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ZzzQuil Side Effects & Adverse Reactions (List)

ZzzQuil is an over-the-counter medication utilized most frequently to enhance sleep quality among individuals with allergies or the “common cold.”  However, because ZzzQuil is a potent sleep aid, individuals without health problems sometimes use the medication to help manage insomnia.  On occasion, ZzzQuil is even administered for the treatment of motion sickness and extrapyramidal symptoms associated with neuropsychiatric disorders (e.g. Parkinson’s disease).

The primary active ingredient in all ZzzQuil formulations is diphenhydramine, an antihistamine.  More specifically, diphenhydramine binds to the H1 histamine receptor and functions as an inverse agonist whereby it agonizes the H1 receptor to induce the opposite effect of a conventional agonist.  Essentially, this H1 inverse agonism is what alleviates symptoms such as sneezing, runny nose, watery eyes, hives, skin rash, itchiness, and various allergy-like symptoms.

ZzzQuil ingredients

  • Diphenhydramine (50 mg per 30 mL)
  • Alcohol: 10%. Certain formulations of ZzzQuil such as Calming Vanilla Cherry Liquid and Warming Berry Liquid contain 10% alcohol. Other formats such as LiquiCaps and Alcohol-Free Liquid do not contain alcohol.
  • Miscellaneous: Citric acid anhydrous, FD&C Blue No. 1, FD&C Red No. 40, flavor, High fructose corn syrup, Polyoxyl 40 stearate, Propylene glycol, Purified water, Saccharin sodium, Sodium benzoate, and Sodium citrate.

Although many people find ZzzQuil a very effective over-the-counter medication for managing their medical symptoms, most users will experience some ZzzQuil side effects.  These side effects can be relatively mild for some, yet downright debilitating for others.  In fact, some individuals might even end up with severe unexpected adverse reactions to ZzzQuil.

ZzzQuil Side Effects (List of Possibilities)

If you’re already using ZzzQuil or are considering it to reduce medical symptoms (e.g. allergies) and/or enhance your sleep, you should be cognizant of potential ZzzQuil side effects that can occur.  Understand that ZzzQuil side effects are largely subject to interindividual variation, meaning: the specific side effects, total number of side effects, and severity of side effects – will be contingent upon the specific user.  More specifically, the ZzzQuil side effects that you experience will be unique to you; others may have a different experience.

Nevertheless, due to the mechanism of ZzzQuil’s action, it is known that certain side effects are more common among users than others.  According to data released by the manufacturer, the most common ZzzQuil side effects include: somnolence (sleepiness); drowsiness; dry mouth; fatigue; dizziness; and poor concentration.  Included below is a full list of side effects associated with ZzzQuil.  If you ever have questions about ZzzQuil side effects, it is recommended to consult a medical professional.

  • Brain fog: Most ZzzQuil users will experience some degree of “brain fog” or unclear thinking while under its influence. If you feel mentally foggy under the influence of ZzzQuil, realize that this is a normal reaction as a result of the H1 inverse agonism exerted by diphenhydramine.  If you’re using a combination containing 10% alcohol, the sedative effect of alcohol mediated by GABA(A) receptors may play also contribute to the foggy thinking.  In short, ZzzQuil is not a medication to use if your goal is to maintain mental clarity.  That said, the brain fog will eventually fade as the drug exits your system.
  • Cognitive impairment: In addition to the aforementioned “brain fog,” many ZzzQuil users will experience cognitive impairment. It is known that the neurotransmitter histamine plays a role in maintaining arousal (alertness and vigilance), as well as various cognitive processes.  When the effects of histamine are blocked by the diphenhydramine within ZzzQuil, the user’s arousal decreases to a suboptimal level for cognitive performance.  Predictably, many ZzzQuil users report poor concentration and/or memory problems while under its influence.
  • Dizziness: Some individuals will become noticeably dizzier than usual after taking ZzzQuil. The dizziness may be accompanied by lightheadedness and attributable to decreased histaminergic activity within the central nervous system (CNS).  Among those who use ZzzQuil formulas containing alcohol, dizziness could be a reaction to the ingestion of alcohol; alcohol is known to disrupt equilibrium by affecting the semicircular canals of the ear.  Other possible causes of dizziness as a side effect include changes in blood flow throughout the brain and/or low blood pressure.
  • Drowsiness: Because ZzzQuil is a sleep aid, it should come as no surprise that one of its most common side effects is drowsiness. The technical definition of drowsiness is feeling a combination of lethargy and sleepiness.  Obviously if you are drowsy from ZzzQuil, it is recommended to abstain from operating motor vehicles and/or machinery.  For most users, drowsiness is a precursor to a good night’s sleep.
  • Dry mouth: A somewhat unpleasant ZzzQuil side effect that you might experience is dry mouth. The severity of dry mouth will vary among users, however, most individuals who experience this side effect will report that it’s barely noticeable – rather than excessive.  If you experience severe dry mouth, you may want to find a ZzzQuil alternative.  Moreover, if you’re a long-term ZzzQuil user who experiences dry mouth as a side effect, you may want to visit your dentist to ensure that your mouth stays healthy – as cavity risk increases when the mouth is chronically dry.
  • Fatigue: Under the influence of ZzzQuil, you will likely experience some fatigue as a side effect. The fatigue will probably emerge within 25 minutes of taking the medication, and may persist even after the drug is out of your system.  Due to the fatigue, you won’t want to take ZzzQuil if you need physical energy (such as for a workout) and/or mental energy (such as to function at work).
  • Headaches: While some individuals find that ZzzQuil alleviates their headaches, others report that ZzzQuil causes headaches and/or migraines. Individual brain chemistry and genetic predisposition likely determine who will experience a headache on ZzzQuil – and who won’t.  If you experience a headache from ZzzQuil, you may want to evaluate whether you’re adequately hydrated.  Assuming you’re drinking enough water, the headaches might be due to changes in blood flow within certain regions of the brain.
  • Lightheadedness: Certain ZzzQuil users report lightheadedness as a side effect. In the event that you become lightheaded after taking ZzzQuil, it is recommended to check your blood pressure.  Sometimes ZzzQuil can cause low blood pressure, which in turn, may lead to lightheadedness, dizziness, and possibly even fainting episodes.  For most individuals, the lightheadedness that occurs as a side effect won’t be overwhelming or severe.
  • Sedation, sleepiness, somnolence: At standard doses, most ZzzQuil users will experience some degree of sedation, sleepiness, and/or somnolence. If ZzzQuil didn’t induce sleepiness as an effect, it would likely be ineffective as a sleep aid.  The sedation and somnolence are induced primarily by diphenhydramine’s inverse agonism upon H1 receptors.
  • Unsteadiness: ZzzQuil may cause unsteadiness or balance issues as a side effect. The unsteadiness or poor balance is usually a result of decreased arousal mediated by H1 receptors, and possibly GABA(A) receptors (in ZzzQuil formats containing alcohol).  That said, unsteadiness might be related to changes in activity within the semicircular canals of the ear, altered vestibular nerve signaling, reduced blood pressure, and/or blood flow changes within the brain.

Note: The above list of ZzzQuil side effects may be incomplete.  If you know of additional side effects that can occur while using ZzzQuil, mention them in the comments.

ZzzQuil Adverse Effects & Reactions

Included below is a list of ZzzQuil adverse effects and reactions.  For many of these adverse effects, the frequency at which they occur in the general population remains unknown.  That said, of the adverse effects that have been studied, most occur at rates between 0.01% and 0.1% – making them extremely unlikely to occur.  If these adverse effects occurred more frequently, it’s unlikely that ZzzQuil would be approved for over-the-counter retail.  Nonetheless, if you or someone you know experiences adverse effects from ZzzQuil – seek emergency medical attention.

  • Blood pressure reduction: As a CNS depressant, ZzzQuil has potential to induce hypotension (or low blood pressure) in a subset of users. When taken at standard doses, low blood pressure is unlikely to occur.  However, if administered at higher-than-recommended dosages (e.g. with the intent of getting “high”), low blood pressure may be more likely.  Low blood pressure could result in dizziness, lightheadedness, fainting, or blacking out.  If you have a history of blood pressure abnormalities or suspect low blood pressure on ZzzQuil, talk to a medical doctor about this reaction.
  • Blurred vision: Although ZzzQuil can help reduce eye watering and sometimes prevents blurred vision attributable to allergies, other times the drug could actually cause blurry vision. Blurred vision as a side effect or adverse effect of ZzzQuil might be related to changes in neurotransmission within regions of the brain implicated in visual processing.  That said, it’s also possible that constituents of ZzzQuil are adversely affecting your eyes such as by altering eye pressure.  For this reason, it is recommended to see an eye doctor (ophthalmologist) for evaluation if you’re dealing with blurred vision as a ZzzQuil side effect.
  • Confusion: It was mentioned that many people experience brain fog (unclear thinking) and cognitive impairment as ZzzQuil side effects. Even with the brain fog and cognitive deficits, most individuals who use ZzzQuil won’t experience pure “confusion.”  That said, some individuals might end up with extreme mental confusion as an adverse reaction to ZzzQuil.  Persons who use abnormally high doses of ZzzQuil, mix ZzzQuil with other substances, and/or individuals with neuropsychiatric conditions – may be at increased risk of confusion as a reaction.
  • Constipation & indigestion: Certain individuals might experience constipation as a side effect of ZzzQuil. Constipation may be related to a drug-induced slowing of food through the digestive tract.  As a result of this digestive slowing, some persons might experience constipation – perhaps with indigestion.  If you become constipated while using ZzzQuil, you may want to eat more fibrous foods, drink more water, and stay active throughout the day before using ZzzQuil at night.
  • Convulsions, tremors, shakiness: Convulsions, or sudden irregular bodily movements, may occur as a reaction to ZzzQuil. If you have a history of convulsions or neurological disorders, you may be at increased risk for experiencing convulsions while using ZzzQuil.  In the event that you experience a convulsion, tremor, or twitching after using ZzzQuil, this should be reported to a medical professional as soon as possible.
  • Diarrhea: For certain users, ZzzQuil may irritate the gastrointestinal tract such as to speed up the movement of food through the digestive tract and/or provoke bowel movements, ultimately causing diarrhea. If you experience diarrhea each time you take ZzzQuil, it is recommended to discontinue the medication and talk to your doctor about alternative options (that are less likely to cause gastric distress).  That said, taking ZzzQuil on an empty stomach (as opposed to after eating a large meal) might minimize odds of diarrhea occurring as an adverse reaction.
  • Depression: A subset of ZzzQuil users may experience depression (or depressed mood) as a side effect. The depression is likely attributable to inverse agonism of the H1 histamine receptor, which in turn, causes cloudy thinking, mental fatigue, and decreased arousal.  If you become depressed after ZzzQuil administration, refraining from further usage is recommended.  Those at highest risk of depression from ZzzQuil are persons with preexisting neuropsychiatric disorders.
  • Difficulty breathing: Dyspnea, or shortness of breath, has been reported as an adverse reaction to ZzzQuil. If you experience shortness of breath or labored breathing after taking ZzzQuil, it could be due to inflammation within the nasopharynx.  Persons with preexisting medical conditions like asthma may be at greater risk of experiencing dyspnea while taking ZzzQuil.  Anyone who experiences difficulty breathing from ZzzQuil should discuss this reaction with a doctor as soon as possible.
  • Extrapyramidal effects: ZzzQuil is sometimes useful for decreasing extrapyramidal symptoms such as: akathisia, akinesia, and dyskinesia – associated with neuropsychiatric conditions like Parkinson’s disease. That said, some individuals may actually experience extrapyramidal effects as a reaction to ZzzQuil.  If extrapyramidal effects are occurring from ZzzQuil, it is recommended to discontinue the medication and seek medical attention as soon as possible – presentation of extrapyramidal effects should be taken very seriously.
  • Fainting: A small percentage of ZzzQuil users might end up fainting as an adverse reaction to this medication. Persons who administer abnormally high doses (e.g. doses exceeding the recommended amounts) and/or individuals who mix ZzzQuil with another CNS depressant (e.g. alcohol) may be at highest risk of fainting from treatment.  If you end up fainting, it might be attributable to hypotension (low blood pressure) or orthostatic hypotension (low blood pressure upon standing from a seated or prone position).  Anyone who faints following ZzzQuil ingestion should receive immediate medical attention.
  • Hallucinations: A very rare adverse reaction to ZzzQuil is hallucinations. Hallucinations refer to false sensory perceptions: sounds, sights, smells, touches, and/or tastes.  For example, someone might see visuals (that aren’t real) or hear voices in their head after taking ZzzQuil.  The odds of experiencing hallucinations from ZzzQuil are low, however, odds increase among: persons with psychiatric disorders, individuals using other substances along with ZzzQuil, and/or those who don’t follow proper dosing instructions.
  • Heart rate changes: Some ZzzQuil users may report experiencing heart rate changes such as slower, faster, or abnormal heart rate as an adverse reaction. If you experience heart rate changes, it is recommended to stop using ZzzQuil and seek immediate cardiovascular evaluation via a medical professional.  Anyone with a history of cerebrovascular problems should monitor their heart rate closely while using ZzzQuil and report heart rate irregularities to a doctor.
  • Irritability: After taking ZzzQuil, you might find yourself grouchy, irritable, or angrier than usual. Irritability may occur as an adverse reaction due to changes in histaminergic neurotransmission, arousal, and/or emotional dysregulation.  For some, the irritability may persist throughout the entire morning or day after administering ZzzQuil.  Individuals who have a history of anger issues may be most prone to ZzzQuil-induced irritability.
  • Liver dysfunction: It is estimated that less than 0.1% of individuals who use ZzzQuil will experience liver dysfunction. Nevertheless, if you suspect that regular ZzzQuil ingestion is damaging your liver, it is recommended to share this with a medical doctor.  A medical doctor will be able to evaluate your liver function while using ZzzQuil, as well as help treat preexisting liver damage.  Persons with a history of liver dysfunction prior to using ZzzQuil should avoid using ZzzQuil unless considered safe by a doctor.
  • Nausea: In many cases, ZzzQuil is a useful intervention for allergy-related nausea. However, some individuals might actually experience nausea or become more nauseous after taking ZzzQuil.  If you become nauseous from ZzzQuil, this may be a sign that your body is unable to tolerate its contents (e.g. diphenhydramine, alcohol, etc.).  Nausea might also result from taking too high of a ZzzQuil dose or related to ZzzQuil-induced gastric irritation.
  • Paradoxical reactions: Paradoxical reactions to ZzzQuil are very rare but can occur as a result of variations in neurochemistry and/or genetics of the user. Paradoxical reactions are responses to ZzzQuil that would be unexpected or seemingly implausible based on its mechanism of action.  Examples of paradoxical reactions to ZzzQuil include: anxiety, agitation, restlessness, insomnia, elevated blood pressure, poor sleep, and/or increased energy.
  • Paresthesia: Paresthesia refers to burning, prickling, numbness, or crawling-like sensations throughout the skin. Certain ZzzQuil users might notice paresthesia while under its influence, possibly related to alterations in the neurotransmission of histamine.  If mild, paresthesia may be relatively easy to manage.  Nevertheless, it is worth reporting this reaction to your doctor in case it’s the sign of something more serious.
  • Restlessness: Among the most common of paradoxical reactions to ZzzQuil is restlessness. Those who experience restlessness from ZzzQuil may have preexisting neurochemistry that’s incompatible with the sleep inducing effect of diphenhydramine and/or might metabolize diphenhydramine at an unusual rate (as a result of unique CYP450 enzyme expression).
  • Vomiting: Those who vomit after using ZzzQuil should stop taking the medication and speak with a medical doctor. Vomiting could be the sign of an allergic reaction, especially if accompanied by swelling and/or shortness of breath.  Vomiting may also be related to ZzzQuil-induced gastrointestinal distress and nausea.

Note: The likelihood of adverse reactions to ZzzQuil increases significantly when administered with another substance.  For example, using ZzzQuil and alcohol simultaneously (e.g. drinking beer after taking ZzzQuil) may put you at high risk for many of the adverse reactions listed above.

Variables that influence ZzzQuil side effects

There are a host of variables that may influence ZzzQuil side effects that you experience, as well as their severities.  These variables include things like: ZzzQuil dosage (and format); co-administered agents; the specific ZzzQuil user; and the cumulative duration of regular ZzzQuil administration.  Differences in side effects among ZzzQuil users can usually be explained by these variables.

  1. ZzzQuil dosage & format

In general, the higher the dosage of ZzzQuil administered, the more likely an individual will be to experience ZzzQuil side effects.  Side effects tend to be more severe and numerous among persons using high doses of ZzzQuil compared to low-dose users.  Moreover, certain side effects and/or adverse reactions might only occur at high doses (or doses above the recommended amounts).

The packaging inserts for ZzzQuil formulations recommend never exceeding more than 1 standard dose per day.  In addition to dosing, the specific format of ZzzQuil utilized may influence the side effects that occur.  Persons using ZzzQuil formulations with alcohol might experience more total and/or severe side effects due to the presence of alcohol – than those using alcohol-free formats.

  1. Co-administered substances

Using other substances such as medications, supplements, and/or illicit drugs – along with ZzzQuil might also affect the side effects that you experience.  It is known that ZzzQuil decreases activation of the central nervous system (CNS).  If ZzzQuil is combined with another CNS depressant (e.g. alcohol), there may be an interaction or synergistic effect that triggers severe adverse reactions (e.g. fainting, hypotension, vomiting, etc.).

Additionally, it is understood that ZzzQuil constituents like diphenhydramine undergo metabolism via CYP450 enzymes: CYP2D6 and CYP3A4.  If any co-administered substances also interact with these enzymes via metabolism, this may increase likelihood of severe interaction-related side effects.  Overall, most co-administered substances will increase risk of side effects for ZzzQuil users.

  1. Individual factors

Individual factors such as a person’s: genetics, preexisting medical conditions, and lifestyle might determine the severity of ZzzQuil side effects.  Someone who: lives a healthy lifestyle, is genetically classified as a CYP2D6 extensive metabolizer, and has no medical conditions – might tolerate ZzzQuil much better than an individual: with several medical conditions, abnormal CYP2D6 expression, and living an unhealthy lifestyle.

  • Administration specifics: The specific details associated with ZzzQuil administration might influence side effects. Someone who administers ZzzQuil on an empty stomach might experience more side effects than if they took it with food; or vice-versa.  Furthermore, taking ZzzQuil earlier in the night might result in more noticeable side effects than taking it right before bed.
  • Genetics: Genetics determining expression of enzymes used to metabolize ZzzQuil constituents (e.g. diphenhydramine) may influence side effects. Diphenhydramine is metabolized 80% by CYP2D6 and 20% by CYP3A4.  If you have atypical CYP450 expression, you’re at increased risk of side effects compared to the general population.  Moreover, genetics that influence your neurochemistry might also determine how you respond to ZzzQuil (increasing or decreasing risk of side effects).
  • Lifestyle (diet, sleep, stress): A person’s lifestyle might determine how severe ZzzQuil side effects end up. Someone who eats an unhealthy diet, is highly stressed, and not sleeping well – might experience more severe side effects than someone who aims to live a healthy lifestyle.
  • Medical conditions: Preexisting medical conditions might increase your risk of ZzzQuil side effects and/or adverse reactions. Furthermore, any medications used to treat medical conditions might increase likelihood of an interaction effect.  For this reason, you should never take ZzzQuil without prior authorization from a medical doctor.
  1. Duration of ZzzQuil usage (Short-Term vs. Long-Term)

The duration over which you’ve consistently used ZzzQuil might determine whether you experience side effects, and if so, how severe they end up.  Persons who use ZzzQuil for a very short-term may experience some side effects due to the fact that their body hasn’t had a chance to adjust itself to the regular daily ingestion of the drug.  With consistent daily use, some short-term side effects might eventually fade or diminish.

That said, some individuals might experience side effects that occur as a result of long-term administration.  If ZzzQuil is used for an extended duration, it may alter neurochemistry, epigenetic expression, and gut bacteria – increasing risk of certain side effects.  Moreover, many long-term users end up taking higher-than-recommended doses due to tolerance which puts them at greater risk of side effects.

ZzzQuil: Do the benefits outweigh the side effects?

If you’re using ZzzQuil, you may want to closely monitor your experience and determine if the benefits of treatment outweigh the side effects.  Most ZzzQuil users will report major benefits such as a reduction of allergy symptoms and sleep enhancement – with few unwanted side effects.  If you’re getting major benefit without any severe side effects, it makes sense to continue using ZzzQuil as directed until you no longer need it.

On the other hand, if you’re experiencing severe side effects or adverse reactions – you’ll probably want to discontinue ZzzQuil and talk to your doctor about trying another medication.  Nobody should continue using ZzzQuil if the side effects are unbearable or debilitating.  In some cases, ZzzQuil might not cause many side effects – but might be of suboptimal efficacy in managing your symptoms.

If ZzzQuil isn’t helping with your symptoms, it also makes no sense to continue using it.  To help gauge your response to ZzzQuil while using it, you may want to write in a journal – documenting side effects that you experience.  By documenting side effects in a journal, you’ll have exact documentation of how you reacted to ZzzQuil to share with your doctor.

Possible ways to reduce ZzzQuil side effects

There may be some ways in which you can reduce ZzzQuil side effects without discontinuing the medication.  Understand that you should never attempt to implement these side effect reduction strategies without first ensuring that they’re safe with a medical doctor.  That said, things like: dosage reduction, administration modification, and/or discontinuing co-administered substances might help decrease your ZzzQuil side effects.

  1. Dosage reduction: It is never recommended to exceed the standard dosage of ZzzQuil as indicated on the ZzzQuil label. Nevertheless, if you’re experiencing side effects at this standard dose, you may want to decrease it even more. Sometimes taking a very tiny dose can still help control your symptoms without side effects.  In other words, you should strive to take the “minimal effective dose.”
  2. Modify administration: Some people may find it helpful to alter the timing of their ZzzQuil administration and/or whether they take it with food vs. an empty stomach. If you take ZzzQuil early in the night, you might want to try taking it later – or vice-versa. Similarly, if you take ZzzQuil on an empty stomach, you may want to try taking it with food; or vice-versa.
  3. Discontinue unneeded substances: Many medications and/or supplements can interact with the metabolism and/or neurotransmitter actions of ZzzQuil. For this reason, it is recommended to discontinue all medically-unnecessary substances while using ZzzQuil. Certain individuals may notice that their side effects abate once they quit using certain things along with ZzzQuil.
  4. Continue using: In some cases, side effects of ZzzQuil are attributable to short-term adaptation effects whereby the body hasn’t fully adjusted itself to the drug. Simply continuing to use ZzzQuil for a longer-term may lead to bodily adaptation and predictably, the cessation of certain side effects.

Note: If you don’t tolerate ZzzQuil well and experience unwanted side effects, it’s probably smart to stop using it.  Because ZzzQuil stays in your system for a very short-term, most of its side effects will stop once your body has eliminated the drug from systemic circulation.

Have you experienced ZzzQuil side effects?

If you’ve used ZzzQuil and experienced side effects, share your experience in the comments section below.  Mention things like the specific side effects that you experienced and/or the worst side effects that you experienced.  to help others get a better understanding of your situation, provide additional details such as: the format of ZzzQuil you used, the dosage you used, whether you took other medications or substances with ZzzQuil, whether you have medical conditions (that increase risk of side effects), and the number of days over which you consecutively administered ZzzQuil.

If you were taking other substances with ZzzQuil, are you sure that your side effects weren’t related to some sort of interaction effect?  Did you talk to your doctor before taking ZzzQuil to ensure that it is safe based on your current medication regimen and/or medical status?  Overall, know that no over-the-counter medication, including ZzzQuil is perfect – most have side effects.  If you cannot tolerate ZzzQuil well, there are always other options.

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