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BACKGROUND AND AIMS Stimulant drug users have a greater prevalence of risky driving behaviour. This study aimed to assess how far this association remains after adjusting for aggressiveness. DESIGN Cross-sectional interview study assessing associations between measures of risky driving behaviours as outcomes, measures of stimulant drug use as predictors and a measure of aggressiveness as a covariate. SETTING United States. PARTICIPANTS Data were drawn from wave 3 (2012-13) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III) (n = 36 309 aged ≥ 18 years). MEASUREMENTS Stimulant drug use, past-year DSM-5 stimulant use disorder, aggression and measures of risky driving were assessed using face-to-face interviews conducted using the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-5) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). FINDINGS Overall, 2714 (8.3%) respondents indicated life-time stimulant use, and 112 (0.3%) met criteria for past-year DSM-5 stimulant use disorder. More than 10% of ongoing stimulant users and one-third of respondents with DSM-5 stimulant use disorder reported stimulant-specific driving under the influence of drugs (DUID) in the past-year (both P

Individuals who work nonstandard schedules, such as rotating or night shifts, are more susceptible to workplace injuries, performance decrements, and reduced productivity. This population is also almost twice as likely to use illicit drugs as individuals working a standard day shift. The purpose of this study was to examine the effects of smoked marijuana on performance, mood, and sleep during simulated shift work. Ten experienced marijuana smokers completed this 23-day, within-participant residential study. They smoked a single marijuana cigarette (0, 1.9, 3.56% Δ9-THC) one hour after waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the study, and shift conditions were separated by an ‘off’ day. When participants smoked placebo cigarettes, psychomotor performance and subjective-effect ratings were altered during the night shift compared to the day shift: performance (e.g., vigilance) and a few subjective ratings were decreased (e.g., “Self-Confident”), whereas other ratings were increased (e.g., “Tired”). Objective and subjective measures of sleep were also disrupted, but to a lesser extent. Marijuana attenuated some performance, mood, and sleep disruptions: participants performed better on vigilance tasks, reported being less miserable and tired and sleep a greater number of minutes. Limited negative effects of marijuana were noted. These data demonstrate that abrupt shift changes produce performance, mood, and sleep decrements during night shift work and that smoked marijuana containing low to moderate Δ9-THC concentrations can offset some of these effects in frequent marijuana smokers.

Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes.Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion.Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events.A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.

Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention.Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout).Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events.A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs. money later, we evaluated the effect on cocaine use of a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine, which converging evidence suggests may work to correct problematic neuroadaptations and restore motivation for non-drug rewards. We found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 hours post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.

BACKGROUND AND OBJECTIVES: In light of the rapidly changing legal status of marijuana in the U.S., there has been increased interest in the potentially adverse outcomes of heavy marijuana use among young persons. The goal of this study was to investigate frequent marijuana use among undergraduates, and its association with the use of illicit substances, mental health problems, and stress. METHODS: Undergraduates from one university in the Northeast were surveyed using a questionnaire derived from the American College Health Association-National College Health Assessment (N = 1,776). Logistic regression analyses were used to examine relationships between frequency of marijuana use and other substance use, binge drinking, negative consequences of drinking, mental health problems, and perceived stress. Analyses were adjusted for demographics differences such as gender, race, year in school, and sorority/fraternity membership. RESULTS: Approximately 1 in 12 undergraduates (8.5%) reported using marijuana more than 10 days in the past month. Frequent marijuana use was associated with increased likelihood of other substance use and alcohol-related negative outcomes. Marijuana use was associated with increased reports of anxiety, and frequent use was associated with depression and substance use problems. Perceived stress was not associated with marijuana use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These findings, indicating that frequent use is related to depression, other substance use and negative outcomes, contribute to our understanding of marijuana use among undergraduates. Given the relatively high prevalence of marijuana use among young persons, future studies should seek to uncover potentially causal relationships between frequent marijuana use and a variety of negative outcomes. (Am J Addict 2015;XX:XX -XX). Language: en

Background Despite growing concern about the increased rates of synthetic cannabinoid (SC) use and their effects, only limited data are available that addresses these issues. This study assessed the extent of SC product use and reported effects among a cohort of adult marijuana and tobacco users. Methods A brief telephone interview was conducted with individuals who had given permission to be contacted for future research while screening for a cannabis/nicotine dependence medication development study (NCT01204723). Results Respondents ( N = 42; 88% participation rate) were primarily young adults, male, racially diverse, and high school graduates. Nearly all currently smoked tobacco and cannabis, with 86% smoking cannabis on 5 or more days per week. Nearly all (91%) were familiar with SC products, half (50%) reported smoking SC products previously, and a substantial minority (24%) reported current use (i.e., past month). Despite a federal ban on 5 common SCs, which went into effect on March 1, 2011, a number of respondents reported continued SC product use. Common reasons reported for use included, but were not limited to, seeking a new “high” similar to that produced by marijuana and avoiding drug use detection via a positive urine screen. The primary side effects were trouble thinking clearly, headache, dry mouth, and anxiety. No significant differences were found between synthetic cannabinoid product users (ever or current) and nonusers by demographics or other characteristics. Conclusions Among current marijuana and tobacco users, SC product consumption was common and persisted despite a federal ban. The primary reasons for the use of SC-containing products seem to be to evade drug detection and to experience a marijuana-like high.

Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24h postinfusion.Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48h were received: lorazepam (2mg) and two doses of ketamine (0.41mg/kg and 0.71mg/kg, with the former dose always preceding the latter). Infusions were followed within 15min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure).Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71mg/kg was associated with significantly higher HMS scores than was the 0.41mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24h postinfusion.These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

Black men currently comprise a substantial percentage of prisoners in the United States. Drug dependence is common among prison populations, and US prisons are high-risk environments for drug use. Prison drug use exacerbates health problems disproportionately prevalent among Black men and prisoners.The goal of this research was to examine predictors of prison drug use among incarcerated Black men.This study examined drug use within the prison environment in a random sample of 134 Black men incarcerated in maximum-security correctional institution. The Addiction Severity Index (ASI) was used to measure illicit drug use history and the extent to which drug use occurred within the prison environment.Seventy-five percent of the participants reported a history of illicit drug use. Overall, 20% (n 25) of the participants, or 25% of those with a history of drug use, reported using drugs during a time frame consistent with incarceration. Participants with lengthier histories of drug use (OR: 1.1, 95% CI 1.0-1.2) and those who were incarcerated longer (OR: 1.1, 95% CI 1.0-1.2) were more likely to use drugs in prison. Drug use in prison was associated with history of injection drug use and with probation/parole status when arrested.Prisoners are engaging in illicit drug use while incarcerated, suggesting that they could benefit from harm reduction and drug treatment services offered during incarceration.Drug treatment programs that address long-standing addictions and coping mechanisms for lengthy prison stays, specifically, would be especially useful for this population.

Marijuana withdrawal contributes to the high relapse rates in individuals seeking treatment for marijuana-use disorders. Quetiapine, an atypical antipsychotic, reduces characteristic symptoms of marijuana withdrawal in a variety of psychiatric conditions, including mood lability, sleep disruption and anorexia. This human laboratory study investigated the effectiveness of quetiapine to decrease marijuana withdrawal and relapse to marijuana use in non-treatment-seeking marijuana smokers. Volunteers were maintained on placebo or quetiapine (200 mg/day) in this double-blind, counter-balanced, within-subject study consisting of two 15-day medication phases, the last 8 days of which were in-patient. On the first in-patient day, active marijuana [6.2% delta (9)-tetrahydrocannabinol (THC)] was repeatedly smoked under controlled conditions. For the next 3 days, inactive marijuana (0.0% THC) was available for self-administration (withdrawal). On the subsequent 4 days, active marijuana (6.2% THC) was available for self-administration (relapse). Volunteers (n = 14) who smoked an average of 10 marijuana cigarettes/day, 7 days/week, completed the study. Under placebo, withdrawal was marked by increased subjective ratings of negative mood, decreased sleep quality, and decreased caloric intake and weight loss. Compared with placebo, quetiapine improved sleep quality, increased caloric intake and decreased weight loss. However, quetiapine increased marijuana craving and marijuana self-administration during the relapse phase. These data do not suggest that quetiapine shows promise as a potential treatment for marijuana dependence.

Cannabis, the most commonly used illicit substance, exerts its primary psychoactive effect via delta-9 tetrahydrocannabinol (Δ(9) -THC) agonism of cannabinoid receptor type 1 (CB1). Some users develop a cannabis use disorder and physical dependence manifested by withdrawal symptoms during abstinence. Hence, there is growing public health concern about increasing use of a new generation of synthetic cannabinoid (SC) agonists (eg, JWH-018, CP 47,497) marketed as natural herbal incense mixtures under brand names such as "Spice" and "K2." Anecdotal reports suggest overlapping effects with marijuana when the mixtures are smoked, however, systematic evaluation of SC-related psychoactive properties and adverse effects is lacking. We conducted a systematic review of published reports on SC clinical effects in humans. Most highlight potential toxicity such as acute anxiety and psychosis. In addition, we carefully document three cases in which experienced marijuana users meeting criteria for cannabis dependence with physiologic dependence smoked SC products regularly. The SC mixture effects were reportedly similar to marijuana and well tolerated. The individuals all reported that SC product use effectively alleviated cannabis withdrawal. Biopsychosocial factors associated with SC initiation and usage by the cases help to shed light on psychopharmacologic, clinical, and public health aspects of SC product consumption.

Aims There are no studies directly comparing self-administration of methamphetamine and d-amphetamine by humans. This study compared intranasal methamphetamine- and d-amphetamine self-administration and characterized the mood, performance and physiological effects produced by the drugs. Design A randomized, double-blind, placebo-controlled, cross-over study. Setting An out-patient research unit at the New York State Psychiatric Institute. Participants Male recreational methamphetamine users (n = 13). Measurements Five 2-day blocks of sessions were conducted. On the first day of each block, participants ‘sampled’ a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamine plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money). Findings There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines increased self-administration dose-dependently, with 41% drug choices overall. Under the $20 condition, only 17% drug options were selected. Both drugs increased cardiovascular activity and ‘positive’ mood, although methamphetamine produced more prominent effects on some measures (e.g. heart rate and ratings of ‘high’). Conclusions Methamphetamine and d-amphetamines appear to produce a similar dose-related profile of effects in humans, which supports their equivalence for abuse potential.

3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT(2A) receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT(2A) receptors. Positron emission tomography studies using the SERT ligand [¹¹C]DASB and the 5-HT(2A) receptor ligand [¹¹C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT(2A) receptor availability (binding potential, BP(ND)) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BP(ND) and higher 5-HT(2A) receptor BP(ND) in cortical, but not subcortical regions. Decreased SERT BP(ND) was regionally associated with upregulated 5-HT(2A) receptor BP(ND). In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established.

The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy.

Zolpidem attenuates shift-change-related sleep and performance disruptions. It is unknown whether these benefits alter the reinforcing effects of the drug during shift work. This study examined zolpidem-related reinforcing effects during simulated shift work. Eleven volunteers (3F, 8M) completed this 16-day within-participant, residential laboratory study. Each day participants were given an opportunity to self-administer oral zolpidem (10 mg) or receive a $1 voucher immediately following a 9-h work period and immediately before going to bed. Participants worked under two shift conditions: (1) during the night shift, participants completed computerized task batteries from 00:30 to 09:30 h and went to bed at 16:00 h and (2) during the day shift, participants completed task batteries from 08:30 to 17:30 h and went to bed at 24:00 h. Shift conditions alternated three times during the study. Despite the fact that sleep, psychomotor performance, and some ratings of mood were disrupted during night-shift work, there was no significant effect of shift on choice to take zolpidem. Overall, participants selected markedly fewer zolpidem doses than monetary vouchers (17% versus 83%). Thus, zolpidem did not serve as a reinforcer even when sleep was disrupted. These data are consistent with previous reports indicating that sedatives produce limited reinforcing effects in individuals without a history of drug abuse.

Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be because of the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine vs. heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants' perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g., with friends, family, or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug.

The purpose of this double-blind, randomized, outpatient study was to evaluate the reinforcing and subjective effects of modafinil (200, 400, or 600 mg) in cocaine abusers. Twelve participants (2 female, 10 male) completed this study, consisting of 3 blocks of 7 sessions; each block tested a difference dose of modafinil. During the first 2 sessions of each block, participants "sampled" 1 of the doses of modafinil, and placebo. These doses of modafinil and placebo were available for the subsequent five choice sessions of the block. In each choice session, participants had an opportunity to administer active or placebo capsules. Modafinil administration did not differ from placebo administration, and subjective-effects ratings were not systematically altered as a function of modafinil dose. Results suggest that modafinil does not have abuse liability in cocaine abusers.

A post hoc analysis examined depressive symptoms in regular marijuana smokers interested in nontreatment, laboratory studies, and marijuana-dependent treatment-seekers considering clinical trial participation. Among marijuana-dependent treatment-seeking patients screened for a clinical trial, the mean Beck Depression Inventory Score (BDI) was significantly higher than for marijuana-using volunteers screened for nontreatment laboratory studies. Mean self-reported baseline marijuana use was not significantly different between groups, and BDI score was not correlated with use. Although the methods by which the two groups were selected influenced their characteristics (i.e., treatment-seekers are more likely to be experiencing some degree of clinical distress), it is notable that treatment-seeking, and not marijuana use per se, is associated with significantly higher rates of depression.

The Iowa Gambling task, which typically incorporates hypothetical monetary earnings and losses for performance, has been widely used to measure decision-making in substance abusers. We examined the effects of a cash monetary contingency on Gambling task performance in cocaine abusers and control participants.Twenty-two long-term cocaine smokers who met DSM-IV criteria for cocaine dependence and 24 non-cocaine-using control participants completed this study. Both groups were similar in terms of age, executive function, and self-reported alcohol and marijuana use. All participants performed the Gambling task under two counterbalanced conditions: under one condition, earnings and losses were hypothetical, and under the other condition, earnings and losses were in cash.Condition x group interactions on card selection and task completion time were noted (p0.05). Under the hypothetical payment condition, cocaine abusers selected a greater proportion of cards from disadvantageous decks than advantageous decks (p0.05), but took a similar amount of time to complete the task, relative to control participants. However, under the cash payment condition, no group differences were seen for card selection and cocaine abusers took more time than controls to complete the task (p0.05).The application of tangible consequences improved the decision-making and effort of cocaine abusers on the Gambling task, relative to control participants. These findings underscore the importance of considering population-specific factors (e.g., sensitivity to instructional vs. consequential control) when conducting neuropsychological research in substance abusers.

Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days.

Interest in the relationship between cannabis use and psychosis has increased dramatically in recent years, in part because of concerns related to the growing availability of cannabis and potential risks to health and human functioning. There now exists a plethora of scientific articles addressing this issue, but few provide a clear verdict about the causal nature of the cannabis-psychosis association. Here, we review recent research reports on cannabis and psychosis, giving particular attention to how each report provides evidence relating to two hypotheses: (1) cannabis as a contributing cause and (2) shared vulnerability. Two primary kinds of data are brought to bear on this issue: studies done with schizophrenic patients and studies of first-episode psychosis. Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder. Rather, the evidence leads us to conclude that both early use and heavy use of cannabis are more likely in individuals with a vulnerability to psychosis. The role of early and heavy cannabis use as a prodromal sign merits further examination, along with a variety of other problem behaviors (e.g., early or heavy use of cigarettes or alcohol and poor school performance). Future research studies that focus exclusively on the cannabis-psychosis association will therefore be of little value in our quest to better understand psychosis and how and why it occurs.

Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses.

Previously, we reported that gabapentin, a nonselective gamma-aminobutyric acid agonist, reduced 'positive' subjective effects of cocaine without reducing cocaine self-administration. We speculated that the self-administration procedure used in that study was not sensitive to subtle shifts in the reinforcing effects of cocaine. Thus, this study examined the effects of gabapentin maintenance on cocaine self-administration using a purchase-cocaine choice procedure. During this 48-day inpatient/outpatient study, nontreatment-seeking cocaine abusers (n = 12) were maintained on gabapentin (0, 600, 1200 mg/day); four doses of cocaine (0, 12, 25, 50 mg) were each tested twice under each gabapentin condition. All cocaine testing was conducted while participants were inpatients. Before the start of each session, participants were provided with 25 dollars (five 5 dollar bills, one for each choice opportunity) and smoked the 'sample' cocaine dose once. Subsequently, participants were given five opportunities to purchase the sampled dose of cocaine (at 5 dollars per dose) or to keep 5 dollars for that choice trial. Choice to self-administer cocaine increased significantly with escalating cocaine doses; gabapentin maintenance did not alter choice to self-administer cocaine. These results concur with findings from our previous investigations of gabapentin and with those from a clinical trial examining the effects of larger gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals. Together, the data indicate that gabapentin does not show promise as a treatment medication for cocaine dependence.

Methamphetamine use has increased significantly and become a global health concern. Craving is known to predict methamphetamine use and relapse following abstinence. Some have suggested that cravings are automatic, generalized, and uncontrollable, but experimental work addressing these claims is lacking. In two exploratory studies we tested the boundary conditions of methamphetamine craving by asking: (1) is craving specific to users’ preferred route of administration? and (2) can craving be regulated by cognitive strategies? Two groups of methamphetamine users were recruited. In Study 1, participants were grouped by their preferred route of administration (intranasal vs. smoking), and rated their craving in response to photographs and movies depicting methamphetamine use (via the intranasal vs. smoking route). In Study 2, methamphetamine smokers implemented cognitive regulation strategies while viewing photographs depicting methamphetamine smoking. Strategies involved either focusing on the positive aspects of smoking methamphetamine or the negative consequences of doing so – the latter strategy based on treatment protocols for addiction. In Study 1, we found a significant interaction between group and route of administration, such that participants who preferred to smoke methamphetamine reported significantly stronger craving for smoking stimuli, whereas those who preferred the intranasal route reported stronger craving for intranasal stimuli. In Study 2, participants reported significantly lower craving when focusing on the negative consequences associated with methamphetamine use. Taken together, these findings suggest that strength of craving for methamphetamine is moderated by users’ route of administration and can be reduced by cognitive strategies. This has important theoretical, methodological, and clinical implications.

Non-therapeutic research with drugs of abuse in humans is important for a more comprehensive understanding of substance abuse and for the development of more effective treatments. However, the administration of substances from drug classes with abuse potential to human volunteers raises ethical questions regarding potential risk to study volunteers.The purpose of this study was to assess the psychosocial functioning and reported drug-taking behavior of volunteers before and after participating in a residential laboratory study, during which either marijuana, methamphetamine or zolpidem was administered.Twenty-two volunteers were administered Addiction Severity Index (ASI) interviews at intake and approximately six months following their study participation.No significant differences between intake and follow-up assessments were found on any ASI composite or drug/alcohol-taking variable.These preliminary data suggest that participation in residential laboratory studies involving the administration of drugs from classes with abuse potential does not alter subsequent psychosocial functioning or reported drug use.

Despite the fact that rates of cannabis dependence have increased substantially over the past several years, there are no medications approved for the treatment of cannabis dependence. This paper reviews data from recent research on cannabinoids that may be relevant for the development of pharmacotherapies for cannabis dependence. Included in the discussion are findings from studies that have assessed the ability of medications to ameliorate cannabis-related abstinence symptoms in laboratory animals and human research participants. Data from studies that have investigated the effects of pharmacological agents on cannabis self-administration are also reviewed because these data may provide information critical for informing relapse prevention medication development efforts. The majority of published studies evaluating cannabis pharmacotherapies have focused on decreasing withdrawal symptoms: a growing number of medications reduce symptoms in laboratory animals, but the majority of these medications have not been tested in humans. Fewer studies have assessed the effects of potential cannabis treatment medications on cannabinoid-related reinforcing effects. In laboratory animals, only the CB1 cannabinoid antagonist rimonabant has shown promise. In humans, this medication has not been tested on cannabis reinforcing effects. To date, no medication has been shown to alter cannabis self-administration by humans.

Use of cocaine, alcohol, and the two drugs simultaneously is common and the risk of morbidity and mortality associated with these drugs is widely reported. This double-blind, placebo-controlled, randomized study examined gender differences in response to administration of these drugs alone and in combination.Current users of cocaine and alcohol (n = 17) who met diagnostic criteria (DSM-IV) for cocaine dependence and alcohol abuse or dependence (not physiologically dependent on alcohol) and who were not seeking treatment for substance use disorders gave voluntary, written, informed consent to participate in three drug administration sessions:1) four doses of intranasal cocaine (1 mg/kg every 30 min) with oral alcohol (1 g/kg following the initial cocaine dose and a second drink at +60 min (120 mg/kg) calculated to maintain a plasma alcohol concentration of approximately 100 mg/dL; 2)four doses of cocaine and alcohol placebo; 3) cocaine placebo and alcohol. Pharmacokinetics were obtained by serial blood sampling, physiological measurements (heart rate and blood pressure) were obtained with automated equipment, and subjective effects were assessed using visual analog scales over 480 min.Responses to cocaine, alcohol, and cocaine-alcohol were equivalent by gender for most measurements. Women had higher heart rates following alcohol administration (p = .02). Women consistently reported higher ratings for "Feel Good:' a measure of overall mental/physical well-being, for all study conditions, reaching statistical significance for cocaine (p = .05) and approaching significance for alcohol administration (p = .1).Women showed equivalent responses to drug administration with the exception of perception of well-being, which was significantly increased for women. These findings may have implications for differential risk for acute and chronic toxicity in women.

Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.

The effects of zolpidem, a nonbenzodiazepine hypnotic, on psychomotor task performance, subjective effects, and food intake were examined during simulated shift work. Seven participants completed this 23-day, within-participant design, residential laboratory study. They received a single oral zolpidem dose (0, 5, or 10 mg) 1 hr before bedtime for 3 consecutive days under 2 shift conditions: day shift and night shift. When participants received placebo, next-day performance and subjective effects were disrupted, and food intake was decreased during the night shift. Zolpidem improved subjective reports of sleep quality and, to a lesser extent, next-day performance. Next-day mood, however, was worsened by zolpidem. Food intake was unaffected by zolpidem. These data indicate that shift changes produce performance impairments, mood alterations, and decreases in food intake, and that zolpidem attenuates some shift-change-related disruptions.

Studies have shown that the Delta(9)-tetrahydrocannabinol (Delta(9)-THC) concentration in marijuana cigarettes is an important factor for the maintenance of marijuana self-administration. Yet, the impact of oral Delta(9)-THC treatment on marijuana self-administration is unknown. Because other agonist therapies have been demonstrated to be effective for the treatment of substance use disorders, the objective of this study was to evaluate the influence of oral Delta(9)-THC maintenance on choice to self-administer smoked marijuana. During this 18-day residential study, 12 healthy research volunteers received one of three doses of oral Delta(9)-THC capsules (0, 10, 20 mg q.i.d.) for 3 consecutive days, followed by 3 consecutive days of matching placebo. The order of active Delta(9)-THC administration was counterbalanced. Each morning, except on days 6, 12, and 18, participants smoked the 'sample' marijuana cigarette (1.8% Delta(9)-THC w/w) and received a $2 voucher (redeemable for cash at study's end). Following the sample, volunteers participated in a four-trial choice procedure during which they had the opportunity to self-administer either the dose of marijuana they sampled that morning or to receive the $2 voucher. Relative to placebo Delta(9)-THC maintenance, participants' choice to self-administer marijuana was not significantly altered by either of the two active Delta(9)-THC maintenance conditions. Some 'positive' subjective drug-effect ratings following the sample marijuana cigarette were reduced: by day 3 of active oral Delta(9)-THC maintenance, participants' rating of 'Good Drug Effect' and 'High' were significantly decreased. Smoked marijuana-related total daily caloric intake was not significantly altered under any maintenance conditions. Finally, the effects of smoked marijuana on psychomotor task performance were only minimally affected by oral Delta(9)-THC maintenance. These data indicate that participants' choice to self-administer marijuana was unaltered by the oral Delta(9)-THC dosing regimen used in the present investigation.

Although the ability to perform complex cognitive operations is assumed to be impaired following acute marijuana smoking, complex cognitive performance after acute marijuana use has not been adequately assessed under experimental conditions. In the present study, we used a within-participant double-blind design to evaluate the effects acute marijuana smoking on complex cognitive performance in experienced marijuana smokers. Eighteen healthy research volunteers (8 females, 10 males), averaging 24 marijuana cigarettes per week, completed this three-session outpatient study; sessions were separated by at least 72-hrs. During sessions, participants completed baseline computerized cognitive tasks, smoked a single marijuana cigarette (0%, 1.8%, or 3.9% Delta(9)-THC w/w), and completed additional cognitive tasks. Blood pressure, heart rate, and subjective effects were also assessed throughout sessions. Marijuana cigarettes were administered in a double-blind fashion and the sequence of Delta(9)-THC concentration order was balanced across participants. Although marijuana significantly increased the number of premature responses and the time participants required to complete several tasks, it had no effect on accuracy on measures of cognitive flexibility, mental calculation, and reasoning. Additionally, heart rate and several subjective-effect ratings (e.g., "Good Drug Effect," "High," "Mellow") were significantly increased in a Delta(9)-THC concentration-dependent manner. These data demonstrate that acute marijuana smoking produced minimal effects on complex cognitive task performance in experienced marijuana users.

Background There is consistent evidence that hookah use is as, if not more, harmful than cigarette use. Yet, hookah users underestimate the potential deleterious effects of hookah use. This study examined the rates of hookah use and associated demographic characteristics in a sample of undergraduates at a small Northeastern university. This study also examined the relationships between hookah use and other substance use, mental health problems, and perceived levels of stress. Methods Data were drawn from the Spring 2009 American Health Association-National College Health Assessment (ACHA-NCHA) at one small, Northeastern university ( N = 1799). The relationships between hookah use and other substance use, mental health problems, and perceived stress levels were examined using logistic regression analyses. Results Hookah use (in the past month) was reported among 14.1% (253/1799) of this sample of undergraduates. Hookah users were more likely to use other substances, including cigarettes, cannabis, alcohol, cocaine, and amphetamines. The strongest associations emerged between hookah use and alcohol and cigarette use. There were no significant associations found between hookah use and any mental health problems or perceived stress levels. Conclusions Hookah users are significantly more likely to use other substances, including alcohol, cigarettes, cannabis, cocaine, and amphetamines compared with non-hookah users. In contrast to cigarette smoking, hookah use does not appear to be associated with mental health problems or perceived stress levels in this sample of undergraduates. Further investigation into the prevalence and correlates of hookah use is needed in representative population samples.

Cigarette craving is an important contributor to cigarette smoking, and clinical approaches that focus on regulation of craving are effective in reducing rates of relapse. However, a laboratory model that targets the use of cognitive strategies to regulate craving is lacking. To develop such a model, twenty heavy cigarette smokers (>12/day), twenty-two tobacco “chippers” (

Seventeen non-treatment seeking cocaine-dependent individuals participated in three-week longitudinal inpatient studies of cognitive changes during drug use and abstinence. Protocols included three days drug-free baseline, three days cocaine self-administration, and two weeks complete abstinence. A repeatable cognitive battery showed attention and delayed verbal recognition memory but not working memory to be impaired in cocaine users compared to age- and sex-matched normative values. Attention was significantly poorer during the first and second week of abstinence compared to days on which cocaine was used suggesting that certain cocaine-induced impairments may be acutely normalized by cocaine use, but resurface during abstinence.

Cocaine-dependent individuals demonstrate attentional bias when measured by Stroop color-naming tasks that have been modified to include cocaine-related words. However, the relationship between attentional bias and the treatment-seeking status of cocaine-dependent individuals has never been explored. The purpose of this study was to compare attentional bias towards cocaine-related verbal stimuli between treatment-seeking and nontreatment-seeking cocaine abusers.We examined performance on a Stroop task modified to include drug-related words in 17 cocaine-dependent treatment-seeking male participants and 20 cocaine-dependent nontreatment-seeking male participants.Although treatment seekers reported less experience with cocaine than nontreatment seekers, they exhibited increased response latency and made more errors when identifying the colors of cocaine-related words, relative to neutral words (p.05), whereas nontreatment seekers did not.Factors other than a high frequency of cocaine use may contribute to the difference in attentional bias towards cocaine cues between these subgroups of cocaine users.

Modafinil has been reported to reduce cocaine use in a clinical sample of infrequent users (2 days/week), but the effects of modafinil on cocaine self-administration in the laboratory have not been studied. The present study investigated the effects of modafinil maintenance on cocaine self-administration by frequent users (4 days/week) under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of modafinil maintenance (0, 200, and 400 mg/day) on response to smoked cocaine (0, 12, 25, and 50 mg) were examined in nontreatment-seeking cocaine-dependent individuals (n=8). Cocaine significantly increased self-administration, subjective-effect ratings, and cardiovascular measures; modafinil at both doses (200 and 400 mg/day) markedly attenuated these effects. These findings agree with data from previous human laboratory and clinical investigations of modafinil as a potential cocaine abuse treatment medication. Thus, our data support the potential of modafinil as a pharmacotherapy for cocaine dependence.

Previously, we reported that gabapentin, a λ-aminobutyric acid (GABA) agonist, significantly reduced “positive” subjective effects of cocaine without reducing cocaine self-administration. We speculated that the gabapentin doses used in that study were too low to detect subtle shifts in the reinforcing effects of cocaine. Thus, the present study examined the effects of larger gabapentin maintenance doses on cocaine-related effects, including self-administration. During this 48-day double-blind, crossover design study, the effects of gabapentin maintenance (0, 2400, 3200 mg/day) on response to cocaine (0, 12, 25, 50 mg) were investigated in six cocaine-dependent individuals not seeking treatment for their cocaine use. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., “Good Drug Effect”), blood pressure, and heart rate. Gabapentin did not decrease cocaine self-administration, cardiovascular measures, or most subjective effects of cocaine. These data agree with findings from a clinical trial examining the effects of similar gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals and suggest that gabapentin does not show promise as a treatment medication for cocaine dependence.

Preclinical and clinical studies suggest that GABAB receptor agonists selectively decrease cocaine use. The behavioral mechanism for the interaction between baclofen and cocaine in humans is not known, nor have its effects been characterized in individuals dependent on both cocaine and methadone. The objective of this study is to determine how maintenance on baclofen influences smoked cocaine's reinforcing and subjective effects, mood and cocaine craving prior to and after the initiation of cocaine use in cocaine-dependent volunteers with and without concurrent opioid dependence. Nontreatment-seeking volunteers (10 nonopioid dependent; seven methadone maintained), residing on an in-patient research unit for 21 days, were maintained on each baclofen dose (0, 30, 60 mg po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice: on days 3-4 and days 6-7 of each baclofen maintenance condition. Cocaine sessions began with a sample trial, when participants smoked the cocaine dose available that session, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one 5 dollars merchandise voucher. The results show that in the nonmethadone group, baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In the methadone group, baclofen decreased craving for cocaine. In both groups, baclofen decreased cocaine's effects on heart rate. Baclofen did not alter cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group. The results from this laboratory study appear consistent with clinical evidence showing that baclofen decreases cocaine use in nonopioid-dependent patients seeking treatment for cocaine dependence. The distinct pattern of effects in methadone-maintained participants suggests baclofen may not be effective in opioid-dependent cocaine users.

Common complaints among shift workers are sleep disruptions and increased sleepiness while working, which may contribute to shift workers being more susceptible to diminished performance and work-related accidents. The purpose of this double-blind, within-participant study was to examine the effects of the alerting agent modafinil on cognitive/psychomotor performance, mood, and measures of sleep during simulated shift work. In all, 11 participants completed this 23-day residential laboratory study. They received a single oral modafinil dose (0, 200, 400 mg) 1 h after waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the study, and shift conditions were separated by an ‘off’ day. When participants received placebo, cognitive performance and subjective ratings of mood were disrupted during the night shift, relative to the day shift. Objective and subjective measures of sleep were also disrupted, but to a lesser extent. Modafinil reversed disruptions in cognitive performance and mood during the night shift. While modafinil produced few effects on sleep measures during the night shift, the largest dose produced several sleep alterations during the day shift. These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work. Therapeutic doses of modafinil attenuated night-shift-associated disruptions, but the larger dose produced some sleep impairments when administered during day-shift work.

Five cocaine-dependent individuals completed a 22-day inpatient study of sleep and cognition. Following 3 days of drug-free baseline, participants underwent 3 days of twice-daily smoked cocaine base self-administration (6 50-mg doses, 14 minutes apart), followed by 15 days of abstinence. Each morning and afternoon, the CDR repeatable, multiple-version, computerized cognitive battery (whose stability following practice has been documented) was administered. During abstinence, performance deteriorated on vigilance tasks (especially reaction time) as well as on immediate and delayed verbal recognition tasks but not on working memory tasks. Declines were most evident in the afternoon. Data suggest that abstinence can unmask cognitive deficits induced by chronic cocaine use and circadian factors may mediate their severity.

γ-Aminobutyric acid (GABA) agonists, such as the GABA analogue, gabapentin, may provide new avenues for pharmacological treatment of cocaine dependence. The purpose of this study was to develop a smoked cocaine drug discrimination procedure in humans to test the effects of gabapentin maintenance on the discriminative stimulus, subjective, cognitive and cardiovascular effects of smoked cocaine. Eight male, nontreatment-seeking, cocaine-dependent volunteers, residing on an inpatient research unit for 47 days completed a within-subjects, counter-balanced design. Participants learned to discriminate between cocaine (25 mg) and placebo, and once the criterion for discrimination was met, smoked cocaine dose-effect functions (0, 6, 12, 25 and 50 mg) were determined under three gabapentin maintenance conditions (0, 600 and 1200 mg/day po). The highest dose of gabapentin tested (1200 mg/day) decreased the discriminative stimulus effects of cocaine (6 mg), decreased cocaine craving by 41–53% following cocaine administration (6 and 12 mg), and increased heart rate following either placebo or cocaine (12 mg) administration. Gabapentin did not significantly affect psychomotor task performance or the subjective effects of cocaine. Although the direction of gabapentin's effects was appropriate for a potential treatment medication, i.e., a decrease in cocaine-elicited craving and a decrease in cocaine's discriminative stimulus effects, these effects were limited to low doses of cocaine. The results suggest gabapentin may not produce effects sufficiently robust to be clinically useful, at least at this dose regimen.

The purpose of this double-blind, outpatient study was to evaluate the reinforcing and subjective effects of the uncompetitive N -methyl- d -aspartate (NMDA) antagonist memantine in cocaine-dependent humans. Eight participants (two females, six males) completed this study which consisted of three blocks of seven sessions; each block tested a different dose of memantine. During the first two sessions of each block, participants “sampled” the memantine capsule (10, 20, or 30 mg) and the placebo capsule that were available for the next five sessions. During the five subsequent sessions, participants had an opportunity to self-administer either the active or placebo capsule. Memantine was not reinforcing and subjective-effects ratings were not altered as a function of dose. Results suggest that these doses of memantine do not have abuse liability in cocaine-dependent individuals.

Data from research with laboratory animals indicate that cocaine self-administration can be reduced by λ-aminobutyric acid (GABA) agonists. Yet, the effectiveness of GABA agonists to decrease human cocaine self-administration has not been investigated under controlled laboratory conditions. The purpose of this study was to assess the effects of gabapentin, a GABA agonist, on cocaine-related behaviors, including self-administration, in human research participants under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of gabapentin (0, 600, and 1200 mg/d) maintenance on response to cocaine (0, 12, 25, and 50 mg) were investigated in seven cocaine abusers. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., “Good Drug Effect”), blood pressure and heart rate (HR). Gabapentin did not reduce cocaine choice or cardiovascular measures, but it did decrease some subjective effects of cocaine (e.g., “Good Drug Effect” and “Anxious”). These data suggest that the cocaine–gabapentin combination was well-tolerated, and because some cocaine-related subjective effects were reduced by maintenance on relatively low gabapentin doses, future studies should test higher gabapentin doses.

The effects of maintenance on venlafaxine, which blocks both norepinephrine and serotonin reuptake, on the response to smoked cocaine (0, 12, 25, or 50 mg) in 7 opioid-free and 7 methadone-maintained cocaine abusers was examined during a 42-day study. Participants received venlafaxine (225 mg daily) and placebo as part of a double-blind crossover design. Cocaine significantly increased heart rate, blood pressure, cocaine choice, cocaine ratings, and ratings of positive subjective effects (e.g., "I feel high") in both groups. Venlafaxine significantly decreased the subjective effects of cocaine by 10-20% without affecting cocaine choice or cardiovascular response in both groups. Although the reduction in cocaine's effects was small, further studies using a longer venlafaxine maintenance period or a larger venlafaxine dose are warranted.

This study examined the effects of escalating doses of smoked cocaine in non-treatment-seeking cocaine users. Cocaine sessions were conducted twice per day for 3 consecutive days. During each session, one group of participants smoked a 12 mg cocaine dose, followed by a 25 mg dose, followed by four 50 mg doses at 14 min intervals (escalating-dose group); another group of participants smoked six 50 mg cocaine doses at 14 min intervals (fixed-dosing group). Cocaine produced dose-dependent increases in heart rate (HR), blood pressure, ratings of positive drug effect, e.g., "good drug effect", and ratings of cocaine dose, e.g., "liking", in the escalating-dose group. The 50 mg dose also increased these measures in the fixed-dosing group to a level that was not different than that observed following the initial 50 mg dose in the escalating-dose group. The largest effects of 50 mg cocaine were observed following the initial dose, with the latter 50 mg doses maintaining but not increasing these effects in both groups. The effects of cocaine in both groups were consistent for most measures within a day and between days. Resting baseline heart rate, blood pressure and cocaine craving were lower during the first session and higher thereafter. These results demonstrate that increasing the dose of cocaine during a bout, i.e., "binge", of cocaine use can increment the effects of cocaine, but administering the same cocaine dose maintains, but does not increment the effects of cocaine.