The rise (and fall?) of drug discrimination research

doi:10.1016/j.drugalcdep.2015.04.001

Cited by 22 publications

(12 citation statements)

References 36 publications

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“…One factor that has potentially led to the decrease in enthusiasm for drug-discrimination studies in substance-abuse research is that the role of discriminative-stimulus effects in substance abuse may be less apparent relative to behavioral processes that are the focus of other experimental approaches. McMahon (2015) articulates a particularly poignant example regarding the downward trend in the publication of drug-discrimination compared with the continued increase in the publication of drug self-administration research. Specifically, that article states that drug discrimination lacks the face validity of drug self-administration because operant behavior maintained by a drug reinforcer more closely resembles the observable behavioral phenomenon of substance abuse (McMahon, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Fourth, the investigation of the specific role(s) of various molecular sites of action (e.g., transporters, receptor systems, and specific receptor subtypes) in the discriminative-stimulus effects of drugs in humans is relatively limited because medications that are approved for use with humans by the U.S. Food and Drug Administration are typically used in human drug-discrimination studies. Finally, in the context of the study of substance-use disorders, drug-discrimination procedures lack the face validity of other experimental approaches such as drug self-administration (e.g., McMahon, 2015). Although the drug-discrimination paradigm may lack a certain degree of external validity, it has strong predictive validity with respect to the underlying neurobiological and neuropharmacological mechanisms of drugs and determination of the abuse potential of novel compounds (e.g., Colpaert, 1999; Brauer, Goudie, & de Wit, 1997; Holtzman & Locke, 1988; Huskinson, Naylor, Rowlett, & Freeman, 2014; Kelly et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Human drug discrimination: A primer and methodological review.

Bolin¹,

Alcorn²,

Reynolds³

et al. 2016

Experimental and Clinical Psychopharmacology

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Drug-discrimination procedures empirically evaluate the control that internal drug states exert over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs. Historically, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have also been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This review gives some general history and background concerning the major theoretical concepts and principles of drug-discrimination research as well as its relevance to substance-use disorders. This article also provides a procedural overview and discusses key methodological issues that must be considered when designing and conducting a human drug-discrimination study. Although drug discrimination is unequivocally one of the most sophisticated and useful behavioral assays to investigate the underlying neuropharmacology of drugs in vivo, enthusiasm for its use has steadily declined in the last decade and a half. We conclude by commenting on the current state of drug-discrimination research and suggest potential avenues for future drug-discrimination research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human drug discrimination: A primer and methodological review.

Bolin¹,

Alcorn²,

Reynolds³

et al. 2016

Experimental and Clinical Psychopharmacology

View full text Add to dashboard Cite

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“…Although the use of preclinical drug discrimination procedures appears to be diminishing (McMahon, 2015), these procedures are particularly useful, compared to drug self-administration procedures, for understanding the relationship between abuse-related behavioral effects as a consequence of changing plasma drug levels (Banks et al , 2013, Banks et al , 2015, Lamas et al , 1995). For example, a clockwise hysteresis loop related plasma cocaine levels and cocaine discriminative stimulus effects suggesting cocaine levels were the primary mediator of the behavioral effects (Lamas et al , 1995).…”

Section: 0 Introductionmentioning

confidence: 99%

Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys

Banks

Smith

Kisor

et al. 2016

Pharmacology Biochemistry and Behavior

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Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18 mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32 mg/kg), and (+)-amphetamine (0.032-0.32 mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to methamphetamine's abuse-related subjective effects.

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“…These results are consistent with a primary role for the mu receptor in the ability of repeated opioid administration and dosing cessation to induce dependence and withdrawal, respectively (reviewed in Bailey and Connor, 2005). This neuropharmacological overlap in clinically relevant effects suggests that opioid drug-discrimination procedures could be used for medications development (McMahon, 2015). Opioid drugs with decreased abuse potential that share discriminative-stimulus effects with abused opioids might be effective pharmacotherapies for opioid dependence.…”

Section: Underlying Neuropharmacology Of Commonly Abused Illicit Drugsmentioning

confidence: 99%

“…Fifth, as noted above, a significant challenge relative to animal models is that humans vary in their behavioral and pharmacological histories, which can affect study results and complicate the interpretation of the findings. Finally, in the context of the study of substance-use disorders, drug-discrimination procedures lack the face validity of other experimental approaches such as drug self-administration (e.g., McMahon, 2015). Although the drug-discrimination paradigm may lack a certain degree of face validity relative to other experimental approaches, it has predictive validity with respect to the underlying neurobiological and neuropharmacological mechanisms of drugs and determination of the abuse potential of novel compounds (e.g., Colpaert, 1999; Brauer, Goudie, and de Wit, 1997; Holtzman and Locke, 1988; Huskinson et al, 2014; Kelly et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs

Bolin

Alcorn

Reynolds

et al. 2016

The Behavioral Neuroscience of Drug Discrimination

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Drug-discrimination procedures empirically evaluate the control that internal drug states have over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs in vivo. As a result, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This chapter provides a basic overview of human drug-discrimination procedures and reviews the extant literature concerning the use of these procedures to elucidate the underlying neuropharmacological mechanisms of commonly abused illicit drugs (i.e., stimulants, opioids, and cannabis) in humans. This chapter is not intended to review every available study that used drug-discrimination procedures in humans. Instead, when possible, exemplary studies that used a stimulant, opioid, or Δ-tetrahydrocannabinol (the primary psychoactive constituent of cannabis) to assess the discriminative-stimulus effects of drugs in humans are reviewed for illustrative purposes. We conclude by commenting on the current state and future of human drug-discrimination research.

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The rise (and fall?) of drug discrimination research

Cited by 22 publications

References 36 publications

Human drug discrimination: A primer and methodological review.

Human drug discrimination: A primer and methodological review.

Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys

Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs

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