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.
"Opioid receptor antagonists block the effects generated by opioid agonists without producing any agonist effects of their own (Figure 1). Thus, they have no abuse liability, no overdose potential, and they do not require special waivers to be prescribed.26–28 Currently, naltrexone (Depade®, Mallinckrodt Specialty Chemicals Company; Revia®, Bristol-Myers Squibb Pharma Company, Princeton, NJ) is a recommended opioid antagonist both for opioid withdrawal and for maintenance. "
[Show abstract][Hide abstract] ABSTRACT: The United States Food and Drug Administration (FDA) approved naltrexone, a synthetic competitive antagonist at opioid receptors, in oral form in 1984 for use in the management of opioid abuse and addiction. Because naltrexone and its major metabolite, 6-β-naltrexone, are both competitive antagonists at opioid receptors - and thereby inhibit opioid agonist-induced effects including those desired by abusers - it was hypothesized that once maintained on naltrex-one, opioid-induced desirable effects would be diminished to the point that relapse to illicit use would decline because it was no longer rewarding. However, good medication compliance is a requisite for such a strategy to be effective and a systematic review of oral naltrexone concluded that this method of treatment was not superior for any outcomes measured (ie, retention, abstinence, or side effects) to placebo, psychotherapy, benzodiazepines, or buprenorphine treatment. In addition, the retention rate on oral naltrexone was very low (less than 30%). Recently, the FDA approved an extended-release formulation (intramuscular depot injection) of naltrexone for prevention of relapse to opioid dependence following opioid detoxification and to be used along with counseling and social support. Since it needs to be administered only monthly, as opposed to the daily administration required for the oral formulation, naltrexone injection has the potential for increasing adherence and retention rates. Concerns include liver damage at high doses (oral formulation) and possible opioid overdose if an attempt is made to surmount receptor antagonism by taking higher doses of an opioid agonist or if opioid receptors become "sensitized" under long-term antagonism. The focus of the present review is the current information regarding the safety and efficacy of naltrexone extended-release therapy.
"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. "
[Show abstract][Hide abstract] 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 · 3.42 Impact Factor
"The major biologically active metabolite is 6-β-naltrexol, which has a half-life of from 12 to 18 hours . In healthy volunteers, naltrexone is not associated with any significant adverse events , . Naltrexone has been employed successfully in pain studies as an alternative to intravenously-administered naloxone . "
[Show abstract][Hide abstract] ABSTRACT: The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg) at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.
PLoS ONE 02/2009; 4(4):e5180. DOI:10.1371/journal.pone.0005180 · 3.23 Impact Factor
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