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ABSTRACT: Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ(9) tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the Cold-Pressor Test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared to placebo, marijuana and dronabinol decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56%; 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana.Neuropsychopharmacology accepted article preview online, 22 April 2013; doi:10.1038/npp.2013.97.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 04/2013; · 6.99 Impact Factor
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ABSTRACT: Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ(9)-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. The FDA-approved synthetic analogue of THC, nabilone, has higher bioavailability and clearer dose-linearity than dronabinol. This study tested whether nabilone administration would decrease marijuana withdrawal symptoms and a laboratory measure of marijuana relapse relative to placebo. Daily, nontreatment-seeking marijuana smokers (8 M, 3 F), who reported smoking 8.3±3.1 marijuana cigarettes/day completed this within-subject study comprising three, 8-day inpatient phases; each phase tested a different nabilone dose [0, 6, 8 mg/day, administered in counter-balanced order on days 2-8]. On the first inpatient day, participants took placebo capsules and smoked active marijuana (5.6% THC) at six timepoints. For the next 3 days, they had the opportunity to self-administer placebo marijuana (0.0% THC; Withdrawal), followed by 4 days in which active marijuana was available for self-administration (5.6% THC; Relapse). Both nabilone dose conditions decreased marijuana relapse and reversed withdrawal-related irritability and disruptions in sleep and food intake (p<0.05). Nabilone (8 mg/day) modestly worsened psychomotor task performance. Neither dose condition increased ratings of capsule 'liking' or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment.Neuropsychopharmacology accepted article preview online, 26 February 2013; doi:10.1038/npp.2013.54.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 02/2013; · 6.99 Impact Factor
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ABSTRACT: BACKGROUND: Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. METHODS: Study 1: data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal, and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers (n = 51; 10 ± 5 marijuana cigarettes/day) were enrolled. Study 2: to isolate the effects of cigarette smoking, marijuana intoxication, withdrawal, and relapse were assessed in daily marijuana and cigarette smokers (n = 15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU), and after at least 5 days without cigarettes (Quit). RESULTS: Study 1: 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (odds ratio: 19, p < .01). Individuals experiencing more positive subjective effects (i.e., feeling "high") after marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes (p < .05). Study 2: most participants (>87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. CONCLUSIONS: Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse, and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse.
Biological psychiatry 08/2012; · 8.93 Impact Factor
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ABSTRACT: Background: Little is known about whether the duration of cocaine use or an individual's age may influence the acute effects of cocaine, patterns of use, and specific treatment needs. Objectives: This post hoc analysis determined whether the duration of cocaine use or current age influenced the acute subjective response to cocaine. Data from four smoked cocaine self-administration laboratory studies were combined and analyzed to determine whether the subjective effects of a 25-mg smoked cocaine dose varied as a function of years of cocaine use or current age. Methods: Thirty-six nontreatment-seeking healthy cocaine users (ages 32-49) were admitted to studies lasting from 12 to 105 days. Participants rated the subjective effects of each cocaine dose from 0 to 100 by completing a computerized self-report visual analogue scale (VAS). The main outcome measures were the change in VAS ratings between a baseline placebo dose and the first 25-mg dose of smoked cocaine. Results: No significant relationship was found between the subjective effects of cocaine and years of cocaine use (mean 20.9, range 5-30) or current age (mean 41.1, range 32-49). Conclusion: Among long-term cocaine users between the ages of 32 and 49, the acute subjective effects of cocaine did not vary as a function of years of cocaine use or current age. Scientific Significance: These data fail to support the incentive sensitization theory for addiction by Robinson and Berridge, as cocaine "liking" and "wanting" remained the same regardless of age or years of cocaine use.
The American Journal of Drug and Alcohol Abuse 07/2012; 38(6):530-4. · 1.55 Impact Factor
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ABSTRACT: 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.
Addiction Biology 06/2012; · 4.83 Impact Factor
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ABSTRACT: Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration; yet, this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine whether tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone (0, 5, and 20 mg/70 kg, orally) were compared, using a within-session cumulative dosing procedure, on the first and fifth days of the 'daily' dosing phase to assess for tolerance; active oxycodone was administered on the second and fourth days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the first and the fifth day of a 5-day 'intermittent' dosing phase; placebo medication was administered on the second and fourth days of the intermittent dosing phase. A 9-day 'washout' period occurred between phases during which no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the cold pressor test, pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the first and the fifth days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the fifth compared with the first day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the first and the fifth days of either dosing phase were detected. Although obtained under limited experimental conditions, these findings suggest that tolerance may not develop to the analgesic effects of therapeutic doses of oxycodone under short-term daily dosing conditions, even though some of its subjective effects may decrease. These data also suggest that intermittent administration may enhance the analgesic effects of oxycodone, while also increasing some of the drug's positive subjective effects related to abuse liability.
Behavioural pharmacology 04/2012; 23(3):271-9. · 2.85 Impact Factor
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ABSTRACT: Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.
Addiction Biology 01/2012; · 4.83 Impact Factor
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ABSTRACT: Laboratory studies in which drugs of abuse are self- or experimenter-administered to non-treatment-seeking research volunteers provide valuable data about new pharmacotherapies for substance use disorders, as well as behavioral and performance data for understanding the neurobiology of drug abuse. This paper analyzed follow-up data from six smoked cocaine self-administration laboratory studies, in order to determine whether changes in substance use occurred 1 and 3 months after study participation compared to pre-study baseline.
Ninety-eight healthy, non-treatment-seeking cocaine users were admitted to inpatient and combined inpatient/outpatient studies lasting from 12 to 105 days. The studies allowed participants to self-administer repeated doses of smoked cocaine (0, 6, 12, 25, and/or 50mg per dose) on multiple occasions. Participants returned for follow-up at 1 and 3 months, at which time self-reported consumption of cocaine, alcohol, marijuana, and nicotine was assessed.
Compared to baseline ($374.04/week, S.D. $350.09), cocaine use significantly decreased at 1 month ($165.13/week, S.D. $165.56) and 3 months ($118.59/week, S.D. $110.48) after study participation (p<0.001; results based on the 39 participants who completed all 3 time points). This decrease was not accompanied by a change in other drug use, e.g., a compensatory increase in alcohol, marijuana or nicotine use.
Study participation was not associated with increased post-study cocaine, alcohol, marijuana, or nicotine use. Thus, human laboratory models of cocaine self-administration, conducted in non-treatment-seeking research volunteers, are relatively safe, and study participation does not exacerbate ongoing drug use.
Drug and alcohol dependence 08/2011; 120(1-3):162-7. · 3.60 Impact Factor
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ABSTRACT: Despite their chemical similarities, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) produce differing neurochemical and behavioral responses in animals. In humans, individual studies of methamphetamine and MDMA indicate that the drugs engender overlapping and divergent effects; there are only limited data comparing the two drugs in the same individuals.
This study examined the effects of methamphetamine and MDMA using a within-subject design.
Eleven adult volunteers completed this 13-day residential laboratory study, which consisted of four 3-day blocks of sessions. On the first day of each block, participants received oral methamphetamine (20, 40 mg), MDMA (100 mg), or placebo. Drug plasma concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and after. Food intake and sleep were also assessed. On subsequent days of each block, placebo was administered and residual effects were assessed.
Acutely, both drugs increased cardiovascular measures and "positive" subjective effects and decreased food intake. In addition, when asked to identify each drug, participants had difficulty distinguishing between the amphetamines. The drugs also produced divergent effects: methamphetamine improved performance and disrupted sleep, while MDMA increased "negative" subjective-effect ratings. Few residual drug effects were noted for either drug.
It is possible that the differences observed could explain the differential public perception and abuse potential associated with these amphetamines. Alternatively, the route of administration by which the drugs are used recreationally might account for the many of the effects attributed to these drugs (i.e., MDMA is primarily used orally, whereas methamphetamine is used by routes associated with higher abuse potential).
Psychopharmacologia 06/2011; 219(1):109-22. · 4.08 Impact Factor
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ABSTRACT: Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence.
This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D(2) receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers.
In order to achieve steady-state concentrations, participants (n = 8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a "sample" trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00.
Cocaine's reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo.
These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence.
Psychopharmacologia 03/2011; 216(3):379-87. · 4.08 Impact Factor
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ABSTRACT: The quantification method for collecting self-reported marijuana use data is not standardized as it is for alcohol or cigarettes, which presents a methodologic challenge for marijuana use disorder treatment studies. Serum and urine markers of marijuana use have a long half-life, limiting their utility as a clinical trial outcome measure. Structured calendar-based interview procedures can accurately measure the frequency of self-reported marijuana use, but are unable to reliably address issues such as quantity of use or potency. This study compared the quantity and assigned-dollar value among users of blunts, joints, and pipes enrolled in two clinical trials testing pharmacotherapies for marijuana dependence. The timeline follow-back method was modified to incorporate using a surrogate substance to represent marijuana to enable participants to estimate the amount and value used. Blunt users were mostly black and Hispanic, while users of joints and pipes were primarily white. Participants reported that they placed 50% more marijuana in blunts than in joints and placed more than twice the amount of marijuana in blunts than in pipes. These findings demonstrate the feasibility of using a surrogate weight estimation procedure to augment calendar-based methods of measuring self-reported marijuana use. Individual variability in use practices limits the utility of this method to estimating within-subject comparisons, rather than between subject comparisons.
Drug and alcohol dependence 01/2011; 113(2-3):249-51. · 3.60 Impact Factor
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ABSTRACT: Dronabinol (Δ(9)tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects.
Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication.
Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1-8 and 9-16; we compared dronabinol's effects with placebo in each 8-day phase to investigate tolerance.
Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol's mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects.
In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.
Psychopharmacologia 12/2010; 212(4):675-86. · 4.08 Impact Factor
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ABSTRACT: 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 (10mg) 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 09:30h and went to bed at 16:00h and (2) during the day shift, participants completed task batteries from 08:30 to 17:30h and went to bed at 24:00h. 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.
Drug and alcohol dependence 11/2010; 112(1-2):168-71. · 3.60 Impact Factor
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ABSTRACT: Studies in laboratory animals strongly suggest reciprocal modulation of the opioidergic and endocannabinoid systems, a relationship that has not been demonstrated in humans. This study sought to clarify this interaction by assessing how a range of naltrexone doses altered the subjective, cognitive, and cardiovascular effects of marijuana.
Daily marijuana smokers (n = 29) participated in this within-subject, randomized, double-blind, placebo-controlled study. Naltrexone (0, 12, 25, 50, or 100 mg) was administered before active or inactive marijuana (3.27 or 0% THC) was smoked.
Active marijuana increased subjective ratings of marijuana 'Strength,' 'High,' and positive subjective ratings of marijuana quality and drug effect including 'Liking,' 'Good,' and 'Take Again' compared to inactive marijuana. Naltrexone alone decreased ratings of 'Liking,' 'Take Again,' and 'Stimulated' compared with placebo, but increased ratings of drug 'Strength,' 'High,' 'Good,' 'Liking,' 'Stimulated,' and 'Take Again' when administered under active marijuana conditions. Active marijuana did not affect performance on cognitive tasks relative to inactive marijuana, whereas naltrexone decreased performance when administered alone or in combination with active marijuana. Active marijuana increased heart rate compared to inactive marijuana under placebo naltrexone conditions. Although naltrexone alone decreased heart rate, it further increased marijuana's cardiovascular effect.
In heavy marijuana smokers opioid-receptor blockade enhanced the subjective and cardiovascular effects of marijuana, suggesting that endogenous opioids dampen cannabinoid effects in this population. These findings demonstrate that a broad range of clinically used doses of naltrexone potentially increases the abuse liability and cardiovascular risks of cannabinoids.
Psychopharmacologia 08/2010; 211(2):141-8. · 4.08 Impact Factor
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ABSTRACT: Only a small percentage of individuals seeking treatment for their marijuana use achieves sustained abstinence, suggesting more treatment options are needed.
We investigated the effects of baclofen (study 1) and mirtazapine (study 2) in a human laboratory model of marijuana intoxication, withdrawal, and relapse.
In study 1, daily marijuana smokers (n = 10), averaging 9.4 (+/-3.9) marijuana cigarettes/day, were maintained on placebo and each baclofen dose (60, 90 mg/day) for 16 days. In study 2, daily marijuana smokers (n = 11), averaging 11.9 (+/-5.3) marijuana cigarettes/day, were maintained on placebo and mirtazapine (30 mg/day) for 14 days each. Medication administration began outpatient prior to each 8-day inpatient phase. On the first inpatient day of each medication condition, participants smoked active marijuana (study 1: 3.3% THC; study 2: 6.2% THC). For the next 3 days, they could self-administer placebo marijuana (abstinence phase), followed by 4 days in which they could self-administer active marijuana (relapse phase); participants paid for self-administered marijuana using study earnings.
In study 1, during active marijuana smoking, baclofen dose-dependently decreased craving for tobacco and marijuana, but had little effect on mood during abstinence and did not decrease relapse. Baclofen also worsened cognitive performance regardless of marijuana condition. In study 2, mirtazapine improved sleep during abstinence, and robustly increased food intake, but had no effect on withdrawal symptoms and did not decrease marijuana relapse.
Overall, this human laboratory study did not find evidence to suggest that either baclofen or mirtazapine showed promise for the potential treatment of marijuana dependence.
Psychopharmacologia 08/2010; 211(2):233-44. · 4.08 Impact Factor
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ABSTRACT: Human laboratory studies have shown that, once initiated, cocaine self-administration is difficult to disrupt using non-drug alternatives. This inpatient study examined whether binge self-administration of cocaine could be altered by an immediate, non-drug reinforcer. Ten cocaine-dependent participants completed 5 consecutive laboratory session days with 2 sessions per day (a model binge), 9 days where cocaine was not available, and subsequent 2 laboratory session days where cocaine was again available (a second model binge). In each laboratory session, participants could choose to either self-administer smoked cocaine or play a game of chance by drawing a pre-determined number of balls from a bingo wheel. Balls were worth monetary amounts from $0 to $20. Participants' choice to smoke cocaine varied as a function of number of balls drawn. Thus, this game of chance served as an alternative reinforcer to smoking cocaine. Choice varied lawfully as a function of the number of opportunities to earn money indicating that an immediate behavioral alternative can reduce cocaine self-administration after initiation of use. The current model could be used to evaluate whether behavioral and pharmacological manipulations shift choice from cocaine to a non-drug alternative.
Drug and alcohol dependence 03/2010; 110(1-2):144-50. · 3.60 Impact Factor
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ABSTRACT: Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD) produces selective anticocaine antibodies, yet the impact of these antibodies on cocaine's direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving, and cardiovascular effects.
Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0 mg, 25 mg, 50 mg) were determined before vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 microg, n = 4; 360 microg, n = 6) were administered at weeks 1, 3, 5, and 9.
Peak plasma antibody levels, which were highly variable, significantly predicted cocaine's effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55%-81%) reduction in ratings of good drug effect and cocaine quality, while those in the lower half showed only a nonsignificant attenuation (6%-26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p < .12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia.
The TA-CD vaccine substantially decreased smoked cocaine's intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence.
Biological psychiatry 10/2009; 67(1):59-65. · 8.93 Impact Factor
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ABSTRACT: 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.
Drug and alcohol dependence 09/2009; 106(2-3):233-6. · 3.60 Impact Factor
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ABSTRACT: 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.
Journal of substance abuse treatment 07/2009; 37(4):431-4. · 2.90 Impact Factor
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ABSTRACT: Recent increases in marijuana smoking among the young adult population have been accompanied by the popularization of smoking marijuana as blunts instead of as joints. Blunts consist of marijuana wrapped in tobacco leaves, whereas joints consist of marijuana wrapped in cigarette paper. To date, the effects of marijuana smoked as joints and blunts have not been systematically compared. The current within-subject, randomized, double-blind, placebo-controlled study sought to directly compare the subjective, physiological, and pharmacokinetic effects of marijuana smoked by these two methods. Marijuana blunt smokers (12 women and 12 men) were recruited and participated in a 6-session outpatient study. Participants were blindfolded and smoked three puffs from either a blunt or a joint containing marijuana with varying Delta(9)-tetrahydrocannabinol (THC) concentrations (0.0, 1.8, and 3.6%). Subjective, physiological (heart rate, blood pressure, and carbon monoxide levels) and pharmacokinetic effects (plasma THC concentration) were monitored before and at specified time points for 3h after smoking. Joints produced greater increases in plasma THC and subjective ratings of marijuana intoxication, strength, and quality compared to blunts, and these effects were more pronounced in women compared to men. However, blunts produced equivalent increases in heart rate and higher carbon monoxide levels than joints, despite producing lower levels of plasma THC. These findings demonstrate that smoking marijuana in a tobacco leaf may increase the risks of marijuana use by enhancing carbon monoxide exposure and increasing heart rate compared to joints.
Drug and alcohol dependence 06/2009; 103(3):107-13. · 3.60 Impact Factor
