As an alternative possibility, the prolonged brain MOR occupancy by opioid antagonists like naltrexone and nalmefene may be due to slow dissociation from MORs consequent to their very high MOR affinity (<1.0 nM).Naltrexone blocks the effects of MOR agonists like morphine, heroin, and hydromorphone in humans via its MOR antagonism. Following a single 100 mg dose of naltrexone, the subjective and objective effects of heroin were blocked by 90% at 24 hours, with blockade then decreasing up to 72 hours. Similarly, 20 to 200 mg naltrexone dose-dependently antagonized the effects of heroin for up to 72 hours. Naltrexone also blocks the effects of KOR agonists like salvinorin A, pentazocine, and butorphanol in humans via its KOR antagonism. In addition to opioids, naltrexone has been found to block or reduce the rewarding and other effects of other euphoriant drugs including alcohol, nicotine, and amphetamines.The opioid receptors are involved in neuroendocrine regulation. MOR agonists produce increases in levels of prolactin and decreases in levels of luteinizing hormone (LH) and testosterone. Doses of naltrexone of 25 to 150 mg/day have been found to produce significant increases in levels of β-endorphin, cortisol, and LH, equivocal changes in levels of prolactin and testosterone, and no significant changes in levels of adrenocorticotrophic hormone (ACTH) or follicle-stimulating hormone (FSH). Naltrexone influences the hypothalamic–pituitary–adrenal axis (HPA axis) probably through interference with opioid receptor signaling by endorphins.Blockade of MORs is thought to be the mechanism of action of naltrexone in the management of opioid dependence—it reversibly blocks or attenuates the effects of opioids.
Its overall benefit has been described as "modest".Acamprosate may work better than naltrexone for eliminating alcohol abuse, while naltrexone may decrease the desire for alcohol to a greater extent.The Sinclair method is a method involving opiate antagonists such as naltrexone to treat alcoholism. The person takes the medication once, about an hour before consuming alcohol, to curb the urge to drink. The opioid antagonist is thought to block the positive reinforcement effects of alcohol and may assist the person to stop or reduce their drinking. Opioid use
Long-acting injectable naltrexone is an opioid receptor antagonist, blocking the effects of heroin and other opioids, and decreases heroin use compared to a placebo. Unlike methadone and buprenorphine, it is not a controlled medication. It may decrease cravings for opioids after a number of weeks, and decreases the risk of overdose, at least during the time period that naltrexone is still active, though concern about risk of overdose for those stopping treatment remains. It is given once per month and has better compliance and effect for opioid use than the oral formulation.A drawback of injectable naltrexone as compared to methadone and buprenorphine is the requirement for a period of opioid abstinence before starting the medication, as the injection can otherwise cause sudden and intense opioid withdrawal. This "hurdle" is responsible for worse patient uptake with long-acting injectable naltrexone as compared with buprenorphine.