Brain and cortisol responses to smoking cues are linked in tobacco-smoking individuals.

Cues associated with smoking can induce relapse, which is likely driven by cue-induced neurobiological and physiological mechanisms. For instance, greater relapse vulnerability is associated with increases in cue-induced insula activation and heightened cortisol concentrations. Determining if there is a link between such cue-induced responses is critical given the need for biomarkers that can be easily measured in clinical settings and used to drive targeted treatment. Further, comprehensively characterising biological reactions to cues promises to aid in the development of therapies that address this specific relapse risk factor. To determine whether brain and cortisol responses to smoking cues are linked, this study recruited 27 nicotine-dependent tobacco-smoking individuals and acquired whole-brain functional activation during a cue reactivity task; salivary cortisol was measured before and after scanning. The results showed that increases in blood-oxygen-level-dependent activation in the right anterior insula and right dorsolateral prefrontal cortex (DLPFC) when viewing smoking versus neutral cues were positively correlated with a post-scan rise in salivary cortisol concentrations. These brain regions have been previously implicated in substance use disorders for their role in salience, interoception and executive processes. These findings show that those who have a rise in cortisol following smoking cue exposure also have a related rise in cue-induced brain reactivity, in brain regions previously linked with heightened relapse vulnerability. This is clinically relevant as measuring cue-induced cortisol responses is a more accessible proxy for assessing the engagement of cue-induced neurobiological processes associated with the maintenance of nicotine dependence.

Long-term agro-management strategies shape soil bacterial community structure in dryland wheat systems.

Soil microbes play a crucial role in soil organic matter decomposition and nutrient cycling and are influenced by management practices. Therefore, quantifying the impacts of various agricultural management practices on soil microbiomes and their activity is crucial for making informed management decisions. This study aimed to assess the impact of various management systems on soil bacterial abundance and diversity, soil enzyme activities and carbon mineralization potential in wheat-based systems. To accomplish this, soil samples from 0 to 15 cm depth were collected from ongoing long-term field trials in eastern Oregon region under wheat (Triticum aestivum L.)-fallow (WF), WF with different tillage (WT), wheat-pea (Pisum sativum L.) (WP), WF under different crop residue management (CR) and natural undisturbed/unmanaged grassland pasture (GP). These trials consisted of an array of treatments like tillage intensities, nitrogen rates, organic amendments, and seasonal residue burning. This study was a part of the Soil Health Institute's North American Project to Evaluate Soil Health measurements (NAPESHM). Bacterial community structure was determined using amplicon sequencing of the V4 region of 16SrRNA genes and followed the protocols of the Earth Microbiome Project. In addition, extracellular enzyme activities, and carbon mineralization potential (1d-CO2) were measured. Among different trials, 1d-CO2 in WT, WP, and CR studies averaged 53%, 51% and 87% lower than GP systems, respectively. Enzyme activities were significantly greater in GP compared to the other managements and followed similar trend as respiration. We observed higher evenness in GP and higher richness in spring residue burning treatment of CR study. Our results indicated that species evenness is perhaps a better indicator of soil health in comparison to other indices in dryland wheat systems.

Chronic cannabis use alters dACC-striatal glutamatergic balance.

Prefrontal and striatal glutamate plays an important role in modulating striatal dopamine levels and an imbalance in regional glutamate has been identified in several psychiatric conditions. We hypothesized that this imbalance also exists in cannabis use disorder (CUD). We recently quantified the difference in glutamate of dorsal anterior cingulate (dACC) and striatum regions in the frontostriatal pathway using proton MRS at baseline and on verified abstinent days 7 and 21 in chronic users of cannabis (n = 20) in comparison with age- and sex- matched non-using controls (n = 10). In addition, the Barratt Impulsiveness Scale-11 (BIS) was collected as a measure of inhibitory impulse control of the participants. We found that the difference in glutamate concentrations between the dACC and striatum (ΔdACC-strGlu) of the controls was significantly higher than that of cannabis users across the study timeline (F(1,28) = 18.32, p < 0.0005). The group difference was not affected by age, sex, or alcohol/cigarette consumption. On abstinent day 7, ΔdACC-strGlu was significantly correlated with the corresponding ΔdACC-strGABA among the users (r = 0.837, p < 0.00001). On day 21, ΔdACC-strGlu was negatively associated with monthly cannabis use days (Spearman's rho = -0.444, p = 0.05). Self-reported BIS and its subscales were significantly altered among the users compared to the controls across the study timeline (total F(1,28) = 7.0, p = 0.013; non-planning F(1,28) = 16.1, p < 0.0005; motor F(1,28) = 5.9, p = 0.022; cognitive F(1,28) = 6.1, p = 0.019). These data provide preliminary evidence that chronic cannabis use may lead to a dACC-striatal glutamate imbalance in conjunction with poor impulse control.

Multi-modal assessment of reward functioning in adolescent anhedonia.

BACKGROUND: Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear. METHODS: We recruited a sample of adolescents (n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life. RESULTS: Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome. CONCLUSIONS: Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.

Leaf Tissue Macronutrient Standards for Northern Highbush Blueberry Grown in Contrasting Environments.

Leaf tissue testing is a useful tool for monitoring nutrient requirements in northern highbush blueberry (Vaccinium corymbosum L.; abbreviated as "blueberry") but may require adaptation to specific growing environments. The objective of this study was to evaluate macronutrient concentrations in early-, mid-, and late-season blueberry cultivars grown in two contrasting environments, specifically eastern and western Washington. Climate and soil conditions between these two regions differ tremendously with eastern Washington being more arid with naturally calcareous soils lower in soil organic matter. Sampling was conducted over a 3-year period in commercial fields. Leaf tissue nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg) and sulfur (S) concentrations were affected by year (Y), growing region (R), cultivar (C), and Day of Year (DOY) that the samples were collected with many interactions. Leaf nutrient concentrations were higher, on average, in western than eastern Washington except for Ca and Mg, indicating sufficiency levels should differ between these regions. Leaf macronutrients generally stabilized between DOY 212-243 (1-31 August), suggesting this period is optimal for tissue sampling. Findings from this study demonstrate the importance of considering regional effects and may be applicable for blueberry cultivated in similar pedo-climactic conditions around the world.

When do cover crops reduce nitrate leaching? A global meta-analysis.

The global increases in the surface and groundwater nitrate (NO3 - ) concentrations due to synthetic fertilizer input have emerged as major sustainability threats to terrestrial and aquatic ecosystems. Cover crops can reportedly reduce nitrate leaching from croplands. However, the underlying mechanisms and the effectiveness of cover crops in reducing nitrate leaching across species, soil types, agronomic management, and climates remain elusive. We conducted a global meta-analysis to evaluate the effects of cover crops on nitrate leaching and water drainage. A random-effects analysis was established to investigate seven moderating variables in 41 articles. Results showed that globally, cover crops reduced nitrate leaching by 69% compared with fallow while demonstrating no effect on water drainage. Overall, cover crops from Brassicaceae and Poaceae families showed the greatest effect with 75% and 52% reduction in nitrate leaching, respectively. Cover cropping on Ultisols, Histosols, and Inceptisols resulted in the greatest reduction in nitrate leaching (77%, 78%, and 77%, respectively). Greater efficacy of cover crops at reducing nitrate leaching was evident with increasing soil sand content. In general, cover crops appeared to perform better to reduce nitrate leaching in vegetable systems compared to field crops. Cover cropping on conventional tillage resulted in a 63% reduction in nitrate leaching compared with no-tillage (50%) and reduced tillage (38%) systems. The impact of cover crops on water drainage was nonsignificant which implies that nitrate leaching control by cover crops is unlikely exerted through reducing water drainage. This study brings further insight into the intrinsic factors affecting cover crop efficacy and management practices that enhance cover crop potential in reducing nitrate leaching from agricultural systems.

Lower dACC glutamate in cannabis users during early phase abstinence.

Glutamate plays an important role in continued use of and relapse to abused substances. However, its involvement in cannabis withdrawal is still unclear. We hypothesize that regional glutamate is associated with the cannabis withdrawal syndrome and recently examined possible association of glutamate with cannabis withdrawal, using magnetic resonance spectroscopy (MRS), in non-treatment-seeking cannabis users. We recruited 26 frequent cannabis users and 11 age-matched non-using controls. Of the 37, 20 users (8f/12m) and 10 controls (5f/5m) completed a verified 21-day abstinence protocol. Dorsal anterior cingulate cortex (dACC) glutamate and γ-amino butyric acid (GABA) were measured with proton MRS at baseline and on abstinent days 7 and 21 in conjunction with measures of cannabis withdrawal and craving (MCQ), sleep difficulties (PSQI) and mood state. We used ANOVA to examine group differences in glutamate and GABA from baseline through day 21 and used linear regression to evaluate correlations between intra-individual glutamate and withdrawal symptoms. We found that self-reported anxiety severity (HAMA) was correlated with urinary THC/Cr ratios at baseline (r = 0.768, p = 0.000076) and abstinent day 7 (r = 0.5636, p = 0.0097), dACC glutamate was significantly lower in the users compared with the controls from baseline through day 21 (F = 5.90, p = 0.022), changes in glutamate between baseline and abstinent day 21 had a significantly negative correlation with corresponding changes in craving (r = -0.72, p = 0.005) after adjusting for age, consumption of alcohol/cigarettes, sleep difficulties, and urinary THC levels. These findings provide preliminary evidence that dACC glutamate is associated with the cannabis withdrawal syndrome.

Clinical utility of a hybrid secondary and relapse prevention program in adults with mild intellectual disability in community residential and day habilitation settings.

BACKGROUND: Despite evidence that standard substance use disorder (SUD) treatment may be less effective in people with intellectual disability (ID), there is an absence of appropriate clinical tools with which to support them. OBJECTIVES: This study examined the clinical utility of an alcohol and other drug refusal skills intervention designed to be cognitively accessible to adults with ID METHODS: Thirty individuals at high risk for or in recovery from a SUD in developmental disability services (DDS) community residential and day habilitation settings participated in the two-week refusal skills group. Measures included pretest versus posttest improvement in refusal skill competency and baseline performance on a standardized verbal learning test. RESULTS: There was a strong effect for refusal skill acquisition (p < .001); and the magnitude of skill acquisition was predicted by group attendance (p < .001) and not by individual differences in verbal learning ability (p = .074) or efficiency (p = .35). CONCLUSIONS: The Refusal Skills Group is developmentally appropriate for people with mild ID in that: (1) they can learn and demonstrate refusal skills and (2) their skill acquisition is predicted more strongly by exposure to the intervention than by individual differences in learning characteristics. Delivering refusal skills in DDS settings familiar to clients increased their access to services and minimized disruption to their usual routines and schedules.

Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model.

Brain derived neurotrophic factor (BDNF) promotes the growth, differentiation, maintenance and survival of neurons. These attributes make BDNF a potentially powerful therapeutic agent. However, its charge, instability in blood, and poor blood brain barrier (BBB) penetrability have impeded its development. Here, we show that engineered clathrin triskelia (CT) conjugated to BDNF (BDNF-CT) and delivered intranasally increased hippocampal BDNF concentrations 400-fold above that achieved previously with intranasal BDNF alone. We also show that BDNF-CT targeted Tropomyosin receptor kinase B (TrkB) and increased TrkB expression and downstream signaling in iTat mouse brains. Mice were induced to conditionally express neurotoxic HIV Transactivator-of-Transcription (Tat) protein that decreases BDNF. Down-regulation of BDNF is correlated with increased severity of HIV/neuroAIDS. BDNF-CT enhanced neurorestorative effects in the hippocampus including newborn cell proliferation and survival, granule cell neurogenesis, synaptogenesis and increased dendritic integrity. BDNF-CT exerted cognitive-enhancing effects by reducing Tat-induced learning and memory deficits. These results show that CT bionanoparticles efficiently deliver BDNF to the brain, making them potentially powerful tools in regenerative medicine.

Elevated striatal glutamate + glutamine in recreational cannabis users during abstinence.

Cannabis withdrawal symptoms contribute to relapse, but the underlying mechanism remains unclear. We hypothesize that cannabis withdrawal may be associated with a reset of regional γ-amino butyric acid (GABA) and glutamate concentrations secondary to changes in the endocannabinoid system during abstinence and conducted a study on this issue. We used magnetic resonance spectroscopy (MRS) to detect the associated changes of these neurochemicals in twenty-six frequent, recreational cannabis users and eleven age-matched non-using controls. Twenty users (8F/12M) and ten control (5F/5M) participants completed a verified 21-day abstinence period. Striatal GABA and glutamine concentrations were measured at baseline and on abstinence days 7 and 21 in conjunction with measures of cannabis withdrawal symptoms and mood state. Cannabis users reported increased self-reported ratings of cannabis-withdrawal-symptoms on abstinence day 7 relative to controls. Striatal glutamate + glutamine (Glx) group concentrations were elevated in cannabis users at baseline and abstinence days 7 and 21 (F = 7.16, p = 0.012), and changes in GABA concentration and withdrawal symptoms between baseline and abstinence day 7 were positively correlated (r = 0.550, p = 0.010). In addition, baseline striatal GABA concentrations were negatively correlated with withdrawal symptoms on abstinence day 7 (r = -0.680, p = 0.003). Our data demonstrate that striatal Glx was elevated in cannabis users and baseline striatal GABA correlated with withdrawal during the abstinence. In addition, striatal GABA may temporally correlate with self-reported withdrawal symptoms during the initial days of abrupt cannabis abstinence. These findings provide preliminary evidence that striatal GABA and Glx are associated with the severity of cannabis withdrawal.

Dronabinol inhibits alveolar bone remodeling in tooth movement of rats.

INTRODUCTION: Orthodontic tooth movement is reliant on the process of bone remodeling, and a variety of medications impact the ability of teeth to move through bone. Marijuana is the most widely used recreational drug in the world, and early studies suggest the drug impacts bone remodeling as tetrahydrocannabinol binds to cannabinoid receptors which play a role in bone homeostasis. This study aimed to assess the impact of dronabinol on alveolar bone remodeling in rats with otherwise healthy tissue when subjected to orthodontic forces. METHODS: Thirty male Sprague Dawley rats were equally allocated into 2 groups. Orthodontic appliances were placed in all animals, which consisted of a nickel-titanium coil ligated from the maxillary first molar to the central incisor. The appliance was activated to deliver a force to move teeth together. Over 21 days, daily injections of either dronabinol or the control (solvent) were given to the rats. Cephalometric analysis, histology, and bone remodeling profiles of both groups were analyzed and compared. RESULTS: Teeth moved in both the dronabinol and control groups (P <0.05). Tooth movement in the control group followed the typical process of orthodontic tooth movement: periodontal width narrowing and bone resorption on the compression side of the tooth, with an overall decrease in the height of the alveolar bone. In contrast, the dronabinol group showed an abnormal response to tooth movement: no bone resorption on the compression side of the tooth, increased bone formation on the tension side, and the maintenance of the height of the alveolar crest. In the dronabinol group, there were also significantly more osteoclasts and osteoblasts in the alveolar bone than in the control group. CONCLUSIONS: These results demonstrate that dronabinol attenuates orthodontic tooth movement by decreasing bone resorption, which could have implications for other bone-related recovery processes.

Denoising scanner effects from multimodal MRI data using linked independent component analysis.

Pooling magnetic resonance imaging (MRI) data across research studies, or utilizing shared data from imaging repositories, presents exceptional opportunities to advance and enhance reproducibility of neuroscience research. However, scanner confounds hinder pooling data collected on different scanners or across software and hardware upgrades on the same scanner, even when all acquisition protocols are harmonized. These confounds reduce power and can lead to spurious findings. Unfortunately, methods to address this problem are scant. In this study, we propose a novel denoising approach that implements a data-driven linked independent component analysis (LICA) to identify scanner-related effects for removal from multimodal MRI to denoise scanner effects. We utilized multi-study data to test our proposed method that were collected on a single 3T scanner, pre- and post-software and major hardware upgrades and using different acquisition parameters. Our proposed denoising method shows a greater reduction of scanner-related variance compared with standard GLM confound regression or ICA-based single-modality denoising. Although we did not test it here, for combining data across different scanners, LICA should prove even better at identifying scanner effects as between-scanner variability is generally much larger than within-scanner variability. Our method has great promise for denoising scanner effects in multi-study and in large-scale multi-site studies that may be confounded by scanner differences.

Interactive effects of age and recent substance use on striatal shape morphology at substance use disorder treatment entry.

BACKGROUND: Striatal neuroadaptations are regarded to play an important role in the progression from voluntary to compulsive use of addictive substances and provide a promising target for the identification of neuroimaging biomarkers. Recent advances in surface-based computational analysis enable morphological assessment linking variations in global and local striatal shape to duration and magnitude of substance use with a degree of sensitivity that exceeds standard volumetric analysis. METHODS: This study used a new segmentation methodology coupled with local surface-based indices of surface area and displacement to provide a comprehensive structural characterization of the striatum in 34 patients entering treatment for substance use disorder (SUD) and 49 controls, and to examine the influence of recent substance use on abnormal age-related striatal deformation in SUD patients. RESULTS: Patients showed a small reduction in striatal volume and no difference in surface area or shape in comparison to controls. Between-group differences in shape were likely neutralized by the bidirectional influence of recent substance use on striatal shape in SUD patients. Specifically, there was an interaction between age and substance such that among older patients more drug use was associated with greater inward striatal contraction but more alcohol use was associated with greater outward expansion. CONCLUSIONS: This study builds on previous work and advances our understanding of the nature of striatal neuroadaptations as a potential biomarker of disease progression in addiction.

Craving and Cue Reactivity in Nicotine-Dependent Tobacco Smokers Is Associated With Different Insula Networks.

BACKGROUND: The insula has a well-established role in nicotine dependence and is a node of the salience network, which integrates internal and external information to guide behavior. Recent findings reveal that internal and external processing occurs in the ventral anterior insula (vAI) and dorsal anterior insula (dAI), respectively. Whether vAI/dAI network connectivity differentially reflects internally generated craving and externally triggered smoking cue reactivity was tested. METHODS: Thirty-six male and female nicotine-dependent individuals smoked 1 hour before functional magnetic resonance imaging. Baseline craving was measured, followed by resting-state and smoking cue reactivity scans and then another assessment of craving. Craving and cue reactivity interactions were measured by focusing on specific nodes of the salience network: the vAI/dAI and anterior cingulate cortex. RESULTS: Resting-state vAI/dAI networks overlapped with the prototypical salience network, yet they possessed distinct patterns, linking the vAI with nodes of the internally focused default mode network and the dAI with nodes of the external, goal-related frontoparietal network. Internally generated baseline craving was associated with enhanced vAI connectivity, whereas rostral anterior cingulate cortex reactivity to external smoking cues was associated with greater dAI connectivity. We also found that cue reactivity in the rostral anterior cingulate cortex was associated with a rise in subjective cue-induced craving, whereas baseline subjective craving did not influence brain cue reactivity. CONCLUSIONS: These data show that brain reactivity to smoking cues is associated with a subsequent increase in craving. In addition, separate insula networks have a role in an individual's vulnerability to internally related craving and externally triggered cue reactivity, which could guide the development of new, neurobiologically targeted therapies.

A Preliminary Examination of Nicotine-Free Electronic Cigarette Use During Cessation From Combustible Cigarettes.

Despite the availability of smoking cessation strategies, smoking cue-induced craving remains a relatively untreated relapse risk factor. Utilizing nicotine-free electronic cigarettes (e-cigarettes) to extinguish the motivational influence of smoking cues may be a viable approach to address cue reactivity. In this pilot study, 26 daily tobacco smokers used nicotine-free e-cigarettes while being maintained on daily transdermal sustained-release nicotine replacement therapy (NRT) to mitigate pharmacological withdrawal. Sensitivity to cue-induced craving, measured by the rise in craving after a visual cue exposure task, was assessed at a baseline visit after smoking as usual and again after 2 weeks of nicotine-free e-cigarette and NRT use. Participants' pattern and amount of tobacco cigarette smoking were evaluated on both visits and 1 month posttreatment. Cue-induced craving significantly decreased after the 2-week intervention, yet withdrawal scores increased during this time. One month after study completion, participants continued to report significantly lower overall cigarette craving and conventional tobacco cigarette use. Including the 34.8% that were totally abstinent, 65.2% reported smoking fewer than 10 cigarettes per week (compared to 87.2 per week at baseline for the entire group). A linear regression revealed that greater baseline cue-induced craving predicted better outcomes, whereas more withdrawal at the e-cigarette visit was related to more smoking at 1 month. This proof-of-concept pilot study suggests that the addition of ad libitum nicotine-free e-cigarettes to an existing strategy of transdermal NRT may attenuate cue-induced craving for tobacco smoking. A larger sample that is powered for detecting additional factors and longer-term outcomes is warranted.

Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs.

Over the years, pain has contributed to low life quality, poor health, and economic loss. Opioids are very effective analgesic drugs for treating mild, moderate, or severe pain. Therapeutic application of opioids has been limited by short and long-term side effects. These side effects and opioid-overuse crisis has intensified interest in the search for new molecular targets and drugs. The present review focuses on salvinorin A and its analogs with the aim of exploring their structural and pharmacological profiles as clues for the development of safer analgesics. Ethnopharmacological reports and growing preclinical data have demonstrated the antinociceptive effect of salvinorin A and some of its analogs. The pharmacology of analogs modified at C-2 dominates the literature when compared to the ones from other positions. The distinctive binding affinity of these analogs seems to correlate with their chemical structure and in vivo antinociceptive effects. The high susceptibility of salvinorin A to chemical modification makes it an important pharmacological tool for cellular probing and developing analogs with promising analgesic effects. Additional research is still needed to draw reliable conclusions on the therapeutic potential of salvinorin A and its analogs.

Early onset cigarette smokers exhibit greater P300 reactivity to smoking-related stimuli and report greater craving.

Adolescence is a period during which a number of critical neuromaturation processes occur and the vulnerability for developing nicotine dependence is extremely high. Thus, early-onset (EO; age < 16 years old), relative to late-onset (LO; age ≥ 16 years old), tobacco smoking may be uniquely deleterious for developmentally immature systems that regulate neural signaling reactivity. This study investigated how age of tobacco smoking onset affects neurophysiological measures of smoking cue reactivity and reported craving in adult smokers. EO smokers (EOS; n = 8; 4 females), LO smokers (LOS; n = 10; 5 females), and healthy non-smokers (HNS; n = 10; 5 females) participated in an event-related potential (ERP) cue reactivity study with tactile and image stimuli. Participants handled neutral objects during one interval and smoking-related objects during a second interval. After each interval, they viewed smoking-related, neutral, or arousing images using an oddball paradigm. P300 ERPs and craving for tobacco were recorded during each session. P300 amplitudes were significantly higher in central midline (Cz) channel to smoking, but not neutral or arousing, images after handling smoking objects. Specifically, Cz P300 smoking amplitudes were significantly greater in EOS, relative to LOS and HNS, and associated with greater craving at baseline. There were no other group differences in mood or craving. EOS exhibited greater P300 reactivity to smoking-related stimuli, relative to LOS, suggesting a more sensitized neural response. EO smoking during early neuromaturation may alter neurophysiological signaling involved in responding to smoking-related stimuli, which could impact the outcome of smoking cessation interventions.

Early onset tobacco cigarette smokers exhibit deficits in response inhibition and sustained attention.

BACKGROUND: Initiation of cigarette smoking during adolescence coincides with structural and cognitive neuromaturation. Thus, early onset smokers (EOS; initiated <16 years old) may be at unique risk of altered development of executive function relative to late onset smokers (LOS; initiated >16 years old). This study quantified the effects of age of smoking onset on response impulsivity and inhibitory control using a novel smoking Go/NoGo task (Luijten et al., 2011). METHODS: Nicotine deprived adult EOS (n = 10) and LOS (n = 10) and adult healthy non-smokers (HNS; n = 10) were shown smoking-related and neutral images with either a blue (Go) or yellow (NoGo) frame. Participants were instructed to respond to blue-framed Go trials quickly and accurately, and withhold responding for yellow-framed NoGo trials. RESULTS: EOS made more Go response accuracy errors (p ≤ 0.02) and failed more frequently to inhibit responses to NoGo trials (p < 0.02) than LOS and HNS. EOS also made more errors in inhibiting responses to smoking-related (p ≤ 0.02) and neutral (p ≤ 0.02) NoGo trials. EOS reported greater baseline craving for cigarette smoking than LOS (p < 0.04), and craving was significantly associated with greater omission errors (p ≤ 0.04). CONCLUSIONS: EOS exhibited greater difficulty than LOS in responding accurately to Go stimuli and withholding responses to both smoking and neutral NoGo stimuli, indicating greater response impulsivity, poor attention, and deficits in response inhibition. These findings suggest that EO smoking, in particular, contributes to diminished task-related attention and inhibitory control behaviors in adulthood and provide support for the tobacco-induced neurotoxicity of adolescent cognitive development (TINACD) theory (DeBry and Tiffany, 2008).

Reduced interhemispheric executive control network coupling in men during early cocaine abstinence: A pilot study.

BACKGROUND: Individuals who use cocaine have fewer cognitive resources needed to maintain abstinence. This is evidenced by blunted brain function during cognitive control tasks and reduced communication between brain regions associated with cognitive function. For instance, relapse vulnerability is heightened in individuals with less communication between the right and left frontoparietal executive control network (ECN). Given that recent cocaine use enhances such communication, it is plausible that recency of cocaine use influences interhemispheric ECN communication. However, it is unclear whether ECN communication weakens over the course of early cocaine abstinence, which may then enhance relapse risk. METHODS: In ten men with cocaine use disorder, we conducted a preliminary assessment of the relationship between the number of days since last cocaine use (1-3days) and interhemispheric ECN coupling using resting state functional magnetic resonance imaging (fMRI). RESULTS: Reduced interhemispheric ECN coupling was associated with increasing days since last cocaine use; weaker coupling was also associated with lower urine cocaine metabolite concentrations. This association was more prominent in prefrontal than parietal ECN-subregions. CONCLUSIONS: Preliminary results indicate that resting state interhemispheric ECN coupling weakens within the first few days following last cocaine use. Because of the known link between reduced ECN interhemispheric coupling and relapse vulnerability, these results suggest that relapse risk may increase the longer an individual abstains during an early quit attempt. Treatments focused on reversing this coupling deficit may facilitate abstinence.

Nabilone pharmacotherapy for cannabis dependence: A randomized, controlled pilot study.

BACKGROUND AND OBJECTIVES: We assessed the safety, tolerability, and preliminary efficacy of nabilone, a cannabinoid agonist, to treat cannabis dependence. METHODS: Eighteen adults with DSM-IV cannabis dependence were randomized to receive either 2 mg/day of nabilone (n = 10) or placebo (n = 8) for 10 weeks in addition to medication management. Twelve participants, six in each group, completed treatment. The safety and tolerability of nabilone was assessed at each visit. Any side effects from nabilone or the placebo were documented. Cannabis use outcomes were assessed via self-report of days of use and twice-weekly urine cannabinoid tests; secondary outcomes included cannabis craving and anxiety. RESULTS: We assessed safety and tolerability at each study visit. A total of eight adverse events, all mild or moderate, were reported in two participants in the nabilone group, and six events were reported in four participants in the placebo group during study treatment. A total of eight adverse events were reported in two participants in the nabilone group and six events were reported in four participants in the placebo group during study treatment. All reported adverse events were rated mild-to-moderate. There were no side effects deemed serious enough to be classified as an FDA-defined serious adverse event. In general, participants in both groups reported reduced cannabis use according to self-report over the course of the study, although these reductions were not statistically discernible. Moreover, there was no difference in cannabis use between the nabilone group and the placebo group as measured by self-report. DISCUSSION AND CONCLUSIONS: Nabilone pharmacotherapy was safe and well-tolerated in participants with cannabis dependence. Future studies might evaluate a higher dose of nabilone to determine its effects on cannabis use outcomes in participants with cannabis dependence. SCIENTIFIC SIGNIFICANCE: There remains a clear need for additional pharmacotherapy trials for cannabis dependence, and nabilone remains a candidate for such trials. (Am J Addict 2017;26:795-801).