Oral ketamine as a positive control in human abuse potential studies

Shram, M.J.; Sellers, Edward M.; Romach, Myroslava K.

doi:10.1016/j.drugalcdep.2010.10.002

Cited by 17 publications

(19 citation statements)

References 37 publications

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“…This phenomenon is not limited to opioids. Evidence exists that some drug abusers fail to differentiate between placebo and amphetamine (Shram et al, 2011; Johanson et al, 1998), and similarly sedatives (DeWit and Griffiths, 1991). Future studies may examine other drug classes (e.g., cannabinoids) for this phenomenon and attempt to determine if the current results would be replicated in prescription opioid abusers (vs. the mixed prescription opioid and heroin users in the present study).…”

Section: Discussionmentioning

confidence: 99%

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing

Antoine

Strain

Tompkins

et al. 2013

Drug and Alcohol Dependence

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Background Abuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers. Methods Data were collected from 23 completers of the qualification phase of an abuse liability study. Opioid abusing participants received 30 mg oxycodone and placebo orally on separate days, and were characterized as qualifiers (vs. non-qualifiers) if their peak visual analog scale liking rating for oxycodone was at least 20 points higher than placebo’s peak rating. Groups were compared on demographic characteristics, drug history, and physiologic, subject and observer ratings. Results 61% of participants were qualifiers and 39% were non-qualifiers. Groups had similar demographic characteristics, drug use histories, and pupillary constriction responses. However, unlike qualifiers, non-qualifiers had an exaggerated placebo response for the liking score (p=0.03) and an attenuated oxycodone response for the liking score (p<.0001). Non-qualifiers’ failure to differentiate oxycodone versus placebo was evident for subject and observer ratings. Conclusion Different subjective responses to identical stimuli support the use of a qualification phase in abuse liability assessments. Further research should explore objective measures that may better account for these differences, determine optimal qualification criteria, and explore the developmental course of drug use. This study also documents certain opioid abusers fail to differentiate 30 mg of oxycodone from placebo, a phenomenon deserving further study.

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Section: Discussionmentioning

confidence: 99%

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing

Antoine

Strain

Tompkins

et al. 2013

Drug and Alcohol Dependence

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“…Due to its long lasting effects, ketamine infusions are administered several days apart in clinical settings, and there is evidence to suggest an enhanced antidepressant response over time with this intermittent, repeated treatment timeline compared to a single infusion (Murrough et al , 2013; Cusin et al , 2016). However, ketamine is a powerful hallucinogenic drug of abuse at higher doses, and there are serious health problems associated with its abuse (Shram et al , 2011), and while studies from our lab as well as others have examined the beneficial aspects of ketamine, little is known about potential risks for abuse with intermittent, repeated treatment regimens.…”

Section: Introductionmentioning

confidence: 99%

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

et al. 2017

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Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction.

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“…There are two frequent effects of ketamine whose potential interrelationship has hardly been investigated: a feeling of lightness/floating in healthy participants and recreational users [1-3], and temporary antidepressant benefits in individuals with treatment-refractory depression [4, 5]. Feelings of lightness/floating are a typical occurrence in psychoactive-substance- or psychologically induced altered states of consciousness [6, 7].…”

mentioning

confidence: 99%

The Altered-State-of-Consciousness Aspect of a Feeling of Lightness Is Reported to Be Associated with Antidepressant Benefits by Depressed Individuals Receiving Ketamine Infusions: A Systematic Analysis of Internet Video Testimonials

Stocker

Hasler

Hartmann

2019

Psychother Psychosom

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Oral ketamine as a positive control in human abuse potential studies

Cited by 17 publications

References 37 publications

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

The Altered-State-of-Consciousness Aspect of a Feeling of Lightness Is Reported to Be Associated with Antidepressant Benefits by Depressed Individuals Receiving Ketamine Infusions: A Systematic Analysis of Internet Video Testimonials

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