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Mixing ZzzQuil and Alcohol: Effects & Dangers

ZzzQuil is an over-the-counter (OTC) sleep aid manufactured by Vicks (a subsidiary of Proctor & Gamble) that initially hit the market in 2012.  When administered on an “as-needed” basis, ZzzQuil is thought to alleviate occasional bouts of insomnia and other sleep disturbances with minimal risk of abuse, addiction, and/or dependence – as compared to pharmaceutical hypnotics.  In any regard, because ZzzQuil is available as an over-the-counter drug, many users fail to consider that it may interact with other substances, including alcohol.

Knowing that upwards of 130 million individuals drink alcohol in the United States, and that 20 million persons experience mild sleep disturbances each year, it’s reasonable to assume that a subset of the populace ends up ingesting ZzzQuil with alcohol still in their systems; or vice-versa.  While for some individuals the ingestion of ZzzQuil with alcohol may be unintentional, many will intentionally ingest the two substances simultaneously for a more potent psychoactive effect.

Irrespective of reasons [or lack thereof] for ingesting ZzzQuil plus alcohol, it may be helpful to understand how each substance modulates physiology, as well as the combined effect of the two substances within the CNS when ingested together.  Moreover, persons who mix the aforementioned substances should be cognizant of potential adverse reactions that may result.  If you or someone you know ingested Zzzquil and alcohol, do not hesitate to seek emergency medical attention – as this could be fatal and/or induce permanent physiologic damage.

ZzzQuil and Alcohol: Mechanisms of Action + Synergism

When compared directly, ZzzQuil and alcohol exhibit [mostly] distinct mechanisms of action.  This is because the primary active ingredient within ZzzQuil, known as diphenhydramine, interacts with physiologic targets than alcohol doesn’t – and vice-versa.  That said, it is worth noting that a subset of ZzzQuil formats contain 10% alcohol, indicating a small degree of overlap in pharmacodynamics.

Additionally, because each substance is known to depress CNS activity, their co-administration may yield a synergistic CNS depressant effect.  In other words, the pharmacodynamic actions of ZzzQuil constituents (e.g. diphenhydramine) plus alcohol may facilitate markedly greater CNS depression than the sum of their separate effects.  It is the synergistic effect within the CNS that most are concerned with, however, this will be subject to variation based on the respective dosages of each substance.

ZzzQuil:  According to the product label, every 30 mL of ZzzQuil contains 50 mg of diphenhydramine.  While certain formats of ZzzQuil such as Calming Vanilla Cherry Liquid and Warming Berry Liquid also contain 10% alcohol, others such as LiquiCaps and Alcohol-Free Liquid do not.  Additional ZzzQuil ingredients include: 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.

  • Diphenhydramine: The primary active ingredient within ZzzQuil is diphenhydramine, a compound of the ethanolamine class with antihistaminergic and antimuscarinic properties. Diphenhydramine is understood to act predominantly as a competitive inverse agonist at central and peripheral H1 (histamine) receptors.  Inverse agonism of H1 receptors indicates that diphenhydramine not only inhibits H1 receptor activation, but that it exerts the opposite effect upon each H1 receptor as compared to an endogenous ligand (e.g. histamine).  It is the H1 receptor inverse agonism elicited by diphenhydramine that induces sedation, drowsiness and relaxation – all of which promote sleep induction.  As a secondary mechanism of action, diphenhydramine antagonizes M1 (muscarinic) receptors, indicating that it blocks the stimulatory effect of acetylcholine.  The M1 antagonism is thought to augment H1 inverse agonism for sleep induction.  Assuming one administered standard doses of ZzzQuil, the H1 inverse agonism and, to a lesser extent, M1 antagonism, account for the bulk of its action.  However, if an excessive dosage is ingested (such as during abuse), diphenhydramine can:  inhibit the norepinephrine transporter (NET), antagonize alpha-1 receptors, and inhibit the serotonin transporter (SERT).
  • Alcohol (10%): As was noted, the Calming Vanilla Cherry Liquid and Warming Berry Liquid preparations of ZzzQuil contain 10% alcohol. Alcohol is known to modulate a host of neurotransmitters and receptors including: dopamine, GABA, glutamate, glycine, and serotonin.  Though the quantity of alcohol within the aforestated ZzzQuil preparations is considered low, understand that even a seemingly small quantity will modulate neurotransmission.  Individuals who consume ZzzQuil preparations containing alcohol will likely exhibit increased CNS depression and may report a slightly greater hypnotic effect compared to alcohol-free formats.  If an excessively large dose of ZzzQuil is ingested, not only will the secondary and tertiary mechanisms of diphenhydramine yield a more substantial physiologic effect, but alcohol will also.

Alcohol: The specific alcoholic beverage (constituents, proofing of alcohol, etc.) and the total quantity consumed will influence alcohol’s pharmacodynamics.  Alcohol is a psychoactive drug that interacts with a host of neurotransmitters and receptor sites to elicit a combination of inhibitory and excitatory physiologic effects.  The inhibitory effects of alcohol are mediated primarily by its agonism of GABA(A) receptors and Gly (glycine) receptors plus antagonism of NMDA receptors.  These actions downregulate CNS activation and persons under the influence of alcohol experience predictable effects such as: cognitive deficits, dissociation, intoxication, motor skill impairment, relaxation, and sedation.  In addition to its inhibitory action, alcohol agonizes 5-HT3 (serotonin) to induce neuronal excitation.  Agonism of 5-HT3 receptors prompts increased dopaminergic signaling in the nucleus accumbens, leading individuals to experience mood elevation, pleasure, and reward.  When high doses are ingested, especially by individuals with a low tolerance, the inhibitory effects of alcohol depress CNS activation to the extent that coma, respiratory depression, and/or unconsciousness may result.

ZzzQuil and Alcohol (Combination): Co-ingestion of ZzzQuil and alcohol indicates that physiology will be modulated simultaneously by the pharmacodynamics of each substance.  The specific dosage of each substance will dictate the hierarchy in terms of pharmacodynamic action.  For example, with large doses of ZzzQuil and small quantity of alcohol, we would expect the combination to act as an H1 inverse agonist and M1 antagonist, and to a lesser extent, GABA(A) agonist, glycine (Gly) agonist, NMDA antagonist, 5-HT3 agonist, NET inhibitor, alpha-1 receptor antagonist, and SERT inhibitor.  Oppositely, with a large dose of alcohol and standard or subtherapeutic dose of ZzzQuil, we would expect the combination to principally interact with GABA(A) receptors, glycine receptors, NMDA receptors, and 5-HT3 receptors, and to a lesser extent, H1 receptors.  In any regard, it should be clear that combining ZzzQuil and alcohol could modulate a multitude of neurotransmitter systems including: histamine, GABA, glycine, glutamate, dopamine, acetylcholine, norepinephrine, and serotonin.  Considering the combination of substances, most would expect potentiation of effects such as: cognitive dysfunction, dissociation, intoxication, and sedation – resulting from the H1 inverse agonism and M1 antagonism (facilitated by ZzzQuil) and GABA(A) agonism, glycine (Gly) agonism, and NMDA antagonism (facilitated by alcohol).  Moreover, the co-administration of ZzzQuil and alcohol is likely to synergistically depress CNS activity.

Mixing ZzzQuil and Alcohol: Effects & Dangers (Possibilities)

If ZzzQuil and alcohol are co-administered, or one substance is still in systemic circulation when the other is administered, the user’s physiology will be under the influence of each substance simultaneously.  While under the influence of ZzzQuil and alcohol, physiologic effects and side effects resulting from the combination are often more numerous, of greater significance, and increasingly unpredictable – as compared to being under the standalone influence of either substance.  General medical literature reports cognitive dysfunction, drowsiness, and dizziness as being among the most common effects associated with co-administration of ZzzQuil and alcohol.

Anyone who takes the combination of ZzzQuil and alcohol should understand that the resulting effects will be subject to individual variation.  In other words, one person may report dizziness and nausea as the most notable effects of the combination whereas another may report an entirely different lineup of prominent effects such as dissociation, drowsiness, and hallucinations.  Included below is a comprehensive list of potential effects and side effects that may result from the co-administration of ZzzQuil and alcohol.

  • Allergic reaction: Before combining ZzzQuil with alcohol, most individuals will have used each substance separately to know how they respond.  However, although rare, it’s possible that someone who administers a combination of ZzzQuil with alcohol may have never tested each substance as a standalone to know how they respond.  An unlucky subset of persons who mix ZzzQuil and alcohol may find out that they are allergic to the diphenhydramine within ZzzQuil, leading to symptoms of an allergic reaction such as: difficulty breathing, dizziness, edema, hives, stomach cramps, and/or swelling.  Each of these symptoms may be exacerbated by the effects of alcohol, leading to potentiation of dizziness and stomach cramps.  In some cases, allergic reactions may extreme enough to induce coma, fainting, or death.  Anyone who suspects they are allergic to either substance (diphenhydramine or alcohol) or possibly the combination – should seek emergency medical attention.
  • Balance & coordination deficits: Many individuals struggle maintaining balance, steady gait, and/or coordination while under the influence of ZzzQuil and alcohol. One cause of balance and coordination deficits from this combination of substances is CNS depression.  This CNS depression yields suboptimal physiologic arousal whereby mental alertness is poorer and it becomes increasingly difficult to maintain balance and coordination.  That said, of the two substances, alcohol likely disrupts balance and coordination to the greatest extent.  Alcohol interferes with activity in the cerebellum, a region of the brain implicated in the coordination of muscle movements.  Furthermore, alcohol decreases connectivity between the supplementary motor area of the brain (a region involved in planning an execution of controlled movement) and the primary visual and motor areas.  Considering the [potentially severe] balance and coordination deficits that might result from ZzzQuil plus alcohol, persons who ingest this combination should refrain from: operating a motor vehicle or heavy machinery and/or activities requiring alertness.
  • Blood pressure fluctuations: It is possible that your blood pressure may fluctuate while under the influence of ZzzQuil and alcohol. The diphenhydramine within ZzzQuil is not thought to directly alter blood pressure, however, its action as an H1 inverse agonist may block histaminergic effects on vascular permeability to induce hypotension.  As a result, some individuals may report that their blood pressure increases while under the influence of ZzzQuil.  Although regular alcohol consumption is associated with increased blood pressure, while under the influence of a moderate dose, most will experience decreased blood pressure due to CNS depression.  If blood pressure drops significantly among ZzzQuil and alcohol users, this increases risk of fainting.  Due to increased risk of adverse effects associated with blood pressure changes, anyone with a history of blood pressure and/or cardiac abnormalities is encouraged to seek emergency medical attention if ZzzQuil is ingested with alcohol.
  • Brain fog: Nearly everyone who administers ZzzQuil with alcohol will experience brain fog, or a state of consciousness characterized by disorganized, slow, and/or unclear thinking. While experiencing brain fog, individuals may report feeling disoriented, spaced out, and intoxicated.  It’s relatively obvious as to why brain fog occurs while under the influence of ZzzQuil and alcohol.  The diphenhydramine within ZzzQuil exerts antihistaminergic and antimuscarinic effects and alcohol agonizes GABA(A) plus antagonizes NMDA receptors.  Because each substance can induce foggy thinking when administered as a standalone, brain fog while under the influence of both may be severe.  It may take some individuals between several days and several weeks to reestablish clarity of thought after ingesting the combination of ZzzQuil and alcohol.
  • Cognitive dysfunction: Similar to the effect of brain fog, nearly all individuals taking ZzzQuil and alcohol will experience some degree of cognitive dysfunction. The diphenhydramine within ZzzQuil blocks histamine and acetylcholine signaling, each of which can interfere with learning, memory, and attention.  Furthermore, alcohol alters NMDA receptor function, which in turn, inhibits prefrontal cortex activation.  Diminished activity in the prefrontal cortex interferes with aspects of cognition such as attention, cognitive flexibility, critical thinking, decision-making, judgment, planning, and self-regulation.  Moreover, because both ZzzQuil and alcohol suppress CNS function, arousal of the user will be suboptimal for cognitive performance in accordance with the Yerkes-Dodson law.
  • Confusion: The intoxication resulting from being under the concurrent influence of ZzzQuil and alcohol may result in mental confusion. Users of this combination may seem easily confused while conversing with others and/or while trying to engage in even mild cognitively-demanding tasks.  Mental confusion from ZzzQuil and alcohol is probably attributable to: lack of excitatory transmission (histamine, glutamate, acetylcholine); increased inhibitory transmission (GABA); decreased prefrontal activation; and downregulation of CNS function.
  • Depersonalization: Another effect that can result from co-administration of ZzzQuil and alcohol is depersonalization. Depersonalization is loosely defined as the perception of detachment from one’s mind or body.  If you experience depersonalization, it may feel as if you’re not in control [or have minimal control over] cognitive and/or physical faculties.  As the effect of each drug subsides, the depersonalization should also diminish.  Antagonism of NMDA receptors and inverse agonism of H1 receptors may be most culpable for depersonalized reactions.  That said, the cumulative modulation of regional activation, neurotransmitter systems, and depressed CNS activity may each contribute to depersonalization while under the influence of ZzzQuil and alcohol.  It should be noted that the significance of depersonalization from ZzzQuil plus alcohol may be worst for persons with preexisting psychiatric conditions.
  • Depression: In select cases, the combination of ZzzQuil and alcohol is considered unpleasant due to the fact that it induces a negative or depressed mood. There are many potential reasons as to why individuals may experience depression after ingesting this combination of substances.  Mechanisms of action such as: GABA(A) receptor agonism, glycine receptor agonism, H1 receptor inverse agonism, M1 receptor antagonism, and/or NMDA antagonism may interfere with excitatory transmission implicated in the maintenance of a stable or positive mood.  Additionally, because alcohol inhibits activity in areas of the prefrontal cortex and interferes with signaling between the frontal lobe and hind brain, this may yield emotional dysregulation and depression.  Anyone experiencing severe depression and/or suicidal thoughts after ingestion of ZzzQuil with alcohol should pursue emergency medical care.
  • Dizziness: Among the most commonly reported reactions to ZzzQuil and alcohol is dizziness. Although the diphenhydramine in ZzzQuil might cause dizziness, the alcohol is probably more culpable.  Alcohol may cause dizziness by interfering with the cerebellum and primary visual/motor centers within the brain.  That said, the most likely reason for dizziness and/or vertigo (sensation as though the room is spinning) has to do with alcohol’s effect on the inner ear.  When alcohol reaches the inner ear, it alters the density between the cupula and fluid within the ear canal, thereby modifying the cupula’s shape.  As a result, your brain receives a signal that you’re rotating – even if you’re standing still – leaving you feeling as if the room is spinning.  As alcohol is cleared from systemic circulation via excretion, the dizziness should subside.  Nonetheless, dizziness may also signify a severe adverse reaction to the combination of ZzzQuil and alcohol such that emergency medical attention is warranted.
  • Drowsiness: An effect that nearly everyone will experience while taking ZzzQuil and alcohol is drowsiness. ZzzQuil administered as a standalone agent causes drowsiness for 6 to 8 hours as a result of H1 inverse agonism [and possibly M1 antagonism] elicited by diphenhydramine.  Consumption of alcohol along with ZzzQuil facilitates intensification of drowsiness through the upregulation of inhibitory transmission (e.g. GABA) and downregulation of excitatory transmission (e.g. glutamate).  What’s more, the synergistic depressant effect exerted by the combination of ZzzQuil and alcohol upon the CNS should decrease arousal so significantly, that for most, drowsiness is inevitable.  In some cases, the drowsiness resulting from ZzzQuil plus alcohol may be so significant that users “pass out” and sleep for an extended duration.
  • Dry mouth: Another effect that individuals may notice after taking ZzzQuil with alcohol is dry mouth. In most cases, of the two substances ingested, alcohol is most causally implicated in the dry mouth.  Alcohol decreases the body’s production of antidiuretic hormone which is utilized in the reabsorption of water.  Because antidiuretic hormone concentrations are reduced from alcohol, the body loses more fluid than usual via urinary excretion, leading to dehydration, and dryness within the mouth.  ZzzQuil may exacerbate alcohol-induced dry mouth via M1 antagonism, an action that’s known to reduce saliva production.  In addition to dry mouth, some individuals may experience dryness within the nose and/or throat.
  • Euphoria: When taking ZzzQuil and alcohol together, most individuals report feeling intoxicated, dissociated, and downright unpleasant. That said, a subset of individuals may experience slight mood enhancement or possibly even euphoria.  Because diphenhydramine is not associated with mood enhancement, any mood elevation derived from the combination of ZzzQuil and alcohol will be largely attributable to the alcohol.  At moderate doses, alcohol agonizes 5-HT3 receptors which initiates increased dopaminergic signaling within the nucleus accumbens.  Increased dopaminergic signaling in the nucleus accumbens is associated with pleasure, reward, and elevated mood.  It should be suspected that persons with a history of neuropsychiatric disorders, particularly bipolar disorder, may be more likely to experience euphoria due to an underlying predisposition to mania or hypomania.
  • Fainting: A large enough dose of either ZzzQuil or alcohol can lead to fainting and/or passing out. Because ZzzQuil and alcohol are likely synergistic in the depression of CNS function, the dosage of each needed to induce fainting [when ingested together] is probably low – especially among persons without a tolerance to either substance.  Users with a low tolerance may faint unexpectedly after taking a single ZzzQuil dose and drinking a small amount of alcohol.  In general, the larger the dose of each substance ingested, the greater the likelihood of fainting.
  • Fatigue: When taking ZzzQuil, most individuals will experience some degree of fatigue for the duration of 6 to 8 hours. The fatigue occurs as a result of H1 receptor inverse agonism and goes hand-in-hand with drowsiness, making it easier to ZzzQuil users to drift off to sleep.  Drinking alcohol can also induce fatigue via GABA(A) receptor agonism.  For most individuals, the fatigue associated with ZzzQuil plus alcohol will eventually lead to the onset of sleep.  However, among persons who remain awake while under the influence of both substances, possibly due to high tolerance, it’s likely that fatigue will be so extreme that it may seem impossible to accomplish basic tasks.
  • Gastrointestinal distress: It is relatively rare for the diphenhydramine within ZzzQuil to cause gastrointestinal distress. In fact, some ZzzQuil users report subjective improvements in gastrointestinal function while under its influence.  That said, some individuals have reported severe gastrointestinal distress while under the simultaneous influence of ZzzQuil and alcohol.  In large part, gastrointestinal distress among users of this combination is attributable to the alcohol.  Alcohol increases the production of acid in the stomach, which can lead to gastritis or inflammation of the stomach lining.  The alcohol-induced inflammation of the stomach lining can lead to diarrhea, nausea, stomach pain, and vomiting.  Generally, the greater the amount of alcohol consumed with ZzzQuil, the more likely users will be to experience gastrointestinal distress.
  • Heart rate changes: Because the diphenhydramine within ZzzQuil can affect heart rate, as can alcohol, the combination of these substances will probably lead to heart rate changes. Unless you closely monitor your heart rate while under the influence of each substance, you probably won’t know the extent to which your heart rate changed from homeostatic baseline.  Inverse agonism upon H1 receptors elicited by ZzzQuil may counter normative histamine-mediated cardiac processes such as: vascular permeability-induced hypotension, reflex tachycardia, and atrioventricular node conduction.  As a result, individuals may be prone to marked heart rate changes and arrhythmias while under the influence of ZzzQuil.  When alcohol is ingested, it first causes a modest increase in heart rate via vasodilation, however, as consumption continues, heart rate generally slows.  Because heart rate may significantly change from ZzzQuil and alcohol, anyone with cardiac abnormalities and/or a history of cardiovascular problems is encouraged to seek emergency medical attention while under the combination’s influence.
  • Irritability: Some individuals may become increasingly irritable from the combination of ZzzQuil and alcohol. The ZzzQuil may contribute to irritability by interfering with cognitive function and/or creating a “foggy” state of mind.  When individuals are unable to think clearly and struggle to stay cognitively engaged, some may become frustrated and end up feeling irritable.  Alcohol may intensify the cognitive impairment-related onset of irritability.  Furthermore, alcohol modulates a host of neurotransmitter systems in ways that might trigger irritability in a subset of vulnerable persons.  Due to the fact that alcohol consumption decreases prefrontal activation, persons who become irritable may struggle to cope with irritability when it arises.  Research suggests that individuals with impulsive (i.e. “live-in-the-moment”) personality traits are most prone to irritability and anger from alcohol – and possibly this combination.
  • Liver damage: The liver is an organ implicated in a host of physiologically-necessary processes such as: bile production, coagulant production, metabolism of macronutrients, blood filtration, and vitamin/mineral storage. Although neither ZzzQuil nor alcohol are likely to damage the liver when ingested as standalone substances in small quantities, when ingested together (especially in large quantities), the combination may lead to liver damage and/or impairment.  The co-administration of ZzzQuil and alcohol places a significant burden on the liver to metabolize and each substance (primarily via CYP450 enzymes) prior to excretion.  This increased hepatic burden can provoke cellular inflammation and/or damage.  Signs of liver damage may include: abdominal pain, appetite reduction, bruising, fatigue, itchiness, jaundice, and weakness.  Anyone who suspects liver damage and/or dysfunction from ZzzQuil and alcohol necessitates emergency medical care.  Persons with a history of hepatic dysfunction may be most at risk of experiencing liver damage from this drug combination.
  • Memory impairment: Mixing ZzzQuil and alcohol may be disastrous in terms of the combination’s effect on memory. When taken over a long-term, diphenhydramine and other anticholinergics have been linked to dementia and permanent memory impairment.  Even a single standard dose of ZzzQuil will impair memory due to H1 inverse agonism.  When the H1 receptor is blocked, spatial memory and working memory are impaired.  Alcohol impairs memory via numerous mechanisms, including by: disrupting GABA and NMDA transmission needed for long-term potentiation (LTP); damaging hippocampal CA1 and CA3 cell layers; interfering with activation of the anterior cingulate cortex (ACC) and parietal lobe; and impairing communication between the prefrontal cortex and hippocampus.  Anyone who takes ZzzQuil and alcohol may experience memory lapses and/or be unable to remember what happened after taking the combination.
  • Nausea: A reaction that can occur when ingesting ZzzQuil and alcohol is nausea. Because ZzzQuil contains diphenhydramine which typically reduces nausea through an antiemetic effect.  That said, if a large quantity of alcohol is ingested (especially relative to quantity of ingested ZzzQuil), it may provoke nausea.  The nausea induced by alcohol may occur as a result of gastrointestinal irritation and/or inflammation, interactions with function of the inner ear, activation of the chemoreceptor trigger zone, and/or hepatic impairment.  For some, the nausea may be accompanied by stomach pain, appetite reduction, and in severe cases, vomiting.
  • Psychosis: Although a rare adverse reaction, some individuals who mix ZzzQuil and alcohol will experience drug-induced psychosis. While psychotic, individuals may exhibit bizarre behaviors, delusions, hallucinations (e.g. hearing voices, seeing disturbing visuals, etc.), and appear disconnected from reality.  It should be stated that there are numerous accounts in medical literature of individuals experiencing psychosis while under the standalone influence of diphenhydramine, as well as while under the standalone influence of alcohol.  What’s more, some research suggests that certain individuals my experience psychosis from a standard single dose of diphenhydramine.  While large doses of each substance most commonly provoke psychosis, combining the two substances may increase odds of psychotic reactions at lower doses.  Individuals with neuropsychiatric disorders and/or a family history of mental illness may be at highest risk of experiencing psychosis from ZzzQuil and alcohol.
  • Relaxation: Though not everyone using ZzzQuil and alcohol will experience pleasurable or euphoriant-like effects, most will report an increase in relaxation. For most users, an increase in relaxation is generally perceived as a favorable reaction to this substance combination.  The diphenhydramine within ZzzQuil can induce relaxation through H1 inverse agonism and M1 antagonism, and predictably, this makes it a useful sedative-hypnotic.  (Certain persons derive significant therapeutic benefit from diphenhydramine for anxiety).  Even at low doses, alcohol induces a combination of anxiolytic and myorelaxant effects, likely through its agonism of GABA(A) receptors, whereby users feel psychologically and physically relaxed.  The greater the dose of alcohol ingested along with ZzzQuil, the greater the relaxation is likely to be.
  • Respiratory depression: Persons taking ZzzQuil and alcohol may experience respiratory depression as an adverse reaction. Respiratory depression is characterized by an abnormally slow rate of respiration that is insufficient for lung expansion and inhalation of oxygen.  Anyone experiencing respiratory depression will exhibit elevated concentrations of carbon dioxide and respiratory acidosis.  If respiratory depression is moderate or severe, individuals will feel extremely sedated, disoriented, and/or confused – and may struggle or gasp for air.  Large quantities of alcohol or ZzzQuil may lead to respiratory depression, and possibly failure.  In the event of respiratory failure, persons may: lose consciousness, slip into a coma, and/or stop breathing.  Alcohol as a standalone can induce respiratory depression, and the antihistaminergic effect of ZzzQuil can potentiate its significance and duration.  If you suspect respiratory depression from this combination of substances, contact emergency medical services.
  • Sedation: Extremely common as an effect of mixing ZzzQuil and alcohol is sedation. A single standard dose of ZzzQuil alone can cause sedation via H1 receptor inverse agonism.  This sedative effect of ZzzQuil is what makes it an efficacious intervention for persons who struggle to sleep.  A moderate amount of alcohol also induces sedation in most persons, probably by upregulating GABA and/or blocking glutamate, making it difficult to remain alert.  The combination of ZzzQuil plus alcohol will yield unavoidable sedation for most persons.  Because of this sedation, all tasks that require alertness (e.g. operating motor vehicles / machinery, weightlifting, etc.) should be avoided until the sedation subsides.
  • Shortness of breath: Another reaction that ZzzQuil plus alcohol may provoke is shortness of breath. The most likely reason shortness of breath occurs while under the influence of ZzzQuil and alcohol is related to CNS depression.  When ZzzQuil and alcohol exert simultaneous effects, they downregulate CNS activity.  In extreme cases, such as after taking high doses of each, this may lead to respiratory depression.  Respiratory depression indicates slowed breathing and diminished oxygen uptake with inhalation, and often yields shortness of breath or gasping for air.  Shortness of breath after taking ZzzQuil and alcohol should be treated as a serious medical emergency, because if left unchecked, it may lead to respiratory failure and permanent adverse physiologic effects or death.
  • Stomach aches: When administered at recommended dosages, ZzzQuil is unlikely to provoke an upset stomach. If administered at excessively large dosages, upset stomach becomes increasingly likely to occur.  Alcohol as a standalone can cause heartburn, inflame the intestinal lining, and provoke gastrointestinal distress.  The combined effect of ZzzQuil plus alcohol on the stomach may lead to significant stomach pain accompanied by constipation or diarrhea and/or indigestion.  Moreover, some individuals may experience stomach aches as a result of substance-induced hepatotoxicity.
  • Sweating: Though relatively uncommon, a subset of persons who ingest ZzzQuil and alcohol will notice increased sweating. The diphenhydramine within ZzzQuil isn’t usually known to provoke sweating, however, sweating may be triggered by some sort of an interaction effect between diphenhydramine and alcohol.  An interaction effect might modulate thermoregulatory processes and initiate signaling for increased sweat production.  That said, the most likely cause of sweating after taking ZzzQuil plus alcohol, is the alcohol.  Alcohol is known to dilate blood vessels near the skin which often leads to sweating.  Anyone sweating profusely while on this combination of substances should immediately see a doctor to rule out a serious adverse reaction.
  • Tinnitus: A rare adverse effect that may occur in a small percentage of individuals who ingest ZzzQuil and alcohol simultaneously is tinnitus or a perceived ringing in the ears. Tinnitus can be caused by damage to hair cells within the ear as a result of ototoxicity and/or abnormal electrical signaling within regions of the brain such as the auditory cortex – while under the influence of these substances.  Low-to-moderate doses of alcohol and ZzzQuil are not associated with tinnitus or hearing loss.  That said, high doses of alcohol and/or ZzzQuil might damage structures within the ear via an interaction effect, leading to the perception of ringing or buzzing.
  • Urinary changes: Some will notice changes in the frequency of urination while under the influence of ZzzQuil and alcohol. Alcohol is a diuretic that acts on the kidneys to promote increased urination.  For every 1 gram of alcohol consumed, urinary output is thought to increase by approximately 10 mL.  Further, alcohol decreases secretion of vasopressin, a hormone that signals the kidneys to reabsorb water rather than excrete it.  Persons who consume a lot of alcohol, regardless of the amount of ZzzQuil ingested, will probably experience frequent urination.  That said, select individuals may report difficulty urinating (i.e. incontinence) if the ZzzQuil dose is large and alcohol intake is minimal.
  • Vomiting: There are numerous reasons as to why individuals who take ZzzQuil and alcohol may end up vomiting. For some, the two substances may interact in a way that leads to nausea and vomiting.  That said, because diphenhydramine within ZzzQuil is known for its antiemetic effects, it’s unlikely that the ZzzQuil is liable for vomiting induction.  In a majority of cases, alcohol is the substance in this combination that provokes vomiting.  Alcohol irritates the stomach lining through increased acid production and inflammation, each of which might lead to nausea and vomiting.  Additionally, alcohol is perceived as a toxin by the body which may stimulate the chemoreceptor trigger zone to provoke vomiting as a means of detoxification.  Anyone who vomits after taking this combination should replenish lost fluids and electrolytes to avoid dehydration, as well as seek emergency medical care to prevent serious complications.  Vomiting while under the influence of these sedative/hypnotic agents can be dangerous in that some individuals may pass out and choke on their vomit – leading to death.
  • Visual disturbances: When blended, the diphenhydramine content in ZzzQuil and alcohol can induce visual disturbances. Each substance as a standalone can alter visual perception, however, when the two are combined, visual alterations become more significant.  Examples of visual alterations that some have reported from ZzzQuil and alcohol include: blurred vision, double vision, and tunnel vision.  Others have reported complete distortion of vision along with floaters or fuzzy shapes “floating” in the visual field.  It’s also possible that you might exhibit hypersensitivity to bright light.  Although most suspect that the combination of these substances won’t cause eye damage, consult an ophthalmologist for an eye examination if you’re concerned.  Moreover, understand that visual disturbances may be difficult to distinguish from visual hallucinations.
  • Weird dreams: Most individuals who consume ZzzQuil and alcohol together will drift off to sleep, but while sleeping, they may experience exceptionally crazy, vivid, and/or nightmarish dreams. Diphenhydramine within ZzzQuil is thought to reduce the amount of REM sleep, which would suggest that it should [hypothetically] minimize odds of bizarre dreams.  However, some suspect that it may lead to prolonged sleep duration which might increase odds of waking during REM sleep and you recalling a dream as vivid.  Furthermore, when taken at high doses, the anticholinergic action of diphenhydramine increases which might alter sleep architecture and subjective perceptions of dreams.  If a reasonable amount of alcohol is consumed before falling asleep, a person’s sleep will be shallower, they’ll spend more time in REM sleep, and experience more vivid dreams and/or nightmares.  The exact effect of ZzzQuil and alcohol on sleep architecture is unknown and likely contingent upon dosing.  In any regard, users of this combination may report some weird dreams, and possibly hypnagogic and/or hypnopompic hallucinations.

Note: Realize that the above list of effects resulting from ZzzQuil and alcohol may be incomplete.  If you know of another effect that commonly occurs while under the influence of this combination, be sure to report it in the comments section below.  If you have any questions about any adverse reactions and/or side effects attributable to ZzzQuil, alcohol, or their combination – be sure to contact a medical professional.

Variables that influence severity of effects from mixing ZzzQuil and Alcohol

There are numerous variables that influence the specific effects, total number of effects, and the severity of effects that occur while under the influence of ZzzQuil and alcohol.  These variables include: dosages [of each substance]; administration details (e.g. co-ingested vs. latency between ingestions); other substances administered (e.g. drugs, supplements, etc.); degree of tolerance to each substance; and individual factors (e.g. age, body composition, medical conditions, sex, etc.).  When contemplating the effects and/or reactions that you experienced from the ZzzQuil and alcohol combination, it may be helpful to reflect upon these variables.

  1. Dosages

The significance of physiologic effect resulting from the simultaneous ingestion of ZzzQuil and alcohol is principally mediated by dosing.  Individuals who ingest lower respective dosages of ZzzQuil and alcohol will exhibit a less significant shift from homeostatic physiology as compared to persons who ingest high doses.  For this reason, it is reasonable to suspect that low dose users will experience fewer severe side effects and/or adverse reactions than high dose users.  Put simply, someone ingesting a single dose of ZzzQuil after taking a sip of red wine will experience fewer side effects than someone who ingests several doses of ZzzQuil after a few glasses of rum.

  • Low doses: If a combination of ZzzQuil and alcohol is ingested, yet the dosages of each substance within the combination are low, likelihood of serious adverse reactions and/or interaction effects is minimized – compared to higher doses. At low doses, a less significant burden is placed upon enzymes in the liver and kidneys as compared to higher dosages.  This means the body can metabolize and excrete the diphenhydramine [within ZzzQuil] and the alcohol more efficiently than if dosages of each were high.  More efficient metabolism and elimination decreases likelihood of hepatic and/or renal toxicity and pharmacokinetic-related interactions.  Additionally, the pharmacodynamic effect of each substance is less prominent at low dosages, meaning there’s less neurochemical modulation and corresponding CNS depression.  For this reason, most healthy adults who ingest a low dose of the combination (ZzzQuil and alcohol) probably won’t experience adverse reactions.
  • High doses: If high doses of ZzzQuil and alcohol are ingested simultaneously, likelihood of serious adverse reactions is amplified. At high doses, a significant burden is placed upon enzymes within the liver and kidneys during metabolism and excretion.  High doses of each substance administered simultaneously may prolong hepatic metabolism, induce hepatotoxicity, and/or induce nephrotoxicity.  In other words, there may be some serious pharmacokinetic-related interactions that only occur when high doses of diphenhydramine [within ZzzQuil] and alcohol are ingested together.  Furthermore, at high doses, we know that the pharmacodynamic effect of each substance is more prominent.  For example, large doses of ZzzQuil yields more significant anticholinergic effects than smaller doses, plus exerts relevant noradrenergic and serotonergic effects – neither of which are noticeable at small doses.  Not only will intoxication-related side effects be more numerous and severe from high doses of ZzzQuil and alcohol, but the synergistic CNS depression may be significant enough to induce respiratory depression, respiratory failure, and/or death.

ZzzQuil to Alcohol ratio:  Because ZzzQuil and alcohol are distinct psychoactive drugs and everyone responds differently to each based on individual factors, it’s difficult to estimate dosing equivalency in regards to potency of physiologic effect.  For this reason, it may be challenging to know whether taking 2 ZzzQuil and drinking 1 beer yields a more potent physiologic effect than drinking 2 beers and taking 1 ZzzQuil.  When compared, most would suspect that a single dose of ZzzQuil is of greater potency than 1 beer because, on average, a single dose of ZzzQuil is enough to induce extreme sedation and/or sleep, yet this does not usually occur with 1 beer.

Moreover, the sedative/hypnotic effect of diphenhydramine within ZzzQuil persists for a duration of 6 to 8 hours, which is usually longer than the effect of alcohol.  If the hypothesis that a single dose of ZzzQuil exerts a more potent physiologic effect than a single standard alcoholic beverage (e.g. 1 beer) is accurate, we’d expect persons who ingest a greater number of ZzzQuil doses relative to standard alcoholic beverages to be most susceptible to severe side effects from the combination of substances relative to others.  If forced to estimate dosing equivalency in terms of potency, one might speculate that a single ZzzQuil dose is roughly as potent as the number of drinks it takes to reach a blood-alcohol content reading of 0.04.

Assuming that a single ZzzQuil dose is equal to a BAC of 0.04 in terms of physiologic potency, and you (personally) require 2 beers to reach a BAC of 0.04, we could suggest that a combination of 5 beers and 1 ZzzQuil yields increased susceptibility to severe side effects as compared to a combination of 2 ZzzQuil and 1 beer.  In any regard, the greater the amount of alcohol present within the combination, the more severe the alcohol-related side effects will be.  The greater the amount of ZzzQuil present within the combination, the more severe the ZzzQuil-related side effects will be.  If large amounts of both substances are present within the combination, the more severe the alcohol-related and diphenhydramine-related side effects will be, as well as interaction effects between alcohol and diphenhydramine.

Note: The aforementioned estimations are hypothetical and should not be considered factual.  To accurately gauge the physiologic potency of each substance, you’d need to undergo scientific testing.  Even after this testing, it would still be difficult to compare ZzzQuil with alcohol due to differences in pharmacokinetics and pharmacodynamics.

  1. Administration details

The details associated with administration of ZzzQuil and alcohol may also influence the specific effects and/or reactions reported by users of this combination.  Examples of administration details to consider include: empty vs. full stomach, ingestion latency, rate of administration, and time of administration.  Someone who administered ZzzQuil and alcohol rapidly in the morning on an empty stomach may experience totally different reactions than if he/she administered ZzzQuil and alcohol slowly in the afternoon after a large meal.

  • Empty vs. Full stomach: It is known that the consumption of ZzzQuil and alcohol on an empty stomach leads to faster onset of intoxication as compared to drinking with a full stomach (e.g. after a large meal). The presence of food within the stomach prolongs the rate at which ZzzQuil and alcohol are absorbed, metabolized, and distributed.  As a result, individuals who ingest ZzzQuil with alcohol on a full stomach will report less rapid onset of intoxication, but a longer duration of intoxicating effect – as compared to those who ingest the combination while fasted.  Food within the stomach prior to taking this combination may also help minimize gastric distress by soaking up stomach acid and/or inflammation.  To get technical, the macronutrient / micronutrient composition of foods consumed, the total quantity of food consumed, and the time between your last meal and ZzzQuil plus alcohol ingestion (e.g. 2 minutes, 20 minutes, 3 hours, etc.) may influence the physiologic effects that you endure from this combination.  Moreover, the extent to which you are hydrated before ingesting ZzzQuil and alcohol can influence your experience on this combination.  Dehydration and/or electrolyte imbalances may provoke and/or exacerbate adverse reactions to ZzzQuil and alcohol.
  • Ingestion latency: Another detail to consider is whether ZzzQuil and alcohol were ingested simultaneously, or whether there was a time gap (i.e. latency) between respective ingestions. Someone who co-administers ZzzQuil along with alcohol might experience a different reaction to this substance combination than if he/she had administered ZzzQuil 20 minutes after drinking a beer (or vice-versa).  It is reasonable to suspect that the lesser the ingestion latency, the more likely interactions are to occur.  Oppositely, the greater the amount of time between respective administrations of ZzzQuil and alcohol, the lower the likelihood of interactions.  When time between administration of multiple substances increases, there’s less overlap in respective pharmacokinetics and pharmacodynamics thereby minimizing odds of adverse effects.  This is because the first substance administered will have undergone some degree of metabolism and elimination before the second is administered.
  • Time of administration: The time of day at which you administer ZzzQuil and alcohol may also influence the severity of side effects that you experience and your ability to manage them. This is because concentrations of neurochemicals and hormones shift throughout the day in accordance with a person’s circadian rhythm.  Most individuals feel alert in the late morning and/or early afternoon (from production of CNS activators like cortisol) and naturally drowsier in the evening (from production of CNS depressants like melatonin).  Knowing that ZzzQuil and alcohol induce CNS depression, and that CNS function is more depressed in the evening for most [in accordance with the circadian biology], it’s possible that the nighttime ingestion of these substances may yield [marginally] increased CNS depression as compared to morning or afternoon administration of an equivalent dose.  This may increase risk of respiratory depression and/or failure among those who administer the combination in the evening.
  • Rate of administration: The rate at which ZzzQuil and alcohol are administered should also be considered. Rapid administration (and corresponding ingestion) will often provoke a more significant physiologic reaction and side effects than slower administration.  Someone who chugs a beer with a dose of ZzzQuil in 2-minute duration may endure more significant physiologic reactions and side effects than if he/she slowly sipped a beer with a ZzzQuil over 20-minute span.  Because ZzzQuil doses are not usually divided, rate of administration may apply mostly to alcohol consumption.  Nonetheless, a slower rate of administration may allow for more efficient metabolism and/or elimination as compared to rapidly administering a large dose.
  • Mode of administration: The respective modalities of ZzzQuil and alcohol administration can also influence the specific reactions that occur from co-ingestion. Someone who administers ZzzQuil orally and administers alcohol intravenously may react differently than if he/she administered both substances orally.  Because ZzzQuil and alcohol are ingested orally by a majority of the populace, it’s not really worth discussing how each particular mode of administration would influence physiologic effect.  Just know that various modes of administration such as: insufflation, subcutaneous, intravenous, rectal, etc. – may alter responses to this combination [as compared to other modes of administration].
  1. Additional substances

In addition to the ingestion of ZzzQuil and alcohol, it is necessary to know whether other substances (e.g. dietary supplements, pharmaceutical drugs, illicit drugs) were administered.  The administration of substances in addition to ZzzQuil and alcohol may alter pharmacokinetics and/or pharmacodynamics of the combination.  Diphenhydramine within ZzzQuil undergoes first-pass metabolism via CYP2D6, but other enzymes such as CYP1A2, CYP2C9, and CYP2C19 also contribute.

Alcohol is metabolized by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 (2E1), and catalase.  Any additional substance that either inhibits or induces activation of the aforestated enzymes can alter metabolism, potency, and duration of effect resulting from ZzzQuil and alcohol.  For example, the drug Fomepizole inhibits alcohol dehydrogenase which would interfere with alcohol metabolism and potentiate its intoxicating effect if administered with this combination.

Other substances may alter metabolism in ways that inhibit the physiologic effect of ZzzQuil and alcohol, thereby decreasing odds of adverse pharmacokinetic-related reactions.  Additionally, some substances may not interact with the pharmacokinetics of ZzzQuil and alcohol, but might increase hepatic and/or renal burden, whereby hepatotoxicity and/or nephrotoxicity occur.  It’s also possible that administration of substances may augment the pharmacodynamic action and/or cumulative CNS effect of ZzzQuil and/or alcohol for enhanced intoxication.

For example, administration of a benzodiazepine along with ZzzQuil and alcohol may potentiate the GABAergic effect of alcohol and synergistically enhance cumulative CNS depression.  On the other hand, administration of a psychostimulant like caffeine with ZzzQuil and alcohol may reverse some degree of CNS depression and corresponding effects of drowsiness and fatigue.  Also understand that certain substances ingested along with ZzzQuil and alcohol may have no effect upon physiologic responses to the combination.

Note: The greater the number of substances administered along with ZzzQuil and alcohol, the increased likelihood of interaction effects.  Furthermore, if another substance is administered that interacts with ZzzQuil and/or alcohol, the dosing may dictate the severity of that interaction.

  1. Degree of Tolerance

The extent to which you’ve developed physiologic tolerance to diphenhydramine (the chief psychoactive substance within ZzzQuil) and/or alcohol will also influence how you respond to the co-ingestion of ZzzQuil and alcohol.  Specifically, the lower a person’s tolerance relative to the dosage of ZzzQuil and alcohol administered, the more substantial the physiologic reaction will be, thereby increasing likelihood of serious adverse reactions.  On the other hand, the greater a person’s tolerance relative to the dosage of ZzzQuil and alcohol administered, the less substantial the physiologic reaction will be, thereby minimizing likelihood of deleterious effects.

  • Zero tolerance: First-time users of diphenhydramine and alcohol will have zero tolerance prior to an ingestion of the combination.  Due to lack of previous exposure to diphenhydramine and alcohol, a first-time user will not have undergone pharmacokinetic-related adaptations (which allow for more efficient metabolism and excretion of each substance) nor pharmacodynamic-related adaptations (which reduce the significance of psychoactive effect derived from each substance).  For this reason, a greater burden will be placed upon the liver and kidneys during absorption, metabolism, and excretion following the ingestion of ZzzQuil and alcohol relative to the dosage among persons without tolerance, likely increasing risk of hepatotoxicity and/or nephrotoxicity.  Moreover, because zero neuroadaptation will have occurred from previous exposure, a person’s neurochemistry will be especially sensitive to the psychoactive effect exerted by each substance, ultimately increasing likelihood of severe adverse reactions.
  • Moderate tolerance: Individuals who use diphenhydramine and alcohol on a semi-regular basis will likely have some degree of tolerance prior to ingestion of the combination. Because these persons will have ingested diphenhydramine and alcohol before, physiology will have adapted in a few ways to each drug.  Enzymes implicated in metabolism and excretion of each substance will have shifted for greater efficiency such that the body breaks down and eliminates each at a faster rate relative to dosage.  Additionally, some neuroadaptation will have occurred such that the user will be less sensitive to the psychoactive effect exerted by each substance, thereby reducing likelihood of an adverse reaction relative to dosage – as compared to someone with zero tolerance.
  • High tolerance: Anyone who uses diphenhydramine and alcohol on a regular or frequent basis probably exhibits a high degree of tolerance to each substance. The physiology of persons with high tolerance allows for highly efficient metabolism plus excretion of diphenhydramine and alcohol – compared to infrequent and/or first-time users.  Furthermore, more substantial neuroadaptation will have occurred among persons with high tolerance such that neurotransmitter receptor sites will have significantly upregulated and downregulated to maintain homeostasis, which in turn, minimizes the psychoactive effect of each substance.  For this reason, it’s logical to suspect that high tolerance [relative to dose of diphenhydramine and alcohol] should minimize odds of adverse reactions from this substance combination.

It should be noted that some individuals may have a high tolerance to alcohol but not diphenhydramine – or vice-versa.  Common sense would suggest that, the larger the dose of the substance ingested to which you have low tolerance, the more significant the effect of that particular substance on your physiology from the combination.  In other words, someone with a high tolerance to alcohol and a low tolerance to diphenhydramine will probably experience fewer alcohol-related side effects and/or adverse reactions from the combination of ZzzQuil and alcohol with a greater number of diphenhydramine-related side effects – relative to the dosages.

Also worth emphasizing is that the impact of tolerance on responses to ZzzQuil and alcohol is relative to dose.  If relativity of dosing weren’t taken into consideration, one might speculate the high tolerance individuals might be more prone to serious adverse reactions from the combination of ZzzQuil and alcohol – possibly as a result of incurring deleterious long-term physiologic adaptations from frequent ingestion of each substance.  Moreover, high tolerance users may be at increased risk of exceeding safe dosing thresholds for ZzzQuil and alcohol, some of which may yield severe adverse reactions and/or prove to be fatal.

  1. Individual factors

Individual-specific factors play a significant role in determining how someone reacts to a specific substance or combination of substances (e.g. ZzzQuil and alcohol).  Examples of relevant individual-specific factors include: age, body type, genetics, preexisting medical conditions, and sex.  It is these factors that explain why two persons with the same degree of tolerance who identically administer equivalent dosages of ZzzQuil and alcohol may respond differently.  For example, one individual may report dizziness, hallucinations and vomiting – whereas the other may report fainting with respiratory depression.  If attempting to understand a particular reaction to ZzzQuil and alcohol, it should prove useful to account for the individual factors listed below.

  • Age: A person’s age may play a substantial role in determining how the body responds to co-ingestion of ZzzQuil and alcohol. Elderly individuals are more likely to: utilize medications for the treatment of age-related medical conditions (some of which may interact with ZzzQuil or alcohol), exhibit impaired organ function (e.g. brain, liver, kidneys), and exhibit decreased water distribution volume, and– ultimately increasing risk of adverse effects from the ingestion of ZzzQuil plus alcohol.  Furthermore, research suggests that the metabolism and elimination of both diphenhydramine and alcohol are less efficient with age.  Alcohol is also metabolized at a slower rate among older adults due to age-related decreased activation of acetaldehyde dehydrogenase and CYP2E1 enzymes.  Additionally, the elimination half-life of diphenhydramine is ~13.5 hours in elderly adults compared to ~9.2 hours in young adults and ~5.4 hours in children.  Due to age-related physiologic degeneration, elderly individuals may be more prone to hepatotoxicity, nephrotoxicity, and a host of other adverse reactions from the combination of ZzzQuil and alcohol.  Although children may metabolize and excrete substances quicker than adults, they’re smaller than adults and lack fully developed brains, making them highly susceptible to severe adverse reactions from a combination of ZzzQuil and alcohol.  Healthy young adults should be best equipped to tolerate the combination of ZzzQuil and alcohol due to full physical and CNS development (compared to children), as well as lack of marked degeneration (as is seen in the elderly).
  • Genetics: A person’s genetics and epigenetic expression can also influence how they are affected by ZzzQuil and alcohol. Genes that are most relevant in terms of influencing physiologic responses to ZzzQuil and alcohol are the ones involved in metabolism of diphenhydramine and ethanol.  Diphenhydramine within ZzzQuil is subject to first-pass metabolism principally via the isoenzyme CYP2D6, however, enzymes such as CYP1A2, CYP2C9, and CYP2C19 also contribute.  Alcohol is metabolized by ADH (alcohol dehydrogenase), ALDH (aldehyde dehydrogenase), CYP2E1, and catalase.  Because expression of genes that encode for these enzymes is subject to variation, certain individuals will metabolize diphenhydramine and/or alcohol faster or slower than average.  Metabolism speed can dictate the potency and duration of physiologic effect derived from a particular dose of ZzzQuil and alcohol.  For example, individuals with ultrarapid CYP2D6 metabolism have been reported to experience paradoxical excitation from diphenhydramine. Certain variants will make individuals less susceptible to adverse reactions than others.  In addition to genes encoding for enzymes implicated in metabolism, numerous genes encode for synthesis of neurotransmitters and receptors.  Someone with a specific neurochemical signature mediated by his/her genes may be more or less susceptible to adverse psychoactive effects from the combination of ZzzQuil and alcohol – than another person with an entirely different expression.  Moreover, there may be genes that regulate detoxification speed from the combination of substances, possibly leading to more rapid homeostatic reversion in certain individuals than others.
  • Medical conditions: Anyone diagnosed with medical conditions will be at increased risk of severe side effects and/or adverse reactions from the combination of ZzzQuil and alcohol. That said, the adverse reactions persons with preexisting medical conditions are likely to experience (after taking ZzzQuil and alcohol) will be contingent upon their specific conditions.  For example, someone with a neuropsychiatric disorder such as schizophrenia may be at increased risk of experiencing psychosis while under the influence of ZzzQuil and alcohol – compared to individuals without any neuropsychiatric disorders.  Persons with a history of hepatic impairment and renal impairment may exhibit increased risk of hepatotoxicity and nephrotoxicity after dosing with ZzzQuil and alcohol, respectively, compared to persons without preexisting organ dysfunction.  Moreover, the effect of ZzzQuil and alcohol may intensify symptoms of preexisting medical conditions – and vice-versa.  As was already mentioned, persons taking medications to treat medical conditions may be at risk of serious interaction effects resulting from ZzzQuil and/or alcohol interacting with those medications.  Examples of conditions that may increase risk of adverse reactions following ingestion of ZzzQuil and alcohol include: gastrointestinal disorders, hepatic dysfunction, hormone imbalances, neuropsychiatric disorders, and renal dysfunction.
  • Physical attributes: A person’s physical attributes such as body size (height / weight) and composition (fat / muscle mass) could also influence the effect of ZzzQuil and alcohol upon their physiology. On average, it is known that larger-sized individuals can handle larger dosages of drugs and more alcohol than smaller-sized persons.  This is primarily due to the fact that a larger body size yields greater distributional volume for alcohol and drugs.  For this reason, most would predict that someone who’s 6’2” tall and weighs 200 lbs. would have an easier time tolerating a large dose of ZzzQuil and alcohol than an individual who’s 5’2” tall and weighs 100 lbs.  That said, body composition also plays a role in determining how someone will respond to ZzzQuil and alcohol.  The diphenhydramine in ZzzQuil is lipophilic and soluble in adipose tissue or body fat, whereas alcohol is hydrophilic and soluble in water stores throughout the body (which are usually greater among persons with a lot of muscle).  Two individuals may exhibit the same height and weight (e.g. 6’5” / 200 lbs.), yet may fall into different categories such as: high fat/low muscle and low fat/high muscle.  Assuming the same dosage of ZzzQuil and alcohol are co-administered, responses would be influenced by body composition.  The person with high fat/low muscle should experience fewer diphenhydramine-related side effects and more alcohol-related side effects, whereas the low fat/high muscle individual should experience fewer alcohol-related side effects and more diphenhydramine-related side effects.
  • Sex: Whether a person is male or female may also influence responses to the combination of ZzzQuil and alcohol. Because females are, on average, smaller-sized than males, we would expect females to have a difficult time tolerating higher dosages of ZzzQuil and alcohol than males – making them more prone to adverse reactions.  Sex-specific differences in hormone production (e.g. estrogen, testosterone, etc.) and body composition (fat / muscle mass) could also influence responses.  Moreover, research suggests that females are at greater risk for adverse effects from alcohol consumption compared to males.  Fatalities among female alcoholics are estimated as being 50-to-100-fold those associated with male alcoholics, possibly indicating that female physiology is more sensitive to alcohol.  For all of the aforestated reasons, it’s reasonable to speculate that females are at highest risk of adverse reactions to the combination of ZzzQuil and alcohol.

Why Do People Mix ZzzQuil and alcohol?

It’s reasonable to wonder why anyone would resort to mixing ZzzQuil and alcohol.  For most, the physiologic effects are unpleasant and there’s risk of potentially serious adverse reactions.  That said, many still ingest the combination intentionally for intoxication, self-experimentation, and/or as a suicide attempt.  A smaller percentage of individuals will have ingested these substances [somewhat] unintentionally – without considering potential interaction effects.

  1. Intentional: Most people are consciously aware of their decision to use ZzzQuil and drink alcohol. A subset of persons who administer ZzzQuil with alcohol will have done so intentionally to experience a unique intoxication characterized by antihistaminergic, anticholinergic, and GABAergic effects. These individuals may have read about experiences in online forums of others who mixed ZzzQuil and alcohol, leading them to try the combination for themselves.  Many of those who administer this substance combination for intoxication have a history of drug abuse, impulsive behavior, and/or novelty-seeking.  That said, other individuals may administer the combination intentionally with the hypothesis that ZzzQuil plus alcohol will enhance their sleep.  Not everyone is well-versed with scientific literature and some believe (based on their own experience and/or anecdotes) that alcohol improves sleep.  They might then see an over-the-counter sleep aid like ZzzQuil and believe that its combination with alcohol will further bolster sleep quality.  Nevertheless, another percentage of individuals may administer the combination of ZzzQuil and alcohol as a [bizarre] self-experiment or suicide attempt.
  2. Unintentional: Though unlikely, it’s possible that certain individuals will administer ZzzQuil and alcohol together without the conscious intent of doing so. Individuals with memory impairment may forget that they had been drinking and then administer ZzzQuil – or may forget that they had administered ZzzQuil prior to initiation of drinking. Also possible is that a person develops a habit of taking ZzzQuil nightly and maintains this habit (subconsciously) even after returning home from a night of drinking – leading to unintentional co-ingestion.  Yet another possibility is that while intoxicated with alcohol certain persons see ZzzQuil and unconsciously or randomly decide to take it.

Note: Some may ingest ZzzQuil with alcohol intentionally, suspecting that the combination is safe due to the fact that ZzzQuil is an over-the-counter drug.

What to do if you mixed ZzzQuil and alcohol…

If you co-ingested ZzzQuil and alcohol, there are some steps you can take to minimize the likelihood of severe adverse reactions.  Most obviously, after simultaneous ingestion of ZzzQuil and alcohol, it is recommended to seek emergency medical care.  Failure to seek emergency medical care after ingestion of this combination may lead to long-term physiologic complications, permanent physiologic damage, or death.  Other ways to mitigate adverse reactions include: using activated charcoal; modulating CNS function; avoiding potentiators; and consuming sufficient food, water, and electrolytes.

  1. Emergency medical attention: While not everyone will experience serious adverse or life-threatening reactions to this combination of substances, some individuals will. Because you probably aren’t medically trained to recognize serious adverse reactions (e.g. respiratory depression) nor treat them, it is imperative to seek emergency medical attention while under the influence of ZzzQuil and alcohol.  Receiving timely medical attention after co-ingestion of this substance combination may save your life.  Failure to seek emergency medical attention may yield permanent organ damage or result in a preventable death.  Call 911 and get to the hospital if you’ve ingested ZzzQuil with alcohol.  Professionals may administer substances to help rid the body of diphenhydramine and/or alcohol.  Moreover, they may need to administer oxygen therapy (to offset CO2 toxicity), intravenous fluids and/or vitamins (to treat dehydration and vitamin depletion), and will carefully monitor patients to prevent breathing or choking.
  2. Consider activated charcoal: If you have access to activated charcoal (e.g. a bottle around the house), it may help to administer some in the aftermath of ZzzQuil and alcohol ingestion. Activated charcoal is an effective acute intervention for the prevention of drug toxicity. It functions through adsorption (not to be confused with “absorption”) whereby its tiny pores bind to ZzzQuil and alcohol to prevent systemic circulation.  In some cases of drug toxicity, activated charcoal exhibits efficacy in adsorption of toxins up to 1-hour after drug administration.  Communicate with emergency medical services to determine whether activated charcoal is a safe and/or efficacious intervention for your particular scenario.
  3. Opposing CNS effect: In most cases, individuals who receive ZzzQuil and alcohol will exhibit depressed CNS function. If CNS depression is significant, this could lead to respiratory depression with CO2 toxicity and/or possibly respiratory failure – followed by death. To oppose this CNS depressant effect, it may be beneficial to administer a mild psychostimulant (e.g. caffeine).  Caffeine has been shown to offset respiratory depression associated with morphine by upwards of 30%, making it potentially useful for persons with downregulated CNS activation from ZzzQuil and alcohol.  Keep in mind that if a psychostimulant is administered immediately after taking activated charcoal, it probably won’t have much of an effect – the charcoal will adsorb it.
  4. Avoid other substances: In addition to contacting emergency medical services and [potentially] administering activated charcoal and/or a substance capable of reversing CNS depression, anyone who ingests ZzzQuil and alcohol should refrain from the administration of other substances (dietary supplements, illicit drugs, pharmaceutical medications, etc.) unless recommended and/or confirmed to be safe by a medical professional. The administration of other substances while under the influence of ZzzQuil and alcohol may lead to exacerbation of preexisting interaction effects and/or induction of new interaction effects. Perhaps most dangerous are substances that would potentiate preexisting CNS depression [from ZzzQuil and alcohol] such as:  antihypertensive agents, barbiturates, benzodiazepines, neuroleptics, nonbenzodiazepines, opiates/opioids, etc.  The aforementioned CNS potentiators will increase risk of carbon dioxide toxicity, organ damage, respiratory failure, and/or fatality.  Though common sense for most, it should also be emphasized to cease further ingestion of ZzzQuil, alcohol, and diphenhydramine-based products.
  5. Food, water, electrolytes: Assuming you’ve already contacted emergency medical services and/or utilized other mitigation strategies (e.g. activated charcoal) to offset unwanted side effects or interaction effects from the combination of ZzzQuil and alcohol, you may want to consider snacking on some food and drinking some fluids. Ramping up food and fluid intake may help slow the absorption and/or metabolism of ZzzQuil and alcohol, potentially minimizing the acute potency of intoxication. Additionally, consumption of foods like saltine crackers, white rice, and pretzels can help soak up excess stomach acid [associated with alcohol consumption] to minimize the severity of gastrointestinal-related side effects.  Various foods can also help replenish electrolyte imbalances lost to alcohol-induced diuresis.  Moreover, increasing intake of fluids (especially those containing electrolytes) should decrease likelihood or severities of side effects associated with electrolyte loss and dehydration.

Have you ever mixed ZzzQuil and Alcohol?

If you’ve ever co-administered ZzzQuil and alcohol, share your experience in the comments section below.  While under the combined influence of ZzzQuil and alcohol, what were the most noticeable effects and/or side effects that you endured?  If you had to rate the significance of these effects and/or side effects on a scale from 1 to 10 (with “1” being least significant and “10” being most significant) – what numeric rating would you assign each?

Also document your reason for ingesting the combination of ZzzQuil and alcohol (e.g. intoxication, sleep enhancement, experimentation, etc.).  To help others get a better understanding of your experience, mention the respective dosages of ZzzQuil and alcohol that you ingested (e.g. 1 dose of ZzzQuil + 1 beer) and whether you had any degree of tolerance to either substance prior to ingestion of the combination.  Moreover, provide some personal details that may have influenced your reaction to the combination of ZzzQuil and alcohol such as:  age, body size and composition, gene expression (associated with metabolism of each substance), preexisting medical conditions, and usage of other substances (e.g. medications, supplements, etc.).

For clarification, note whether ZzzQuil and alcohol were administered simultaneously OR if there was latency between dosing (e.g. alcohol ingested an hour before ZzzQuil).  Reflecting upon your experience, do you regret mixing ZzzQuil and alcohol? (Explain).  Do you plan on ingesting this combination again in the future?

Understand that it is not recommended to co-administer ZzzQuil and alcohol.  In some cases, [depending dosages and the specific user], the combination of ZzzQuil and alcohol may lead to serious adverse reactions, long-term complications, and/or death.  If you have any questions about ZzzQuil, alcohol, or their combination – contact a medical professional rather than soliciting advice from the internet.

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