Relationship between oral D-amphetamine self-administration and ratings of subjective effects

Bolin, B. Levi; Reynolds, Anna R.; Stoops, William W.; Rush, Craig R.

doi:10.1097/fbp.0b013e3283645047

Cited by 12 publications

(3 citation statements)

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“…Self-administration and subject rating outcomes are not isomorphic, however, and the magnitude of their correlation appears weak. 66 Naltrexone maintenance did enhance some of the “negative” (i.e., Performance Impaired and Sedative effects) subject-rated effects of 30 mg methamphetamine. These results are partially consistent with other human laboratory studies have demonstrated a modest decrease in “positive” subject-rated drug effects and an increase in “negative” subject-rated effects during naltrexone treatment relative to placebo.…”

Section: Discussionmentioning

confidence: 94%

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Marks

Lile

Stoops

et al. 2016

Journal of Clinical Psychopharmacology

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Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric acid type A (GABAA) receptors (e.g., alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of d-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and “positive” subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone. Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6–7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected. Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like “positive” subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10 mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.

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Section: Discussionmentioning

confidence: 94%

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Marks

Lile

Stoops

et al. 2016

Journal of Clinical Psychopharmacology

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“…For example, studies indicate that early positive subjective reactions to marijuana and alcohol predict greater use later in life [ 7 – 10 ]. In addition, in laboratory studies when volunteers are allowed to choose a drug (e.g., alcohol (ALC), amphetamine (AMP) or diazepam) over a placebo, those who choose the drug typically report more positive subjective experiences from the preferred drug [ 11 – 14 ]. Overall, these studies suggest that positive subjective responses to drugs, such as “liking” the drug, during the early stages of drug use, may form part of a liability for future drug use and abuse.…”

Section: Introductionmentioning

confidence: 99%

A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

2015

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Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants’ drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21–31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs’ effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants’ responses to the three drugs were unrelated. Unexpectedly, “wanting more” alcohol was inversely correlated with “wanting more” THC. Additionally, in women, but not in men, “disliking” alcohol was negatively correlated with “disliking” THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a “drug of choice” model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs.Trial RegistrationClinicalTrials.gov NCT02485158

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“…That phendimetrazine did not persistently increase ratings on measures indicative of abuse potential in the current study provides additional support for its use to treat cocaine dependence. Although subjective-effects measures are useful and reliable indicators of abuse potential, they do not always parallel patterns of naturalistic drug-taking behavior (Bolin et al, 2013). Drug self-administration procedures more effectively evaluate the reinforcing effects of drugs (Bolin et al, 2013; Comer et al, 2008; Jones and Comer, 2013) and future studies are needed to assess the reinforcing effects of phendimetrazine and its effect on cocaine self-administration in humans.…”

Section: Discussionmentioning

confidence: 99%

Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals

Bolin

Stoops

Sites

et al. 2016

Journal of Addiction Medicine

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Objectives Phendimetrazine is a prodrug for the monoamine releaser phenmetrazine, a drug with known abuse potential. Preclinical studies suggest that phendimetrazine has limited abuse potential and may have promise as an agonist-like replacement therapy for cocaine dependence. This study evaluated the abuse potential of phendimetrazine in humans. Methods Nine cocaine-dependent individuals (N = 9) were enrolled to investigate the abuse potential of phendimetrazine and d-amphetamine using a double blind, placebo-controlled, within-subject design. Subjective and cardiovascular effects of oral phendimetrazine (35, 70, and 105 mg), d-amphetamine (10, 20, and 30 mg), and placebo were assessed in quasi-random order across eight sessions lasting approximately eight hours each. Results d-Amphetamine (20 and 30 mg) significantly increased cardiovascular measures in a time- and dose-related manner but phendimetrazine did not systematically alter cardiovascular measures. Although d-amphetamine and phendimetrazine significantly increased ratings indicative of abuse potential (e.g., drug liking) and stimulant-like effects relative to placebo, these increases were generally small in magnitude, with phendimetrazine producing significant effects on fewer abuse-related measures and at fewer time points than d-amphetamine. Conclusions These preliminary findings suggest that oral phendimetrazine and d-amphetamine may have limited abuse potential in cocaine-dependent individuals. These findings collectively emphasize that the clinical utility of medications to treat cocaine-use disorders should be weighed carefully against their potential for abuse and diversion, with careful attention paid to evaluating abuse potential in a clinically relevant population of interest. Future studies are needed to further elucidate the potential utility of phendimetrazine as an agonist-like replacement therapy for cocaine dependence.

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Relationship between oral D-amphetamine self-administration and ratings of subjective effects

Cited by 12 publications

References 55 publications

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals

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