Trial of Naltrexone/Bupropion for the Treatment of Methamphetamine Use Disorder
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What is naltrexone, and what is it used for?
Naltrexone is an opioid antagonist: it blocks the brain's opioid receptors, so opioids have little effect and alcohol's reward is dampened. It does not produce a high, does not cause dependence, and cannot be misused. The FDA has approved it for two conditions. For opioid use disorder, it blocks opioid effects after full withdrawal, as a daily tablet or monthly injection (Vivitrol, 2010). For alcohol use disorder, it reduces craving and heavy drinking; in a six month trial of the injection, heavy drinking days fell about 25 percent more than with placebo. It is one of only three approved alcohol use disorder medicines, and still few of the roughly 29 million Americans with the condition ever receive any of them.
Two other uses drive most of the research here. First, weight: naltrexone combined with bupropion (Contrave, 2014) is approved for weight loss, and studies now test how it fits alongside GLP-1 medicines and surgery; the same combination also showed the first clear positive signal ever seen for a medication in methamphetamine use disorder, in a 2021 NEJM trial, and is now in Phase 3. Second, low dose naltrexone, or LDN: a dose far below standard, compounded by pharmacies, used off label for fibromyalgia, chronic pain, ME/CFS, long COVID, and autoimmune conditions, on the theory that tiny doses calm overactive immune cells rather than block opioids. Evidence so far is small trials with mixed results, which is why several studies here exist. For more, see our alcohol use disorder treatment guide and opioid use disorder guide.
Types of naltrexone clinical trials
Alcohol use disorder studies. Trials of who responds best to naltrexone, for example people who drink mainly for reward rather than to relieve stress, studies of starting it in the emergency department, and research on how trauma, inflammation, and sex differences shape response.
Opioid use disorder and overdose prevention studies. Trials of naltrexone as a protective medicine for people at high risk of overdose, and studies of how low and high doses behave in the body in people with opioid use disorder.
Weight and metabolic studies. Trials of naltrexone with bupropion in people with obesity, including people with bipolar disorder, studies of whether genetics predict who loses weight on it, whether it can maintain weight lost on GLP-1 medicines, and whether it improves results after bariatric surgery.
Methamphetamine use disorder. A Phase 3 trial, funded by the National Institute on Drug Abuse, of extended release naltrexone injections combined with bupropion, following the 2021 study in which about 1 in 8 participants responded versus 1 in 40 on placebo. No medicine is approved for methamphetamine use disorder; this is the leading candidate.
Low dose naltrexone for pain and fatigue. The largest group on this page. Trials test LDN for fatigue in men with prostate cancer on hormone therapy, for painful diabetic neuropathy, for nerve pain in people with HIV, for chronic migraine with fibromyalgia, and for ME/CFS and long COVID. These are the controlled studies the LDN field has lacked for 20 years.
Other mechanism and specialty studies. Naltrexone with propranolol added to immunotherapy in advanced melanoma, brain imaging of naltrexone in teenagers with eating disorders, and studies using naltrexone to understand how ketamine works in OCD. These test naltrexone as a scientific tool or add on rather than as a stand alone treatment.
Does naltrexone help with weight loss?
On its own, it is not approved or typically used for weight. Combined with bupropion (Contrave), it is an approved weight loss medicine, working on appetite and reward pathways. Current studies test who responds to the combination, how it compares with or follows GLP-1 medicines, and whether it helps after bariatric surgery.
Who can participate in naltrexone clinical trials?
Because the studies span such different conditions, eligibility depends on which group you belong to. Alcohol and methamphetamine studies enroll adults who meet criteria for the disorder and want to reduce or stop, confirmed at screening. Opioid related studies require that you are not currently taking opioids, because naltrexone blocks them and can trigger withdrawal in someone who is; this is the single most important exclusion for any naltrexone trial. Weight studies enroll adults with obesity, sometimes with a specific additional condition such as bipolar disorder or a history of bariatric surgery. Low dose naltrexone studies enroll people with the specific pain or fatigue condition being tested, and usually exclude anyone taking opioid pain medicines. Most studies exclude significant liver disease and pregnancy. Eligibility always varies by study.
What is low dose naltrexone?
A dose roughly one tenth of the standard one, made by compounding pharmacies because no approved low dose product exists. It is used off label for fibromyalgia, chronic pain, ME/CFS, long COVID, and some autoimmune conditions, based on the theory that tiny doses calm immune cells in the nervous system. Evidence so far comes from small trials with mixed results, and several of the studies on this page are the larger controlled trials the field has been missing.
How to find and enroll in a naltrexone clinical trial
Identify your study. Use the condition filter first: the same medicine is being tested for very different problems, and the title tells you which. "Low dose" or "LDN" means a pain, fatigue, or autoimmune study; "naltrexone/bupropion" means weight or methamphetamine; "extended release" or "XR" means the monthly injection.
Check the setting. Some studies run in clinics with regular visits and blood work; others run largely by phone with medicine mailed to you. The details say how often you visit and whether urine testing or imaging is involved.
Complete the health profile. Click "Get started" to begin the 5-step application. Have three things ready: the condition you are applying for and how it is currently treated, whether you take any opioid medicines including for pain, and other health conditions, especially liver problems. Your information is protected under research privacy rules.
Submit the application. A study coordinator reviews it and contacts you. Nothing is decided until you have gone through informed consent, participation is voluntary at every step, and joining does not require leaving your own doctor.