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Naltrexone & Weight Loss: What Should You Expect?

Naltrexone is a chemical initially synthesized in 1963 and patented thereafter by the pharmaceutical company Endo Laboratories in 1967.  It is considered a substituted derivative of oxymorphone in that the tertiary amine methyl-constituent is replaced with an allyl group (specifically an N-cyclopropylmethyl group) – or a longer chain of carbon atoms.  It was initially approved by the FDA in 1984 for the treatment of heroin dependence.

In 1995, naltrexone was approved by the FDA as part of a multidisciplinary intervention for alcohol abuse.  These days, naltrexone is still commonly utilized for the management of opioid and alcohol dependence, and is occasionally utilized off-label for the treatment of impulse control disorders.  Naltrexone is also recognized as an important constituent of the FDA-approved weight loss drug Contrave (bupropion-naltrexone).

Although clinically significant weight loss is known to occur when naltrexone is administered in combination with bupropion, it is possible that select individuals may lose a considerable amount of weight [perhaps unexpectedly] from standalone naltrexone treatment.  In most cases, the weight loss occurring as a result of naltrexone treatment is perceived as a favorable side effect.  Nevertheless, it may be helpful to understand the specific mechanisms by which naltrexone stimulates weight loss, as well as know how much weight you should expect to lose during treatment.

Naltrexone & Weight Loss: A Reported Experience

There are numerous theories attempting to explain why individuals lose weight from taking naltrexone.  Before analyzing these theories, it is necessary to consider that some individuals may have experienced weight gain from alcohol or opioids, and now that they’re using naltrexone (and off of the alcohol or opioids), their body weight is normalizing.  Additionally, certain naltrexone users could’ve also taken up an exercise regimen and/or healthier diet, as is common among those attempting to detoxify from addictive drugs and maintain sobriety.

The discontinuation of alcohol or opioids plus an overall healthier lifestyle may have promoted weight loss among those using naltrexone – perhaps to a greater extent than the naltrexone itself.  Nevertheless, there is significant reason to believe that naltrexone also promotes weight loss.  Naltrexone acts as an opioid receptor antagonist which is thought to indirectly modulate activation of pleasure and reward centers such as the mesolimbic dopamine system.

This results in decreased pleasure and/or reward associated with food consumption, especially addictive foods like Oreos (high-sugar / high-fat).  Other mechanisms that may contribute to weight loss from naltrexone include: hormonal alterations, metabolism enhancement, and/or neurochemical changes.  Keep in mind that although weight loss is a fairly common side effect of naltrexone, it is not a guarantee – and the amount of weight lost will be individualized.

How Naltrexone May Cause Weight Loss (Possibilities)

Though naltrexone may decrease the pleasure and/or reward associated with food consumption to promote weight loss, there are other possible ways by which it may help users lose weight.  Naltrexone may help individuals stay sober from alcohol and/or opioids (each of which are linked to weight gain).  It may also change appetite, energy level, hormones, and satiety threshold after a meal.

  • Alcohol cessation: Drinking alcohol is generally understood to promote weight gain for a majority. Metabolism of alcohol can reduce fat oxidation, slow metabolism, prevents nutrient absorption, and alter hormones.  Regular alcohol consumption also adds extra calories to one’s overall diet, can increase hunger, and impair judgment [of healthy food choices].  Since naltrexone helps individuals remain sober, these individuals may gradually lose weight that they packed on while drinking.  Although the chief reason for weight loss in some naltrexone users may be a result of alcohol cessation, since naltrexone helps users discontinue alcohol, it may deserve partial credit for the weight loss.
  • Appetite reduction: Some individuals may notice that their appetite is significantly reduced and/or suppressed while taking naltrexone. A decrease in appetite means that users will likely consume less food and/or total calories per day.  The mechanisms associated with appetite reduction may be subject to individual variation.  Altered activation of neural circuitry and/or changes in concentrations of hunger-related hormones such as ghrelin may facilitate appetite attenuation. (Source: http://www.ncbi.nlm.nih.gov/pubmed/3628520).
  • Cognitive function: Research suggests that naltrexone is unlikely to affect cognitive function. That said, for a subset of users, treatment with naltrexone is capable of improving mental clarity and reducing brain fog.  Assuming you’re able to get any sort of cognitive enhancement or experience clearer thinking during naltrexone treatment, it is reasonable to speculate that this may affect your decision making in regards to dietary intake.  If you’re able to think clearer, you may make better choices about the foods that you consume – resulting in weight loss.
  • Decision making: The decision to take immediate gratification over a delayed reward is mediated in part by the orbitofrontal cortex (OFC). Research has shown that during decision-making tasks, activity within the OFC is significantly reduced among those with various forms of addiction; leading them to choose the immediate pleasure regardless of potential deleterious long-term implications.  Naltrexone treatment bolsters activation in the orbitofrontal cortex during decision-making tasks, possibly making it easier for everyone to [hypothetically] choose broccoli instead of a candy bar.  Moreover, usage of alcohol and/or opioids often is detrimental to the prefrontal cortex, another region implicated in decision-making.  The ability to abstain from alcohol and/or opioids as a result of naltrexone treatment may ameliorate prefrontal function, allowing users to resist unhealthy foods and/or only eat when necessary.  (Source: http://www.ncbi.nlm.nih.gov/pubmed/19258022/).
  • Decreased food cravings: A reason many individuals gain weight and/or become obese is because they’re unable to resist food cravings. Certain individuals are more susceptible to food cravings than others, and there are numerous neurobiological explanations as to what may trigger them.  In any regard, regular administration of naltrexone is understood to decrease food cravings for a subset of individuals.  Attenuation of cravings for high-fat and/or high-sugar foods may reason as to why naltrexone treatment yields weight loss.
  • Energy increase: Some naltrexone users will experience an increase in energy levels. This increased energy may result in more overall physical activity, thereby burning calories and speeding up metabolism for weight loss.  If prior to using naltrexone you were highly sedentary, but during treatment you have the urge to stay active – it makes logical sense that this increased activity will help you lose some weight.
  • Gut bacteria: Studies of low-dose naltrexone (LDN) for the treatment of small-intestine bacterial overgrowth (SIBO) indicate that the drug significantly improves symptoms. Symptomatic improvement may be related to the fact that naltrexone inhibits proliferation of deleterious gut bacteria and simultaneously reverses dysbiosis.  It may be that modulation of gut bacteria play an important role in the weight loss associated with naltrexone.
  • Hormonal modulation: Hormones such as leptin, ghrelin, and thyroid can significantly affect satiety, hunger, and metabolism. Administration of naltrexone may increase concentrations of leptin, a satiety-signaling hormone that tells the brain you’ve had enough to eat.  Conversely, naltrexone may reduce concentrations of the hunger-signaling hormone ghrelin, as well as inhibit its effect upon opioid receptors in the brain.  An experiment by Skibicka et al. (2012) noted that naltrexone injections inhibited ghrelin-mediated sucrose-motivated behavior [in rodents], suggesting that it reduced the urge to consume sweets.  Additionally, naltrexone is capable of modulating the immune system to stimulate production of thyroid hormone, which could also speed metabolism, increase energy, and promote weight loss. (Source: http://www.ncbi.nlm.nih.gov/pubmed/22210742).
  • Impulsivity reduction: Some individuals may find that naltrexone significantly reduces impulsive behaviors by decreasing impulsive urges. To attain the effect of significant impulse reduction among those with impulse control disorders – the drug needed to be administered at dosages above 50 mg/day.  That said, it is possible that even slight decreases in impulsive urges provided by standard doses could reduce likelihood of impulsive food consumption or compulsive eating.
  • Insulin reduction: There’s evidence to suggest that naltrexone significantly reduces basal concentrations of insulin among obese individuals. Assuming it suppresses insulin to a significant extent, this may be an important mechanism by which weight loss occurs.  Decreasing the secretion of insulin is associated with improved insulin sensitivity, body mass index (BMI) changes, decreased caloric intake, and increased leptin – all of which can promote weight loss. (Source: http://www.ncbi.nlm.nih.gov/pubmed/9368834).
  • Mood improvement: It is necessary to consider that naltrexone could improve your mood, perhaps to a significant extent – which could significantly affect your eating habits and dietary choices. A subset of individuals tends to eat unhealthy, overeat, or binge eat – in effort to cope with depression or low mood.  If you are among the individuals that overeat when depressed, and naltrexone alleviates some of the depression, there’s a chance overeating behaviors may stop as a result, ultimately leading to some weight loss.
  • Neural activation: A critical mechanism by which naltrexone may help you lose weight is by altering brain activation. It has been hypothesized that naltrexone attenuates overactivation of subregions within pleasure centers of the brain, as well as the mesolimbic dopamine system implicated in reward processing.  The changes in neural activation may reduce food cravings, as well as decrease some of the pleasure associated with food consumption.  If your cravings for food (especially junk foods) are reduced, and you don’t look forward to eating (because you get less pleasure from it), an expected outcome would be weight loss.
  • Neurotransmission: It is understood that naltrexone acts as an opioid receptor antagonist. This means that endorphins, enkephalins, and exogenous opioid agonists will be displaced from opioid receptor sites; rendering opioid receptors inactive.  That said, opioid receptor antagonism may have implications for systems of other neurotransmitters, neurohormones, and neuropeptides throughout the brain.  For example, study by Baron, Testa, and Gintzler (1985) noted that 8 days of naltrexone treatment altered concentrations of dopamine and norepinephrine in a region-specific manner.   Based on this finding, it should be hypothesized that the opioid antagonism of naltrexone yields an indirect cascade of additional neuromodulation that aids in weight loss. (Source: http://www.ncbi.nlm.nih.gov/pubmed/2862958).
  • Opioid cessation: While many individuals abusing opioids are underweight as opposed to overweight, this is often correlation as opposed to causation. It is logical to presume that some individuals may actually end up gaining weight while taking opioids – for numerous reasons including: increased preference for sugary/sweet foods, CNS suppression (reducing likelihood of physical activity), and alterations in hormonal biomarkers (e.g. testosterone).  Since naltrexone should help individuals maintain sobriety, it should prevent them from gaining weight as a consequence of additional opioid usage.  Although the opioid cessation may be the sole reason for weight loss, naltrexone may deserve partial credit for making this possible.
  • Side effects: Some individuals may lose weight solely due to naltrexone side effects such as: diarrhea, nausea, and/or vomiting. Assuming you feel nauseous each time you administer naltrexone, you may not find food to be very appetizing.  A reduction in appetite as a result of nausea, or even fear of vomiting, may lead to reduced caloric intake and weight loss.  Though losing weight as a result of side effects (e.g. diarrhea, nausea, vomiting) is uncomfortable, and the resulting weight loss is often unsustainable – it is another explanation as why some naltrexone users end up losing weight.

Note: There may be numerous other reasons as to why individuals taking naltrexone lose weight.  Keep in mind that the specific mechanisms by which naltrexone enables weight loss for one individual may be different than those for another.  For example, one naltrexone user may lose weight mostly because it helped them stay sober (from alcohol), whereas another may find that it alters hormones and decreases food cravings – each of which help lose weight.

Variables that may influence Naltrexone weight loss

There are many variables that may influence naltrexone-related weight loss.  It is the synergistic effect of these variables that may explain why one naltrexone user loses 20 lbs., yet another doesn’t lose any weight.  Important variables to consider regarding weight loss from naltrexone include: dosage, duration of use, co-administered substances, and individual factors (such as dietary intake, genetics, and health-related habits).

  1. Dosage (Low vs. High)

The dosage of naltrexone that you’re currently taking may influence the amount of weight that you lose.  Assuming you lose weight from a small dose of naltrexone, it is reasonable to assume that increasing the dosage would stimulate greater weight loss.  This is because the effect of the naltrexone upon your neurobiology would increase, likely amplifying the specific mechanisms that contributed to weight loss.

The standard daily dosage of naltrexone administered for the management of opioid OR alcohol dependence is 50 mg.  That said, some users will end up using smaller doses of 25 mg and others may end up using supratherapeutic doses of 75 mg or even 100 mg.  A large dose of 100 mg could be thought to exert nearly 2-fold the effect upon a user’s neurobiology than a 50 mg dose, and a 4-fold effect compared to a 25 mg dose.

If a user taking 25 mg lost 10 lbs., he/she may end up losing double the amount (20 lbs.) with an increase in dosing.  Understand that the amount of weight lost on a 50 mg dose may not always be double compared to a 25 mg dose, however, it will likely be more.  That said, it could also be that weight loss occurs within a specific dosage range – and diminishes or even reverses outside of this range.

Keep in mind that the weight you’re losing during naltrexone treatment may be related to the specific dose that you take.  You may find that increasing or decreasing your dosage results in predictably more or less weight loss, respectively.  Moreover, understand that your body size (height / weight) and composition (muscle / fat) may dictate how your body responds to certain dosages in regards to weight loss.

  1. Duration of use (Short-Term vs. Long-Term)

The cumulative duration over which you’ve been taking naltrexone may dictate how much weight you’ve lost.  Someone that’s only been taking the drug for a day is unlikely to have been on it long enough to notice any reductions in body weight.  Conversely, someone that’s taken the drug for a long-term may lose significantly more weight than they ever expected.  In brief, the amount of time you’ve taken naltrexone can affect the amount of weight loss you experience.

  • Short-term: If you’ve only been taking naltrexone for a week, you may not notice much weight loss. Some may still report weight loss within a week of treatment, possibly a result of side effects such as diarrhea, nausea, vomiting, etc.  Furthermore, the first few weeks of treatment may involve taking an introductory dose (e.g. 25 mg), meaning it’ll have less of an influence on neurobiological processes to facilitate weight loss.  Short-term naltrexone usage shouldn’t result in much weight change.
  • Moderate-term: After taking naltrexone for several months, you may notice that you lost some weight as a result of treatment. At this point, you’ll likely have titrated up from the smaller 25 mg dose to a standard 50 mg dose – resulting in greater (perhaps 2-fold) neurobiological modulation responsible for weight loss.  Also consider that if naltrexone reduced your appetite and/or junk-food cravings – it takes time (often months) for significant weight changes to take place.  Simply cutting out candy and/or reducing your total caloric intake doesn’t cause much noticeable weight loss after a week, but the cumulative weight loss may be noticeable after a moderate-term of months.
  • Long-term: If you lost weight after a moderate-term (months), you may continue losing additional weight over a long-term of years. The cumulative amount of weight you lost since beginning naltrexone treatment may be most significant after several years.  Additional weight loss may occur over a long-term due to the fact that you may have increased the dosage of naltrexone – yielding greater neurobiological change associated with weight loss.  Moreover, you may have had fewer cravings and/or a suppressed appetite (as a result of the drug) for a longer duration, making weight loss more noticeable after a year or two of naltrexone usage.  That said, some individuals may have hit a plateau in weight loss after a moderate-term, resulting in no additional weight loss over a longer-term, or possibly even weight gain.

Understand that cumulative weight loss relative to duration of naltrexone usage is not always predictable.  Someone who uses naltrexone for several years may find that their weight loss plateaus after the first year without any additional loss thereafter.  Another individual may report losing weight during the first 6 months of treatment, but also gaining most of it back after a full year.  Theoretically, if naltrexone is administered for a long-term at a consistent dose, the body will adapt and weight loss resulting from the drug should plateau.

  1. Co-administered substances

Anyone taking another drug and/or supplement along with naltrexone should be cognizant that the other agent(s) may affect the amount of weight lost on naltrexone.  Some substances may act synergistically with naltrexone to promote weight loss, whereas others may inhibit naltrexone-induced weight loss – or even cause weight gain.  An example of a drug that synergistically promotes weight loss when concurrently administered with naltrexone is Wellbutrin (Bupropion); hence the contriving of Contrave.

Bupropion is just one of many drugs that acts synergistically with naltrexone to promote weight loss.  Other agents such as caffeine, eugeroics (Armodafinil, Modafinil), and psychostimulants (Adderall, Ritalin, Vyvanse) – may also stimulate additional weight loss when concurrently administered with naltrexone because some are understood to cause weight loss on their own.  Even various hormone replacement therapies such as testosterone replacement therapy or thyroid replacement therapy may augment naltrexone-induced weight loss.

Oppositely, certain co-administered substances associated with weight gain may offset any weight loss from naltrexone.  In some cases, the weight gain resulting from another agent may override any weight loss that would’ve occurred with standalone naltrexone.  As an example, antipsychotics (e.g. Zyprexa) are linked to significant weight gain, and when co-administered with naltrexone, weight gain is a likely outcome.

Additionally, you may want to consider that the substances used along with naltrexone could be causing all of the weight loss (or most of it) and that the naltrexone may be having a minimal effect upon your bodyweight; it isn’t guaranteed to cause weight loss for everyone.  And unless you’re taking standalone naltrexone, it’ll be difficult to pinpoint which agent(s) are facilitating most of your weight loss.  Moreover, some co-administered substances with naltrexone may be weight neutral – and have no synergistic nor antagonistic effect on naltrexone-induced weight loss.

When attempting to decipher the degree to which co-administered substances are either overriding or enhancing naltrexone’s effect upon your weight, consider: potency (in regards to weight), dosage administered, and dosage of naltrexone used.  Someone taking a high dose of a potent drug that promotes weight gain may override any potential for weight loss from naltrexone – regardless of its dose.  On the other hand, a person using a low dose of an agent associated with modest weight gain may find that naltrexone overrides its effect and weight loss ensues.

  1. Individual factors

Theoretically, two individuals may have started standalone naltrexone treatment at the same time and are using the same daily dose (50 mg).  Since these individuals are using the same dose, have been taking the drug for the same duration, and neither are taking other substances – should we expect weight loss to be identical?  No.  In fact, one of these individuals may end up losing a significant amount of weight, while another may gain some weight.

The differences in how body weight changes as a result of naltrexone treatment may be best explained by specific individual factors.  These factors include things such as: time since discontinuation of alcohol or opioids, body size and composition (relative to naltrexone dose), dietary intake, exercise frequency, genetics, pre-treatment fitness, and sex.  Consider that these individual factors could explain why some naltrexone patients lose more weight than others.

  • Body size: The size of your body (height and weight), as well as composition (muscle and fat), may affect whether you lose weight while taking naltrexone. Assuming naltrexone exerts a weight loss effect within your particular physiology, the greater the dosage you’re taking relative to your body size, the more likely you will be to lose weight.  In other words, a person who’s 5’5” and weighs 100 lbs. would likely be under greater physiological influence of a 50 mg naltrexone dose than a person who’s 6’6” and weighs 300 lbs.  Moreover, your body composition in terms of muscle and fat may also dictate whether you lose weight while taking naltrexone, and if so, exactly how much.
  • Dietary intake: It is possible that some individuals taking naltrexone lose a significant amount of weight as a result of their diet, and mistakenly assume that the weight loss is from naltrexone. That said, it may be that certain diets act synergistically with naltrexone to facilitate weight loss, whereas other diets may offset any weight loss associated with treatment.  For example, someone eating a diet comprised of high-sugar and processed foods may not lose as much weight during naltrexone treatment than if that same person was eating low/no sugar and zero processed foods.  Consider that your diet, and possibly even meal timing – may explain why you’re losing weight and/or how much weight you’re losing while taking naltrexone.
  • Duration since discontinuation: How long has it been since you’ve stopped using alcohol or opioids? The length of time may matter in regards to whether you lose weight while taking naltrexone.  Assuming you gained weight while drinking alcohol or abusing opioids, the longer it’s been since you’ve used, the more likely you’ll have lost some weight.  This is due to the fact that your neurobiology will have had more time to repair itself – altering hormone levels, autonomic nervous system activation, and metabolism.  Keep in mind that duration since discontinuation (of alcohol or opioids) may be a more important factor for certain individuals compared to others.
  • Exercise: The frequency, duration, and type of exercise that you regularly get is understood to influence body weight. If you’re losing a significant amount of weight while taking naltrexone, it could be a result of optimizing the frequency and/or duration of certain physical exercises.  Exercise can change your entire neurobiology, especially if done consistently.  That said, it may be that exercise acts synergistically with certain mechanisms of naltrexone to decrease body weight.  Also understand that if you lost weight on naltrexone without exercise, the addition of exercise may increase the amount of weight lost.  Over-exercising, under-exercising, or doing the optimal amount (frequency, duration, type of exercise) – can influence weight.
  • Genetics: It is well-documented that individuals with the G allele of the A118G polymorphism of the OPRM1 gene derive more substantial therapeutic benefit from naltrexone for the treatment of alcohol dependence than those without it. Based on this finding, it could be hypothesized that individuals with this specific polymorphism may lose more weight during treatment than those without it.  There are numerous reasons as to why more weight loss may occur among those with the aforestated OPRM1 anomaly, but one may be that the drug is utilized more efficiently and/or exerts a more potent effect.  That said, it may also be that this polymorphism is irrelevant in regards to weight change on naltrexone.  Moreover, there may be other lesser known genes and/or sets of genes that predict who is likely to gain or lose weight during naltrexone treatment.
  • Pre-treatment fitness: Anyone who is overweight and/or obese prior to taking naltrexone may be more likely to lose weight than someone who is already in good shape. This is because someone who is already in good shape may not have much weight to lose, whereas the severely out-of-shape individual may have a lot of excess weight to lose.  For example, someone who’s 400 lbs. overweight may have an easier time losing 50 lbs. than someone who’s just 200 lbs. – this is because the 200 lb. person isn’t as overweight.
  • Sex: Differences in the amount of weight loss from naltrexone may be contingent upon an individual’s sex. It is documented that concentrations of naltrexone and its chief active metabolite (6β-naltrexol) differ between men and women.  Specifically, women tend to exhibit greater concentrations of 6β-naltrexol compared to its parent chemical naltrexone – than men.  One study reported ratios of 6β-naltrexol to naltrexone were approximately: 5 to 1 for women and 3.14 to 1 for men.  6β-naltrexol has less of an affinity for mu-opioid receptor than its parent, but its concentrations are up to 30-fold greater at steady state.  Assuming naltrexone’s effect upon body weight is mediated by degree of opioid receptor antagonism, weight loss may be more likely in men.  Should modulation within the peripheral have a greater effect upon weight, women may lose more weight. (Source: http://www.ncbi.nlm.nih.gov/pubmed/24659754).
  • Sleep / Stress: Someone who’s getting a good night’s sleep and keeping stress levels low may end up losing more weight while taking naltrexone than someone getting poor sleep with high stress. A good night’s sleep and lower stress can favorably affect neurotransmission, hormone production, and function of the prefrontal cortex (helping resist unhealthy foods).  As a result, the neurobiology of a person with good sleep hygiene and low stress may be more conducive to weight loss, possibly augmenting any weight loss from naltrexone.  Oppositely, chronic high stress and poor sleep may interfere with and/or offset any weight loss from naltrexone.

Naltrexone and Weight Loss (Review of Research)

Below is a summary of various studies investigating whether administration of standalone naltrexone causes weight loss or changes in eating habits that may lead to weight loss.  Realize that not all of these studies should be considered high-quality nor relevant to humans.  Nonetheless, reviewing these studies should help you get a better understanding of how naltrexone may cause weight loss.  Understand that the evidence presented below focuses on research of standalone naltrexone, not combined therapies such as naltrexone/bupropion.

2014: A randomized, double-blind, placebo-controlled pilot study of naltrexone to counteract antipsychotic-associated weight gain: proof of concept.

Researchers Tek et al. (2014) highlighted that individuals with schizophrenia are more prone to obesity than the general population.  In addition, those with schizophrenia are also at increased risk for cardiovascular disease and diabetes.  A major reason as to why obesity and comorbid medical conditions affect those with schizophrenia has to do with the usage of antipsychotic medications; particularly D2 receptor antagonists and/or partial agonists.

It was hypothesized that naltrexone, an opioid receptor antagonist, may be useful for the attenuation of antipsychotic-induced weight gain among those with schizophrenia.  Researchers believed that naltrexone’s modulation of opioidergic transmission could decrease appetite and promote weight loss.  The researchers organized a study with 24 women with diagnoses of schizophrenia or schizoaffective disorder, all of whom were considered overweight.

The 24 women were assigned at random to receive either naltrexone (25 mg/day) or a placebo for a duration of 8 weeks.  Efficacy of naltrexone was determined based on change in body weight after the 8 weeks compared to pre-treatment (baseline).  Results indicated that patients receiving the naltrexone experienced an average weight loss of ~7.5 lbs.

Conversely, patients receiving the placebo gained an average of ~1.32 lbs.  This study provides preliminary evidence to support the idea that naltrexone promotes weight loss in overweight women with schizophrenia.  It is unknown as to whether similar findings would occur in a group of overweight men with schizophrenia or among overweight individuals without schizophrenia.  Authors noted that a larger-scale follow-up trial is currently in progress.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25102328

2013: Naltrexone reduction of long-term smoking cessation weight gain in women but not men: a randomized controlled trial.

Researchers King et al. (2013) documented the effect of naltrexone among men and women that stopped smoking for an extended duration.  It is known that smoking often promotes weight loss via numerous mechanisms such as appetite reduction and enhancement of metabolism.  When individuals quit smoking cigarettes they often experience unwanted weight gain as a rebound effect; appetite increases and metabolism slows.

Preliminary evidence suggests that naltrexone is capable of inhibiting weight gain during medical treatment.  The goal for this study was to determine whether naltrexone could prevent rebound weight gain over a long-term among those who ceased smoking.  The study involved a total of 700 participants that were attempting to quit smoking.

The body weight and body mass index (BMI) of these 700 participants was recorded prior to smoking cessation, as well as after 6-months and 12-months.  Participants were assigned at random to receive either: naltrexone OR a placebo – during their smoking cessation.  For the first 4 to 6 weeks after smoking cessation, behavioral counseling and open-label nicotine patches were permitted.

Only individuals that were biochemically-verified as abstinent from smoking after 6-months and 12-months were included in the results.  Of the 700 participants, a total of 159 participants (77 women) remained abstinent after 6 months, and 115 (57 women) remained abstinent after a full year.  Results indicated that women treated with naltrexone experienced significantly less weight gain than those taking a placebo.

Specifically, female naltrexone users gained just 7.28 lbs. after 6 months, whereas female placebo users gained 12.13 lbs. after 6 months.  After 12 months, female naltrexone users gained 13 lbs. and female non-naltrexone users gained 16.31 lbs.  This suggests that naltrexone effectively minimizes weight gain associated with cessation of smoking or nicotine among women.

Interestingly, the attenuation of weight gain associated with smoking cessation was sex-specific; the effects were not observed in men.  Though it remains unclear as to why similar effects didn’t occur in men, it could be a result of sex-specific differences in concentrations of naltrexone metabolites.  Women exhibit greater concentrations of the chief metabolite 6β-naltrexol compared to men, possibly explaining reduced weight gain.

Other research suggests that neurobiological reactions to naltrexone in areas such as the HPA axis differ between men and women naltrexone users.  Perhaps these differences account for less significant weight change during long-term smoking cessation.  Results from this study indicate that it is a legitimate pharmacological option for preventing weight gain among women who’ve stopped smoking.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23177384

2012: Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women.

Prior to the larger 2013 study investigating the effect of naltrexone on weight change among individuals that ceased smoking, a smaller study was conducted by King et al. (2012).  This study sought to determine whether naltrexone could help patients with smoking cessation, as well as prevent weight gain that generally occurs after cessation.  Researchers also wanted to determine whether prevention of weight gain could be predicated upon sex (male vs. female).

To test their hypotheses, researchers organized a double-blinded, randomized trial among 316 individuals who were nicotine-dependent; all wanted to kick their smoking habits.  Of the 316 participants, a total of 162 received naltrexone, whereas the remaining 154 received a placebo.  The dosage of naltrexone was titrated upwards to 50 mg during the week before the date of quitting, and maintained thereafter for 12 additional weeks.

It should be mentioned that for the first 4 weeks after cessation, participants received a nicotine patch to curb nicotine withdrawal symptoms.  Participants were also permitted to attend weekly counseling sessions in the form of CBT (cognitive-behavioral therapy) for psychological support.  To determine efficacy of naltrexone for long-term smoking cessation and prophylaxis of weight gain, follow-up assessments were then conducted at 26-week and 52-week checkpoints after cessation.

Results indicated that naltrexone improved rates of cessation, reduced the urge to smoke, and decreased weight gain – for the 12-week treatment phase.  However, follow-up assessments indicated that there was no effect of naltrexone on cessation rates.  Benefits derived from naltrexone were sex-specific in that the drug resulted in greater cessation among men than women, whereas prophylaxis of weight gain (associated with smoking cessation) was superior in women than men.

Reasons as to why naltrexone prevents weight gain in women but not in men are unclear.  As was already mentioned, it may have something to do with concentrations of metabolites and/or sex-specific neural modulation following is administration.  Based on this study, it may be reasonable to hypothesize that naltrexone could promote weight loss among normal, healthy women who aren’t subject to a rebound weight gain effect resulting from smoking cessation.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22926596

2012: Effects of naltrexone on food intake and body weight gain in olanzapine-treated rats.

An animal study by Kurbanov et al. (2012) assessed the effect of naltrexone on the rats treated with the antipsychotic olanzapine.  The researchers specifically analyzed whether naltrexone administration would alter food intake, as well as the body weight of these rats.  For the study, Wistar Hans IGS rats were divided into 4 groups and given either: standalone olanzapine (2 mg/kg, b.i.d.), olanzapine plus naltrexone (50 mg/kg), standalone naltrexone (50 mg/kg), or a placebo vehicle – for a duration of 28 days.

Food intake and body weight of the rats were recorded on a daily basis for the first 9 days, and every-other-day thereafter.  Results noted an increase in food intake and body weight of rats treated with standalone olanzapine.  By comparison, rats receiving olanzapine plus naltrexone experienced less significant increases in food and body weight – suggesting that naltrexone helps mitigate some of the weight gain resulting from antipsychotic treatment.

The group of rats receiving standalone naltrexone didn’t exhibit significant reductions in food intake nor body weight compared to the vehicle placebo.  Based on these findings, we can conclude that naltrexone appears to attenuate drug-induced weight gain [possibly via anorectic mechanisms], but does not promote weight loss (as evidenced by no changes in weight during standalone treatment).  Although results from this study cannot be generalized to humans, we can hypothesize that a similar weight loss-attenuating effect provided by naltrexone would occur among those taking olanzapine.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22723540

2011: Course of weight change during naltrexone versus methadone maintenance for opioid-dependent patients.

A study by Mysels et al. (2011) investigated whether how naltrexone and methadone affected the body weight of opioid-dependent individuals.  Researchers conferred that opioid receptor agonism, such as that provided by methadone, has been associated with weight gain.  Oppositely, antagonism of opioid receptors, such as that provided by naltrexone, has been associated with no change in weight, and in some cases, weight loss.

A total of 36 opioid-dependent patients were recruited to participate in this study, 16 of which received methadone, and 20 of which received naltrexone.  Prior to pharmacological treatment for opioid dependence, body weight of all 36 patients was recorded for a baseline measure.  To determine the effect of methadone (an opioid agonist) and naltrexone (an opioid antagonist) on body weight, change in body weight of all participants was measured after 3 months, as well as after 6 months.

Results documented no significant differences in body weight of the patients taking naltrexone compared to those taking methadone at baseline.   What’s more, changes in baseline weight after 3 months, after 6 months and between 3 and 6 months – were of no significant difference between the naltrexone and methadone groups.  Specifically, records indicated that after 3 months, methadone users experienced an average weight increase of 1.86% (from baseline), whereas naltrexone users experienced an average weight increase of 4.63% (from baseline).

After 6 months of treatment, patients taking methadone experience a weight increase of 3.67% from baseline, whereas patients taking naltrexone experienced a weight increase of 6.69% from baseline.  Furthermore, there were no relationships discovered between an abnormally low or high baseline weight and percentage gain within (and between) each group.  Based on these findings, some may speculate that naltrexone usage may induce a slight amount of weight gain among those with opioid dependence.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21434584

2009: Methylnaltrexone potentiates body weight and fat reduction with leptin.

We may be able to learn a bit about how naltrexone could cause weight loss as a result of studies investigating the effects of a related drug, methylnaltrexone on body weight.  Naltrexone and methylnaltrexone function as mu-opioid receptor (MOR) antagonists, however, they yield markedly different effects.  Naltrexone is centrally-acting, crosses the blood-brain-barrier (BBB), and is used to treat opioid dependence.

Methylnaltrexone is peripherally-acting, does not cross the blood-brain-barrier (BBB), and is used to treat opioid-induced constipation.  A study by Yuan et al. (2009) assessed how methylnaltrexone affected body weight, fat accumulation, and leptin concentrations – in neonatal rats.  Results indicated that methylnaltrexone significantly attenuated weight gain of neonatal rats compared to the control group.

Researchers concluded that methylnaltrexone appears to potentiate the effect of leptin (a satiety hormone) on body weight.  When methylnaltrexone is administered with leptin, significant weight reduction and fat loss tends to occur.  Though these results cannot be generalized to humans, nor naltrexone, nor humans receiving naltrexone – they may help us better understand how naltrexone facilitates weight loss.

It could be that, similar to methylnaltrexone, the drug naltrexone and/or its peripherally-selective metabolite (6β-naltrexol) enhances the effect of leptin, perhaps facilitating appetite reduction and satiation.  These effects may be more prominent in women compared to men due to the fact that women a greater amount of the peripherally-selective 6β-naltrexol metabolite.  Moreover, it could be hypothesized that increasing leptin may enhance weight loss resulting from naltrexone.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20073411

2009: Methylnaltrexone reduced body weight gain in ob/ob mice.

Another study by Yuan et al. (2009) analyzed the effect of methylnaltrexone on the body weight of adult obese (ob/ob) mice.  The researchers administered 3.0 mg/kg methylnaltrexone to adult obese (ob/ob) mice for a duration of 12 days and discovered that it inhibited additional weight gain compared to a control group.  The body weight of the mice given methylnaltrexone was 55.9 grams, whereas the body weight of the control group was 63.9 grams – suggestive of the fact that methylnaltrexone prevented additional weight gain.

It was noted that there was a dose-dependent effect of methylnaltrexone on weight change, the greater the dose, the more significant the weight reduction.  Daily food intake was also significantly reduced among the mice receiving methylnaltrexone compared to the non-drug controls.  What’s more, the methylnaltrexone didn’t affect body temperature nor expenditure of energy.

The researchers concluded that methylnaltrexone modulates food intake in a dose-dependent manner and may warrant investigation for the management of obesity.  Keep in mind that these results are discussing methylnaltrexone (not naltrexone) in mice (not humans).  We cannot assume that similar results would’ve occurred with the centrally-acting naltrexone – especially in humans.

Nevertheless, it may be that greater formation of the metabolite 6β-naltrexol in humans predicts efficacy of naltrexone in modulating food intake and body weight.  Since 6β-naltrexol is peripherally-selective as an antagonist, greater formation of this metabolite may result in more significant reduction of food intake and more substantial weight loss.  It should be considered that larger doses of naltrexone may form a greater amount of 6β-naltrexol metabolites than lower doses, ultimately inducing more substantial appetite reduction or weight loss via peripheral opioid antagonism.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19736901

2000: Naltrexone does not prevent the weight gain and hyperphagia induced by the antipsychotic drug sulpiride in rats.

A study by Baptista et al. (2000) examined the effect of naltrexone on the body weight and appetite of rats taking the antipsychotic sulpiride.  Sulpiride is an antipsychotic of the benzamine class typically administered for the treatment of psychosis.  It functions primarily by antagonizing dopamine receptor sites (D3, D2, D4) which treats positive symptoms (e.g. hallucinations and delusions), however, this mechanism typically increases appetite and causes weight gain.

The fact is that most patients treated for psychosis face a catch-22 scenario: treat psychotic symptoms and gain weight (to the extent of obesity) OR experience psychosis and maintain a normative body weight.  Since attenuation of psychosis is necessary for a patient to function in society, pharmacological treatment with an antipsychotic is always advised.  That said, researchers have long been seeking to determine whether adjunct agents may combat some of the unhealthy weight gain associated with antipsychotic treatment.

In this particular study, researchers tested the efficacy of naltrexone, an opioid receptor antagonist, in preventing antipsychotic-induced weight gain [from sulpiride].  They theorized that modulation of opioidergic neurotransmission with naltrexone could reduce appetite and/or feeding behaviors, ultimately reducing weight gain of those taking antipsychotics.  To test this theory, they administered naltrexone to multiple groups of rats: drug-free rats and sulpiride-treated rats for 21 days.

Results indicated that naltrexone at dosages exceeding 4 mg/kg significantly reduced food intake and weight gain among drug-free rats.  Oppositely, naltrexone was unable to prevent weight gain among the rats treated with sulpiride, and counterintuitively facilitated an increase in food intake.  Based on these findings, we could form the hypothesis that similar outcomes may occur in humans taking naltrexone.

In other words, high doses of naltrexone may promote weight loss (or prevent weight gain) when administered as a standalone [without an antipsychotic].  On the other hand, when administered with an antipsychotic (e.g. sulpiride), naltrexone may have no effect upon body weight, or could even exacerbate weight gain.  To conclude, naltrexone may not prevent weight gain induced by another co-administered drug, but it may prevent weight gain among drug-free individuals – when administered at high doses.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10744894

1995: Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters.

Researchers Drewnowski et al. (1995) hypothesized that endogenous opioid peptides influenced hedonic responses to high-sugar and high-fat foods among binge eaters.  To test this hypothesis, researchers recruited 41 women to participate in an experiment.  Of the 41 women, 16 were considered obese and 25 were of normal weight.  A total of 10 obese and 10 normal-weight women fit diagnostic criteria for bulimia (in accordance with the DSM-III-R).

To determine whether opioidergic neurotransmission is implicated in pleasure associated with food consumption, researchers administered: naloxone (an opioid antagonist), butorphanol (an opioid agonist), and a saline placebo – intravenously.  While infused with the drugs, the participants were instructed to taste and rate 20 sweetened dairy products and were given 8 snack foods of varying sugar and fat content.  Upon analysis of the results, it was discovered that the administration of naloxone suppressed hedonic responses associated with consumption of high-sugar and high-fat foods in binge eaters – but had no effect in non-bingers.

Moreover, the total food intake of obese women remained unchanged as a result of naloxone.  Administration of the opioid agonist butorphanol had no significant influence in any group upon hedonic responses associated with high-sugar/high-fat foods, nor did it alter total food intake.  Some may speculate that since naltrexone effectively modulates hedonic responses among binge eaters, that the neurochemistry and/or neural activation of binge eaters differs from non-bingers.

A larger-scale, follow-up study (utilizing neuroimaging to measure hedonic responses) would likely be useful to support this preliminary finding that naltrexone mitigates hedonic response associated with high-fat/high-sugar foods among binge eaters.  Nevertheless, we can speculate that a subset of naltrexone users (perhaps not just binge eaters) may experience a reduction in hedonic response associated with consumption of high-fat/high-sugar “junk foods.”  This reduced hedonic response may prevent cravings and/or overeating of unhealthy foods, each of which may contribute to weight loss.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7762518/

1995: Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa.

A report by Marrazzi et al. (1995) documented that inhibition of opioid receptors may be therapeutically effective in management of the conditions anorexia nervosa and bulimia nervosa.  The report reflected upon the finding that, outpatient administration of naltrexone significantly reduced binge-purge symptoms in 18 of 19 patients with bulimia or anorexia (bulimia subtype) – compared to a placebo.  Although the finding is from a small-scale trial, the trial was randomized, double-blinded, and implemented a crossover design.

These results indicate that modulation of opioidergic neurotransmission with naltrexone may affect eating behaviors – especially among a subset of those with eating disorders.  It is reasonable to speculate that naltrexone may also modify eating habits among those without eating disorders.  Since naltrexone appears most effective among those with bulimia, it could be that naltrexone reduces binge eating tendencies, possibly resulting in healthy weight loss.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8675969/

1994: Naltrexone plasma levels, clinical response and effect on weight in autistic children.

In the 1990s, it was hypothesized that the degree to which naltrexone influenced behavior may be related to its concentration within plasma.  To test this hypothesis, Gonzalez et al. (1994) organized a double-blinded, placebo-controlled, parallel-group study incorporating 41 children diagnosed with autism.  All children had been hospitalized and were assigned at random to receive either: naltrexone OR a placebo.

During treatment, plasma concentrations of naltrexone were assessed with GC/MS (gas chromatography, mass spectrometry) and the body weight of each child was recorded weekly.  Among 17 participants, naltrexone concentrations within plasma fell within the range of 0.12 ng/mL to 5.6 ng/mL (for an average of 0.71 ng/mL).  There appeared to be no relationship between plasma concentrations and: age, intellect, psychiatric rating scale scores, clinical global impressions, or hyperactivity.

This suggests that plasma concentrations of naltrexone do not have a significant impact upon behavior of children with autism.  Furthermore, naltrexone didn’t appear to significantly affect the body weight of those treated.  That said, there were trends (p = 0.06) indicating that high-weight children who received naltrexone experienced a modest average weight loss of 0.93 lbs.

Contrastingly, low-weight children who received naltrexone experienced a negligible average weight gain of 0.07 lbs. as a result of naltrexone.  From this study we can conclude that naltrexone is unlikely to affect the body weight of children with autism, and that plasma concentrations may not correlate with therapeutic efficacy.  That said, since there was a slight trend of weight loss among high-weight children treated with naltrexone, it is reasonable to speculate that a subset of overweight or obese individuals may lose a modest amount of weight from naltrexone.

Researchers may want to consider that naltrexone’s effect on body weight may be contingent upon whether the patient is: pediatric or adult, autistic or neurotypical, or any permutations of these two factors (e.g. pediatric neurotypical, adult autistic, etc.).  Furthermore, it may have been useful for these researchers to determine whether plasma concentrations of naltrexone are affect body weight [in addition to behavior].  Although this study provides evidence that naltrexone doesn’t promote weight loss in all patients, the trend of modest weight loss in high-weight patients may warrant further investigation.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7831456

1989: A placebo-controlled, double-blind crossover study of naltrexone hydrochloride in outpatients with normal weight bulimia.

Mitchell et al. (1989) noted that endogenous opioidergic activity controls feeding behavior.  Prior research demonstrated that antagonism of endogenous opioids is able to suppress feeing in some human and animal models.  For this reason, Mitchell et al. set-up a placebo-controlled, double-blinded, crossover trial investigating the effect of naltrexone on 16 female patients with normative-weight bulimia.

All 16 patients were treated with low-dose naltrexone (LDN) OR a placebo control.  Contrary to other research, the administration of naltrexone failed to attenuate binge eating and purging episodes.  This suggests that naltrexone may not have an effect on eating behaviors among those with eating disorders, and for this reason, it may have no significant impact on body weight.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/2656781/

1985: Effects of long-term therapy with naltrexone on body weight in obesity.

Food intake is thought to be significantly influenced by the neurotransmission of endogenous opioids.  What’s more, animal studies have shown that administration of opioid antagonists reduces food intake.  Since no controlled trials of opioid antagonists had been conducted in humans, Atkinson et al. (1985) organized a double-blind, placebo-controlled, randomized study.

The aim of the study was to determine the effect of naltrexone on the body weight of obese humans.  A total of 60 individuals classified as “obese” were recruited and assigned at random to receive: 0 mg (placebo), 50 mg, or 100 mg of naltrexone – for a duration of 8 weeks in an outpatient setting.  Prior to treatment, body weight was documented and effect of naltrexone on body weight was assessed based on change in weight after 8 weeks.

Results indicated that weight loss was insignificant among those receiving 50 mg and 100 mg naltrexone compared to the placebo.  Despite this finding, a sex-specific analysis revealed that women lost a significant amount of weight (P < 0.05) from naltrexone compared to the placebo, whereas men did not.  On average, women lost around 3.75 lbs. from pre-treatment baseline through 8 weeks.

It was concluded that the inefficacy of naltrexone for weight loss in humans was unexpected based on findings from animal studies.  That said it is important to highlight the fact that a modest amount of weight loss occurred in female users – perhaps due to sex-specific neurobiological reactions to the drug, possibly related to greater concentration of peripherally-selective metabolites in females.  Authors noted that larger naltrexone doses (e.g. over 100 mg) may be necessary for weight loss in humans.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/4042525

1980: Naltrexone reduces weight gain, alters “beta-endorphin”, and reduces insulin output from pancreatic islets of genetically obese mice.

A study by Recant et al. (1980) assessed the effect of naltrexone on young obese (ob/ob) and lean mice for a duration of 5 weeks.  Naltrexone was administered subcutaneously at a dosage of 10 mg/kg (b.i.d.) and saline injections were given to controls.  Throughout the study, mice had continuous access to food and researchers documented body weight and concentrations of beta-endorphin.

It was discovered that administration of naltrexone resulted in slower weight gain over the first 3 weeks in naltrexone-treated obese mice compared to the obese controls.  Results also indicated that certain forms of genetic obesity facilitate elevations in concentrations of endogenous opioids, as well as heightened sensitivity to opioid antagonism.  In conclusion, it may be that certain genes and/or concentrations of endorphins influence the effect of naltrexone on body weight.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/6272240

Limitations associated with research of Naltrexone for weight loss

There are some limitations associated with the investigation of naltrexone for weight loss.  Until these limitations are addressed, it will remain unclear as to whether naltrexone is useful as a weight loss intervention.  Examples of some limitations include: the shortage of large-scale, robustly designed (RCT) human trials; failure to test high dosages; short-term investigation; and trials only in select populations (e.g. opioid dependence).

  • Dosage for weight loss: Some literature has hinted at the fact that high dosages of naltrexone may be needed for a significant weight loss effect. Most of the research in humans fails to test naltrexone at dosages exceeding 100 mg.  This may be due to the fact that the standard dose of naltrexone is 50 mg and propensity of adverse events (e.g. hepatotoxicity) increases at higher dosages.  That said, it may be that a supratherapeutic dose (e.g. 200 mg) may be needed for weight loss.
  • Lack of human studies: Several trials have investigated the effect of naltrexone on the body weight of animal such as mice and rats. While these trials are useful to help form a preliminary hypothesis regarding whether naltrexone is likely to promote weight loss in humans, they cannot be generalized to humans.  More human trials are needed to elucidate whether naltrexone promotes weight loss as a standalone agent.
  • Males vs. Females: Multiple studies have noted weight loss among women taking naltrexone, whereas none have found an effect among men. Perhaps researchers should attempt to pinpoint reasons as to why naltrexone promotes weight loss in female patients rather than males.  Moreover, it may be useful to conduct more trials with only female participants to determine the amount of weight loss occurring after naltrexone.
  • Number of participants: Currently the largest trial assessing weight changes from naltrexone treatment involved 60 participants – most trials are much smaller. To determine the effect of naltrexone upon body weight, trials incorporating hundreds of participants would be useful.  While the smaller trials aren’t necessarily inaccurate, the accuracy of existing findings can be strengthened with larger-scale studies.
  • Patient demographics: It is necessary to consider that the demographics of specific patients may affect whether naltrexone facilitates weight loss, is weight neutral, or even promotes weight gain. It could be that age (pediatric vs. adult), genes (expression of a particular gene), and/or medical diagnoses (e.g. autism) influence whether someone is likely to lose weight from naltrexone.  Researchers should attempt to determine whether specific patients may be more likely to lose weight from naltrexone than others.
  • Study designs: Although several studies evaluating naltrexone’s effect upon body weight are classified as randomized controlled trials (RCTs), others are not. To determine whether naltrexone is capable of inducing weight loss [or preventing weight gain], further research should seek to implement randomized, placebo-controlled, double-blinded designs.
  • Trial duration: While a few trials investigate the effect of naltrexone on body weight for a full year (12 months), others are shorter-term. Perhaps some are too short-term for any significant weight loss to occur.  It is reasonable to assume that significant weight loss may require several months of naltrexone usage – perhaps at a supratherapeutic dose.

Does the research suggest that naltrexone causes weight loss?

Assessment of the research suggests that, in most cases, naltrexone does not cause clinically significant weight loss.  In other words, individuals administering naltrexone at standard, medically recommended dosages (e.g. 50 mg/day) should not experience significant fluctuations in body weight.  That said, some studies indicate that naltrexone may slow or attenuate weight gain associated with antipsychotic treatment or nicotine cessation.

It should be clear that in these cases, weight gain attenuation is not the same as weight loss.  It should be mentioned that naltrexone appears to reduce binge/purging behaviors among those with bulimia nervosa, as well as curbs [perhaps exaggerated] hedonic responses to junk foods (high-sugar/high-fat) among individuals with binge eating disorder.  Perhaps the reductions in binge/purge tendencies and/or hedonic reactivity may facilitate weight loss in certain users.

There is some evidence to suggest that naltrexone causes weight loss among individuals that are overweight and/or obese prior to treatment, as well as of the female sex.  In the already-discussed trial investigating the effect of naltrexone on the body weight of children with autism, there was a trend (P < 0.06) towards weight loss among high-weight children treated with naltrexone.  On average, these high-weight children lost ~0.93 lbs. after naltrexone treatment.

It is plausible that since only 17 children in the study received naltrexone, and not all were high-weight, the efficacy of naltrexone for weight loss among overweight children may remain unclear.  Such a small sample size of high-weight children is at risk of underpowered results.  In any regard, this small trend of weight loss observed in high-weight children may warrant further investigation.

Two randomized controlled trials (RCTs) discovered that naltrexone can cause a modest amount of weight loss in obese/overweight female users.  The first trial (from 1985) noted that administration of naltrexone at a dose of 50-100 mg per day resulted in weight loss of ~3.75 lbs. after 8 weeks – among obese females.  The second trial (from 2014) reported an average weight loss of ~7.5 lbs. among overweight female patients with schizophrenia – after 8 weeks.

Does everybody lose weight from taking naltrexone?

No.  Clearly not everyone will lose weight from taking naltrexone.  In fact, interpretation of the research indicates that most users (especially men) should expect no significant change in body weight from naltrexone treatment.  As an example, consider results from the aforementioned 1994 study involving hospitalized children receiving an 8-week course of naltrexone for autism.

Results from the study documented zero change in body weight from start-date to finish among the participants.  What’s more, it appeared as though individuals with a low-weight prior to treatment ended up gaining 0.07 lbs. (less than one tenth of 1 lb.) – a statistically negligible amount of weight.  Therefore, it could be theorized some individuals may actually gain an insignificant amount weight from naltrexone.

Whether you lose weight, gain weight, or remain the same weight while taking naltrexone is unpredictable.  Hypothetically, someone in peak physical shape prior to treatment may find that naltrexone interferes with energy levels (by causing fatigue), possibly making it more difficult than usual to finish workouts.  Conversely, an obese individual may find that naltrexone increases their energy level, making it easier to workout and lose weight.

Those most likely to lose weight may be overweight females (possibly with binge eating tendencies), and those most likely to remain weight neutral or gain weight may be underweight or average-weight men without binge eating tendencies.  Other already-discussed factors such as the dosage, duration of usage, and/or co-administered substances – can also affect weight change from naltrexone.  In summary, only a subset of naltrexone users will experience clinically significant weight loss.

Who may be more likely to lose weight while taking naltrexone?

Research shows and/or implies that certain individuals may be more likely to lose weight while taking naltrexone than others.  The two biggest predictors regarding whether you’ll experience weight loss from naltrexone may be: sex and pre-treatment weight.  Female naltrexone users are significantly more likely to lose weight than males, and those who are overweight/obese prior to treatment are more likely to lose weight than normal-weight or underweight individuals.

  • Female users: In several studies investigating the effects of naltrexone upon body weight, no significant changes occurred. However, examination of sex-specific body weight changes from naltrexone treatment revealed that significant weight loss occurred in female patients; no change was discovered in male patients.  Knowing this information, realize that if you’re a female naltrexone user, the odds are in your favor for weight loss (compared to males).
  • Obese or overweight: Individuals that are overweight and/or obese prior to using naltrexone are more likely to lose weight than those who aren’t. Specifically, overweight or obese females tend to lose more weight than overweight/obese males.  That said, trends (from possibly underpowered studies) suggest that high-weight individuals of both sexes may benefit more from naltrexone than normative-weight or underweight individuals.
  • Binge eaters: A study with obese and lean binge eaters discovered that administration of naltrexone suppressed hedonic response generated during consumption of high-sugar/high-fat foods. Among those without binge eating disorder, naltrexone had no effect on hedonic responses during consumption of junk (high-sugar/high-fat) food.  Based on this finding, we can speculate that those with binge eating disorder may lose more weight during naltrexone treatment as a result of decreased hedonic response.
  • Multifaceted weight loss approach: There’s a big difference between relying on a drug for weight loss and working with the drug for weight loss. Although naltrexone may increase weight loss potential by reducing cravings for unhealthy foods, decreasing appetite, or increasing energy levels to workout – a person can still choose to remain sedentary and shovel down junk food like it’s a full-time job, ultimately overriding all weight loss potential.  Someone who puts forth a bit of effort and works with naltrexone by: hitting the gym each morning and/or cutting intake of sugar and processed foods – may experience significant weight loss.
  • High-dose users: Although merely speculation, some studies imply that higher doses of naltrexone may be more likely to cause weight loss than lower doses. There are certainly more risks associated with high doses (e.g. hepatotoxicity), however, weight loss may be more significant.  Reasons as to why weight loss may be more significant aren’t fully elucidated, but may have something to do with increased potency and corresponding neurobiological changes from high doses.
  • *Genetics: It is known that the G allele of A118G polymorphism of OPRM1 results in greater efficacy of naltrexone for the treatment of alcohol dependence. Reasons as to why this polymorphism facilitate better treatment outcomes are unclear.  It is reasonable to hypothesize that it may increase the potency of the drug and/or stimulate certain neurobiological reactions that differ from the norm – possibly promoting more significant weight loss.

Who may be less likely to lose weight with naltrexone?

The research indicates that certain individuals may be less likely to lose weight while taking naltrexone.  Research notes that male naltrexone users shouldn’t expect to lose any weight during treatment.  Additionally, individuals using low dosages who aren’t obese/overweight nor binge eaters – may have a tougher time losing any weight from naltrexone.

  • Male users: Though the research analyzing the effect of naltrexone on the body weight of men is limited, a randomized controlled trial from 1985 documented zero change in body weight after 8 weeks of treatment. What’s more, the men in the trial were all classified as obese, which should’ve made it easier to lose weight with naltrexone.  Another study from 2012 documented that naltrexone inhibited weight gain during smoking cessation among females, but not males.  If you’re a guy trying to lose weight with naltrexone, it could be more challenging.
  • Drug-only approach: Individuals expecting naltrexone to miraculously transform their body from a blob of cellulite into a muscle machine without exercising or altering their diet likely won’t lose much weight. Relying on a drug to do all the work is generally a highly ineffective strategy.  Naltrexone may slightly reduce appetite and/or curb cravings, but these effects can be overridden as a result of failure to work with the drug.  If you don’t put forth a conscious effort to exercise and eat healthier while taking naltrexone, you probably won’t lose any weight.
  • Low-dose users: The lower the dosage of naltrexone you take, the less significant its effect on your neurobiology. A less significant effect means that homeostatic processes may not shift to a sufficient enough extent to promote weight loss.  Generally, the lower the dose administered of any drug associated with weight loss, the less significant the weight loss.
  • Non-binge eaters: In binge eaters, naltrexone is known to decrease pleasurable responses generated within the brain during consumption of unhealthy foods. However, this reduction in pleasure during consumption of unhealthy foods does not occur among non-binge eaters.  For this reason, it could be suggested that non-binge eaters may derive less benefit from naltrexone for weight loss.
  • Normal or underweight: Users that are normal and/or below-average body weight prior to taking naltrexone shouldn’t expect to lose additional weight. In fact, those who are underweight may end up gaining a bit of weight as a result of certain modulatory effects of naltrexone on neurobiology.  If you are already at a normal or healthy weight, you probably shouldn’t expect much weight loss from naltrexone.

How much weight could you lose while taking naltrexone?

Assuming you fit the criteria for a person that’s likely to lose weight with naltrexone (e.g. female, obese, binge eater), you may be interested in learning how much weight you can lose, as well as how quickly you can lose the weight.  According to results from a 1985 randomized controlled trial, obese female patients may lose approximately 3.75 lbs. after 2 months of naltrexone treatment – at dosages of 50 mg or 100 mg per day.  Clearly this weight loss over a 2-month period is extremely modest.

Another 2-month randomized controlled trial published in 2014 reported weight loss of 7.5 lbs. among overweight women with schizophrenia.  In other words, overweight female naltrexone users may lose between 4 and 8 lbs. after 2 months.  It is unclear as to whether additional weight loss would occur over a longer duration and/or if increasing the naltrexone dosage would amplify weight loss efforts.

Overall, the weight loss from naltrexone appears to be very modest.  Those considering using naltrexone specifically for losing weight could probably attain superior weight loss results by focusing on diet/nutrition and exercise.  Simple lifestyle interventions such as going for a 20 minute walk each morning or doing some push ups, eliminating junk foods, and intermittent fasting – can likely facilitate healthier, more sustainable weight loss than any medication, including naltrexone.

Have you lost weight from taking naltrexone?

If you ended up losing weight on naltrexone (expectedly or unexpectedly), feel free to share a comment.  Approximately how much weight did you lose while taking naltrexone, and how long did it take to lose?  To help others get an accurate understanding of your situation, provide some additional details [in your comment] such as your: naltrexone dosage (e.g. 50 mg/day), duration of treatment (e.g. 3 months), and the medical condition for which it was prescribed.

Also mention whether you are: male or female, were obese/overweight before treatment, have dealt with binge eating disorder, and whether you take any other substances (drugs or supplements) with naltrexone.  If you’re among those that administer other substances with naltrexone, have you considered that the other co-administered substances could affect your body weight – possibly to a greater extent than naltrexone?  Among the long-term users that lost weight, how long did it take for the weight loss from naltrexone to plateau?

For those that are convinced that the weight loss they’ve experienced is a direct result of naltrexone, discuss some reasons as to how the drug may have caused weight loss such as: appetite reduction, suppression of cravings, decreased pleasure from eating, etc.  Everything considered, most individuals taking standalone naltrexone shouldn’t expect to lose weight.  Even if some weight loss occurs, there’s no evidence to suggest that it’ll be significant.

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{ 1 comment… add one }
  • Cherri September 17, 2016, 3:22 pm

    For the obese female over 200 pounds, an eight pound weight loss in two months is not necessarily modest and to state so in an article while adding that such results could as easily be achieved by traditional methods like restrictive dieting and exercise as though none of us had ever thought of that or tried it is a bit traditionally condescending. Perhaps this type of article and research and writing would be better performed by someone either more empathetic, more experienced or with more largesse.

    Speaking as someone who has achieved and maintained a twenty pound weight loss each portion of which took a year to wipe off with the assistance of a personal trainer at $75 per forty five minutes and a professional sports trainer at that, vitamin supplementation as advised by a naturopath with an MD, medical assistance and organic only diet and leisure time exercise and several OTHER lifestyle changes, you have your head in your hat. For 8 pounds it’s worth a shot IMHO. And I’m already sober 28 years. Hell, 4 pounds sounds good. It’s all relative, smarty/skinny pants.

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