-
[show abstract]
[hide abstract]
ABSTRACT: Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ(9)-THC. The aim of the present study was to determine the potential involvement of the GABA(B) receptor subtype by assessing the separate and combined effects of the GABA(B)-selective agonist baclofen and Δ(9)-THC using pharmacologically specific drug-discrimination procedures.
Eight cannabis users learned to discriminate 30mg oral Δ(9)-THC from placebo and then received baclofen (25 and 50mg), Δ(9)-THC (5, 15 and 30mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected.
Δ(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50mg) substituted for the Δ(9)-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ(9)-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ(9)-THC-like subjective responses when administered alone.
These results suggest that the GABA(B) receptor subtype is involved in the abuse-related effects of Δ(9)-THC, and that GABA(B) receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABA(A)) to determine the contribution of the different GABA receptors in the effects of Δ(9)-THC, and by extension cannabis, in humans.
Drug and alcohol dependence 06/2012; 126(1-2):216-23. · 3.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cocaine use disorders are an unrelenting public health concern. Behavioral treatments reduce cocaine use by providing non-drug alternative reinforcers. The purpose of this human laboratory experiment was to determine how response cost for non-drug alternative reinforcers influenced cocaine choice. Seven cocaine-using, non-treatment-seeking subjects completed a crossover, double-blind protocol in which they first sampled doses of intranasal cocaine (5, 10, 20 or 30 mg) and completed a battery of subject-rated and physiological measures. Subjects then made eight discrete choices between the sampled dose and an alternative reinforcer (US$0.25). The response cost to earn a cocaine dose was always a fixed ratio (FR) of 100 responses. The response cost for the alternative reinforcer varied across sessions (FR1, FR10, FR100, FR1000). Dose-related increases were observed for cocaine choice. Subjects made fewer drug choices when the FR requirements for the alternative reinforcers were lower than that for drug relative to when the FR requirements were equal to or higher than that for drug. Intranasal cocaine also produced prototypical stimulant-like subject-rated and physiological effects (e.g., increased ratings of Like Drug; elevated blood pressure). These data demonstrate that making alternative reinforcers easier to earn reduces cocaine self-administration, which has implications for treatment efforts.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2012; 36(1):189-93. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this experiment was to determine the influence of acute bupropion pre-treatment on subject-rated effects and choice of intranasal cocaine versus money.
A randomized, within-subject, placebo-controlled, double-blind experiment.
An out-patient research unit.
Eight cocaine-using adults.
Subjects completed nine experimental sessions in which they were pre-treated with 0, 100 or 200 mg oral immediate release bupropion. Ninety minutes later they sampled an intranasal cocaine dose [4 (placebo), 15 or 45 mg] and made six choices between that dose and an alternative reinforcer (US$0.25), available on independent, concurrent progressive ratio schedules. Subjects also completed a battery of subject-rated, performance and physiological measures following the sample doses of cocaine.
After 0 mg bupropion, the high dose of cocaine (45 mg) was chosen five of six times on average compared to 2.25 of six choices for placebo cocaine (4 mg) (P < 0.05). Active bupropion reduced choice of 45 mg cocaine to 3.13 (100 mg) or 4.00 (200 mg) out of six drug choices on average. Bupropion also consistently enhanced positive subject-rated effects of cocaine (e.g. good effects; willing to take again) while having no effects of its own.
The atypical antidepressant, bupropion, acutely appears to reduce preference for intranasal cocaine versus a small amount of money but to increase reported positive experiences of the drug.
Addiction 12/2011; 107(6):1140-7. · 4.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The involvement of non-cannabinoid neurotransmitter systems in the abuse-related behavioral effects of cannabis has not been well characterized in humans. GABAergic drugs have overlapping effects with cannabis and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) on certain behavioral measures, but those measures lack the specificity to draw conclusions regarding the involvement of GABA in cannabinoid effects. The aim of this study was to assess the separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ(9)-THC using more pharmacologically specific drug-discrimination procedures.
Eight cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received tiagabine (6 and 12 mg), Δ(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected.
Δ(9)-THC produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on psychomotor performance tasks. The higher tiagabine dose substituted for the Δ(9)-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Δ(9)-THC when administered alone. In combination, tiagabine shifted the discriminative-stimulus effects of Δ(9)-THC leftward/upward and enhanced Δ(9)-THC effects on other outcomes.
These results indicate that GABA is involved in the clinical effects of Δ(9)-THC, and by extension, cannabis. Future studies should test selective GABAergic compounds to determine which receptor subtype(s) are responsible for the effects observed when combined with cannabinoids.
Drug and alcohol dependence 10/2011; 122(1-2):61-9. · 3.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There is accumulating evidence that sex plays a critical role in drug abuse. Female sex hormones have been shown to affect central nervous system function and modulate the effects of drugs of abuse. For example, γ-aminobutyric acid type A (GABA(A)) receptor function is positively modulated by progesterone metabolites. There is evidence from preclinical in-vitro and in-vivo studies as well as some clinical research suggesting that progesterone and its metabolites may enhance the behavioral effects of benzodiazepines, which also serve as positive modulators of GABA(A) receptors. The purpose of this experiment was to determine the independent and combined discriminative stimulus, subjective and psychomotor effects of progesterone and triazolam in healthy adult premenopausal women. Oral micronized progesterone (100 mg), triazolam (0.06, 0.12 and 0.25 mg/70 kg) and placebo were administered to healthy, premenopausal women (n=9) under conditions of low circulating sex hormones. Triazolam alone functioned as a discriminative stimulus and produced prototypical sedative-like effects (e.g., performance impairment, enhanced reports of sedative effects). Progesterone alone produced sedative-like effects on several subjective and performance measures, and the dose combination effects of progesterone and triazolam on several subjective measures of drug effect were similar to the summation of the two drug effects in isolation. Progesterone did not substitute for or modify the discriminative stimulus effects of triazolam. These results suggest that the parent hormone, progesterone, and triazolam have discordant neuropharmacological mechanisms of action. Additional research is necessary to determine the degree to which neurosteroids influence sex differences in benzodiazepine use and abuse.
Behavioural pharmacology 09/2011; 22(5-6):441-9. · 2.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
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.
Pharmacology Biochemistry and Behavior 07/2011; 100(1):40-7. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABA(A) activity following chronic stimulant use, and that positive modulation of GABA(A) receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABA(A) modulators could be useful as pharmacotherapies for stimulant-use disorders.
This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1mg/day).
Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment.
The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABA(A) positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABA(A) positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment.
Drug and alcohol dependence 07/2011; 119(3):187-93. · 3.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent reports indicate an increase in intranasal use of prescription oral stimulant medication. However, there do not appear to be any published clinical studies that have characterized the behavioral and cardiovascular effects of intranasally administered d-amphetamine, which is commonly prescribed for Attention Deficit Hyperactivity Disorder. In this study, a range of d-amphetamine doses (0, 16, 24, and 32 mg/70 kg) were administered as an intranasal solution delivered using a mucosal atomization device. Equal oral doses were included for comparison. Assessments were conducted before and at regular intervals for 3 hours following drug administration and included self-reported drug-effect questionnaires, cardiovascular indices, a performance task, and 2 measures of impulsivity. d-Amphetamine produced prototypical stimulant effects (eg, increased subject ratings of Stimulated and Like Drug, elevated heart rate and blood pressure, and improved rate and accuracy on the digit symbol substitution task) irrespective of dose, but the onset of these effects was generally earlier following intranasal administration, with significant effects emerging 15 to 30 minutes after intranasal dosing and 45 to 60 minutes after oral dosing. These results demonstrate that intranasal administration of d-amphetamine results in a more rapid onset compared to oral dosing, which could be associated with the popularity of intranasal prescription stimulant use and an enhanced potential for abuse.
The Journal of Clinical Pharmacology 06/2011; 51(6):888-98. · 2.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gender plays a critical role in the effects of drugs and drug abuse liability. Biological factors, including ovarian hormones, may contribute to gender differences in drug abuse. Preclinical and some clinical research suggests that progesterone and its metabolites have activity at the GABA(A) receptor and may enhance the effect of GABAergic compounds (e.g., benzodiazepines). Because women are exposed to varying levels of progesterone from puberty until menopause, and appear more sensitive to the negative consequences of benzodiazepine use, it is important to understand the impact of progesterone on GABAergic drug effects.
The purpose of this experiment was to characterize the behavioral effects of progesterone, alone and in combination with the short-acting benzodiazepine, triazolam, to determine if progesterone potentiates the behavioral effects of triazolam.
Oral micronized progesterone (0, 100, and 200 mg) and oral triazolam (0.00, 0.12, and 0.25 mg/70 kg) were administered to healthy, premenopausal women (n = 11) under conditions of low circulating sex hormones. The subjective, performance and physiological effects of progesterone, alone and in combination with triazolam, were assessed.
Triazolam alone produced prototypical sedative-like effects. Progesterone alone also engendered some sedative effects, although the time course of the effects was more limited than that of triazolam. Progesterone increased and extended the duration of triazolam effects and delayed the onset of triazolam peak effects, most notably at the 0.12 mg/70 kg dose.
Progesterone potentiates the behavioral effects of benzodiazepines and may contribute to benzodiazepine use and abuse among women.
Psychopharmacologia 02/2011; 215(3):429-39. · 4.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment.
Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected.
Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures.
These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.
Drug and alcohol dependence 01/2011; 116(1-3):86-92. · 3.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
This experiment determined the subjective and physiological effects of intranasal methamphetamine during D: -amphetamine maintenance in eight non-treatment-seeking stimulant-dependent participants. We predicted D: -amphetamine maintenance would attenuate the acute subjective effects of intranasal methamphetamine. We also predicted intranasal methamphetamine would be well tolerated during D: -amphetamine maintenance.
After at least 7 days of maintenance on sustained-release D: -amphetamine (0 and 45 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 2.5, 5, 10, and 20 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.
Intranasal methamphetamine produced prototypical subjective and physiological effects (e.g., increased ratings of Like Drug; increased heart rate, blood pressure, and body temperature). The acute effects of intranasal methamphetamine were significantly diminished during D: -amphetamine maintenance relative to placebo maintenance.
These results are concordant with those of clinical trials and provide further support for the use of agonist replacement therapy to manage methamphetamine dependence. Additional research in humans is needed to determine the effectiveness of D: -amphetamine under different experimental conditions that more closely reflect use in the natural environment (e.g., higher methamphetamine doses) and behavioral arrangements that are predictive of pharmacotherapy effectiveness (e.g., drug self-administration).
Psychopharmacologia 11/2010; 214(3):665-74. · 4.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cocaine dependence continues to be a worldwide public health concern. Although the majority of individuals reporting cocaine use do so via the intranasal route, relatively few laboratory experiments have examined the reinforcing effects of cocaine administered intranasally. The purpose of this experiment was to measure the reinforcing effects of intranasal cocaine using a progressive ratio schedule in which eight cocaine-using subjects chose between doses of cocaine (4 [placebo], 15, 30 and 45 mg) and an alternative reinforcer ($0.25). During each session, subjects first sampled the dose of cocaine available that day and then made six choices between that dose and money, which were available on concurrent progressive ratio schedules of responding. Break points for active cocaine doses were higher than those for placebo but no statistically significant active versus placebo dose effects were observed on subject-rated or physiological measures. These data demonstrate that intranasal cocaine functions as a reinforcer under a progressive ratio schedule in humans. Future research should test higher cocaine doses and larger values of the alternative reinforcer. These procedures may be useful for examining the influence of putative pharmacological and behavioral interventions on intranasal cocaine self-administration.
European journal of pharmacology 10/2010; 644(1-3):101-5. · 2.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aripiprazole is a dopamine D(2) receptor partial agonist undergoing evaluation as a pharmacotherapy for stimulant-use disorders. Acutely administered aripiprazole attenuates the discriminative stimulus and other behavioral effects of d-amphetamine in humans; however, whether aripiprazole attenuates the effects of more commonly abused stimulants is unknown. The aim of this experiment was to assess the discriminative stimulus, subject-rated and cardiovascular effects of oral cocaine alone and following acute administration of aripiprazole in humans. Eight cocaine-dependent subjects learned to discriminate 150 mg cocaine from placebo. After acquiring the discrimination, the effects of cocaine (0, 25, 50, 100 and 200 mg) administered alone and in combination with aripiprazole (15 mg) were determined. Significant effects of cocaine were observed for the drug discrimination task, stimulant-like subject-rated effects and heart rate. Limited effects of aripiprazole were revealed. However, for most measures, fewer doses of cocaine were significantly greater than placebo when combined with aripiprazole, suggesting a reduction in the discriminative stimulus, self-reported and cardiovascular effects of cocaine. These data are consistent with previous studies that have tested acutely administered aripiprazole in combination with d-amphetamine and suggest that the ability of aripiprazole to modify stimulant effects is a function of the duration of treatment (acute vs. chronic).
Journal of Psychopharmacology 10/2010; 25(11):1469-79. · 3.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cocaine dependence continues to be a significant public health concern. Contingency management, wherein alternative reinforcers are made available upon cocaine abstinence, has shown promise for decreasing cocaine use. Other research has modeled this effect and demonstrated that alternative reinforcers also reduce cocaine self-administration in the laboratory. Results from both clinical and laboratory studies suggest that the type and value of alternative reinforcers influences their ability to decrease drug choice. The purpose of the present experiment was to determine the effect of money or food alternative reinforcers, valued at $0.01, 0.25, 0.50 and 1.00, on intranasal cocaine (4 [placebo] and 30 mg) choice. Cocaine was chosen to a greater extent than placebo across alternative reinforcer types and values, but the monetary alternative reinforcer suppressed drug choice to a greater degree than the food reinforcer. These results are concordant with previous findings and suggest that money may be a more effective alternative reinforcer for decreasing cocaine use. Future research should determine the sensitivity of this model to specific behavioral aspects of contingency management and whether food could compete with drugs as reinforcers in humans under laboratory conditions.
Pharmacology Biochemistry and Behavior 04/2010; 95(2):187-91. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pre-clinical studies indicate that changes in progesterone levels across menstrual cycle phases modulate the behavioral effects of sedative drugs acting at GABA(A) receptor sites. In this study, seven healthy women learned to discriminate triazolam (0.25 mg/70 kg) from placebo. After acquiring the discrimination, a range of triazolam doses (0.00, 0.06, 0.12 and 0.25 mg/70 kg) was tested during the early follicular and mid-luteal menstrual cycle phases. During the mid-luteal phase, when progesterone levels were elevated, 0.12 mg/70 kg triazolam was identified as the active triazolam training dose (0.25 mg/70 kg), whereas 0.12 mg/70 kg triazolam was identified as placebo during the early follicular phase, when progesterone levels were low. Triazolam engendered prototypical sedative effects on subjective effect, performance and cardiovascular measures that were generally independent of cycle phase. These results suggest that the discriminative stimulus effects of the positive GABA(A) modulator, triazolam, are sensitive to menstrual cycle phase in healthy adult women.
Drug and Alcohol Dependence 05/2008; 94(1-3):276-80. · 3.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Individual differences that may contribute to vulnerability to abuse drugs have been identified. Sensation-seeking status has been shown to influence both vulnerability to drug use and response to acute drug administration. The purpose of the present experiment was to examine the reinforcing effects of d-amphetamine in high and low sensation-seeking subjects using a modified progressive-ratio procedure. A battery of subject-rated, performance, and cardiovascular measures was also included to better characterize the effects of d-amphetamine in these groups. Ten high sensation seekers and ten low sensation seekers that were matched for education, age, drug use, height, and weight, first sampled doses of d-amphetamine (0, 8, and 16 mg). In subsequent sessions, subjects were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. d-Amphetamine functioned as a reinforcer and produced prototypical stimulant-like effects (e.g., increased subject-ratings of Like Drug, enhanced performance, and increased heart rate). High sensation seekers were more sensitive than low sensation seekers to the reinforcing and some of the subject-rated effects of d-amphetamine. The results of the present experiment extend those of previous findings by demonstrating that the reinforcing effects of d-amphetamine vary as a function of the biologically based sensation-seeking personality trait. These results suggest that increased stimulant drug use and abuse among high sensation seekers may be related, in part, to increased sensitivity to the reinforcing effects of stimulants among these individuals.
Addictive Behaviors 07/2007; 32(6):1177-88. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaine-using individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified progressive-ratio procedure in two sessions in which they received pretreatment with either 0 or 15 mg oral d-amphetamine 2 h prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressive-ratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.
Pharmacology Biochemistry and Behavior 06/2007; 87(1):20-9. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although cocaine dependence remains a significant public health concern, efforts to identify a pharmacotherapy have been unsuccessful. The purpose of this study was to assess the safety, tolerability, and subject-rated effects of intranasal cocaine during maintenance on aripiprazole, a novel antipsychotic with partial agonist activity at monoamine receptors implicated in the effects of cocaine. To this end, eight cocaine dependent subjects were maintained on 10 mg oral aripiprazole and placebo in counterbalanced order prior to assessing the physiological and subject-rated effects of intranasal cocaine (4, 20, 40, and 60 mg). Aripiprazole was generally devoid of effects, but did alter temperature-increasing and subject-rated effects of cocaine as a function of cocaine dose.
The American Journal of Drug and Alcohol Abuse 02/2007; 33(6):769-76. · 1.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite increased reports of amphetamine abuse and dependence, a putative pharmacotherapy has yet to be identified. In a previous study from our laboratory, 20 mg aripiprazole, an atypical antipsychotic that has partial agonist activity at D(2) receptors, attenuated many of the behavioral effects of d-amphetamine. Aripiprazole (20 mg) also impaired performance on a computerized version of the DSST when administered alone, indicating that the attenuation observed may have been functional as opposed to receptor mediated. The present experiment was conducted to determine whether a lower dose of aripiprazole (10 mg) could acutely attenuate the discriminative-stimulus, subject-rated, and physiological effects of d-amphetamine (2.5-15 mg) without impairing performance as measured with a computerized version of the DSST. The results of the present experiment indicate that 10 mg aripiprazole attenuated some abuse-related behavioral effects of d-amphetamine and was generally devoid of effects, including significant performance impairment, when administered alone. These findings suggest that 10 mg aripiprazole would be a reasonable starting dose for the treatment of stimulant abuse and dependence. Future research should examine the effects of chronic aripiprazole administration in combination with methamphetamine or cocaine.
Drug and Alcohol Dependence 10/2006; 84(2):206-9. · 3.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Atomoxetine is marketed as a nonstimulant medication indicated for the treatment of attention-deficit/hyperactivity disorder in adults. Previous laboratory research suggests that atomoxetine has limited abuse potential but that some of its behavioral effects might overlap with traditional psychomotor stimulants like methylphenidate and d-amphetamine. A drug with this profile might be useful for the treatment of stimulant dependence. The aim of this experiment was to compare the discriminative-stimulus and self-reported effects of atomoxetine with methylphenidate, damphetamine, and triazolam in humans who had acquired a methylphenidate (30 mg) discrimination. Six healthy subjects with a recent history of nontherapeutic stimulant use were enrolled in this outpatient study. After subjects acquired the methylphenidate discrimination, a range of doses of methylphenidate (5-30 mg), atomoxetine (15-90 mg), d-amphetamine (2.5-15 mg), triazolam (0.06-0.375 mg), and placebo were tested. To more fully characterize the behavioral effects of atomoxetine, a battery of self-reported drug-effect questionnaires, a performance task, and cardiovascular assessments were also included. Methylphenidate and d-amphetamine increased drug-appropriate responding and produced typical stimulant-like effects (e.g., increased ratings of "Active, Alert, Energetic"). Atomoxetine partially substituted for methylphenidate (i.e., 33%-50%) and produced some dose-dependent, stimulant-like, subject-rated drug effects, although the magnitude of these effects was less than d-amphetamine and methylphenidate and generally did not attain statistical significance. These data suggest that the behavioral effects of atomoxetine overlap to a small degree with psychomotor stimulants and that it has low abuse potential.
Experimental and Clinical Psychopharmacology 06/2006; 14(2):136-47. · 2.58 Impact Factor
