[12] Naltrexone has been shown to decrease the quantity and frequency of ethanol consumption by reducing the dopamine release from the brain after consuming alcohol.

In contrast, initiation of buprenorphine only requires delay of the first dose until the patient begins to manifest at least mild opioid withdrawal symptoms.

[32] Among patients able to successfully initiate injectable naltrexone, long-term remission rates were similar to those seen in clinical buprenorphine/naloxone administration.

Naltrexone taken orally remains an ideal treatment for a small number of people with opioid use, usually those with a stable social situation and motivation.

Some patients report that LDN helps reduce their symptoms of ME/CFS, multiple sclerosis (MS), fibromyalgia, or autoimmune diseases.

[3] These adverse effects are analogous to the symptoms of opioid withdrawal, as the μ-opioid receptor blockade will increase gastrointestinal motility.

[48][49][50][51] In early studies of normal and opioid-abstinent individuals, acute and short-term administration of naltrexone was reported to produce a variety of aversive effects including fatigue, loss of energy, sleepiness, mild dysphoria, depression, lightheadedness, faintness, confusion, nausea, gastrointestinal disturbances, sweating, and occasional derealization.

[50][56][55] According to one source:[49] Based on available evidence, naltrexone seems to have minimal untoward effects in the aforementioned areas, at least with long-term therapy.

Concerns for liver toxicity initially arose from a study of nonaddicted obese patients receiving 300 mg of naltrexone.

[81] 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.

[83][82] Occupancy of the opioid receptors in the brain by naltrexone has been studied using positron emission tomography (PET).

[9][89][10][90] A single 50 mg oral dose of naltrexone has been found to block brain MORs and opioid effects for at least 48 to 72 hours.

[93][94][95][74] In addition to opioids, naltrexone has been found to block or reduce the rewarding and other effects of other euphoriant drugs including alcohol,[57] nicotine,[96] and amphetamines.

The role of KOR modulation by naltrexone in its effectiveness for alcohol dependence is unclear but this action may also be involved based on theory and animal studies.

[113] It was characterized by Blumberg, Dayton, and Wolf in 1965 and was found to be an orally active, long-acting, and very potent opioid antagonist.

[113][114][115][14] The drug showed advantages over earlier opioid antagonists such as cyclazocine, nalorphine, and naloxone, including its oral activity, a long duration of action allowing for once-daily administration, and a lack of dysphoria, and was selected for further development.

Clinical trials for opioid dependence began in 1973, and a developmental collaboration of DuPont with the National Institute on Drug Abuse for this indication started the next year in 1974.

[117][118][119][120] Naltrexone is or has been sold under a variety of brand names, including Adepend, Antaxone, Celupan, Depade, Destoxican, Nalorex, Narcoral, Nemexin, Nodict, Revia, Trexan, Vivitrex, and Vivitrol.

[123] The FDA authorized use of injectable naltrexone (Vivitrol) for opioid addiction using a single study[124] that was led by Evgeny Krupitsky at Bekhterev Research Psychoneurological Institute, St Petersburg State Pavlov Medical University, St Petersburg, Russia,[125] a country where opioid agonists such as methadone and buprenorphine are not available.

Critics charged that the study violated ethical guidelines since it compared the formulation of naltrexone not to the best available, evidence-based treatment (methadone or buprenorphine), but to a placebo.

[30] Despite these findings, naltrexone's manufacturer and some health authorities have promoted the medicine as superior to methadone and buprenorphine since it is not an opioid and does not induce dependence.

The manufacturer has also marketed directly to law enforcement and criminal justice officials, spending millions of dollars on lobbying and providing thousands of free doses to jails and prisons.

"[129][130] The company's marketing techniques have led to a Congressional investigation,[131] and warning from the FDA about failure to adequately state risks of fatal overdose to patients receiving the medicine.

[132] In May 2017, United States Secretary of Health and Human Services Tom Price praised [Vivitrol] as the future of opioid addiction treatment after visiting the company's plant in Ohio.

[128] His remarks set off sharp criticism with almost 700 experts in the field of substance use submitting a letter to Price cautioning him about Vivitrol's "marketing tactics" and warning him that his comments "ignore widely accepted science".

[133] The experts pointed out that Vivitrol's competitors, buprenorphine and methadone, are "less expensive", "more widely used", and have been "rigorously studied".

Price had claimed that buprenorphine and methadone were "simply substitute[s]" for "illicit drugs"[128] whereas according to the letter, "the substantial body of research evidence supporting these treatments is summarized in guidance from within your own agency, including the Substance Abuse and Mental Health Services Administration, the US Surgeon General, the National Institute on Drug Abuse, and the Centers for Disease Control and Prevention.

Buprenorphine and methadone have been demonstrated to be highly effective in managing the core symptoms of opioid use disorder, reducing the risk of relapse and fatal overdose, and encouraging long-term recovery.

[135][136] Naltrexone has been used off-label at low doses for diseases not related to chemical dependency or intoxication, such as multiple sclerosis.

[142] One study suggests that self-injurious behaviors present in persons with developmental disabilities (including autism) can sometimes be remedied with naltrexone.