The importance of considering polysubstance use: lessons from cocaine research

Liu, Yiyang; Williamson, Victoria; Setlow, Barry; Cottler, Linda B.; Knackstedt, Lori A.

doi:10.1016/j.drugalcdep.2018.07.025

Cited by 119 publications

(80 citation statements)

References 94 publications

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“…However, such cocaine and ceftriaxone-induced effects identified in rodents may not translate into the clinic, as 50–90% of cocaine users also use alcohol ( Grant and Harford, 1990 ; Rounsaville et al, 1991 ; Anthony et al, 1994 ; Brookoff et al, 1996 ; Kedia et al, 2007 ; Liu et al, 2018 ). Alcohol consumption in outbred Sprague-Dawley rats leads to increased NA core basal glutamate levels during early abstinence, with no changes in GLT-1 and xCT expression, and ceftriaxone is ineffective at changing GLT-1 expression after alcohol ( Pati et al, 2016 ; Stennett et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens

Stennett

Knackstedt

2020

Front. Neurosci.

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Preclinical models of cocaine use disorder are widely utilized to identify neuroadaptations underlying cocaine seeking and to screen medications to reduce seeking. However, while the majority of cocaine users engage in poly-substance use (PSU), a minority of preclinical studies employ PSU models. We previously reported that when rats consume alcohol after daily intravenous cocaine self-administration, nucleus accumbens (NA) core basal glutamate levels are reduced below those of rats that consumed only cocaine, and do not increase during cue + cocaine-primed reinstatement of cocaine-seeking. Here we used the same model of sequential cocaine and alcohol self-administration to test the hypothesis that a similar pattern of glutamate changes would be observed in the NA core prior to and during a cocaine-primed reinstatement test. Rats underwent intravenous cocaine self-administration followed by access to unsweetened alcohol in the home cage for 12 days. Rats underwent a minimum of 12 daily extinction sessions prior to a cocaine-primed reinstatement test conducted during microdialysis procedures. Contrary to our previous work using the same model, here we found that access to alcohol increased cocaine intake and increased responding during early extinction training. We found that as in our previous work, cocaine + alcohol-consuming rats displayed basal glutamate levels below those of rats that self-administered only cocaine. During the cocaine-primed reinstatement test, rats that consumed only cocaine displayed increased glutamate efflux in the NA core while those that consumed cocaine + alcohol did not. These results indicate that preclinical models of PSU should be utilized to develop experimental therapeutics for the reduction of cocaine seeking.

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Section: Introductionmentioning

confidence: 99%

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens

Stennett

Knackstedt

2020

Front. Neurosci.

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“…Previous studies have shown that cocaine users concurrently use other substances frequently, including alcohol ( Blow et al, 2011 ; Borders & Booth, 2013 ; Evans-Polce, Lanza, & Maggs, 2016 ; Hedden, Malcolm, & Latimer, 2009 ; Liu, Williamson, Setlow, Cottler, & Knackstedt, 2018 ), tobacco ( Winhusen et al, 2013 ), marijuana ( Gonçalves & Nappo, 2015 ; Liu et al, 2018 ), heroin ( Leeman, Sun, Bogart, Beseler, & Sofuoglu, 2016 ; Ojha, Sigdel, Meyer-Thompson, Oechsler, & Verthein, 2014 ; Oviedo-Joekes et al, 2015 ), and prescription medications ( Al-Tayyib, Rice, Rhoades, & Riggs, 2014 ; Chen et al, 2014 ; Evans-Polce et al, 2016 ; Herman-Stahl, Krebs, Kroutil, & Heller, 2006 ; Winhusen et al, 2013 ). Polysubstance users have been found to have a higher risk of overdose, emergency department (ED) visits, violence, accidental injury ( Macdonald et al, 2014 ), traffic accidents ( De Boni et al, 2014 ), and lower addiction treatment effectiveness ( Evans et al, 2015 ; Hou, Zhan, Zheng, Zhan, & Zheng, 2014 ; Liu et al, 2018 ) compared to mono-substance users. Polysubstance use has also been associated with worse physical health ( Quek et al, 2013 ; White et al, 2013 ), lower quality of life ( Kelly et al, 2017 ) and higher rates of mental health conditions, such as anxiety, depression, social phobia, and personality disorders ( Agrawal, Lynskey, Madden, Bucholz, & Heath, 2007 ; Chen et al, 2014 ; Evans et al, 2015 ; Kelly et al, 2017 ; Leeman et al, 2016 ; Quek et al, 2013 ; White et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

A latent class analysis of the past-30-day substance use patterns among lifetime cocaine users: Findings from a community sample in North Central Florida

Liu

Elliott

Serdarevic

et al. 2019

Addictive Behaviors Reports

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Objectives Cocaine use is increasing and many cocaine users engage in polysubstance use. Within polysubstance use, relationships among use of individual substances are necessarily complex. To address this complexity, we used latent class analysis (LCA) to identify patterns of polysubstance use among lifetime cocaine users and examine associations among these patterns, demographics, and risk profiles. Methods Members of HealthStreet, an ongoing community engagement program, were asked about lifetime and past 30-day use of cocaine, alcohol, tobacco, marijuana, and prescription medications, mental health conditions, recent Emergency Department (ED) visits and demographics. LCA was used to identify classes of past 30-day polysubstance use among individuals who endorsed lifetime cocaine use. Multinomial logistic regression identified factors associated with these classes. Results Among 1797 lifetime cocaine users, a five-class LCA model was identified: 1) past 30-day tobacco use only (45%), 2) past 30-day alcohol, marijuana and tobacco use (31%), 3) past 30-day tobacco, prescription opioid and sedative use (13%), 4) past 30-day cocaine, alcohol, marijuana and tobacco use (9%), 5) past 30-day cocaine and multiple polysubstance use (2%). Demographics, ED visits and mental health conditions were associated with class membership. Conclusions Approximately 11% of lifetime cocaine users used cocaine in the past 30 days with two different concurrent substance use patterns. Prescription medication (opioids and sedatives) and complex polysubstance use patterns were stronger indicators of negative outcomes than current cocaine use. Cocaine was not used frequently with other stimulants. In addition to polysubstance use, prescription medication use should be targeted for intervention among lifetime cocaine users.

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“…However, in substance-using populations, polydrug use is common [23]. Considerations of drug-drug interactions with SCs are important clinically [24], but possible or unexpected biotransformation due to co-ingested compounds should also be considered.…”

Section: Introductionmentioning

confidence: 99%

Evidence of enzyme-mediated transesterification of synthetic cannabinoids with ethanol: potential toxicological impact

et al. 2019

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Purpose Synthetic cannabinoids (SCs) represent a large proportion of novel psychoactive substances on the black market and have caused a number of deaths. Polydrug use including combination of SCs and ethanol could further complicate the toxicological impact. To the best of our knowledge, there have been no reports presenting evidence of transesterification between SCs and ethanol in vitro. Methods The in vitro metabolism of the four carboxylate SCs PB-22, NPB-22, 5-fluoro-PB-22 (5F-PB-22), and 5-fluoro-NPB-22 (5F-NPB-22) in the presence of ethanol using human liver microsomes with and without appropriate enzyme inhibitors was studied. Newly identified SC ethyl esters were chemically synthesised and fully characterised. The activity of these SCs and their ethanol transesterification products were assessed using cannabinoid receptor (CB 1 and CB 2) activation assays. Results SCs/ethanol transesterification products were detected and studied using liquid chromatography-high-resolution mass spectrometry. We have shown that the SC ethyl ester formation is mediated by human carboxyl esterase enzymes. The ethyl esters exhibited a reduced activity for the CB receptors compared with their parent compounds. Conclusions These novel ethyl esters may be useful additional markers of cannabinoid administration, and especially so if they prove to have longer half-lives than their parent compounds.

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The importance of considering polysubstance use: lessons from cocaine research

Abstract: Based on the prevalence and known consequences of PSU, consideration of PSU in both human and animal research is vital for understanding patterns of substance use.

Cited by 119 publications

References 94 publications

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens

A latent class analysis of the past-30-day substance use patterns among lifetime cocaine users: Findings from a community sample in North Central Florida

Evidence of enzyme-mediated transesterification of synthetic cannabinoids with ethanol: potential toxicological impact

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