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Opioid physical dependence development in humans: effect of time between agonist pretreatments

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Abstract

We examined the effect of morphine pretreatment spacing on intensity of subsequent precipitated withdrawal response to test the hypothesis that withdrawal intensity would be inversely related to pretreatment spacing. Subjects were ten nondependent male volunteers who reported using opioids an average of 2.5 times per week. Three IM morphine injections (each 18 mg/70 kg) were administered during each of four experimental conditions. The experimental conditions involved spacing injections at 12-, 24-, 48- or 72-h intervals. Naloxone (10 mg/70 kg IM) was administered 24 h after the last morphine exposure. A comparison condition was included in which a naloxone challenge was given at 24 h following a single IM morphine pretreatment (18 mg/70 kg). Subject rated measures of symptoms and observer-rated measures of signs indicated that withdrawal intensity was inversely related to the morphine spacing interval and in particular that intensity of withdrawal precipitated after three pretreatments spaced at 12-h intervals was greater than that precipitated after a single morphine pretreatment. Physiological data supported a more intense withdrawal response in the 12-h spacing condition and provided evidence of overshoot on blood pressure and skin temperature measures. These findings are pertinent to the transition between acute and chronic physical dependence; they suggest that there is a temporal window during which repeated opioid administrations result in escalation of physical dependence but that dependence levels after widely spaced multiple exposures may be no greater than after a single exposure.

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Authors and Affiliations

  1. Division of Addiction Research and Treatment, Department of Mental Health Sciences, Hahnemann University School of Medicine, Broad and Vince Streets, MS 984, 19102-1192, Philadelphia, PA, USA

    Kimberly C. Kirby

  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Suite 3000, 5510 Nathan Shock Dr., 21224, Baltimore, MD, USA

    Maxine L. Stitzer

Authors
  1. Kimberly C. Kirby
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  2. Maxine L. Stitzer
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Additional information

This research was supported by USPHS Grant DA-04011 and Research Training Grant T32 DA-07209 from the National Institute on Drug Abuse

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Kirby, K.C., Stitzer, M.L. Opioid physical dependence development in humans: effect of time between agonist pretreatments. Psychopharmacology 112, 511–517 (1993). https://doi.org/10.1007/BF02244902

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  • DOI: https://doi.org/10.1007/BF02244902

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