Besides humans, naltrexone has been found to produce aversive effects in rodents as assessed by conditioned place aversion. Liver damage
Naltrexone has been reported to cause liver damage when given at doses higher than recommended. It carries an FDA boxed warning for this rare side effect. Due to these reports, some physicians may check liver function tests prior to starting naltrexone, and periodically thereafter. Concerns for liver toxicity initially arose from a study of nonaddicted obese patients receiving 300 mg of naltrexone. Subsequent studies have suggested limited or no toxicity in other patient populations and at typical recommended doses such as 50 to 100 mg/day. Overdose
No toxic effects have been observed with naltrexone in doses of up to 800 mg/day in clinical studies. The largest reported overdose of naltrexone, which was 1,500 mg in a female patient and was equivalent to an entire bottle of medication (30 × 50 mg tablets), was uneventful. No deaths are known to have occurred with naltrexone overdose. Pharmacology
Pharmacodynamics
Opioid receptor blockade
Naltrexone and its active metabolite 6β-naltrexol are competitive antagonists of the opioid receptors. Naltrexone is specifically an antagonist preferentially of the μ-opioid receptor (MOR), to a lesser extent of the κ-opioid receptor (KOR), and to a much lesser extent of the δ-opioid receptor (DOR). However, naltrexone is not actually a silent antagonist of these receptors but instead acts as a weak partial agonist, with Emax values of 14 to 29% at the MOR, 16 to 39% at the KOR, and 14 to 25% at the DOR in different studies.
Among patients able to successfully initiate injectable naltrexone, long-term rates were similar  Another concern is that while methadone and buprenorphine patients maintain high drug tolerance in the event of return to street drug use, naltrexone allows tolerance to fade, leading to risk of overdose in people who relapse and thus higher mortality. Guidelines from the World Health Organization cite evidence of superiority in reducing mortality and retaining patients in care with opioid agonists (methadone or buprenorphine), concluding that most patients should be advised to use agonists rather than antagonists like naltrexone.A 2011 review found insufficient evidence to determine the effect of naltrexone taken by mouth in opioid dependence. While some do well with this formulation, it must be taken daily, and a person whose cravings become overwhelming can obtain opioid intoxication simply by skipping a dose. Due to this issue, the usefulness of oral naltrexone in opioid use disorders is limited by the low retention in treatment. Naltrexone by mouth remains an ideal treatment for a small number of people with opioid use, usually those with a stable social situation and motivation. With additional contingency management support, naltrexone may be effective in a broader population. Others
Naltrexone is not useful for quitting smoking. Naltrexone has also been under investigation for reducing behavioral addictions such as gambling or kleptomania as well as compulsive sexual behaviors in both offenders and non-offenders (e.g. compulsive porn viewing and masturbation). The results were promising.