Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Gardner, Natwaine Sherune; Luke, Kedon J. S.; Wheatley, Andrew O.; Haye, Winston G. De La; Bahado-Singh, Perceval S.; Dilworth, Lowell; McGrowder, Donovan; Barton, E N; Young, Lauriann; Salako-Akande, Ajibike; Morrison, Errol; Eldemire-Shearer, Denise; Lowe, Henry; Asemota, Helen N.

doi:10.4018/ijmtie.2015070103

Cited by 2 publications

(3 citation statements)

References 30 publications

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“…These findings are also consistent with the sex difference we noted from daily health observations where severe health complications led to the removal of both males and females in the control-chow group; whereas, among SMAASH-C treated rats, only females developed severe health complications indicating that SMAASH-C treatment may improve the overall health of males, but not females, during cocaine abstinence. A previous study reported that SMAASH-C offers protective effects against chronic cocaine exposure by increasing plasma clearance of cocaine and its toxic metabolites through increasing the activity of the liver enzyme CYP450 [ 18 ]. One caveat is that while both males and females were included in this previous study, sex was not considered so it is still possible that effects on liver activity were driven by males.…”

Section: Discussionmentioning

confidence: 99%

“…Anecdotal reports and open label observational data from patients indicate that oral SMAASH-C (0.1-0.4 g/kg/day; 6-12 months) treatment during abstinence improves markers of general health (e.g., one patient with co-morbid AIDS-related herpes simplex virus infection reporting marked improvement in viral symptoms) and reduces drug-craving, frequency of relapse, and withdrawal symptoms. Results from subsequent preclinical studies were also promising and showed that chronic SMAASH-C treatment (oral, 0.04-0.12 g/kg, 8 weeks) markedly and selectively reduced cocaine- and amphetamine-induced conditioned place preference and markers of drug-induced toxicity in male and female rats [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

Towers,

Williams,

Aristidou

et al. 2024

Transl Psychiatry

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Relapse to drug use after abstinence is a major challenge in treating substance use disorder. Exposure to drug-associated cues during abstinence can trigger intense craving and precipitate relapse. New and more effective anti-relapse interventions are critically needed, particularly for cocaine use disorder since no effective pharmacological intervention is available. We discovered that a nutritional supplement we developed as part of a nutritional approach for managing patients with substance use disorder reduced patient reports of drug craving and relapse. The goal of this study was to determine the efficacy of this supplement, SMAASH-C, at reducing drug-craving/relapse vulnerability in males and females in rat models with cocaine. Effects were determined following extended-access cocaine self-administration (24-hr/day for 10 days) and a two-week treatment regimen at a moderate and moderate-to-high dose (0.4 and 0.8 g/kg/day) as well as a 6-week regimen at a moderate dose (0.4 g/kg/day; Experiment 2). We also determined its efficacy to offset serum markers of organ toxicity in response to chronic cocaine self-administration and abstinence (aspartate transaminase, alanine transaminase, amylase; urea nitrogen). In females, both the 2- and 6-week SMAASH-C treatment regimens reduced cocaine-seeking (extinction or cue-induced reinstatement), particularly when drug-seeking was heightened (e.g., during estrus). Despite a lack of efficacy to reduce drug-seeking in males, SMAASH-C treatment normalized cocaine/abstinence-induced increases in serum levels of aspartate transaminase and amylase, which are markers of liver and pancreatic toxicity respectively. Thus, the beneficial effects of oral SMAASH-C treatment over abstinence following chronic cocaine self-administration appears to be sex-specific.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

Towers,

Williams,

Aristidou

et al. 2024

Transl Psychiatry

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“…Nutritionally supplemented animals were proportionally fed a combination of the named component, at 0.123 g/day, 0.123 g/day and 0.0408 g/day, respectively, over a period of 8 weeks. These doses were calculated based on a 350 g rat, after proportions previously used in other studies for administration to a 75 kg man were scaled down [11].…”

Section: The Conditioned Place Preference Paradigmmentioning

confidence: 99%

Drug Seeking Behavior of Amphetamine Addicted Sprague-Dawley Rats Is Eliminated after Nutritional Supplementation

Webber-Waugh¹,

Nesbeth²,

Anderson-Johnson³

et al. 2017

JBBS

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Aim: The effectiveness of nutritional supplementation on drug-seeking behavior of amphetamine-addicted rats during withdrawal was investigated using a biased conditioned place preference (CPP) paradigm. Method: Twenty-four male Sprague-Dawley rats exhibiting baseline preference for the black chamber during a 20-minute pre-conditioning exploration of the CPP box completed the study. On alternate days of an 8-day schedule, twelve rats (Group AMP) were randomly selected, given either amphetamine sulfate (5 mg/ml, i.p.) and confined to the white chamber; or vehicle (1 ml saline, i.p.) and confined to the black chamber. A significant increased percentage time spent and number of entries made by Group AMP to the drug-paired, white chamber on the test day confirmed amphetamine addiction. Group AMP subsequently received increasing doses of amphetamine over 6 days. Following acute drug withdrawal, their CPP performance was compared with that of vehicle treated rats (Group SAL). Groups AMP and SAL were equally divided and randomly assigned to animals fed chow reconstituted with the nutritional supplement (AMP-S and SAL-S) over 8 weeks or standard rat chow (AMP-N and SAL-N). CPP performances for all rats were determined blindly from video recordings following this period. Results: Nutritionally supplemented, amphetamine withdrawn rats (AMP-S) exhibited significantly decreased percentage entries and time spent in the white chamber (p < 0.05), indicating preference for the black chamber and diminished drug-seeking behavior. ANOVA revealed that after 8 weeks of dietary supplementation, AMP-S rats behaved like drug-naïve, control animals. Conclusion: Drug-seeking behavior by amphetamine-addicHow to cite this paper:

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Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Cited by 2 publications

References 30 publications

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

Drug Seeking Behavior of Amphetamine Addicted Sprague-Dawley Rats Is Eliminated after Nutritional Supplementation

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