Effects of buprenorphine on the self-administration of cocaine by humans

Rw, Foltin; Mw, Fischman

doi:10.1097/00008877-199402000-00009

Cited by 75 publications

(52 citation statements)

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“…Baclofen has also shown promise in a pilot clinical trial for cocaine dependence (Shoptaw et al 2003), but more recent clinical work suggests that baclofen's effects may not be sufficiently robust to reduce ongoing cocaine abuse (S. Shoptaw,3/06,personal communication). Buprenorphine, the only other medication shown to significantly decrease high-dose cocaine self-administration, appeared to do so by significantly enhancing cocaine intoxication, mimicking a cocaine-heroin "speedball" effect (Foltin and Fischman 1994), which is less than ideal for a potential treatment medication.…”

Section: Self-administration Versus Other Modelsmentioning

confidence: 98%

Controversies in translational research: drug self-administration

2008

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Rationale Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable. Objective The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes. Results Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic. Conclusions The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.Keywords Cocaine . Opioid . Naloxone . Dopamine receptor . Drug abuse . Model . Monkey . Human . Reinforcement Laboratory testing of potential pharmacotherapies for drug abuse is an essential component of medication development. Although well-designed clinical trials are the standard by which the efficacy of a new medication is assessed, clinical trials test the effects of a potential treatment medication on a broad sample of patients, which is both costly and potentially risky. Before exposing a large number of treatment seekers to a medication, there needs to be both a strong scientific rationale for combining the medication with a drug of abuse as well as a demonstration that the co-administration of the medication and the abused drug is safe and selectively modifies the behavior of interest: drug taking.Models of drug self-administration in rodents, nonhuman primates, and humans have been used to evaluate the effects of candidate medications for the treatment of drug dependence. The self-administration model provides Psychopharmacology (2008) meaningful behavioral data on the safety and efficacy of potentia...

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Section: Self-administration Versus Other Modelsmentioning

confidence: 98%

Controversies in translational research: drug self-administration

2008

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“…Using an acute pretreatment procedure and lower doses of baclofen than those used by Haney and colleagues (2006), Lile et al (2007) reported that baclofen did not significantly alter the subjective effects of intranasal cocaine and it did not alter responding on the multiple choice procedure. In the case of buprenorphine (Foltin and Fischman, 1994), the nature of the interaction between this partial mu agonist and cocaine on the subjective effect measures was one of potentiation -that is, the combination of the opioid agonist and cocaine produced a constellation of drug responses that reflected the activity of both drugs and increased the magnitude of the response for measures of their shared effects (e.g., ratings of "high"). Under the high dose conditions, buprenorphine reduced cocaine self-administration; however, participants were reported to be significantly intoxicated from the drug combination.…”

Section: Medications Development For Cocaine Dependencementioning

confidence: 99%

The role of human drug self-administration procedures in the development of medications

Comer

Ashworth²,

Foltin

et al. 2008

Drug and Alcohol Dependence

136

148

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The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest -that is, drug taking. The present paper 1) reviews the most commonly used human self-administration procedures, 2) discusses the concordance of subjective reports and selfadministration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and 3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including "abuse deterrent" formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of selfadministration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting.

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“…One hypothesis would be that compared to control participants who relapse, LOTAD would be longer among persons who received buprenorphine but nevertheless relapse. If cocaine LOTAD was lengthened by buprenorphine treatment, as could be expected from studies on people (Foltin and Fischman, 1994;Rothman et al, 2000;Schottenfeld et al, 1993), evidence of buprenorphine's lowering of cocaine's addictive potential in people would be provided. Moreover, the result would strengthen the evidence that our knowledge of the neural mechanisms altered by buprenorphine that underlie cocaine dependence in animals is generalizable to people.…”

Section: Lotad For Transfer Of Animal Research To Human Treatmentmentioning

confidence: 99%

Factors associated with the transition from abuse to dependence among substance abusers: Implications for a measure of addictive liability

Ridenour

Maldonado-Molina

Compton

et al. 2005

Drug and Alcohol Dependence

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This study was conducted to test the validity of a measure that has potential to bridge research on the addictive liability of drugs and on individuals' liability to addiction, which to date have evolved in largely parallel arenas. The length of time between onset of abuse and dependence (LOTAD) has evolved from recent findings on transitions through levels of addiction; it was hypothesized that shorter LOTAD is indicative of greater addictive liability. Hypotheses were based on animal studies and human studies. Retrospective data from the DSM-IV Substance Use Disorders Work Group were reanalyzed using configural frequency analysis, survival curves, bivariate Kendall's tau associations, and linear regression. The sample consisted of participants recruited from community and clinical settings. The measure was the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). The shortest LOTADs were observed for disorders related to use of cocaine and opiates, followed by cannabis and then alcohol regardless of the subsample that was analyzed. As hypothesized, females and early initiators of drug use had shorter LOTADs compared to men and other initiators of drug use; no consistent differences in LOTAD were observed between AfricanAmericans and Caucasians. None of the LOTAD variance associated with differences between drugs could be accounted for by gender, early use of the drug, or ethnicity. Specific areas of research where LOTAD might be useful as well as how LOTAD might be improved are discussed.

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Effects of buprenorphine on the self-administration of cocaine by humans

Cited by 75 publications

References 0 publications

Controversies in translational research: drug self-administration

Controversies in translational research: drug self-administration

The role of human drug self-administration procedures in the development of medications

Factors associated with the transition from abuse to dependence among substance abusers: Implications for a measure of addictive liability

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