Cortisol levels during chronic naltrexone maintenance treatment in ex-opiate addicts

Kosten, Thomas R.; Kreek, Mary-Jeanne; Ragunath, Jayanthi; Kleber, Herbert D.

doi:10.1016/0006-3223(86)90150-2

Cited by 45 publications

(26 citation statements)

References 10 publications

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“…The loss of diurnal variation in cortisol levels is the earliest sign of hypercortisolism and is consistent with previous findings in heroin-dependent patients (12)(13)(14)(15). Prior studies that collected blood samples at only one time point would not be sensitive to this loss of diurnal variation (12,13).…”

Section: Discussionsupporting

confidence: 89%

Serum Cortisol Secretion During Heroin Abstinence Is Elevated Only Nocturnally

Epstein

et al. 2008

The American Journal of Drug and Alcohol Abuse

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Several studies indicate abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) during acute opiate withdrawal, but protracted withdrawal has gotten less study. The current study further characterized the 24-hour time course of plasma cortisol levels in heroin-dependent individuals who were abstinent for 10-15 days, which is beyond the 5 days of acute withdrawal, compared to demographically matched healthy controls using samples collected every 3 hours over 24 hours and assessed with radioimmunoassay (RIA). The abstinent heroin-dependent participants had significantly higher plasma cortisol levels nocturnally suggesting a loss of diurnal variation in these heroin subjects.

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Section: Discussionsupporting

confidence: 89%

Serum Cortisol Secretion During Heroin Abstinence Is Elevated Only Nocturnally

Epstein

et al. 2008

The American Journal of Drug and Alcohol Abuse

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“…Both spontaneous and opioid antagonist-precipitated morphinewithdrawal results in an elevation of plasma b-endorphin, ACTH, and glucocorticoid levels in both rodents (Lightman & Young 1988, Ignar & Kuhn 1990, Martinez et al 1990) and humans (Kreek & Hartman 1982, Kosten et al 1986, Culpepper-Morgan & Kreek 1997. In humans, an earlier study from our laboratory has found that naloxoneprecipitated withdrawal in opiate-dependent individuals results in an increase in HPA hormonal release, which precedes subjective and objective symptoms of withdrawal (Culpepper-Morgan & Kreek 1997).…”

Section: Introductionmentioning

confidence: 90%

Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal

Zhou¹,

Bendor²,

Hofmann³

et al. 2006

Journal of Endocrinology

109

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In this study, we investigated the effects of acute morphine administration, chronic intermittent escalating-dose morphine administration and spontaneous withdrawal from chronic morphine on mRNA levels of mu opioid receptor (MOP-r), and the opioid peptides pro-opiomelanocortin (POMC) and preprodynorphin (ppDyn) in several key brain regions of the rat, associated with drug reward and motivated behaviors: lateral hypothalamus (lat.hyp), nucleus accumbens (NAc) core, amygdala, and caudate-putamen (CPu). There was no effect on MOP-r mRNA levels in these brain regions 30 min after either a single injection of morphine (10 mg/kg, i.p.) or chronic intermittent escalating-dose morphine (from 7$5 mg/kg per day on day 1 up to 120 mg/kg per day on day 10). Activation of the stress-responsive hypothalamic-pituitary-adrenal axis by 12 h withdrawal from chronic morphine was confirmed; both POMC mRNA levels in the anterior pituitary and plasma adrenocorticotropic hormone levels were significantly elevated. Under this withdrawal-related stress condition, there was an increase in MOP-r mRNA levels in the lat.hyp, NAc core, and CPu. Recent studies have demonstrated a novel role for the lat.hyp orexin (or hypocretin) activation in both drug-related positive rewarding, and withdrawal effects. Around 50% of lat.hyp orexin neurons express MOP-r. Therefore, we also examined the levels of lat.hyp orexin mRNA, and found them increased in morphine withdrawal, whereas there was no change in levels of the lat.hyp ppDyn mRNA, a gene coexpressed with the lat.hyp orexin. Our results show that there is an increase in MOP-r gene expression in a region-specific manner during morphine withdrawal, and support the hypothesis that increased lat.hyp orexin activity plays a role in morphine-withdrawalrelated behaviors.

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“…Hypothetically, the effects of an opioid antagonist, such as naltrexone, in modulating tonic inhibition of the opioid system at various receptors, including primarily , but also ␦ and , may relate to treatment response and its association with stress responsive opioid activity. Prior collaborative studies by our group have indicated that heroin addicts show continued elevated HPA hormone levels during intermediate-term treatment with daily oral naltrexone (Kosten et al 1986a(Kosten et al , 1986b. Therefore, continued investigation of acute and long-term neuroendocrine response to oral naltrexone, the only available opioid antagonist for opioid and alcohol dependence treatment, may help elucidate the role of the stress responsive endogenous opioid system in these processes.…”

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confidence: 98%

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

King

Schluger

Gunduz

et al. 2002

Neuropsychopharmacology

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We examined HPA axis response to 50 mg oral naltrexone compared with placebo in 17 healthy male and female nonalcoholic subjects, approximately half of whom had a positive family history of alcoholism (FH ϩ ) and half of whom who did not (FH Ϫ)The endogenous opioid system plays a role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis (Cushman and Kreek 1974;Johnson et al. 1992;Kreek 1972Kreek , 1973Kreek , 1978. Opioid antagonist administration blocks the tonic opioid inhibition of HPA axis activity, thereby resulting in release of POMC-derived hormones in the pituitary and cortisol from the adrenal gland. Indeed, numerous studies have demonstrated acute increases in adrenocorticotropin (ACTH) and cortisol levels in man after intravenous infusion of the opioid antagonists naloxone (Cohen et al. 1983;Conaglen et al. 1985;Delitala et al. 1994;Naber et al. 1981;Martin del Campo et al. 1994;Morley et al. 1980;Schluger et al. 1998;Volavka et al. 1979a) and nalmefene . However, few studies have examined acute neuroendocrine response to the opioid antagonist naltrexone, which, in contrast to naloxone and nalmefene, is not available for intravenous administration.The two published studies on the acute HPA axis effects of orally administered naltrexone have both been conducted with relatively small sample sizes (n р 10). NO . 6 Naltrexone, HPA Axis, and Biotransformation 779The first study (Volavka et al. 1979b), conducted in ten normal male subjects, showed that oral naltrexone significantly increased cortisol levels two hours after administration and directionally (but nonsignificantly) increased ACTH levels one hour after administration. However, due to the small sample studied, the power may not have been sufficient to detect differences. The results may also have been confounded by the co-occurrence of pain sensitivity testing (i.e., 2-min cold pressor task) during the protocol, which may have produced independent HPA axis responses. A more recent study in six abstinent alcoholic patients (Farren et al. 1999) showed significant increases in cortisol and ACTH to three doses of oral naltrexone (25, 50, and 100mg) with no dose-dependent effects (Farren et al. 1999). It has been hypothesized that alterations in HPA axis function may play a role in various stages of addiction, including initiation, maintenance, and relapse (Kreek 1992). Naltrexone (50 mg oral) has shown efficacy in the treatment of alcohol dependence (Volpicelli et al. 1992(Volpicelli et al. , 1997O'Malley et al. 1992;Anton et al. 1999), which led to its FDA-approval for adjunctive treatment of alcoholism. Studies examining HPA axis response after oral naltrexone administration might be of potential clinical relevance as neuroendocrine changes and sensitivity to naltrexone could relate to individual differences and treatment response. Hypothetically, the effects of an opioid antagonist, such as naltrexone, in modulating tonic inhibition of the opioid system at various receptors, including primarily , but also ␦ and , may relate to tr...

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Cortisol levels during chronic naltrexone maintenance treatment in ex-opiate addicts

Cited by 45 publications

References 10 publications

Serum Cortisol Secretion During Heroin Abstinence Is Elevated Only Nocturnally

Serum Cortisol Secretion During Heroin Abstinence Is Elevated Only Nocturnally

Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

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