Naltrexone, an antagonist for the treatment of heroin dependence: effects in man. Arch Gen Psychiatry

Archives of General Psychiatry (Impact Factor: 13.75). 07/1973; 28(6):784-91.
Source: PubMed

ABSTRACT Naltrexone (EN 1639A) is approximately 17 times more potent than nalorphine as an antagonist in man. It is virtually devoid of agonistic activity, including the ability to induce nalorphine like dysphoric effects. Its duration of action is longer than that of naloxone, but shorter than that of cyclazocine. It is effective orally. When administered in a dose level of 50 mg/day, it produces a degree of blockade of the effects of morphine and heroin that is comparable to that obtained with 4 mg of cyclazocine per day orally. Naltrexone, thus, appears to be a relatively pure potent narcotic antagonist which is effective orally and which may have utility in the treatment of heroin and narcotic dependence.

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    • "Naltrexone is an opioid receptor antagonist that blocks the reinforcing, subjective, and physiological effects of opioids (Martin et al., 1973; Mello et al., 1981; Schuh et al., 1999; Walsh et al., 1996). Unlike agonist medications such as methadone and buprenorphine, naltrexone has no abuse liability or diversion potential, cannot directly cause overdose, and can be prescribed by any physician without the need for special waivers. "
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    ABSTRACT: Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use.
    Drug and alcohol dependence 07/2011; 120(1-3):48-54. DOI:10.1016/j.drugalcdep.2011.06.023 · 3.28 Impact Factor
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    • "In the US alone, it is estimated that 10–14 million people are alcohol-dependent, while 1 million people suffer from opiate addiction (Grant, 1997). Evidence implicating the functional involvement of the endogenous opioid system in mediating many of the reinforcing aspects of drug consumption (Spanagel et al, 1992; Herz, 1997) has led to the use of opioid receptor antagonists as a pharmacotherapeutic intervention for treating drug dependency syndromes (Martin et al, 1973; Litten and Allen, 1998; Garbutt et al, 1999). The opiate antagonist naltrexone (Resnick et al, 1974) is effective and approved by the FDA (1994) for treating opiate and alcohol dependence (FDA Summary Basis of Approval: NDA 18-932/S-010, 1994). "
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    ABSTRACT: While oral naltrexone is effective in treating alcohol and opiate dependencies, poor patient adherence and widely fluctuating plasma levels limit its efficacy. To overcome these problems, an extended-release formulation of naltrexone (Vivitrex) was developed by encapsulating naltrexone into injectable, biodegradable polymer microspheres. Pharmacokinetic studies in rats demonstrated that this formulation produced stable, pharmacologically relevant plasma levels of naltrexone for approximately 1 month following either subcutaneous or intramuscular injections. While rats receiving placebo microspheres demonstrated a pronounced analgesic response to morphine in the hot-plate test, morphine analgesia was completely blocked in rats treated with extended-release naltrexone. This antagonism began on day 1 following administration and lasted for 28 days. Rats reinjected with extended-release naltrexone 34 days after the initial dose and tested for another 35 days showed consistent suppression of morphine analgesia for an additional 28 days. mu-Opioid receptor density, as measured by [(3)H]DAMGO autoradiography, increased up to two-fold following a single injection of extended-release naltrexone. Saturation binding assays using [(3)H]DAMGO showed changes in the midbrain and striatum at 1 week after extended-release naltrexone administration, and after 1 month in the neocortex. These receptor increases persisted for 2-4 weeks after dissipation of the morphine antagonist actions of naltrexone. These data suggest that therapeutically relevant plasma levels of naltrexone can be maintained using monthly injections of an extended-release microsphere formulation, and that changes in mu-opioid receptor density do not impact its efficacy in suppressing morphine-induced analgesia in the rat. Clinical trials of extended release naltrexone for treating alcohol and opiate dependency are currently ongoing.
    Neuropsychopharmacology 12/2003; 28(11):1973-82. DOI:10.1038/sj.npp.1300274 · 7.83 Impact Factor
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    • "In the present study, the physiological and self-reported subjective effects of dronabinol (Marinol ® , 7.5 or 15 mg), synthetically derived THC, were assessed in regular marijuana users pretreated with either naltrexone (Revia ® , 50 mg) or placebo. Naltrexone is a potent and long-lasting opioid antagonist (Resnick et al., 1971; Martin et al., 1973). Naltrexone plasma levels peak 1 h after oral administration and remain elevated for more than 48 h after an acute dose (Verebey et al., 1976; Wall et al., 1981). "
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    ABSTRACT: Δ9-tetrahydrocannabinol (THC) and opioids have many common effects. In addition, some THC effects in laboratory animals can be blocked or attenuated by opioid antagonists. This suggests that opioid systems mediate or modulate some THC effects. To determine whether opioid systems mediate THC effects in humans, the effects of the opioid antagonist naltrexone on subjective responses to THC were examined in 14 marijuana users. Subjects participated in a double-blinded, cross-over design in which each subject received all combinations of naltrexone (0 or 50 mg) and THC (0, 7.5, or 15 mg). THC increased heart rate and self-reported drug effects, such as euphoria and marijuana-like effects, and decreased psychomotor performance. Naltrexone increased heart rate and decreased self-reported measures of vigor and hunger but did not alter any of the effects of THC. These results suggest that the subjective, physiological, and behavioral effects of THC in humans are not mediated through opioid systems.
    Drug and Alcohol Dependence 06/2000; 59(3-59):251-260. DOI:10.1016/S0376-8716(99)00127-1 · 3.28 Impact Factor
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