A single-day paradigm of self-regulated human cocaine administration

Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs.

Methods

Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed.

Results

Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects (“high”) were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses.

Conclusions

These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).     

Prenatal cocaine exposure and small-for-gestational-age status: effects on growth at 6 years of age

Objective

To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.

Study design

Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.

Results

At birth cocaine-exposed infants (n = 364) had significantly lower growth parameters compared to non-exposed children (n = 771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).

Conclusions

Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.     

CB1 receptors regulate alcohol-seeking behavior and alcohol self-administration of alcohol-preferring (P) rats

Rationale

The endogenous cannabinoid (CB) system mediates a number of behaviors associated with drug-seeking and drug self-administration. In this study the effects of CB1 receptor manipulations on operant ethanol (EtOH) responding during EtOH-seeking, EtOH-relapse as well as on-going EtOH self-administration were determined.

Methods

Alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages without access to EtOH or operant chambers. Rats were then returned to the operant chambers for testing of EtOH-seeking behavior (no EtOH present) for 4 sessions. After a week in their home cages following the EtOH-seeking test, rats were returned to the operant chambers with access to EtOH and water (relapse). Rats were then maintained in the operant chambers for daily 1-h sessions with access to 15% EtOH and water for several weeks.

Results

The CB1 receptor antagonist (SR141716A), at doses of 1 and 2 mg/kg, i.p. reduced EtOH-seeking and transiently reduced EtOH self-administration during relapse and maintenance. Conversely, treatment with the CB1 receptor agonist CP 55, 940, at doses of 1 and 10 μg/kg i.p., increased EtOH-seeking and EtOH self-administration during relapse.

Conclusions

The results of this study demonstrate that activation of CB1 receptors are involved in regulating EtOH-seeking as well as the reinforcing effects of EtOH under relapse and on-going self-administration conditions.     

Physiological and subjective effects of acute intranasal methamphetamine during atomoxetine maintenance

Rationale

Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed.

Objectives

This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients.

Methods

After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.

Results

Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance.

Conclusions

These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined.     

Chronic treatment with curcumin enhances methamphetamine locomotor sensitization and cue-induced reinstatement of methamphetamine self-administration

Objectives

Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH).

Methods

The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days.

Results

Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se.

Conclusions

Curcumin enhanced, rather than inhibited the behavioral effects of METH.     

5-HT induces temporomandibular joint nociception in rats through the local release of inflammatory mediators and activation of local β adrenoceptors

Objectives

The present studies assessed the effects of adolescent and adult ethanol exposure on the rewarding effects of cocaine as measured with the conditioned place preference procedure.

Methods

Male rats were exposed to intraperitoneal (IP) injections of ethanol or vehicle for 10 days [postnatal days (PNDs) 30-39 or PNDs 70-79; 2 mg/kg]. Place preference conditioning began on PND 65 or PND 105, respectively, and consisted of a baseline test followed by four conditioning cycles with either 0, 5, 10 or 20 mg/kg cocaine. Following the fourth conditioning cycle a final preference test was performed. Changes in time on the drug-paired side between the baseline and final test were analyzed.

Results

Animals exposed to vehicle (during adolescence or adulthood) showed a significant place preference at 20 mg/kg cocaine. Animals exposed to ethanol (during adolescence or adulthood) showed a significant place preference at 10 mg/kg cocaine.

Conclusions

Exposure to ethanol (adolescents or adults) sensitized the rewarding effects of cocaine. This may indicate an increase in the abuse liability of cocaine following a history of ethanol exposure.     

Psychosocial treatments for cocaine dependence: the role of depressive symptoms

Background

The association between cocaine use and depression has been frequently observed. However, less is known about the significance of depression in the treatment of cocaine use disorders. This study examined possible interrelations between drug use and depression severity among cocaine-dependent patients in psychosocial treatments for cocaine dependence.

Methods

Monthly assessed drug use and depression severity scores of N = 487 patients during 6-month psychosocial treatments for cocaine dependence were analyzed using hybrid latent growth models.

Results

Results indicated a moderate but statistically significant (z = 3.13, p < .01) influence of depression severity on increased drug use in the upcoming month, whereas drug use did not affect future depression severity.

Conclusions

Findings suggest that depression symptoms are an important predictor of drug use outcomes during psychosocial treatments for cocaine dependence and, hence, underline the importance of adequately addressing depression symptoms to improve treatment outcomes.     

The effects of prenatal cocaine on language development at 10 years of age

Objective

To examine the long term effects of prenatal cocaine exposure (PCE) on the language development of 10-year-old children utilizing a prospective design, controlling for confounding drug and environmental factors.

Participants

Children exposed to cocaine in utero (PCE; n = 175) and non-exposed children (NCE; n = 175) were followed prospectively to 10 years of age and were compared on language subscales of the Test of Language Development-Intermediate 3rd Edition (TOLD-I:3) and phonological processing as measured by the Comprehensive Test of Phonological Processing (CTOPP).

Methods

Multivariate analysis of covariance (MANCOVA), linear regression, and logistic regressions were used to evaluate the relationship of prenatal cocaine exposure to language development, while controlling for confounders.

Results

After controlling for confounding variables, prenatal cocaine effects were observed for specific aspects of language including syntax (Sentence Combining subtest of the TOLD-I:3, p = 0.001), semantics (Malopropism subtest of the TOLD-I:3, p = 0.05) and phonological processing (Phonological Awareness subscale, p = 0.01). The caregiver factors of vocabulary, HOME, and psychological symptoms also had consistent effects on language subtests and phonological processing scores. Children with PCE who experienced foster or adoptive care had enhanced language development compared to those living with birth mothers or in relative care. Cocaine exposed girls had lower scores on the phonological awareness subscale of the CTOPP than non-exposed girls.

Conclusions

PCE has subtle effects on specific aspects of language development and phonological processing at age 10, even after controlling for confounding variables. Environmental factors (i.e., postnatal lead exposure, home environment, and caregiver vocabulary and psychological symptoms) also impact language skills at 10 years. Adoptive or foster care appears to enrich PCE children's linguistic environment and protects children against language delay in the PCE sample.     

Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery

Purpose

Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal dl-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse.

Methods

Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral dl-methylphenidate (7.5 mg/kg) or transdermal dl-methylphenidate (Daytrana®;1/4 of a 12.5 cm² patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate.

Results

An otherwise depressive dose of ethanol significantly potentiated oral dl-methylphenidate induced increases in total distance traveled for the first 100 min (p < 0.05). Transdermal dl-methylphenidate increased total distance traveled after a latency of 80 min, though this effect was not potentiated by concomitant ethanol. Mean 3 h brain d-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding l-ethylphenidate concentrations were 10 ng/g and 130 ng/g.

Conclusions

Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of dl-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of dl-methylphenidate when combined with ethanol.     

Melanin-concentrating hormone receptor 1 (MCH1-R) antagonism: reduced appetite for calories and suppression of addictive-like behaviors

Rationale

The hypothalamic neuropeptide melanin-concentrating hormone and its MCH1 receptor have been implicated in regulation of feeding and energy homeostasis, as well as modulation of reward-related behaviors. Here, we examined whether the MCH system plays a role both in caloric and motivational aspects of sugar intake.

Materials and methods

The non-peptide MCH1-R antagonist GW803430 (3, 10, 30 mg/kg, i.p.) was first tested on self-administration under a fixed ratio schedule of reinforcement of both a caloric (10% w/v sucrose) and a non-caloric (0.06% w/v saccharin) sweet solution. GW803430 was then tested for its ability to alter motivational properties and seeking of sucrose. Lastly, the drug was tested to concurrently examine its effects on the escalated consumption of both sugar and food in animals following intermittent sugar access.

Results

The MCH1-R antagonist reduced sucrose- but not saccharin-reinforced lever pressing, likely reflecting a decreased appetite for calories in GW803430-treated rats. GW803430 reduced sucrose self-administration under a progressive ratio schedule, and suppressed cue-induced reinstatement of sucrose seeking, suggesting effects on rewarding properties of sucrose. GW803430 attenuated food intake in rats on intermittent access to sucrose at all doses examined (3, 10, 30 mg/kg), while reduction of sugar intake was weaker in magnitude.

Conclusion

Together, these observations support an involvement of the MCH system in regulation of energy balance as well as mediation of sucrose reward. MCH may be an important regulator of sugar intake by acting on both caloric and rewarding components.     

Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers

Rationale

Previous studies examining the combined effects of ethanol and cannabis, or its primary psychoactive ingredient, ?⁹-tetrahydrocannabinol (THC), have provided mixed results. Data from an in vitro study suggests that combined, sub-threshold doses of these drugs may interact to produce synergistic effects. Very low doses of the two drugs in combination have not been tested in humans.

Materials and methods

This study assessed whether combinations of acute, very low doses of ethanol and THC produce synergistic effects on subjective, cognitive, and physiological measures. Healthy volunteers (n = 11) received capsules containing placebo or THC (2.5 mg), and beverages containing placebo or ethanol (0.1 and 0.2 g/kg) alone, and in combination, across separate sessions, in a within-subjects, randomized, double-blind design. During each session, participants completed measures of working memory, psychomotor ability, and simple reaction time, and provided subjective mood and drug effect ratings. Cardiovascular measures were obtained at regular intervals.

Results

As intended, when administered alone, these very low doses of ethanol and THC had only moderate effects on isolated measures. The combined effects of these drugs were not synergistic, and in some cases appeared to be less-than-additive.

Conclusions

Our data provide no evidence for synergistic effects of acute combinations of very-low-dose ethanol and THC on subjective or physiologic response, or on cognitive performance.     

Contingency management is efficacious and improves outcomes in cocaine patients with pretreatment marijuana use

Background

Marijuana use is common in patients seeking treatment for cocaine use. Nevertheless, few studies have examined effects of marijuana use on treatment outcomes in general, and even fewer with respect to contingency management (CM) treatment, which has been criticized for potentially increasing non-reinforced drug use.

Methods

Data from three randomized clinical trials of CM versus standard treatment (ST) in cocaine-abusing patients were examined ( [Petry et al., 2004], [Petry et al., 2005a] and [Petry et al., 2006a]; N = 393) to assess effects of pretreatment marijuana use on outcomes. Patients were divided into two groups: (1) no self-reported marijuana use (No Pre-M; n = 315) and (2) any self-reported marijuana use (Pre-M; n = 78) in the 30 days pretreatment.

Results

CM was especially efficacious in enhancing retention in Pre-M patients such that retention nearly doubled among Pre-M patients assigned to CM versus those assigned to ST. In contrast, CM exerted only modest benefits on retention in No Pre-M patients. Pretreatment marijuana use was not related to during-treatment abstinence from cocaine, opioids, and alcohol, or abstinence at a Month 9 follow-up. However, CM treatment and longest duration of abstinence achieved during treatment were significant predictors of Month 9 abstinence. Pre-M patients also evidenced more improvements in drug problems over time when randomized to CM.

Conclusions

CM was especially efficacious in facilitating retention and improving severity of drug-related problems in those who used marijuana in the month before initiating treatment.     

Alcohol use and its consequences in South India: views from a marginalised tribal population

Background

Alcohol consumption in India is disproportionately higher among poorer and socially marginalised groups, notably Scheduled Tribes (STs). We lack an understanding of STs own views with regard to alcohol, which is important for implementing appropriate interventions.

Methods

This study was undertaken with the Paniyas (a previously enslaved ST) in a rural community in Kerala, South India. The study, nested in a participatory poverty and health assessment (PPHA). PPHA aims to enable marginalized groups to define, describe, analyze, and express their own perceptions through a combination of qualitative methods and participatory approaches (e.g. participatory mapping and ranking exercises). We worked with 5 Paniya colonies between January and June 2008.

Results

Alcohol is viewed as a problem among the Paniyas who reported that consumption is increasing, notably among younger men. Alcohol is easily available in licensed shops and is produced illicitly in some colonies. There is evidence that local employers are using alcohol to attract Paniyas for work. Male alcohol consumption is associated with a range of social and economic consequences that are rooted in historical oppression and social discrimination.

Conclusion

Future research should examine the views of alcohol use among a variety of marginalised groups in developing countries and the different policy options available for these populations. In addition, there is a need for studies that untangle the potential linkages between both historical and current exploitation of marginalized populations and alcohol use.     

Use patterns and self-reported effects of Salvia divinorum: An internet-based survey

Background

There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD.

Objectives

To characterize the reasons, methods, and reported consequences of SD use.

Methods

Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD.

Results

Participants (N = 500) were 92.6% male and 23.4 ± 8.7 (mean ± s.d.) years old. They had used a median of six times (range 1-250). 80.6% probably or definitely would use SD again. Most participants (92.6%) typically smoked or vaporized SD product. When smoked, the drug's main effects were estimated to last 14.1 ± 12.8 (range 0.5-120) minutes. When asked to compare SD effects to other methods of altering consciousness, the most common answer was that SD was unique (38.4%). 25.8% reported persisting (≥24 h) positive effects (often described as increased sense of well-being) on at least one occasion. 4.4% reported persisting negative effects (most often anxiety).

Conclusions

SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects, SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically, as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies.     

Epidural, intrathecal and plasma pharmacokinetic study of epidural ropivacaine in PLGA-microspheres in sheep model

Background

Microparticulate local anesthetics-loaded delivery systems are known to provide a controlled release of drug and to reduce systemic toxicity resulting from transient high plasma concentrations. The aim of this study was to evaluate epidural, intrathecal and plasma pharmacokinetics of ropivacaine following epidural administrations of repeated boluses or infusions and to compare them with the epidural administration of polylactide-co-glycolide ropivacaine-loaded microspheres.

Methods

In the first step, the epidural and intrathecal pharmacokinetics was evaluated in 3 Lacaunes ewes, receiving epidural continuous infusion of ropivacaine with increasing doses (20, 50 and 100 mg/h). Then, six animals received an epidural administration of ropivacaine-loaded microspheres (500 mg), three others received ropivacaine in epidural bolus (30 mg) followed by infusion (2 mg/ml during 6 h), and the last three animals received three successive epidural boluses of ropivacaine (50 mg) at 2 h interval. A simultaneous microdialysis technique was used to measure epidural and intrathecal concentrations of ropivacaine.

Results

After epidural administration of ropivacaine-loaded microspheres, Cmax in plasma was around 100 ng/ml while epidural and intrathecal Cmax of ropivacaine were close to 600 and 150 μg/ml, respectively. The ratios of intrathecal to epidural AUC (AUCit/AUCepi) for bolus administration, bolus + infusion administration, and for microspheres were 13.4 ± 2.4; 14.1 ± 6.1 and 33.9 ± 22.6%, respectively. This suggested that administration of ropivacaine as microspheres increased the transmeningeal passage of ropivacaine in comparison to other administration regimens.

Conclusions

Epidural administration of ropivacaine-loaded microspheres led to the sustained levels of ropivacaine in the intrathecal space compared to the boluses of ropivacaine solution. Moreover, epidural administration of microspheres resulted in the highest efficiency in intrathecal uptake of ropivacaine compared to administration in solution.     

Exposure to alcohol during adolescence alters the aversive and locomotor-activating effects of cocaine in adult rats

Objectives

The present study assessed the effect of adolescent alcohol exposure on the later aversive and locomotor-activating effects of cocaine.

Methods

Male rats were exposed to alcohol or vehicle for 10 days [postnatal day (PND) 30-39; 2 g/kg IP]. Taste aversion conditioning began on PND 65. During aversion conditioning, subjects were presented with saccharin followed by cocaine (32 mg/kg; 15, 180 or 300 min post saccharin) or saline. Following each injection, animals were placed in locomotor chambers for 1 h. To determine if any effects seen were specific to the adolescent developmental period, the procedure was replicated in adult animals.

Results

Animals exposed to vehicle during adolescence showed significant aversions at all time delays. Animals exposed to ethanol during adolescence showed a decrease in consumption only at the 15 and 180 min delays. Groups exposed to alcohol during adolescence showed a decrease in gross, and an increase in fine, motor activity in response to cocaine. Animals exposed to alcohol during adulthood also showed attenuated taste aversions.

Conclusions

Exposure to ethanol during adolescence attenuated the aversive effects of cocaine and altered its locomotor-activating effects. Although this effect is not specific to adolescence, this is the time when alcohol use is typically initiated so that such exposure may enhance later abuse liability of cocaine.     

Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand

Background

Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants.

Design

The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte.

Results

MA exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress.

Conclusion

Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress.     

Initiation to drug injection among street youth: a gender-based analysis

Objective(s)

To estimate the incidence rate of initiation into drug injection and to identify predictors of initiation into drug injection separately among street girls and boys.

Design

Data from two consecutive prospective street youth cohort studies (1995-2001 and 2001-2005) were used to conduct these analyses, stratified by gender.

Methods

Data were collected using semi-annual interviewer-administered questionnaires. Variables from the following domains were considered in Cox regression models: socio-demographic characteristics, early and current substance abuse, marginalization, childhood traumatic sexual events and injection exposure.

Results

Of the 946 youth who had never injected drugs at study entry, 86.4% completed at least two questionnaires representing 243 girls and 574 boys. Incidence rates of injection of 7.0 and 5.9 per 100 person-years were observed among these girls and boys respectively. Among girls, cocaine or crack use (adjusted hazard ratio (AHR) = 1.97), heroin use (AHR = 2.86), homelessness (AHR = 2.49) and hanging out regularly with people who inject (AHR = 4.46) all independently increased risk of first injection. Among boys, age decreased risk of initiating injection (AHR = 0.90/year), while cocaine or crack use (AHR = 2.14), heroin use (AHR = 3.56), homelessness before age 16 (AHR = 1.68), incest or rape before age 14 (AHR = 1.98) and hanging out regularly with people who inject (AHR = 1.66) all independently increased this risk.

Conclusions

Our findings suggest similar rates of initiation among girls and boys; however, factors associated with initiation vary by gender. This might lead to the design of more effective programs to prevent initiation into drug injection.     

Violence among men and women in substance use disorder treatment: A multi-level event-based analysis

Background

This study examined associations between acute alcohol and drug use and violence towards others in conflict incidents (overall, partner, and non-partner conflict incidents) by men and women recruited from substance use disorder (SUD) treatment.

Methods

Semi-structured interviews were used to obtain details about interpersonal conflict incidents (substance use, whether specific conflicts were with intimate partners or non-partners) in the 180 days pre-treatment. Participants for this study were selected for screening positive for past-year violence (N = 160; 77% men, 23% women).

Results

Multi-level multinomial regression models showed that after adjusting for clustering within individual participants, the most consistent predictors of violence across models were acute cocaine use (significant for overall, intimate partner and non-partner models), acute heavy alcohol use (significant for overall and non-partner models), and male gender (significant in all models).

Conclusions

This study was the first to explicitly examine the role of acute alcohol and drug use across overall, partner and non-partner conflict incidents. Consistent with prior studies using a variety of methodologies, alcohol, cocaine use and male gender was most consistently and positively related to violence severity (e.g., resulting in injury). The results provide important and novel event-level information regarding the relationship between acute alcohol and specific drug use and the severity of violence in interpersonal conflict incidents.     

Cigarette smoking status in pathological gamblers: association with impulsivity and cognitive flexibility

Background

While the majority of pathological gamblers are current cigarette smokers (CS), some have quit smoking (former smokers, FS) while others never smoked (never smokers, NS). The reasons for elevated smoking rates in pathological gambling are not known, but gamblers may use nicotine as a putative cognitive enhancer. This study evaluated impulsivity and cognitive flexibility in a sample of pathological gamblers with differing smoking status.

Methods

Fifty-five subjects with pathological gambling (CS, n = 34; FS, n = 10; NS, n = 11) underwent cognitive assessments using the Stop-Signal (SST) and Intradimensional/Extra-dimensional (ID/ED) set-shift tasks.

Results

CS reported less severe gambling problems than either FS or NS on the Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling, and CS was associated with significantly fewer directional errors on the SST task, compared to NS. In addition, in CS, higher daily cigarette consumption was associated with fewer total errors on the ID/ED task.

Conclusions

The potential role of nicotine as a cognitive enhancer was supported by objective tests of impulsivity and cognitive flexibility. Human laboratory studies using nicotine challenges in pathological gambling will shed further light on this relationship.