Naltrexone is a pure opioid receptor antagonist utilized principally for the treatment of alcohol and opioid dependence. As an opioid receptor antagonist, naltrexone competitively binds to mu-opioid receptor (MOR) and kappa-opioid receptor (KOR) sites with higher affinity than opioid agonists, thereby attenuating receptor activation. Should an individual administer an opioid agonist (e.g. morphine) while taking naltrexone, the pleasurable or rewarding intoxication associated with that particular agonist will be reduced.
A similar outcome may occur among those who drink alcohol while taking naltrexone, resulting in feelings of malaise – rather than pleasurable drunkenness. Naltrexone is hypothesized to modulate neural circuitry such as the dopamine mesolimbic system – implicated in craving, decision-making, pleasure, and reward processing. This modulation leads naltrexone users to experience fewer cravings, impulsive urges, and/or rewards associated with addictive drugs.
This mechanism may also explain why naltrexone appears efficacious for the treatment of certain impulse control disorders. In any regard, despite the therapeutic practicality naltrexone for the management of severe alcohol and opioid dependence, not every patient finds it tolerable. For some, the side effects resulting from naltrexone are so debilitating, that discontinuation and/or pursuit of an alternative treatment is necessary.
Naltrexone Side Effects & Adverse Reactions (List)
Nearly every pharmaceutical drug has potential to provoke unwanted side effects and naltrexone is no exception. That said, naltrexone is considered safe and tolerable for a majority of individuals with opioid dependence, hence the reason it is FDA-approved and frequently prescribed. Realize that the total number of side effects, severity of side effects, and specific side effects that you experience will be individualized and may be dissimilar from those of another naltrexone user.
You may find that naltrexone gives you headaches, whereas another user may not experience any headaches, but may experience extreme nervousness. Nevertheless, certain side effects resulting from naltrexone administration are clearly more common than others, including: diarrhea, gastrointestinal distress, headache, nausea, upset stomach, and vomiting. Included below is a comprehensive list of potential side effects and adverse reactions associated with naltrexone.
Allergic reactions: In rare cases, patients may experience an allergic reaction to naltrexone. Symptoms of a serious allergic reaction to naltrexone include: coughing, dizziness, shortness of breath, skin rash, swelling, vomiting, and wheezing. Although an allergic reaction is not common, they have been reported and can occur with any medication.
If you suddenly notice that your skin breaks out in a rash, your face has swollen, and you find it difficult to breathe – do not hesitate to consult a doctor. Should anyone experience an allergic reaction, naltrexone treatment will be discontinued and an alternative medication may be prescribed. Fortunately, an overwhelming majority of individuals will not be allergic to naltrexone.
Anxiety: Some people report feeling increasingly anxious and/or nervous while taking naltrexone. When considering that opioid agonists tend to significantly reduce anxiety by decreasing CNS activity, it is necessary to consider that antagonism of opioid receptors may increase anxiety. The anxiety increase may result from inhibition of endogenously manufactured endorphins and/or neuropeptides from stimulating opioid receptors.
Usually increases in anxiety from naltrexone are not extreme, but could be mildly uncomfortable. Sometimes natural interventions such as: aromatherapy, deep breathing, meditation, and/or taking a warm bath – may offset some of the anxiety. If the anxiety becomes so bad that you can’t work or feel out of control – talk to your doctor about discontinuing naltrexone or administering an adjunct anxiolytic.
Appetite loss: Many people taking naltrexone will notice that their appetite is markedly lower than usual. This reduced appetite may be a result of other treatment-induced side effects such as nausea and/or vomiting. Anyone who feels constantly nauseous may have a tougher time than usual in consuming food, especially if this nausea has triggered prior episodes of vomiting.
Assuming emetic reactions to the medication are an issue, administration of an antiemetic agent may be useful for reducing nausea, and ultimately appetite. If you find that your appetite decreases most significantly right after taking naltrexone, a good strategy may be to consume a big meal before you take it. Perhaps the biggest reason why appetite may be blunted for some naltrexone users has to do with neurochemistry.
The drug antagonizes mu-opioid receptors and these opioid receptors crosstalk with the dopaminergic mesolimbic pathway – implicated in pleasure/reward. Since activation in pleasure/reward centers decreases during treatment, it makes sense that food won’t be as appealing and appetite will diminish. Generally, the greater the dosage of naltrexone used, the more pronounced the appetite suppression is likely to be.
Brain fog: While some may find that mental clarity improves significantly while taking naltrexone, others have the opposite experience of brain fog. Any drug that modifies neurochemical processes has potential to induce a state of cloudy thinking in its users. Keep in mind that this clouded thinking may be temporary and often subsides with continued.
Sometimes it may take several weeks for a user’s neurochemistry to adapt to the effects of the drug. While naltrexone proponents often suggest that it can treat brain fog, not everyone finds it beneficial and a subset of individuals may find that it worsens. It is likely that alterations in arousal and neurochemistry contribute to the brain fog.
Chest pain: Another uncommon side effect of naltrexone is chest pain. Since chest pain is also the sign of potentially serious medical conditions, all individuals should report it to their doctor. It may be helpful to consult a cardiologist to rule out cardiac abnormalities, as well as to confirm that the medication is safe to take given your current cardiac function.
Although pure speculation, it could be that chest pain occurs as a result of peripheral opioid receptor antagonism by naltrexone. This antagonism may indirectly affect blood flow to the chest, possibly contributing to some minor pain. It may also be that gastrointestinal distress as a side effect causes upset stomach and pain in the the chest area.
Chills: Becoming chilled or feeling colder than usual can occur with naltrexone usage. If you experience chills, you should first consider that they may be related to withdrawal from a previous substance. If the chills cannot be attributed to a recent drug withdrawal, they may have resulted from slightly altered thermoregulatory processes stemming from naltrexone administration.
At low doses among individuals that aren’t withdrawing from any medications, chills may not be extreme. Most would consider chills to be a very rare side effect of naltrexone, but one that could occur. Some may also speculate that if naltrexone causes some users to sweat more than usual, this increased sweating may contribute partially to the chills.
Confusion: Studies assessing how naltrexone affects cognition have discovered that it neither enhances nor impairs cognitive function. That said, a small percentage of individuals report that the drug makes them confused with foggy thinking (decreased mental clarity). The mechanisms of naltrexone that contribute to confusion aren’t very clear, but it could be that confusion results from decreased arousal.
Some individuals find that naltrexone makes them fatigued and/or drowsy, neither of which are conducive to optimal cognitive function. If the confusion is overwhelming to the extent that your work or academic performance is suffering, ask your doctor about possible adjunct attenuators. For example, it may be helpful to simply drink some coffee to reverse some of the confusion.
Diarrhea: Among the most popular side effects of naltrexone is diarrhea. Diarrhea is likely caused by antagonism of peripheral mu-opioid receptors positioned within the gastrointestinal tract. When a mu-opioid receptor antagonist binds to these receptors, intestinal motility is expedited and things move quicker through the gastrointestinal tract – increasing likelihood of diarrhea.
This may be the opposite mechanism as opioid-induced constipation – caused by peripheral binding of receptor agonists. This side effect could also be caused as a rebound effect characterized by abnormal peripheral opioid receptor activation following discontinuation of an opioid agonist – associated with opioid withdrawal (rather than naltrexone). It could also be that diarrhea is caused by irritation of the gut lining from taking naltrexone on an empty stomach.
If naltrexone-induced diarrhea is significant, it is recommended to consult your doctor. A medical professional may recommend staying hydrated, taking naltrexone with food, and/or using an over-the-counter agent such as Imodium. In some cases, your body may adapt to treatment and the diarrhea from naltrexone treatment may eventually subside. (Source: http://www.ncbi.nlm.nih.gov/pubmed/23881667).
Dizziness: A popularly reported side effect of naltrexone is the feeling of dizziness, sometimes with lightheadedness and/or vertigo. The dizziness may be most extreme when the medication is first introduced and will likely diminish with repeated administration. To reduce the likelihood that you’ll feel dizzy from naltrexone, it may be helpful to start with an extremely small dose and titrate upwards at a gradual pace.
Furthermore, consider that the dizzy feeling may be a result of combining naltrexone with another substance (e.g. alcohol), or possibly a symptom of recent substance discontinuation. To cope with dizzy spells treatment, you may want to simply lie down until they pass. Minor dizziness is to be expected, but if you feel so dizzy that you cannot function – you may need to talk to your doctor about alternative interventions.
Drowsiness: The medical documentation attached with naltrexone prescriptions suggests that it may cause drowsiness. The drowsiness is indicative of the fact that the drug may decrease arousal and provoke feelings of tiredness. Knowing that drowsiness may occur as a side effect, you should avoid operating heavy machinery and/or a motor vehicle until any drowsiness subsides.
Since drowsiness could impair your academic, athletic, or occupational performance – it may be perceived as a highly problematic side effect. Drowsiness experienced from naltrexone may be improved with dosage modifications and/or concurrent usage of a non-contraindicated stimulatory agent. Discuss various interventions for reducing naltrexone-induced drowsiness with a medical professional.
Fatigue: Taking naltrexone may cause you to feel extremely fatigued, possibly to the extent that you want to lie in bed all day. The fatigue may be difficult to cope with and may compromise work-related productivity and/or motivation. Understand that fatigue may be most likely to occur when initially starting naltrexone treatment and may subside (after several weeks) once the body has adapted to the drug’s effects.
The low energy could be a result of decreased stimulatory neurotransmission and/or activity in centers of the brain associated with motivation. It is also necessary to consider that, if you recently stopped drinking alcohol or using opioids prior to using naltrexone, the fatigue may be related to withdrawals. Nevertheless, sometimes fatigue can be reduced by altering the time of day at which naltrexone is taken, the dosage, and/or concurrently-administered stimulatory agents.
Gastrointestinal distress: An unpleasant side effect that most naltrexone users notice is gastrointestinal distress. It is understood that naltrexone is capable of antagonizing peripheral opioid receptors, a mechanism that can reverse opioid-induced constipation – and enhance intestinal motility. You may find that the speed by which food moves through your digestive tract is quicker while taking naltrexone than usual – this may result in GI distress.
It also could be that naltrexone irritates the lining of the gut, causing stomach aches, gassiness, and bloating. Some have found that staying hydrated and taking naltrexone along with food can be helpful for reducing gastrointestinal discomfort. Others recommend trying an antacid and/or over-the-counter agent such as Imodium to normalize gastric function, ultimately decreasing distress.
Headaches: Interestingly, there are numerous anecdotes from naltrexone users suggesting that it miraculously cured their chronic headaches and/or migraines. A reduction in headaches resulting from naltrexone may be related to its ability to indirectly reduce nitric oxide levels, which in turn, can influence vasodilation and vasoconstriction of blood vessels. That said, it is necessary to consider that perhaps the decrease in nitric oxide may also cause headaches as a side effect.
Assuming naltrexone reduces nitric oxide concentrations, intracranial blood vessels may have a more difficult time dilating. The difficulties in dilation may contribute to excessive vasoconstriction and the experience of headaches. If you want to reduce the severity of headaches, consider increasing hydration (water intake) and talk to your doctor about possible headache alleviating agents (e.g. ibuprofen).
Heaviness sensations: A less common reaction to naltrexone is experiencing a sensation of heaviness within the body. Some may report that this heaviness is accompanied by fatigue, muscle weakness, and/or pressure. To be sure that the heaviness isn’t a sign of something more serious, be sure to talk it over with your doctor.
It is possible that the action of naltrexone exerted upon the peripheral nervous system leads some individuals to perceive these heaviness sensations. As the neurophysiology adapts to ongoing naltrexone administration, heaviness may diminish. Even if some heaviness is experienced as a side effect, it is usually not regarded as problematic enough to warrant cessation of naltrexone.
Hepatotoxicity: It is medically established that naltrexone may cause liver damage, especially when administered at high doses. The FDA has issued a boxed warning for hepatotoxicity as a potential side effect – and all patients should be cognizant of this possibility. Individuals with preexisting hepatic impairment, obesity, or those at risk for suboptimal liver function should be especially concerned.
Common signs of hepatotoxicity include: dark or tea-colored urine, stomach aches, yellowing of the skin (jaundice), skin rash, lethargy and/or light-colored bowel movements. If you suspect possible hepatotoxicity resulting from naltrexone, seek immediate medical attention. To reduce likelihood of hepatotoxicity, sticking to a low dose is usually helpful. Pre-drug hepatic assessments are generally useful for evaluating whether someone is more susceptible to drug-induced liver toxicity.
Increased thirst: A less common side effect of naltrexone that some may experience is increased thirst. If you constantly feel thirsty after taking naltrexone, and never had this experience before treatment, it could be a drug-related side effect. Some speculate that the increased thirst may be a natural response to dehydration.
Users of naltrexone could become dehydrated if they experience diarrhea. For this reason, increasing water intake may actually be helpful. Obviously if you’re really thirsty, drinking more than usual, and experiencing frequent urination – you may want to scale back. Most people don’t find that the increased thirst [and possibly increasingly frequent urination] is problematic.
Injection site reactions: The injectable format of naltrexone (sold under the brand Vivitrol) may cause pain, swelling, redness, and/or itchiness – around the site of the injection. Other signs of an injection site reaction include: lumps, blisters, open wounds, and scabs. These injection site reactions (e.g. pain) may not be harmful, but should be professionally evaluated as quickly as possible for patient safety.
Should you experience any injection-related pain or other adverse reactions around the injection site, talk to your doctor. It is important to take these reactions seriously due to the fact that if unaddressed, you may require surgery and/or experience tissue death. If the injection-related reactions aren’t serious (as suggested by your doctor), using an ice pack may help attenuate some of the pain and/or swelling.
Insomnia: If after taking naltrexone you are unable to fall asleep, or find yourself waking up frequently throughout the night – it may be that the drug is causing insomnia. Although insomnia is not considered a common side effect, it can occur. To cope with insomnia, you may want to ensure that you’re taking the drug as was directed by your doctor – and at the same time each day.
Assuming you’re following medical instruction (regarding naltrexone administration), and are still experiencing insomnia – it could be that the insomnia is temporary and will subside within a few weeks of continued treatment. If the insomnia becomes unbearable, consider asking your doctor about an adjuvant medication or supplement that promotes sleep – and is safe to take with naltrexone. Also consider taking steps to reduce your stress level, reduce screen-time before bed (e.g. cell phone usage), and adhere to a strict sleep schedule – each of these may help reduce insomnia.
Irregular heartbeat: Although fairly uncommon, some individuals may notice an irregular heartbeat while taking naltrexone. Irregularities may be perceived as abnormally loud heartbeat, skipping of a heart beat, or an internal sensation of a fluttering heart. Although these irregularities may be nothing more than benign palpitations, it is important to report them to a medical professional as soon as detected.
Consider consulting a cardiologist to assess overall cardiac function and to confirm safety of continued naltrexone use. Keep in mind that irregular heartbeat may also be a withdrawal symptom resulting from recent discontinuation of an opioid medication. It is also plausible that naltrexone increased anxiety or nervousness, ultimately leading to palpitations and cardiac irregularities.
Irritability: Certain individuals claim that naltrexone completely transforms their demeanor from one that is pleasant, to one that is cranky and/or irritable. Any drug that affects brain activity and alters neurochemicals has potential to induce irritability in certain individuals. If you feel irritable each time you take naltrexone, you may want to reevaluate (with your doctor) as to whether there may be a different treatment option to consider.
Feeling irritable all the time can make life less pleasurable and interfere with social relationships. You may want to also consider that irritability may be a result of recently discontinuing alcohol or opioids. Many patients using naltrexone are doing so with the intent to help them kick an addictive habit, but fail to recognize that irritability is more common withdrawal symptom (from drugs and alcohol) than a naltrexone side effect.
Joint or muscle pain: A relatively common side effect of naltrexone is joint and/or muscle pain. This pain is often of mild discomfort and may be exacerbated by using abnormally high doses of naltrexone. It is unclear exactly what causes the pain, but it could be that naltrexone alters nociceptive processes by attenuating endogenous analgesic effects of endorphins and enkephalins.
Endorphins and enkephalins are understood to help alleviate pain, but their effects may be blocked by naltrexone – causing us to experience more pain than usual in joints and muscles. It also could be that the side effect of pain occurs as a result of alterations in peripheral blood flow. A decrease in peripheral blood flow coupled with attenuation of endogenous analgesia may explain joint and muscle pain as a side effect.
Lightheadedness: It is possible to feel lightheaded while taking naltrexone, especially if you consume alcohol or use another drug along with it. This lightheadedness may be a result of a contraindication, and will likely be accompanied by dizziness. If you suspect a possible medication interaction or serious contraindication, this should be treated as a medical emergency.
In rare cases the lightheadedness may be a sign that you’re about to faint, as well as possible blood pressure changes. Monitoring your blood pressure and ruling out contraindications should minimize likelihood of lightheadedness. If your doctor doesn’t think the lightheadedness is anything too serious, you may find that lying down [with eyes closed] to help you cope with it.
Mood changes: Studies have shown that naltrexone does not cause depression among users, and may actually improve mood. That said, it is clear that naltrexone antagonizes opioid receptors and modulates dopaminergic mesolimbic pathway activity. As a result, mild depression and/or mood swings may occur in a subset of individuals taking naltrexone.
If you aren’t experiencing the normal degree of pleasure/reward you would from activities such as eating and sex – it’s no wonder that your mood may become more subdued than usual. While it may be that individuals most at risk for treatment-related mood changes often have preexisting neuropsychiatric conditions (diagnosed or undiagnosed), changes in mood could occur in any user. Increased anger, depression, irritability, and even suicidal ideation – have been reported as adverse reactions to naltrexone.
Nausea: Many users will experience a bit of nausea after taking naltrexone. The nausea is generally mild, sometimes so much so that patients don’t realize that it’s even a side effect of their treatment. That said, nausea from naltrexone may reduce appetite, and in more extreme cases, may lead to vomiting.
If you end up becoming so nauseous after each administration to trigger vomiting, it could be a sign of unrecognized tolerability issues; not everyone tolerates every drug. It could also be that you’re taking too high of a dose for your body to handle. In some cases, users may find that nausea diminishes as they continue to use naltrexone – this is likely a result of neurophysiology adapting to the drug.
Other individuals may continue to experience nausea regardless of their dosage and/or how long they’ve been using the drug. Besides taking naltrexone with food, some may want to consider a safe adjunctive antiemetic agent – this should decrease likelihood of nausea and vomiting. Always consult a medical professional if the nausea is severe enough to significantly impair quality of life or occupational performance.
Opioid withdrawal symptoms: Anyone taking naltrexone should understand that they may experience some opiate withdrawal symptoms within minutes of naltrexone administration. Examples of common discontinuation effects of opioids during naltrexone treatment include: abdominal cramping, diarrhea, hallucinations, mood swings, muscle aches, nausea, restlessness, runny nose, and vomiting. If you recently discontinued any opioid medication or are experiencing these while taking naltrexone, be sure to inform your doctor.
While naltrexone can certainly provoke side effects similar to opioid withdrawal symptoms, the symptoms associated with opioid discontinuation will likely be more severe. Since certain withdrawal symptoms can be debilitating and even dangerous – it is important to communicate with your doctor and keep him/her in the loop. If naltrexone is exacerbating these symptoms, a dosage adjustment may be necessary, but in most cases, they’ll improve significantly within several weeks.
Restlessness: A common reason some individuals become increasingly restless while taking naltrexone is not from the drug itself, rather discontinuation of an opioid. Restless leg is a common reaction to opioid discontinuation and may occur for weeks and possibly months after the last administration. Naltrexone has actually been shown as an effective treatment for restlessness among opioid addicts, hence the reason many suggest it improves their restless leg.
Still, a small number of individuals will experience an increase in restlessness that they attribute to the naltrexone. Whether the naltrexone is causing the restlessness or not isn’t clear, but this has been reported by some medical resources as a side effect. If the drug is causing you to become restless – discuss some mitigation strategies with your doctor.
Sexual dysfunction: Some users will experience sexual dysfunction as a naltrexone side effect. Dysfunction may be characterized by decreased libido, delayed orgasm, or inability to orgasm. The decreased libido may be related to a decrease in dopaminergic mesolimbic pathway activation – ultimately generating less pleasurable reward from normally highly-pleasurable activities (e.g. sex).
In addition, sexual dysfunction could be related to changes in concentrations of neurotransmitters and/or activation of certain regions of the brain. Since some naltrexone users report fatigue as a side effect, it may be that lower arousal also plays a role in aspects of sexual dysfunction such as erectile dysfunction or inability to orgasm. If the sexual dysfunction from naltrexone is impairing your relationship or quality of life, discuss it with a doctor; there may be adjunctive medications that can be used to improve sexual function.
Skin rash: Those receiving naltrexone injections may experience a skin rash around the injection site or potentially widespread throughout the entire body. The rash may be a result of skin irritation associated with the injectable format of the drug, but also could be the sign of an allergic reaction. Skin rash in an allergic reaction may be accompanied by other symptoms such as swelling and shortness of breath.
If you experience a skin rash, realize that it could be the sign of an adverse event and that it is smart to seek immediate medical attention. Keep in mind that it’s not always predictable as to whether the rash will be isolated to a particular area (such as around the injection site) or widespread. Common features of the rash may include patches of redness, changes in skin pigmentation, itchiness, and/or puffiness.
Sleep disturbances: You may notice abnormalities and/or disturbances in sleep while taking naltrexone. Examples of such disturbances include bizarre or vivid dreams and/or frequently waking up during the night. It is possible that naltrexone alters sleep architecture, amount of time spent in each stage of sleep, and/or a user’s brain waves during sleep – all of which may cause some sleep problems or abnormalities.
If you notice that your sleep is disturbed or you are unable to get enough sleep while taking naltrexone, talk to your doctor about an adjunctive sleep aid. Additionally, consider that for certain versions of naltrexone, the time of day at which it is administered may alter circadian rhythms, thereby influencing sleep. For this reason, modifying the specific time of administration may also be useful for minimizing drug-related sleep disturbances.
Stomach aches: A significant number of naltrexone users report mild-to-moderate severity stomach aches as a side effect. It is difficult to pinpoint the specific reason(s) as to why stomach aches occur from naltrexone. One possibility is that naltrexone irritates the stomach lining and/or alters gastric motility, ultimately leading to gastrointestinal distress and stomach pain.
If you’re experiencing stomach aches from naltrexone, some resources suggest that eating a bit of food and/or only taking it after a large meal may be helpful. Another strategy that some users suggest to be effective for reducing naltrexone-related stomach aches is administration of an antacid [under medical supervision]. In most cases, the stomach aches from naltrexone are bearable and aren’t severe enough to warrant treatment discontinuation.
Stiffness: A subset of individuals may report stiffness and/or experience muscular rigidity while taking naltrexone. The side effect of stiffness is usually mild, but may be accompanied by muscle and/or joint aches. You may notice stiffness in one specific area such as the neck, or may notice it in various areas throughout your body.
Although uncommon, certain naltrexone users may experience such extreme stiffness, that a doctor recommends discontinuing treatment. Stiffness may improve with increased hydration, administration of an adjunct, and/or a hot shower. Individuals with preexisting musculoskeletal and/or joint disorders may be most at risk of stiffness as a side effect. Changes in peripheral nervous system activation and blood flow may contribute to stiffness as a side effect.
Sweating: You notice that you sweat a bit more than usual while taking naltrexone than in the past. This may be due to the fact that the drug is modulating neurophysiology in such a way that the sweat glands are stimulated to produce more sweat than usual. It also could be that naltrexone indirectly affects thermoregulatory processes, thereby slightly altering bodily temperature to trigger the increase in sweat.
Users of naltrexone should also consider that they may sweat profusely from recent discontinuation of an opioid; this shouldn’t be considered a naltrexone side effect. If you sweat excessively while taking naltrexone, you may need to increase water intake to avoid dehydration. The side effect of sweating is generally easy to deal with for most naltrexone users and may be less severe or likely to occur at lower doses.
Vision changes: Though the basic mechanisms associated with naltrexone are well-understood, it is unclear as to why certain users experience visual disturbances (e.g. blurred vision) as a side effect. Those experiencing visual changes during treatment may perceive that naltrexone is somehow damaging their eyesight or visual function. Since there aren’t any known cases of naltrexone being hazardous to sight, it is unlikely that naltrexone deleteriously affects eyesight.
Nonetheless, if you are concerned about potential eyesight changes resulting from naltrexone, consult an ophthalmologist for a professional opinion. It is possible that naltrexone reduces arousal and/or simultaneously modulates activity within the visual processing centers of the brain – leading some to perceive visual changes. These vision changes are likely benign, but certainly capable of catching your attention.
Vomiting: An emetic reaction such as vomiting is commonly reported by those taking naltrexone. Those who end up vomiting after taking naltrexone often experience significant nausea, possibly along with upset stomach, lightheadedness, and dizziness. If you are unlucky enough to vomit each time you take naltrexone, it may be a sign that your body is unable to tolerate the drug.
That said, it also could be that you’re taking too high of a dose for your body to tolerate. In this case, starting with a lower dose and titrating upwards may minimize likelihood of vomiting. Assuming allergic reactions to naltrexone are ruled out, the body may eventually adjust to the drug and vomiting may diminish. In the meantime, an antiemetic adjunct may prevent vomiting and reduce likelihood of concurrent nausea.
Weakness: After taking naltrexone, it may feel as if you’ve suddenly become weak. This weakness may be temporary, but may also be an unwanted side effect. It isn’t known why some individuals experience weakness – it could be related to changes in peripheral blood flow and physiological arousal.
Many people taking naltrexone report fatigue and/or tiredness along with muscle aches – the combination of which may be perceived as weakness. Other than increasing energy levels with a doctor recommended stimulatory adjunct and/or dosage modifications, the weakness may be difficult to overcome. Sometimes the weakness may subside completely after several weeks of naltrexone usage.
Weight loss: When considering that naltrexone is an important element in Contrave (a weight loss drug), it shouldn’t be surprising that some users report Naltrexone causes weight loss. There are numerous reasons as to why weight loss occurs as a side effect – one of which may be that users don’t derive as much pleasure from food consumption, ultimately resulting in reduced caloric intake during treatment. The decrease in pleasure associated with food consumption may be related to naltrexone’s indirect modulation of the dopaminergic mesolimbic pathway.
As a result, individuals may report fewer overall cravings – hence the reason naltrexone is often useful for those with compulsive eating. That said, weight loss may not only result from an attenuated pleasure/reward response associated with food. It may be that some users lose weight from uncontrollable, ongoing diarrhea; thankfully this usually can be mitigated with an adjunct (e.g. Imodium).
Moreover, the weight loss experienced from naltrexone may be most significant among individuals who were overweight (or obese) before treatment. If you were not significantly overweight before treatment, you may notice very little weight fluctuation prior to treatment. Although most may perceive weight loss as a positive or healthy side effect, some already-skinny individuals may dislike it.
Note: If you have questions regarding a side effect resulting from naltrexone, be sure to contact a medical professional.
- Source: http://www.ncbi.nlm.nih.gov/books/NBK64042/
- Source: https://www.vivitrol.com/About/SafetyAndSideEffects
Variables that influence Naltrexone side effects
When contemplating the severity and number of side effects that you’re likely to experience, it is useful to consider variables that are known to influence side effects. Some of the most critical variables to consider in regards to influencing side effects of naltrexone include: dosage, co-administered substances, route of administration, duration of usage, and the specific individual. It is these variables that account for differences in side effects among naltrexone users.
Dosage (High vs. Low)
The dosage of naltrexone administered can influence the number and severity of side effects experienced. In general, the higher the dosage of naltrexone ingested [for the management of alcohol or opioid dependence], the greater the likelihood of side effects. Contrarily, the lower the dosage of naltrexone ingested, the less likely a user will experience side effects.
There are numerous reasons as to why someone taking a higher dose of naltrexone will be at increased risk of side effects. Whenever a larger dose of naltrexone is ingested, it exerts a more significant effect upon the user’s neurophysiology. To put things in perspective, a dosage of 100 mg naltrexone will antagonize opioid receptors to a greater extent than a dosage of just 25 mg.
As a result of the greater neurophysiological modulation facilitated by a high dose, side effects often increase in number and often severity. A minor side effect such as nausea resulting from low dose naltrexone (e.g. 25 mg) may become significantly more intense at a higher dose (e.g. 100 mg). The body may be able to tolerate naltrexone up to a certain dose without side effects, but once that threshold dose is exceeded, the body reacts with side effects.
The likelihood that you’ll exceed a threshold of tolerability is greater at high doses and lesser at lower doses. Another reason side effects are more prominent at high doses may be due to pharmacokinetic processes such as absorption, metabolism, distribution, and elimination. When a higher dose of naltrexone is ingested, these processes become less efficient because there’s a larger amount of the drug for the body to handle.
At lower doses, less of the naltrexone necessitates absorption, metabolism, distribution, and elimination – hence these processes are more efficient. As a result of the increased efficiency, pharmacokinetic-related side effects may be reduced at the lower doses. It is also important to consider that dosing may affect activation of internal mechanisms implicated in maintenance of homeostasis.
Since a higher dose of naltrexone likely shifts neurophysiology further from its homeostatic baseline, a more significant neurophysiological compensatory response may be generated via internal mechanisms in effort to restore homeostasis. Theoretically, this compensatory response should be greater after a higher dose compared to a lower dose, ultimately provoking more side effects. Overall, there are many reasons a high dose naltrexone should experience more side effects than a low dose user.
Co-administration of another substance (drug or supplement) along with naltrexone may influence its side effects. Certain co-administered agents (drugs or supplements) are understood expedite the speed of naltrexone metabolism, whereas others are thought to prolong it. Faster metabolism as a result of an interaction with another substance may result in more severe, yet shorter-lived side effects.
On the other hand, abnormally slow metabolism of naltrexone resulting from an interaction may result in longer-lasting, unwanted side effects. Since naltrexone is not metabolized extensively via CYP450 isoenzymes, there are generally fewer hepatic interactions as compared to other drugs. That said, certain agents may still increase hepatic burden, likelihood of hepatotoxicity, and related side effects.
Additionally, the effect of naltrexone upon neurophysiology may be potentiated or attenuated by co-administered substances. A substance that potentiates the opioid receptor antagonism provided by naltrexone will likely induce a greater number of side effects at a smaller dose. Oppositely, a substance that attenuates the opioid receptor agonism of naltrexone may reduce some of the side effects (as well as efficacy) of the drug at standard doses.
Your doctor should know whether any medications you’re taking along with naltrexone are contraindicated and/or associated with increased likelihood of interactions. One well-documented reaction to be aware of is if you’ve recently discontinued (or are still taking) an opioid agonist – along with naltrexone. The naltrexone will displace the opioid agonist from receptor sites, thereby triggering premature [and perhaps unexpected] opioid withdrawal symptoms.
To avoid this unwelcome reaction, most professionals advise waiting up to 14 days after the final dose of an opioid agonist before initiating naltrexone treatment. In addition, it is necessary to consider that various substances administered along with naltrexone may not interact with it, but may increase or decrease the occurrence of some side effects. As a hypothetical example, let’s say that you experience sleep disturbances as a side effect of naltrexone.
If you were to drink a cup of coffee prior to bed, you may find your naltrexone-induced sleep disturbances worsened because the caffeine late at night also interferes with sleep. On the other hand, if you were to utilize an adjunct hypnotic, you may find that your naltrexone-induced sleep disturbances diminished. In each of these examples, the co-administered agents may not necessarily interact with naltrexone, rather they amplified or attenuated the hypothetical sleep disturbance side effect, respectively.
Finally, it is necessary to underscore the fact a subset of individuals may mistakenly attribute the side effects of another drug to naltrexone. If you’re taking a cornucopia of pills each day along with naltrexone, you may want to ensure that they’re all safe to take and ask your doctor whether they could be causing side effects that you perceived to be from naltrexone. A medical professional should help you straighten out all possible contraindications, interactions, and whether other medications are attenuating or potentiating naltrexone side effects.
Duration of Use
The cumulative duration over which an individual has used naltrexone may also dictate the side effects that he/she experiences. Someone that’s been using the drug for an extremely short-term may report a completely different set of side effects than if the same individual had been using it for a long-term. Moreover, the severity of side effects may change in respect to the total duration over which naltrexone has been administered.
Short-term: In some cases, a short-term naltrexone user may experience more side effects than a long-term user for a couple of reasons. Firstly, the short-term user’s neurophysiology may not have adapted to the effects of naltrexone (as would occur in a longer-term user), and the lack of adaptation may result in more side effects. Secondly, short-term users may commence treatment at too high of a starting dose, resulting in side effects associated with suboptimal dosage optimization.
It should also be considered that the opposite may occur as well: short-term users may experience fewer side effects than some long-term users. Over a shorter-term, users may be administering smaller doses (than had they been using for a long-term), and as was already discussed, less side effects occur at smaller doses. Furthermore, cumulative neurophysiological alterations as induced by short-term naltrexone may be less substantial than a long-term, provoking fewer side effects.
Moderate term: After a moderate term of several months, users may notice that some of the side effects occurring at the beginning of treatment have diminished in intensity. This may be due to the fact that the body has had a longer-term to adapt to the regular ingestion of naltrexone. Conversely, it is also plausible to consider that new side effects may have emerged as a result of a longer total duration of neurophysiological modulation.
Additionally, after several weeks of usage, dosage may have been increased from a smaller dose of 25 mg per day to around 50 mg per day. This doubling in dosage may yield a greater number of side effects due to the increased impact of the drug upon neurophysiology. In other cases, side effects may remain relatively constant from short-term to moderate-term.
Long-term: Most individuals that have been taking naltrexone for a long-term tend to tolerate it well – otherwise they wouldn’t have continued it for a long-term; they would’ve discontinued and opted for another intervention. For this reason, it is logical to assume that many long-term users tolerate naltrexone well and don’t experience many debilitating side effects. After several months (or years) of treatment, the user’s neurophysiology will have adapted to the naltrexone.
The dosage will also likely have been optimized, thereby minimizing likelihood of side effects associated with suboptimal dosing. Still, long-term users may build up a tolerance to lower doses, resulting in dosage increases – which may increase some side effects. Further, it is possible that certain cumulative neurophysiological adaptations in reaction to ongoing naltrexone administration may be deleterious, ultimately facilitating emergence of adverse long-term side effects.
Format (Injection vs. Oral)
Naltrexone is manufactured in multiple formats including: oral tablets (sold under the brand Revia) and injections (sold under the brand Vivitrol). While both forms of the drug are considered efficacious for the management of alcohol and opioid dependence, patients that use each format may find that they prefer one over the other as a result of fewer side effects and/or greater efficacy. For this reason, consider that some of the side effects resulting from the injectable format (Vivitrol) such as: skin irritation, minor swelling, and/or soreness around the injection site – will not occur with the oral format.
Conversely, there may be side effects that occur only with the oral tablets (Revia) that may be averted by administering the injections. Unless you’ve tested both injectable and oral formats, it will likely be difficult to know definitively whether one format yields fewer side effects than another. This is because certain format-specific side effects may be a result of interindividual differences in neurophysiology, leading a subset of users to find the oral pills more tolerable, while others find the injections more tolerable.
For example, you may try the injectable naltrexone and notice that it makes you feel nauseous and lightheaded, whereas the oral tablets don’t. Alternatively, you may try the oral tablets and experience severe insomnia and dizziness, but may try the injections and not experience either of these side effects. That said, a subset of patients may find that naltrexone oral (Revia) and injection (Vivitrol) provoke the exact same side effects; in this case format cannot be considered an influencer of side effects.
It should also be noted that in countries outside of the United States, naltrexone is available in the form of implants. These implants consist of pellets that deliver the naltrexone chemical slowly over a span of 2 to 6 months. Understand that some side effects associated with naltrexone implants may be somewhat different than those experienced with the injections and oral tablet formats.
It is necessary to consider that numerous individual factors influence the side effects that someone experiences while taking naltrexone. Assuming two individuals began taking the same dose of injectable naltrexone at the exact same time – without any other substances, we’d expect the number of side effects experienced by each user to be similar. However, it may turn out that side effects reported by these two individuals are significantly different – one may report dizziness and the other may report vomiting.
What explains the differences in side effects between two users administering the same naltrexone format and dose for an equal duration? Individual factors such as: administration details, body size, genetics, medical conditions, sleep, and stress level. These factors should always be taken into consideration when contemplating why you’re experiencing various naltrexone side effects.
Administration details: The specific details of naltrexone administration can make a significant difference in regards to side effects. If you’re taking the oral format – you may want to assess whether you’re taking it at the exact same time every day or whether you end up taking it at a slightly different time each day. Irregular administration frequency such as taking the drug in the morning one day, then at night on another – may provoke more side effects than usual.
Additionally, consider that taking naltrexone in the morning may yield different side effects than had you taken it in the evening. If the drug makes you drowsy – you may not notice the drowsiness as much at night, but may notice it more in the morning if you’re expected to work. In addition to regularity of administration and timing, whether you take it with food or on an empty stomach – could influence side effects.
Some individuals may find that if they take naltrexone after a big meal – various side effects are less noticeable than if they take it on an empty stomach. Others may find that they tolerate the drug better when they take it on an empty stomach. It should also be considered that the type of food consumed with naltrexone, as well as user hydration – may make a slight difference in terms of side effects.
Body size: The body size of the individual taking naltrexone in relation to the dosage administered could influence side effects. A 50 mg dose in a petite 110-pound female may pack a greater punch than the same 50 mg dose in a 300-pound male, inevitably causing more unwanted side effects. As a general rule of thumb, the smaller a person is in relation to the dosage of naltrexone administered – the more susceptible they may be to side effects.
It may also be that percentages of muscle mass and/or body fat affect the drug’s pharmacokinetics, as well as side effects. Drugs that are highly lipophilic tend to get stored in body fat for a longer duration, whereas drugs that are highly hydrophilic may remain in muscle tissue for a longer duration (due to the fact that muscle contains 75% water and fat only 10%). For this reason, it is necessary to speculate that variations in fat and muscle could influence its side effects.
Duration since cessation: The duration since you last used alcohol and/or opioids can affect the side effects that you’ll experience from naltrexone. Medical documentation recommends waiting up to 14 days until you’ve fully ceased usage of an opioid to begin treatment with naltrexone. If you only waited a few days after opioid cessation to begin naltrexone, it will dislodge any remaining agonists (and their metabolites) from receptor sites, ultimately triggering an array of unexpected opiate withdrawal symptoms.
You may inadvertently perceive these withdrawal symptoms as side effects of naltrexone. It is also necessary to consider that the shorter the duration since you discontinued either opioids or alcohol, the greater the likelihood that you’re still experiencing opioid or alcohol withdrawal symptoms, respectively. If you start treatment with naltrexone while in withdrawal, you may have a difficult time distinguishing withdrawal symptoms of other substances from naltrexone side effects.
The possibility that post acute withdrawal syndrome (PAWS) could occur may also make it difficult to determine whether the PAWS or naltrexone are to blame for certain unwanted effects. Generally, the longer it’s been since you last used alcohol or opioids, the easier it will be to know whether the effects you’re experiencing are from naltrexone or withdrawal.
Genetics / Epigenetics: It is understood that genetic expression dictates how well someone is able to tolerate certain drugs. Genetic polymorphisms of hepatic isoenzymes (e.g. CYP450) often cause some individuals to metabolize drugs at a faster or slower rate than the norm. As a result of these genetic variants influencing metabolism speed, susceptibility to experience side effects (and adverse reactions) often increases.
Although polymorphisms of genes encoding for hepatic CYP450 isoenzymes aren’t thought to affect metabolism speed naltrexone, it is necessary to consider that expression of non-hepatic genes could dictate tolerability. Some of these non-hepatic genes may increase ability to tolerate naltrexone, whereas others may decrease this ability. Moreover, epigenetic expression may influence neurophysiological processes in such a way that tolerability is affected; one epigenetic signature may increase tolerability, whereas another may decrease it.
Medical conditions: Anyone with a comorbid medical condition (in addition to alcohol or opioid dependence) taking naltrexone may be more susceptible to side effects. In fact, certain medical conditions such as hepatic impairment are contraindicated with higher doses of naltrexone. This is because higher doses of naltrexone are thought to take a toll on liver function, potentially exacerbating any preexisting impairment – thereby generating side effects.
Other medical conditions such as those with Hashimoto’s thyroiditis, hypothyroidism, and various autoimmune disorders may be at increased risk of side effects – especially at higher doses. This is because naltrexone may decrease autoimmunity, which in turn upregulates production of endogenous thyroid, and decreases need for exogenous thyroid medications. Patients concurrently administering thyroid medications may experience side effects while taking naltrexone as a result of excess thyroid (or hyperthyroidism).
Those that have received organ transplants (and consequently administering an immunosuppressive agent) may be highly susceptible to adverse reactions with naltrexone. Additionally, it should be considered that anyone with a preexisting neuropsychiatric disorder may be more susceptible to psychiatric side effects due to naltrexone’s modulation of neurochemistry. If you have a medical condition, your doctor should know whether it’s safe for you to be using naltrexone, as well as whether you are at increased risk of side effects compared to the normal population.
Sleep / Stress: Individuals that fail to get sufficient sleep or quality sleep – may be at increased risk of naltrexone side effects. Poor sleep alters an array of neurophysiological activity, ranging from hormone levels to neurotransmitters. Those who consistently get poor sleep during naltrexone treatment may find that their bodies are less able to handle naltrexone, and as a result, side effects occur.
A similar experience may occur among those with abnormally high stress. If you’re overly stressed, it can affect neurotransmission, hormones, and even immune function. For this reason, it is necessary to consider that your body may be more sensitive to the administration of naltrexone than if you were less stressed.
Someone taking naltrexone may also find that certain side effects are potentiated (or possibly attenuated) based on sleep and stress. For example, someone already experiencing anxiety as a side effect may find that the anxiety is amplified 4-fold from lack of sleep or work-induced stress. Lastly, naltrexone users may want to evaluate whether the side effects they’re experiencing could be more related to poor sleep or stress (rather than the actual medication).
Naltrexone: Do the benefits outweigh the side effects?
Whenever taking a pharmaceutical drug like naltrexone, it is important to assess whether its therapeutic benefits outweigh its side effects. For a lucky subset of users, naltrexone will provide significant therapeutic benefit in the management of alcohol/opioid dependence and provoke zero noticeable side effects; this is the utopian outcome that all patients want. Conversely, an unlucky subset of naltrexone users may experience debilitating side effects and experience zero therapeutic benefit; this is a dystopian outcome that no one wants.
Most individuals taking naltrexone won’t experience the aforestated utopian nor dystopian outcomes, rather they’ll experience a combination of therapeutic benefits and side effects. Some users will report that naltrexone is highly effective for managing their substance dependence, but also that they experience several unwanted side effects. In this case, assuming the unwanted side effects aren’t overly debilitating, continuation of naltrexone is a logical choice.
For those experiencing less significant benefit from naltrexone, it may be tougher to decide whether to continue treatment. If the therapeutic effect provided by naltrexone is relatively modest and overshadowed by disconcerting side effects, discontinuation of naltrexone (possibly in favor of another intervention) may be a smart choice. In the event that you experience no side effects, but also zero therapeutic effect – it also makes little sense to continue treatment.
Understand that it is ultimately up to you to decide whether the benefits of using naltrexone outweigh the drawbacks, as well as whether it’s worth continuing. You may want to consider maintaining a journal throughout treatment with naltrexone to track its efficacy, as well as any side effects that you experience. This journal may serve as a useful reference when discussing how well you’re responding to naltrexone treatment with your doctor.
Possible ways to reduce Naltrexone side effects
If you’re experiencing unwanted side effects from naltrexone, consider some possible side effect mitigation strategies. Prior to implementation of any side effect mitigation strategy listed below, consult a medical professional to confirm safety and hypothesized efficacy. That said, most of the strategies for attenuating side effects are common sense, including: dosage reduction, format change, altering administration parameters, co-administering substances, eliminating unnecessary substances, and continued usage.
- Dosage reduction: It’s no secret that side effects are more likely to occur after a higher doses of naltrexone than lower ones; higher doses modulate neurophysiology more substantially. For this reason, if you’re experiencing unwanted and/or severe side effects, you may find it helpful to scale back on your dosage. The neurophysiological modulation is less significant, meaning side effects should be less problematic. Some individuals may find it helpful to start at an extremely tiny dose and titrate upwards until they’ve found the “minimal effective dose” – or lowest amount of the drug necessary to manage alcohol and/or opioid dependence. Ensuring that you’re taking the lowest dosage necessary may require a bit of extra experimentation and time, but may be worth it for fewer side effects.
- Format change: There are multiple formats of naltrexone available for usage, including: an extended-release injection (brand name “Vivitrol”) AND an orally-administered tablet (brand name “Revia”). Certain side effects may be format-specific (e.g. skin irritation from injections) and may vary based on the user. Some individuals may find that they tolerate the injectable naltrexone better than the oral tablets, while others may report the opposite. If you’ve only tested one format of naltrexone, consider that trying the other format may yield fewer side effects.
- Adjust administration parameters: Adjusting the parameters associated with administration of naltrexone may reduce certain side effects. Some parameters that you may consider tweaking include: timing of administration (morning, afternoon, evening), consistency of administration, as well as whether it is taken with food or on an empty stomach. Those taking the drug in the morning and experiencing side effects may want to ask their doctor about trying it in the afternoon or evening to determine whether some side effects diminish as a result of a change in timing of administration. If you’ve been taking naltrexone on an empty stomach, you may want to see if taking it with food (or after a meal) reduces some side effects – and vice-versa.
- Co-administered substances: Those experiencing side effects after optimizing dosage and format should consider asking their doctor about safe adjuvant interventions to offset some of the side effects. The specific recommended adjunct substances to administer will be patient-specific based on the side effects reported from naltrexone. For example, someone experiencing somnolence as a side effect may find caffeine to be a helpful side effect attenuator. On the other hand, someone experiencing insomnia as a side effect may benefit more from a hypnotic agent.
- Discontinuation of substances: If you’re concurrently administering an array of drugs and/or supplements along with naltrexone, consider that certain agents may be contraindicated. Others may be interacting with it, amplifying the severity of certain side effects. It is also possible that concurrently administered substances may be causing side effects that you’re mistakenly attributing to naltrexone. To reduce likelihood of side effects, it may be useful to cease usage of any drugs and/or supplements that aren’t medically recommended.
- Continue using: If you recently began using naltrexone, consider that some of the side effects you’re currently experiencing may diminish and/or subside altogether with continued naltrexone usage. Anytime a new medication such as naltrexone is introduced, the body may go through an adjustment phase. This adjustment phase could last several days or weeks – depending on the user. Once the body has adapted or learned to accommodate the regular presence of naltrexone, side effects may lessen.
Have you experienced Naltrexone side effects?
If you’ve experienced side effects from naltrexone, feel free to share them in the comments section below. Mention the specific naltrexone side effects do you consider most noticeable and/or debilitating. To help others get a better understanding of your situation, include some personal details such as: dosage of naltrexone you take, format of naltrexone (e.g. oral tablet, injectable, etc.), how long you’ve been taking it, and any specific drugs or supplements you use along with it.
For those that have used naltrexone for an extended duration, have you found that the severity of side effects changed (increased or decreased) with time? If you’ve tested multiple naltrexone formats, did you find that one yielded fewer side effects than another? Additionally, if you take other drugs or supplements along with naltrexone, have you considered that the side effects you’re currently attributing to naltrexone may actually be from other substances – or possibly an interaction?
Should you know of any coping strategies and/or tricks for dealing with naltrexone side effects (other than those mentioned above), feel free to add them in your comment – it may help a fellow naltrexone user. In any regard, while most individuals will find naltrexone to be tolerable with few unwanted side effects, others may have a less tolerable experience. If your body is reacting poorly to naltrexone and the side effects are overwhelming, your doctor should be able to come up with an alternative intervention.