive projections from orbitofrontal and ventromedial PFC regions, whereas dorsal regions of the striatum receive projections from more dorsolateral PFC regions (24, 25). While tracer studies do not describe the complete trajectory of these white matter tracts, they do confirm that the NAcc receives projections from anterior insula, amygdala, and medial PFC in nonhuman primates, which provides a strong anatomical foundation for inferring the existence of these connections in humans (18). We therefore sought to characterize the trajectory and structural characteristics of these prominent white matter tracts projecting to the NAcc in humans (or a “conNAcctome”) (Fig. 1A) using diffusion-weighted magnetic resonance imaging (DMRI).Open in a separate windowFig. 1.Tracing conNAcctome tracts. (A) Schematic of predicted conNAcctome tracts (in MNI space; z = ‒10). (B) VOIs used for tractography. (C) ConNAcctome tract renderings. All VOIs and renderings shown for a representative individual in their native space. VTA/SN, dopaminergic midbrain regions including ventral tegmental area, substantia nigra, and parabrachial nucleus.DMRI tractography offers a noninvasive method for tracking and characterizing brain structural connections (26, 27) that have previously been identified using more invasive methods [e.g., chemical tracing studies (28) or tissue clearing (29, 30)]. Different DMRI measures model the movement of water in the brain (or conversely, its occlusion) to support inference of underlying fiber bundles. For example, commonly used but distinct diffusion metrics include fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) (27, 31). Reduction of brain lipids using multiple methods [e.g., lipid removal (32), myelin-deficient mice (33, 34), and other animal models (35)] can causally and predictably alter these diffusion metrics (e.g., decreasing FA while increasing RD), implying that they may partially index lipid coherence and/or myelination (34). Increased FA has commonly been associated with tract coherence, based on the implication that tracts with greater coherence might more effectively transmit neural signals. Decreased RD has further been linked to microstructural properties of brain tissue [e.g., fiber spread (36), cell and axon density (37), and axon myelination (33, 35, 38)].Recent meta-analyses of DMRI studies of addiction suggest that patients with stimulant use disorder may have lower overall neural white matter coherence relative to healthy controls (31, 38). Most of this research, however, has employed whole brain approaches (such as tract-based spatial statistics [TBSS]), or focused on prominent large white-matter tracts [e.g., the corpus callosum and inferior longitudinal fasciculus (39–43)], rather than smaller tracts which project to subcortical regions (like the NAcc). Thus, the relevance of the structure of these conNAcctome tracts (Fig. 1A) for stimulant use, maintenance, and relapse has not yet been characterized.DMRI studies of healthy individuals, however, have begun to suggest more precise links between structural properties of projections from cortical regions to the NAcc and individual differences in affect and cognition, and some of these may hold relevance for addiction. First, structural properties of a tract connecting the medial prefrontal cortex (MPFC) to the NAcc have been associated with impulsivity in adults [or valuing present over larger future rewards (44)], and early onset of binge drinking in adolescents (45). Second, we have found associations of measures of right anterior insula (AIns)-NAcc tract coherence with reduced risk seeking (46) and increased control of impulsive responses in the face of large incentives (47). These findings fit with extensive previous work implicating structural properties and correlated activity particularly in the right AIns-NAcc tract region (48) with inhibitory control (49). Third, structural properties of the amygdala (Amy)-NAcc tract have been associated with novelty seeking (50) and impulsivity (51). Fourth, we have reported associations of midbrain-NAcc tract coherence with impulsivity and stimulant use disorder diagnosis, but not with subsequent relapse (52). Addiction initiation and relapse, however, may recruit different psychological processes and associated neural circuits (14, 53, 54).Here, we examined whether diffusion metrics of unidirectional white-matter projections to the NAcc from the MPFC, AIns [particularly on the right given previous findings (46, 47)], and Amy might predict relapse to stimulant use. We predicted that decreased diffusion metrics in these conNAcctome tracts might predict relapse to stimulant use (up to 6 mo after completing treatment) (46, 47). Since previous findings indicated that the structural coherence of a distinct tract connecting the midbrain to the NAcc was related to stimulant use diagnosis but not relapse, we used this midbrain-NAcc tract as a control comparison to test for double-dissociations (52).     

Predictors of pain medication use after percutaneous liver biopsy

The aim of this study is to identify risk factors for analgesic use following liver biopsy. In all, 121 consecutive biopsies were examined prospectively. Five variables were selected that might predict analgesia use: (1) anxiety, (2) request for sedation, (3) chronic use of addictive medications, (4) previous intravenous drug use, and (5) analgesia requirement with previous biopsies. Analgesia and narcotic requirement after liver biopsy were 35% and 15%, respectively. There was a lower average age (43 vs 47) (P = 0.03) and a higher Knodell score (7.2 vs 5.8) (P = 0.04) in those that required analgesics. The diagnosis of HCV (P = 0.007), previous intravenous drug abuse (IVDA) (P = 0.0001), request for medications before biopsy (P = 0.02), anxiety expressed (P = 0.0002), and chronic use of addictive medications (P = 0.03) predicted analgesia use. Previous IVDA (OR 9.3) and anxiety (OR 3.9) are predictive of pain medication use. In conclusion, patient characteristics play an important role in pain medication requirement after liver biopsy. If pain after liver biopsy is to be reduced, one has to understand the predisposing factors. Further studies utilizing behavior modification are warranted.     

A longitudinal assessment of change in marijuana use with other substance use problems

Background: Despite increasing marijuana use rates over the past decade, the longitudinal association between marijuana use and other substance use problems among adults is unclear. Objectives: To examine associations of self-reported changes in marijuana use and marijuana use frequency with self-reported other substance use problems over a 12-month period. Methods: Two waves (W1 and W2) of the Population Assessment of Tobacco and Health Study provided data. The study sample (N = 26,204, female = 13,261; male = 12,943, aged 18+) included W1-W2 never marijuana users, W1-W2 ex-users (used prior to 12 months of W1), and those who either quit, initiated, resumed, or continued marijuana use between W1 and W2. We used multinomial and binary logistic regression analyses. Results: The past-year marijuana use rate was 12.4% at W2. A quarter of W1 users quit using marijuana in the 12 months preceding their W2 interview, and one-third of all the W2 users were new/resumed users since W1. Compared to W1-W2 ex-users, W2 quitters were more likely to report alcohol use problems and tobacco addiction at W2. Compared to quitters, continued users were more likely to report alcohol use problems (RRR = 1.62, 95% CI = 1.27–2.07) and tobacco addiction (RRR = 1.37, 95% CI = 1.11–1.69). New users (RRR = 2.05, 95% CI = 1.12–3.74), resumed users (RRR = 2.69, 95% CI = 1.55–4.70), and continued users (RRR = 3.40, 95% CI = 2.08–5.55) reported more drug use problems. Compared to less frequent marijuana users, frequent users had greater odds of reporting alcohol use problems (RRR = 1.44, 95% CI = 1.21–1.72) and drug use problems (OR = 1.63, 95% CI = 1.19–2.23). Conclusions: Given increased prevalence of marijuana use, polysubstance use problems among marijuana users should be assessed.     

Problematic Internet use and daily difficulties among adolescents with school refusal behaviors: An observational cross-sectional analytical study

Problematic Internet use (PIU) is common and likely to coexist with mental health problems among adolescents with school refusal behavior. To date, no study has revealed to what extent PIU relates to the daily burden compared with other mental health problems. This study has examined the association between daily difficulties and PIU among adolescents with school refusal behaviors.This cross-sectional study involved all first-visit patients, regardless of diagnosis, aged 10 to 18 years at 2 child/adolescent psychiatric outpatient clinics in Yokohama City, Japan, from April 2016 to March 2018. The Questionnaire-Children with Difficulties (QCD) were obtained from parents. Simultaneously, the severity of PIU was evaluated using the Internet Addiction Test and depressive and anxiety symptoms were evaluated using the Patient Health Questionnaire-9 and General Anxiety Disorder-7 scale in the 2 weeks before the first-visit. From 684 first-visit patients, 227 with school refusal behaviors were enrolled in the study.PIU was observed in 40% of adolescents with school refusal behaviors. The QCD scores among patients with PIU were significantly lower than those in patients without PIU. Linear regression analysis revealed relationships between PIU and lower QCD scores throughout the day (except at night) and the total score of the day, after controlling for confounders such as depressive and anxiety symptoms.In conclusion, among adolescents with school refusal behaviors, PIU may affect their parent-assessed daily difficulties particularly experienced throughout the day.     

Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment

Background: There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. Objectives: To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. Method: This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men = 347, women = 169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. Results: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B = .33, p = .01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B = 1.67, p = .01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. Conclusion: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.     

Spirituality,Alcohol and Other Drug Problems

Summary

A brief examination of the history, central figures, and literature of spirituality in addiction studies is followed by a review of central concepts and a look toward the future of spirituality research. Some current initiatives are also examined.     

Evidence-Based Treatment for Opiate-Dependent Clients: Availability,Variation, and Organizational Correlates

The majority of opiate-dependent clients entering substance abuse treatment are referred to “drug-free” (non-methadone) modalities. Given the known challenges of treating these clients in drug-free settings relative to the documented effectiveness of methadone maintenance, these analyses investigate the availability of various clinical and wraparound services for this population among a US sample of addiction treatment programs with and without methadone maintenance services (N = 763). Face-to-face interviews conducted in 2002–2003 gathered data on the number of opiate-dependent clients treated; organizational characteristics, including size, ownership, accreditation, and staffing; treatment practices, including methadone availability, use of other pharmacotherapies, and levels of care; and services offered, including vouchers, transportation, and other wraparound services. Facilities treating proportionately more opiate-dependent clients were significantly more likely to offer a variety of evidence-based services, regardless of methadone availability. Implications for referral linkages and quality of care are discussed.     

Tobacco control and nicotine addiction in Canada: Current trends, management and challenges

Despite a significant decrease in tobacco use over the past four decades, cigarette smoking remains the leading preventable cause of death and disease in Canada. Nicotine addiction, unequal access to available support programs and gaps in continuity of health care are recognized as the main barriers to smoking cessation. To overcome these obstacles and to reach the Federal Tobacco Control Strategy goal of reducing smoking prevalence in Canada from 19% to 12% by 2011, several Canadian health care organizations developed extensive sets of recommendations. Improved access to affordable pharmacotherapies and behavioural counselling, better training of health care professionals and the addition of systemic cessation measures appear to be the key components in all of the proposed recommendations.The present article provides an overview of the current approaches to smoking cessation in Canada, describes the remaining challenges, and outlines recent recommendations that are geared toward not only tobacco control but also overall improvement in long-term health outcomes.     

Predictors of Early Recovery after Treatment for Alcohol use Disorders in Uganda

ABSTRACT

Data on treatment for AUD (Alcohol Use Disorders) in developing countries are scarce. This study explores aspects of early recovery and correlates of alcohol use after residential AUD treatment in Uganda. 78 respondents were followed up using, among others, the ASI-6, HCSL-37A and WHOQOL–BREF. They were interviewed within two weeks after admission in residential treatment and six months later. Significant reductions in addiction severity and psychopathology, as well as improvements in Quality of Life (QoL) were observed after treatment. Treatment environment, individual characteristics and problems with close friends were the main predictors of early recovery from AUD.