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.

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.

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).

Improved low-cost, MR-compatible olfactometer to deliver tobacco smoke odor.

We describe a low-cost, MRI-compatible olfactometer that delivers fresh cigarette smoke odor, a challenging odorant to present, as well as other odorants. This new olfactometer retains all of the advantages of an earlier design that was capable of only delivering volatile odors (Lowen & Lukas, Behavior Research Methods, 38, 307-313, 2006). The new system incorporates a novel switching mechanism that allows it to deliver fresh smoke generated from a burning cigarette during a stimulus presentation paradigm that might be employed in a cue-reactivity experiment. An evaluation study established that the olfactometer reliably delivered smoke to the participants and that tobacco smoke was discriminated from other odorants; there were no adverse reactions to the device.

Default Mode Network Functional Reorganization During Early Abstinence in Polysubstance-Using Emerging Adults Treated for Opioid Dependence.

This study examined default mode network connectivity within the first 30 days of abstinence in emerging adults entering treatment for opioid dependence. There were significant associations between abstinence duration and coupling strength with brain regions within and outside of the network.

Memory retrieval of smoking-related images induce greater insula activation as revealed by an fMRI-based delayed matching to sample task.

Nicotine dependence is a chronic and difficult to treat disorder. While environmental stimuli associated with smoking precipitate craving and relapse, it is unknown whether smoking cues are cognitively processed differently than neutral stimuli. To evaluate working memory differences between smoking-related and neutral stimuli, we conducted a delay-match-to-sample (DMS) task concurrently with functional magnetic resonance imaging (fMRI) in nicotine-dependent participants. The DMS task evaluates brain activation during the encoding, maintenance and retrieval phases of working memory. Smoking images induced significantly more subjective craving, and greater midline cortical activation during encoding in comparison to neutral stimuli that were similar in content yet lacked a smoking component. The insula, which is involved in maintaining nicotine dependence, was active during the successful retrieval of previously viewed smoking versus neutral images. In contrast, neutral images required more prefrontal cortex-mediated active maintenance during the maintenance period. These findings indicate that distinct brain regions are involved in the different phases of working memory for smoking-related versus neutral images. Importantly, the results implicate the insula in the retrieval of smoking-related stimuli, which is relevant given the insula's emerging role in addiction.

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm.

Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or "resting state networks" (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien). Zolpidem is a positive modulator of γ-aminobutyric acid(A) (GABA(A)) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n=12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABA(A) receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects.

Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: a bold FMRI study.

Oral naltrexone reduces heavy drinking, but is less consistent as an abstinence promoter, whereas once-monthly extended-release naltrexone (XR-NTX) also maintains abstinence. The present study sought to determine if alcohol cue reactivity is attenuated by XR-NTX. Twenty-eight detoxified alcohol-dependent adult male and female volunteers received a single i.m. injection of either XR-NTX or placebo under double-blind conditions. An fMRI/cue reactivity procedure was conducted immediately before and two weeks after injection. At baseline, alcohol-related visual and olfactory cues elicited significant increases in orbital and cingulate gyri, inferior frontal and middle frontal gyri. Subsequently, brain activation was significantly altered in XR-NTX-treated individuals. These affected brain regions are associated with the integration of emotion, cognition, reward, punishment, and learning/memory, suggesting that XR-NTX attenuates the salience of alcohol-related cues. Such an effect on brain function may interrupt the processes associated with "slips" and relapse, which may account for XR-NTX's ability to maintain abstinence.

Magnetic resonance spectroscopy study of the glutamatergic system in adolescent males with high-functioning autistic disorder: a pilot study at 4T.

The pilot study aimed at examining the neural glutamatergic activity in autism. Seven adolescent males (mean age: 14 ± 1.8; age range: 12-17 years) with intact intellectual capacity (mean IQ: 108 ± 14.26; IQ range: 85-127) suffering from autistic disorder and an equal number of age- and sex-matched healthy controls underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results indicated significantly high glutamate (Glu) levels in the anterior cingulate cortex of autistic disorder versus control subjects (paired t test p = 0.01) and a trend for lower Glu in the right medial temporal lobe, which was not statistically different between the groups (paired t test p = 0.06). These preliminary findings support the glutamatergic dysregulation hypothesis in autism and need to be replicated in a larger sample.

Cognitive behavioral therapy and the nicotine transdermal patch for dual nicotine and cannabis dependence: a pilot study.

BACKGROUND AND OBJECTIVES: We assessed the feasibility of a new cognitive behavioral therapy (CBT) manual, plus transdermal patch nicotine replacement therapy (NRT), to treat co-occurring nicotine and cannabis dependence. METHOD: Seven of 12 (58.3%) adults with DSM-IV diagnoses of both nicotine and cannabis dependence completed 10 weeks of individual CBT and NRT. RESULTS: Participants smoked 12.6 ± 4.9 tobacco cigarettes per day at baseline, which was reduced to 2.1 ± 4.2 at the end of treatment (F[5] = 23.5, p < .0001). The reduction in cannabis use from 10.0 ± 5.3 inhalations per day at baseline to 8.0 ± 5.3 inhalations per day at 10 weeks was not significant (F[5] = 1.12, p = .37). There was a significant decrease from the mean baseline Fagerstrom Test for Nicotine Dependence scores at weeks 4, 6, 8, and 10 of treatment (F[4] = 19.8, p < .001) and mean Client Satisfaction Questionnaire scores were uniformly high (30.6 ± 1.9). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: A CBT plus NRT treatment program significantly reduced tobacco smoking but did not significantly reduce cannabis use in individuals with co-occurring nicotine and cannabis dependence. There was no compensatory increase in cannabis use following the reduction in tobacco smoking, suggesting that clinicians can safely pursue simultaneous treatment of co-occurring nicotine and cannabis dependence. The intervention was well-liked by the 7 of the 12 enrollees who completed the study.

Effects of sleep deprivation on brain bioenergetics, sleep, and cognitive performance in cocaine-dependent individuals.

In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent ³¹P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, ³¹P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain ß-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

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.

Effects of cognitive impairment on substance abuse treatment attendance: predictive validation of a brief cognitive screening measure.

BACKGROUND AND OBJECTIVES: Neuropsychological impairment among patients with substance use disorders (SUDs) contributes to poorer treatment processes and outcomes. However, neuropsychological assessment is typically not an aspect of patient evaluation in SUD treatment programs because it is prohibitively time and resource consuming. In a previous study, we examined the concurrent validity, classification accuracy, and clinical utility of a brief screening measure, the Montreal Cognitive Assessment (MoCA), in identifying cognitive impairment among SUD patients. To provide further evidence of criterion-related validity, MoCA classification should optimally predict a clinically relevant behavior or outcome among SUD patients. The purpose of this study was to examine the validity of the MoCA in predicting treatment attendance. METHODS: We compared previously collected clinical assessment data on 60 SUD patients receiving treatment in a program of short duration and high intensity to attendance data obtained via medical chart review. RESULTS: Though the proportion of therapy sessions attended did not differ between groups, cognitively impaired subjects were significantly less likely than unimpaired subjects to attend all of their group therapy sessions. CONCLUSION: These results complement our previous findings by providing further evidence of criterion-related validity of the MoCA in predicting a clinically relevant behavior (i.e., perfect attendance) among SUD patients. SCIENTIFIC SIGNIFICANCE: The capacity of the MoCA to predict a clinically relevant behavior provides support for its validity as a brief cognitive screening measure.

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.

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.

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.

Kudzu extract treatment does not increase the intoxicating effects of acute alcohol in human volunteers.

BACKGROUND: Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol's effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis. METHODS: Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double-blinded, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. RESULTS: Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants' subjective responses to the alcohol challenge or to alcohol's effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. CONCLUSIONS: These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences, and furthermore the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol's subjective or psychomotor effects.

Modest abuse-related subjective effects of zolpidem in drug-naive volunteers.

Recent case reports suggest that the short-acting benzodiazepine-like hypnotic, zolpidem, may have abuse potential among individuals who have no personal history of abusing drugs or alcohol, particularly at doses higher than those recommended for treating insomnia. This study recruited drug-naive volunteers to assess the subjective effects of multiple doses of zolpidem (0, 5, 10, or 20 mg) administered in a within-subject double-blind design. Participants (n=11) answered computerized questionnaires (Addiction Research Center Inventory, visual analog scales, and a hypothetical Drug versus Money Choice) to address the hypothesis that a supratherapeutic dose (20 mg) would increase ratings of abuse-related subjective effects, while lower therapeutic doses (5 and 10 mg) would not. Although participants rated some effects as negative at 10 and 20 mg, the highest dose engendered predominantly positive abuse-like effects such as 'High', 'Like', and 'Good Effects'. However, no dose of zolpidem was chosen over money ($0.35-$10) when participants made hypothetical choices between them. Results suggest that although individuals without a drug abuse history are not inclined to choose zolpidem when presented with an alternative reinforcer such as money, it may possess moderate abuse potential that limits its clinical utility.