Introduction
The global rise in obesity and overweight is a major public health challenge. Addressing these conditions requires a multifaceted approach, and pharmacological interventions are sometimes considered. Naltrexone, primarily known for treating opioid and alcohol dependence, has garnered attention for its potential role in weight management, particularly in low doses or combined with other medications. This article explores the mechanisms by which naltrexone may contribute to weight loss, examines the available evidence on its efficacy, and discusses important considerations for its use.
Understanding Naltrexone
Naltrexone: An Opioid Antagonist
Naltrexone is a prescription medication approved by the Food and Drug Administration (FDA) for treating alcohol use disorder and opioid addiction. It is marketed under brand names like Revia and Vivitrol, with Revia and generic naltrexone available in pill form, while Vivitrol is an extended-release intramuscular formulation. Naltrexone functions as an opioid antagonist, blocking the effects of opioids in the brain.
Low Dose Naltrexone (LDN)
While traditional naltrexone doses range from 50 to 100 mg per day, low-dose naltrexone (LDN) typically involves doses between 0.5 mg and 4.5 mg. At these lower doses, naltrexone is believed to have immunomodulating and anti-inflammatory properties. Unlike higher doses that fully block the opioid system, LDN temporarily binds to opioid receptors.
Naltrexone and Weight Loss: Off-Label Use
Although naltrexone is FDA-approved for treating addiction, its use for weight loss is considered off-label, unless it is part of a combination medication specifically approved for weight management.
Mechanisms of Action
Opioid Receptor Modulation
Naltrexone's primary mechanism involves blocking opioid receptors in the brain. It has been reported that opioid antagonists block central opioid receptors and thus reduce the intake of certain foods [17]. Naltrexone, through the action of β-endorphin blockage at the receptor of µ-opioid, would reduce the consumption of food [18].
Read also: Naltrexone: Dosage and Uses for Weight Loss
The Bupropion/Naltrexone Combination
The combined effect of bupropion and naltrexone on weight loss is of particular interest. It has been proposed theoretically that naltrexone could influence the neurological pathways of the brain, while bupropion would suppress the appetite [19] Two studies have reported that bupropion/naltrexone combination was found to be effective in achieving loss of weight in obese individuals [18, 20]. Bupropion/naltrexone combination produced significant weight loss when compared to either medication alone. The mechanisms through which naltrexone/bupropion combination act in reducing weight are not completely clear. α-melanocyte-stimulating hormone and β-endorphin are released by pro-opiomelanocortin producing neurons present in the hypothalamus. α-melanocyte-stimulating hormone regulates the activation of pro-opiomelanocortin and β-endorphin activates opioid receptors on pro-opiomelanocortin neurons causing autoinhibitory feedback [21]. Bupropion monotherapy results in modest loss of weight by increasing the pro-opiomelanocortin firing [22]. The weight loss caused by bupropion might be achieved by β-endorphin-mediated autoinhibitory feedback loop and adding naltrexone to bupropion would prevent this negative feedback loop and may help in sustained reduction of weight and achieving weight loss.
LDN and the Immune System
In very small doses, typically 0.5mg to 4.5mg, it has been shown to have powerful immune-modulating and anti-inflammatory properties with minimal side effects. Many patients report improved sleep quality on LDN, which can further reduce inflammation, stabilize mood, and support metabolism.
Evidence from Clinical Trials and Meta-Analyses
Bupropion and Naltrexone: A Synergistic Effect?
Two studies have reported that bupropion/naltrexone combination was found to be effective in achieving loss of weight in obese individuals [18, 20]. Bupropion/naltrexone combination produced significant weight loss when compared to either medication alone. The mechanisms through which naltrexone/bupropion combination act in reducing weight are not completely clear.
Meta-Analysis Results
Twenty five studies with 22,165 participants’ were included in this article. The pooled findings showed that bupropion administration has an effect on lowering weight (WMD: -3.67 kg, 95% CI: -4.43 to -2.93) and WC (WMD: -2.98 cm, 95% CI -3.78 to -2.19) in compared with control groups. The analysis also showed that the effects of the present intervention on weight and WC during the intervention are > 26 weeks and ≤ 26 weeks compared to the other group, respectively.
Study Characteristics
According to our survey findings, a total of twenty studies have been done in the United States, while three papers have been published in Canada. Additionally, one study each has been carried out in Israel and the Republic of Korea, respectively. The publications included in this study were published between the time frame of 1999 to 2021, and the duration of the follow-up interventions varied from 8 to 104 weeks. At the baseline, the average age and proportion of male participants varied between 35.2 and 61.6 years and 0-100%, respectively. The doses prescribed in the studies were between 90 and 400 mg per day, and Bupropion alone was used in 7 studies and the combination of this drug with naltrexone was used as the intervention group in the rest of the studies. The mean BMI at the baseline level was between 26.1 and 37.1 in the studies included.
Read also: Naltrexone: Uses and Effectiveness
Risks, Side Effects, and Considerations
Common Side Effects
Common side effects of naltrexone use may include:1,2Nausea and vomitingDizzinessSleepinessSleep disturbancesMuscle cramps and joint painHeadache and toothacheFlu-like symptomsAnxiety and irritabilityConstipation or diarrhea
Severe Adverse Effects
Severe adverse effects of taking Revia may include:1,2DepressionHallucinationsPneumoniaConfusionBlurred visionDangerous allergic reaction, including swelling of mouth or tongue, chest pain, trouble breathing, and rashHepatitis or liver damage, including dark-colored urine and jaundiceInjection site reactions, including severe pain, tissue death, blisters, lumps, or open wounds
Overdose Risk
Since naltrexone blocks opioid receptors, people taking this prescription medication are at risk of overdose if they relapse on heroin or a prescription opioid like Vicodin, Percocet, or other chronic pain management medications. This is because they may take a much higher dose in an attempt to overcome the subdued effect caused by naltrexone. The risk of overdose also increases in someone who has been on Revia or Vivitrol for an extended period of time, effectively lowering their tolerance to opioids during the period of abstinence. Returning to opioid use, especially at their previously used dose, can lead to an overdose.1
Mental Health and Eating Disorders
Taking Revia for weight loss can negatively affect your physical and psychological health, especially for those with a history of dieting. This is because dieting is a risk factor for disordered eating and developing an active eating disorder. In fact, research has shown that about one-quarter of individuals who engage in severe dieting develop an eating disorder.5 And although dieting on its own doesn’t directly cause an eating disorder, it can increase the likelihood of developing one, especially in those who are predisposed.
The Influence of Diet Culture
Naltrexone may be misused by people looking to lose weight thanks to diet culture, which prioritizes weight loss and thinness over health and well-being. Anti-fat bias, or fatphobia, is the intense hatred or fear of people living in larger bodies, and it contributes to the popularity of medications like naltrexone.
Read also: Naltrexone for Weight Loss
Importance of Medical Supervision
You should always consult your doctor, and your medical team, before taking medication for weight loss. Trying to lose weight quickly by taking Revia or other medications can cause a host of side effects and health risks.
LDN Dosage and Administration
Typical LDN doses range from 1.5mg to 4.5mg per day. Providers often start at a low dose (0.5mg) and slowly titrate up to find the individual’s optimal dose. Important: Never attempt to split or crush a full-strength naltrexone tablet.
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