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Xanax (alprazolam) is a drug of the benzodiazepine class originally developed by Upjohn, a Michigan-based pharmaceutical company (now a subsidiary of Pfizer).  In the United States, Xanax first received FDA approval for the treatment of panic disorder and hit the market as a prescription medication in 1981.  It eventually received subsequent FDA approval for the management of other anxiety disorders such as: generalized anxiety disorder (GAD) and social anxiety disorder (SAD) – and recognition in the medical community as an off-label intervention for chemotherapy-induced nausea and vomiting.

Since its pharmaceutical inception in the early 1980s, the popularity of Xanax skyrocketed and it went on to become the most prescribed benzodiazepine in the United States.  Independent sources estimate that, in 2012 alone, nearly 50 million prescriptions were filled for Xanax.  Although many regard Xanax as a safe drug when administered in accordance with professional medical instruction, it can become dangerous when misused and/or administered with another substance such as alcohol.

Considering that nearly 140 million U.S. inhabitants consume alcohol on an annual basis, it’s reasonable to suspect that some of these individuals will end up ingesting alcohol and Xanax simultaneously.  In some cases, the co-ingestion of Xanax and alcohol may be deliberate means of intoxication, whereas in other cases, it may be attributable to user negligence (e.g. uninformed of potential interactions).  Nonetheless, anyone who ingests Xanax and alcohol simultaneously should be informed of the serious adverse reactions that may occur.

Xanax and Alcohol: Mechanisms of Action & Possible Synergism

When compared directly, there’s significant overlap in the respective pharmacodynamics of Xanax and alcohol.  Each substance exerts psychoactive effects principally via interaction with GABA(A) receptors and modulation of GABAergic transmission.  Because each substance interacts with GABA(A) receptors, the co-administration of Xanax and alcohol may yield a synergistic GABAergic effect capable of potentiating CNS depression.

It is potentiation of CNS depression that should be of chief concern among users of Xanax and alcohol, as this could be fatal.  Included below is a brief description of the mechanisms by which Xanax and alcohol exert their effects, as well as a hypothesized mechanism of the combination.  Realize that the significance of GABAergic modulation and CNS depression will be subject to variation based on respective dosages of each substance in the combination, as well as the specific user.

  • Xanax (alprazolam): Xanax exerts a psychoactive effect primarily via positive allosteric modulation (PAM) of the GABA(A) receptor sites.  Positive allosteric modulation of GABA(A) implies that Xanax does not bind to the same active site of GABA(A) receptors as the endogenous inhibitory transmitter GABA (gamma-aminobutyric acid).  Instead, it interacts with GABA(A) receptors via binding at a different site on the receptor protein, which in turn, triggers GABA(A) receptors to open their chloride channels more frequently and/or for an extended duration.  The opening of chloride channels allows for an influx of chloride ions to induce neuronal hyperpolarization whereby neurons become inhibited or less likely to fire.  This neuronal inhibition yields depressed CNS function and amnesic, anxiolytic, hypnotic, myorelaxant, and/or sedative effects.  Additionally, as a result of its GABA(A) receptor modulation at the alpha-1 subtype, function of inhibitory interneurons within the ventral tegmental area (VTA) is reduced.  Because inhibitory interneurons decrease firing rates of dopamine-producing neurons, any reduction of their influence will increase dopamine release and extracellular dopamine concentrations.  It is this dopamine release that induces feelings of euphoria and/or pleasure among some Xanax users.
  • Alcohol: Alcohol is a psychoactive substance that interacts with a multitude of neurotransmitters and receptor sites to exert a unique blend of inhibitory and excitatory effects. The inhibitory effects induced by alcohol are more pronounced than excitatory effects and are mediated by its modulation of GABA(A) receptors, Gly (glycine) receptors, and NMDA receptors.  In particular, alcohol acts as a positive allosteric modulator of GABA(A) and Gly receptors and as an antagonist of NMDA receptors.  These actions downregulate CNS activation and yield physiologic changes associated with: cognitive dysfunction, dissociation, intoxication, motor impairment, myorelaxation, and sedation.  While alcohol’s inhibitory action is its most significant, it also induces neuronal excitation via agonism of 5-HT3 receptors.  The agonism of 5-HT3 receptors enhances dopaminergic signaling in the nucleus accumbens, which can boost mood and/or sensations of pleasure and reward.
  • Xanax and Alcohol (Combination): In the event that Xanax and alcohol are co-ingested, a user’s physiology will undergo modulation by both substances. The specific dosage of each will affect pharmacodynamic hierarchy such that, a larger dose of alcohol [relative to Xanax] should increase relevance of alcohol pharmacodynamics and a larger dose of Xanax [relative to alcohol] should increase the relevance of Xanax pharmacodynamics.  In other words, if a large dose of alcohol is administered [relative to Xanax], the user will endure more substantial activation of Gly receptors, NMDA receptors, and 5-HT3 receptors than if a large dose of Xanax is administered [relative to alcohol] – in the combination.  Nevertheless, because each substance acts similarly upon GABA(A) receptors, combining Xanax and alcohol will yield greater GABA(A) receptor activation than if either substance was administered as a standalone.  Essentially, the combination will chloride channels to open more frequently and/or for longer durations, leading to markedly greater: influx of chloride ions, neuronal hyperpolarization, central inhibitory effect, and CNS depression – as compared to each substance as a standalone.  Moreover, due to the fact that both Xanax and alcohol bolster dopamine release, there may be a synergistic dopaminergic effect resulting from their combination that’s associated with greater pleasure and/or euphoria than either substance as a standalone.  In sum, those ingesting the combination of Xanax and alcohol will probably experience a synergistic GABAergic effect, potentially synergistic dopaminergic effects, as well as additional central inhibition and/or intoxication stemming from Gly receptor agonism and NMDA receptor antagonism.

Mixing Xanax and Alcohol: Effects (List of Possibilities)

If Xanax and alcohol are co-ingested, or either substance is still in systemic circulation when the other is ingested, the user’s physiology will be subject to simultaneous influence of both substances.  While under the simultaneous influence of Xanax and alcohol, side effects and/or adverse reactions resulting from the combination are often numerous, significant (in terms of severity), and unpredictable – as compared to being under the standalone influence of either substance.  Medical documentation reports amnesia, coma, respiratory depression, respiratory failure, unconsciousness, vomiting, and death as potential adverse reactions to concurrent ingestion of Xanax and alcohol.

Persons who administer Xanax and alcohol should understand that the resulting reactions to the combination will be subject to individual variation.  In other words, one user may experience dizziness, lightheadedness, and vomiting as the most noticeable side effects, whereas another user may experience acute depersonalization, hallucinations, and respiratory depression.  Included below is a comprehensive list of potential effects that may occur while under the influence of Xanax and alcohol.

  • Aggression: A study from the early 1990s suggests that individuals under the simultaneous influence of Xanax and alcohol may be more prone to behavioral aggression than persons under the influence of either substance as a standalone. Although this substance combination induces psychological and physical relaxation which usually mitigates aggression, a subset of users may behave more aggressively due to extreme intoxication and decreased self-control.  It’s reasonable to suspect that persons at highest risk of acting aggressively after ingesting Xanax and alcohol are individuals with a history of anger, aggression, impulsivity, and/or neuropsychiatric disorders.  If someone you know exhibits aggressive behavior while under the influence of Xanax and alcohol, it is recommended to contact law enforcement as judgment of the intoxicated individual will be severely compromised.
  • Allergic reaction: Though extremely uncommon, an extremely small subset of individuals who combine Xanax and alcohol may experience an allergic reaction. The allergic reaction may be provoked by Xanax, alcohol, or both substances simultaneously.  Persons with a history of favorable tolerability to each substance probably won’t experience an allergic reaction to the combination, however, substance-naïve users may find out that they are allergic to Xanax or alcohol.  An allergic reaction may trigger a host of deleterious adverse effects including:  dizziness, edema, fainting, facial redness, hot flashes, lightheadedness, skin rash, stomach pain, and/or swelling.  Examples of alcohol-specific allergic reactions and/or allergy-like responses include: rhinitis, itching, facial swelling, flushing, sneezing, headache, cough, and difficulty breathing.  Examples of Xanax-specific allergic reactions and/or allergy-like responses include: amnesia, bronchial spasm, vocal cord spasms, fainting, difficulty swallowing, and labored breathing.  Anyone who suspects that they may be experiencing an allergic reaction to Xanax and alcohol should be encouraged to contact emergency medical services.
  • Anger: While many people report feeling pleasure and/or euphoric emotion after taking Xanax and alcohol, others may experience negative emotions like anger. There are many reasons as to why someone might exhibit anger from Xanax, alcohol, or the combination of substances.  Each substance decreases excitatory neurotransmission which impairs the ability to retain mental clarity and/or quick-wit.  For some individuals, the loss of mental clarity is all it takes to incite anger.  Individuals with unresolved anger, a history of anger, intermittent explosive disorder (IED), and/or other neuropsychiatric disorders may be at highest risk of experiencing anger following the administration of Xanax and alcohol, probably due to preexisting neurologic sensitivity and disinhibition.
  • Balance & coordination problems: Anyone who takes Xanax and alcohol together will experience motor impairment to the extent that their balance and coordination become compromised. The co-administration of Xanax and alcohol increases GABAergic transmission and decreases glutamatergic transmission, which in turn, reduces activity within the cerebellum, a region of the brain involved in coordination of muscle activity.  When cerebellar activity is reduced, individuals exhibit deficits in balance and coordination.  Alcohol also impairs connectivity between the supplementary motor area and the primary visual and motor areas of the brain, which decreases the ability to plan and execute controlled movements.  Furthermore, alcohol interacts with vestibular centers to induce dizziness and/or vertigo – each of which might impair balance or coordination.  Moreover, the combination of Xanax and alcohol may induce such significant CNS depression, that users are too drowsy and unfocused to maintain balance and/or retain coordination.  For this reason, anyone who ingests Xanax and alcohol should refrain from operating motor vehicles, using heavy machinery, and engaging activities that require balance and/or coordination (e.g. athletic events, exercise, etc.).
  • Brain fog: After ingesting Xanax with alcohol, it is common to experience “brain fog,” a slang term used to describe deficits of mental clarity. Subjectively, it may feel as though your conscious perception and/or thoughts are fogged or stuck in a cloudy haze.  Signs of brain fog include: cognitive impairment, feeling “spaced out,” fuzzy sensory processing, and diminished brain activity.  There are many reasons as to why individuals will experience brain fog while under the influence of Xanax and alcohol, including: reduced blood flow to the brain, decreased excitatory neurotransmission (e.g. glutamate), increased inhibitory neurotransmission (e.g. GABA), and alterations in regional activation and/or connectivity.
  • Cognitive deficits: Although most individuals using Xanax with alcohol probably aren’t planning on engaging in cognitively-demanding tasks, this combination of substances will significantly impair aspects of cognition such as: attention, cognitive flexibility (i.e. task switching), critical thinking, planning, problem solving, judgment, reasoning, and self-control.  The cognitive deficits resulting from administration of Xanax and alcohol likely occur, in part, as a result of CNS depression.  Substantial CNS depression will decrease arousal significantly such that, in accordance with the Yerkes-Dodson law, it becomes impossible to maintain optimal cognition.  Moreover, excessive GABAergic activity and diminished glutamatergic activity, as well as altered activity in a myriad of brain regions implicated in cognitive processes – might also explain cognitive deficits attributable to the co-administration of Xanax and alcohol.
  • Coma: Coma is characterized as a state of deep unconsciousness that persists for a prolonged duration, resulting from injury to the brain.  While coma is most commonly induced by head injury or illness, it can also occur from administration of drugs and/or drug combinations.  Individuals who administer high doses of Xanax and/or alcohol, such as in an attempted overdose, may be at high risk of entering a coma.  Compared to other benzodiazepines, Xanax does not appear any more or less likely to induce a coma.  That said, anyone who enters a coma from this substance combination may incur permanent deleterious neurological effects.
  • Confusion: Another side effect associated with the co-administration of Xanax and alcohol that some individuals will experience is confusion. Confusion generally goes hand-in-hand with other side effects such as brain fog, cognitive deficits, and memory impairment and may be caused by decreased cerebral blood flow, altered regional activation, and/or low arousal [from CNS downregulation].  While under the influence of this substance combination, confusion may be extreme such that the brain is unable to process and/or make sense of sensory inputs.  Any speech heard (such as in a conversation) or text read (such as in an article) may seem entirely nonsensical until sufficient quantities of Xanax and alcohol have been eliminated from systemic circulation.
  • Decreased blood pressure: Those who monitor their blood pressure while under the influence of Xanax and alcohol may notice a significant drop from homeostatic baseline readings. In many cases, blood pressure will drop below 90/60 – the lower threshold of the normal range.  Although low blood pressure as a standalone side effect is not usually problematic, it may decrease the amount of blood flowing to vital organs such as the brain.  Reduced blood flow to vital organs may cause blurred vision, chills, dizziness, fatigue, lightheadedness, respiratory depression, unsteadiness, and in some cases, fainting.  To minimize risk of fainting, it is recommended to seek medical supervision and avoid rapidly transitioning between lying/seated positions and standing.  Other strategies that may help decrease risk of fainting include: lying down, increasing electrolyte intake (e.g. sodium), maintaining abdominal pressure, staying hydrated, and consciously attempting to control breathing.
  • Depression: Though some individuals will report mood enhancement from co-ingestion of Xanax and alcohol, others may become depressed. Considering that depression is commonly associated with low arousal and decreased excitatory activity, it is logical to suspect that co-administration of two CNS depressants can induce depressive emotion.  Depression as an effect of this substance combination could be especially severe among individuals with a history of neuropsychiatric conditions such as major depressive disorder (MDD), and may be accompanied by suicidal thoughts or ideation.  Anyone who experiences severe depression after ingesting Xanax and alcohol should pursue immediate medical attention for supervision and proper treatment.
  • Difficulty breathing: Mixing Xanax and alcohol may lead to difficulty breathing such that an individual experiences shortness of breath and/or is unable to inhale adequate oxygen. For most who ingest this substance combination, difficulty breathing is probably due to respiratory depression.  Respiratory depression occurs as a result of downregulated CNS activity and can interfere with lung expansion and oxygen intake.  While experiencing respiratory depression, users may struggle to maintain a normative breathing pattern.  In rare cases, difficulty breathing may be caused by an allergic reaction to Xanax and/or alcohol.  If you ever experience difficulty breathing, do not hesitate to call emergency medical services.
  • Dissociation: Certain individuals who administer Xanax and alcohol will experience profound dissociation, characterized by a disconnection from homeostatic consciousness. The dissociation may be accompanied by depersonalization (feeling detached from one’s physiology, almost as if observing oneself from afar) and/or derealization (feeling as though one’s surroundings are not real).  The dissociation and related effects that occur following the ingestion of Xanax and alcohol may be caused by:  neurotransmitter alterations (especially increased GABA signaling), changes in brain region activation, diminished CNS function, and/or decreased blood flow to the brain.
  • Dizziness: The combination of Xanax and alcohol can induce dizziness via numerous mechanisms. One way in which this substance combination may cause dizziness is by decreasing blood pressure.  Any significant reduction in blood pressure decreases blood flow to vital organs such as the brain, which causes individuals to feel dizzy and lightheaded (sometimes prior to fainting).  Another means by which these substances could cause dizziness is by altering the density of fluids within the inner ear.  In particular, alcohol causes the cupula to become less dense than surrounding endolymphatic fluid, leading vestibular centers to falsely signal that head rotation has occurred – causing dizziness and/or spinning sensations.  A third way in which these substances may cause dizziness is by modulating activity in regions of the brain such as the cerebellum and/or supplementary motor areas.  It’s also possible that an allergic reaction may be culpable for dizziness.  In any regard, most individuals will experience some degree of dizziness after taking Xanax with alcohol.
  • Drowsiness: Generally, administering a standalone CNS depressant induces some drowsiness in most users. As a general rule of thumb, the greater a person’s CNS depression, the more significant his/her drowsiness is likely to be.  When Xanax and alcohol are administered together, the degree of CNS depression is amplified.  As a result, individuals who take this substance combination will probably experience extreme drowsiness.  In fact, the drowsiness may be so extreme that users are rendered immobile and/or end up passing out into a slumber.
  • Dry mouth: A blend of Xanax and alcohol might induce dry mouth as a side effect or unwanted reaction. In a subset of users, Xanax may cause dry mouth by interfering with salivary production, whereas alcohol can cause dry mouth via diuresis-related dehydration.  Since each substance can cause dry mouth when administered as a standalone, it’s reasonable to suspect that a combination would increase risk of dry mouth and/or the significance of oral dryness.
  • Euphoria: For many individuals, alcohol induces a mild euphoriant effect, likely as a result of its 5-HT3 receptor agonism. Agonism of the 5-HT3 receptor triggers the downstream release of dopamine within the nucleus accumbens, leading to mood enhancement and/or pleasure for many drinkers.  Although Xanax isn’t typically associated with euphoria, there’s reason to suspect that it may enhance mood in a subset of users via modulation of dopamine release in the ventral tegmental area (VTA) and/or interactions with dopamine receptors.  Perhaps the dopaminergic effects of these substances are synergistic such that when co-administered, euphoria or mood enhancement from the combination is more significant than either substance as a standalone.
  • Fainting: High dosages of either Xanax or alcohol can provoke fainting (i.e. syncope) or temporary loss of consciousness. When the substances are combined, a synergistic CNS depressant effect is induced and low-to-moderate dosages of each may be enough to cause fainting.  With this combination of substances, fainting commonly occurs as a result of low blood pressure stemming from CNS depression.  Low blood pressure leads to a reduction of blood flow to vital organs, and often causes dizziness, lightheadedness, and fainting.  Fainting may be less likely to occur while seated or lying down, and should be preventable if medical attention is received.  Understand that fainting or “passing out” may lead to concussion, head injury, and/or death from choking on vomit.
  • Fatigue: Following the simultaneous ingestion of Xanax and alcohol, it is common to experience extreme psychological and/or physical lethargy or fatigue. Fatigue occurs due to the fact that co-administration of Xanax and alcohol synergistically enhances GABAergic transmission to depress CNS function.  The fatigue may be evidenced by slowing or deceleration of thoughts and/or difficulties summoning enough energy to move.  As a result of the fatigue, most users of this substance combination will want to sit or lie down in a comfortable position rather than standing upright.  Moreover, for some individuals, especially high dose users, fatigue may be an acute reaction that occurs prior to onset of sleep or loss of consciousness.
  • Frequent urination: Xanax does not generally cause increased urination, in fact, it often helps reduce frequent urination associated with anxiety. However, alcohol is known to cause frequent urination via inhibiting the release of vasopressin, a hormone involved in urinary retention.  This blockade of vasopressin release prevents the kidneys from reabsorbing and conserving water stores and amplifies urinary output.  As a result, if you drink a lot of alcohol with Xanax, you’ll probably end up urinating more frequently than usual.  This frequent urination may lead to dehydration and/or electrolyte imbalances.
  • Gastrointestinal distress: A subset of individuals who administer Xanax plus alcohol will report gastrointestinal distress as a side effect. Gastrointestinal distress may be accompanied by constipation, diarrhea, indigestion, intestinal inflammation, nausea, stomach pain, and/or vomiting.  Of the two substances in this combination, alcohol is probably most culpable for gastrointestinal distress.  This is because the ingestion of alcohol causes the stomach to increase production of acid, and this acid production inflames the lining of intestines.  Among persons who ingest large doses of Xanax along with alcohol, it’s possible that the sheer quantity of the drug may irritate the stomach lining and affect gastric function.  Gastrointestinal distress is usually most severe among persons who ingest these substances on an empty stomach and less severe among persons who ingest these substances after a meal (food absorbs some of the acid).
  • Headaches: A reaction that some have reported as a result of ingesting Xanax and alcohol is headache. Because this combination of substances usually typically reduces anxiety, blood pressure, and muscle tension – any headaches experienced should differ from tension-type headaches.  In some cases, individuals may experience headaches as side effect of Xanax, and if a high dose is administered, headaches could become severe.  That said, most individuals can probably attribute their headaches to dehydration and/or electrolyte depletion resulting from alcohol intake.  It’s also possible that the combination of Xanax and alcohol alters intracranial blood flow in certain users, yielding excessive vasodilation or vasoconstriction to provoke migraine or headache, respectively.
  • Heart rate changes: Immediately after a person ingests the combination of Xanax and alcohol, he/she may notice an increased heart rate. An acute heart rate increase occurs from peripheral vasodilation attributable to alcohol intake.  In other words, alcohol causes peripheral blood vessels to dilate and blood flow to increase, which speeds up the heart rate.  That said, the CNS depressant effect of Xanax may negate some of the acute heart rate increase resulting from alcohol.  Furthermore, once the acute phase of alcohol ingestion has passed, both Xanax and alcohol will synergistically cause slowing of the heart rate.  Anyone with a history of cardiac abnormalities who mixes Xanax and alcohol should seek emergency cardiologic attention to avoid cardiac damage and/or serious complications.
  • Hepatic dysfunction: Administering Xanax and alcohol together may increase risk of liver damage and/or dysfunction. Both Xanax and alcohol undergo metabolism via enzymes in the liver, and when administered simultaneously and/or at high dosages, liver cells can be subject to damage.  Damage to liver cells may be permanent and yield symptoms of hepatic dysfunction such as: jaundice (yellow skin and eyes), abdominal pain, fatigue, appetite loss, and confusion.  It is thought that individuals with preexisting hepatic impairment are at highest risk of incurring liver damage from this substance combination, however, anyone who co-administers Xanax with alcohol is at risk.
  • Irritability: Though most persons will experience reduced irritability due to the relaxation derived from each substance, others may experience increased irritability.  Those who are most likely to become irritable while under the influence of Xanax and alcohol are individuals with either: a history of anger, prior suppression of anger, and/or a predisposition to irritability.  This is because Xanax and alcohol lead to disinhibition of personality traits whereby users exhibit less self-regulation and aren’t afraid to express themselves.  Another cause of irritability may be attributable to brain fog or cognitive dysfunction whereby individuals become frustrated and irritable over the inability to think clearly.  Moreover, decreased excitatory activity and altered neural activity (regions, pathways, etc.) may explain irritability increases.
  • Lightheadedness: Those who simultaneously ingest Xanax with alcohol will probably experience some lightheadedness. The most obvious cause of lightheadedness is low blood pressure whereby blood flow to the brain decreases, as does oxygenation.  Any decrease in blood flow to the brain could trigger some degree of lightheadedness, which may be accompanied by dizziness and/or nausea, and might lead to fainting.  Lightheadedness may be especially severe when transitioning from lying down or a seated position to standing.  The greater the dosage of each substance ingested in the combination, the more significant the lightheadedness is likely to be.  As the physiologic influence of each substance diminishes following systemic elimination, lightheadedness should abate.
  • Memory impairment: Both Xanax and alcohol can interfere with the formation and retrieval of memories, as well as induce amnesia, characterized by partial or total loss of memory. Numerous studies indicate that Xanax impairs multiple aspects of memory function compared to a placebo, and that memory impairment typically persists long after the drug is stopped.  Moreover, because emerging evidence highlights links between benzodiazepines and dementia, some believe that Xanax may cause neurodegeneration or permanent damage to regions of the brain implicated in memory function.  Alcohol is known to disrupt hippocampal activation which impairs formation of new memories.  If alcohol intake is significant, individuals may experience partial (fragmentary) or complete (en bloc) blackouts in which the person is unable to recall events while drinking.  When administered together, the degree of resulting memory impairment may be even more significant than administration of each substance as a standalone.
  • Muscle relaxation: The combination of Xanax and alcohol is also known to decrease muscle tone (i.e. tension) and induce myorelaxation. Each substance interacts with GABA(A) receptors throughout the CNS, and when administered at sufficient dosages, muscle relaxation increases.  Muscle relaxation is generally not a side effect most individuals are concerned with.  In fact, most users of this substance combination probably perceive myorelaxation as a favorable reaction.  Although the muscle relaxation may be pleasant, it may leave you feeling sluggish and/or lazy to the extent that you don’t want to get off the couch or out of bed.
  • Nausea: Co-administration of Xanax and alcohol may lead some individuals to experience nausea. There are many potential reasons as to why nausea might occur after taking Xanax with alcohol including: allergic reactions, gastrointestinal distress, hepatic dysfunction, low blood pressure, and/or vestibular dysfunction.  Nausea might also occur as a result chemoreceptor trigger zone (CTZ) activation.  The chemoreceptor trigger zone is an area of the brain implicated in the detection of toxins, and if activated following the ingestion of Xanax and/or alcohol, this may induce nausea and [possibly] vomiting.
  • Psychotic episode: Although rare, some individuals may report drug-induced psychosis as an adverse reaction to Xanax and alcohol. Psychosis resulting from this substance combination may yield various symptoms such as:  dissociation, hallucinations (auditory, visual, and/or tactile), and/or delusions.  Considering that: there are no links between Xanax ingestion and psychosis, there are numerous cases of alcohol-induced psychosis, and that Xanax is often successfully administered as an adjunct treatment for psychosis – it’s reasonable to suspect that alcohol is most culpable for psychotic episodes resulting from this substance combination.  Therefore, one might hypothesize that persons who consume high doses of alcohol relative to Xanax [in this combination] may be at greater risk of substance-induced psychosis.  Individuals with a history of psychotic episodes and/or neuropsychiatric disorders may also exhibit increased susceptibility to psychotic reactions.
  • Renal dysfunction: An adverse reaction that might occur in a small percentage of individuals who administer Xanax and alcohol simultaneously is renal dysfunction. Although there’s not much evidence suggesting that Xanax impairs renal function, there is evidence indicating that acute alcohol consumption can induce renal impairment.  Alcohol intake can alter concentrations of hormones involved in the regulation of kidney function, ultimately leading to renal impairment.  Furthermore, large quantities of alcohol can impair liver function, which can have deleterious downstream consequences for the function of kidneys.  Renal impairment from these substances may cause decreased urination, swelling, nausea, fatigue, and/or shortness of breath.  Persons with preexisting renal impairment and/or high-dose users of Xanax and/or alcohol are at greatest risk of experiencing renal dysfunction.
  • Respiratory depression: A major reason the combination of Xanax and alcohol is regarded as dangerous is due to the induction of respiratory depression. When respiratory depression occurs, most individuals will notice or sense that their breathing has slowed down and/or that they’re taking fewer breaths than usual.  If the respiratory depression becomes severe, breathing rate slows may slow so significantly that it becomes challenging to inhale adequate oxygen.  Individuals may drift in and out of consciousness with temporary lapses in breathing (apnea) and struggle for air.  In extreme cases, Xanax and alcohol may induce respiratory failure in which the inhalation of oxygen and/or exhalation of carbon dioxide are compromised.  This may lead to loss of consciousness, coma, and death.  Anyone experiencing respiratory depression after taking Xanax and alcohol requires emergency medical attention.
  • Sleep disturbances: For substance-naïve individuals, Xanax and alcohol often improve sleep architecture by increasing slow-wave sleep (SWS), leaving them feeling more rested upon waking as compared to a placebo. That said, some individuals may report sleep disturbances such as random awakenings throughout the night, night sweats, weird dreams, and/or nightmares.  It isn’t entirely clear as to what might cause these sleep disturbances, however, some hypothesize that the disturbances are caused by inevitable decreases in systemic concentrations of Xanax and/or alcohol throughout the night.  In other words, systemic concentrations of Xanax and/or alcohol may be high at sleep onset, however, as systemic concentrations plummet, sleep architecture may be altered in such a way as to prompt disturbances.  It’s also possible that sleep disturbances may as a result of hypoxia and/or hypercapnia attributable to substance-mediated changes in breathing patterns (e.g. respiratory depression).
  • Speech disturbances: Another effect resulting from the cumulative physiologic influence of Xanax and alcohol is disturbed speech. Anyone who uses this substance combination may exhibit speech that’s: disorganized, nonsensical, improperly annunciated (e.g. slurred).  Altered activation within certain regions of the brain (e.g. prefrontal cortex) may cause cognitive deficits, which explain disorganized and/or nonsensical speech.  Annunciation abnormalities (e.g. slurring) typically occurs as a result of disrupted activation within motor control centers of the brain.
  • Stomach aches: Though medically-recommended dosages of Xanax don’t usually cause severe stomach aches, large doses could. Furthermore, combining any dose of Xanax with alcohol may irritate the gastrointestinal tract to a greater extent than either substance as a standalone.  That said, alcohol is likely most to blame for stomach aches associated with this combination.  Not only does alcohol prompt increased acid production within the stomach, but it inflames the stomach lining.  Stomach aches may be accompanied by constipation, diarrhea, flatulence, and/or indigestion.  Persons who use this substance combination on an empty stomach may be more prone to stomach aches than individuals with a full stomach – as food can help soak up acid and may prevent some inflammation.
  • Tinnitus: Some might notice that their ears start to ring or buzz after ingesting Xanax with alcohol. The perception that one’s ears are ringing or buzzing, referred to as tinnitus, can sometimes occur after ingesting multiple substances simultaneously.  For certain individuals, tinnitus may be transient and occur as a result of alcohol and/or Xanax interacting with or altering blood flow to parts of the inner ear.  It’s also possible that high doses could provoke an ototoxic reaction in some individuals whereby ears end up ringing and hearing is muffled and/or lost.  Persons who experience tinnitus should seek emergency medical attention and evaluation from an otolaryngologist.
  • Vision changes: It is also relatively common to experience noticeable changes in visual perception after taking Xanax plus alcohol. Examples of such visual changes may include: acuity reduction, brightness, blurred vision, double vision, and/or peripheral floaters.  There are many reasons as to why visual perception may be affected by this substance combination including: altered activity in centers of the brain implicated in visual perception and processing, depressed CNS function, changes in cerebral blood flow, neurotransmitter fluctuations, etc.  If you suspect that the substance combination may have damaged your eyes, it is recommended to contact an ophthalmologist for a comprehensive examination.
  • Vomiting: Some individuals may end up feeling so nauseous from the combination of Xanax and alcohol that they end up vomiting. There are many reasons as to why vomiting may occur after the ingestion of this substance combination, including: gastrointestinal distress, erroneous vestibular signaling, high blood levels of Xanax and/or alcohol, and/or shifts in activity within various brain regions (e.g. cortex, hypothalamus, thalamus, etc.).  Each of the aforestated physiologic changes may stimulate the chemoreceptor trigger zone (CTZ), a region within the brain that provokes an emetic reflex characterized by nausea and vomiting.  In some cases, vomiting may be helpful in that it eliminates Xanax and/or alcohol from systemic circulation quicker than usual, possibly preventing or mitigating physiologic damage from this combination.  That said, vomiting can be a dangerous reaction among persons who are extremely intoxicated and/or sedated, as there’s always risk of the individual dying from choking on his/her vomit.  Moreover, vomiting can lead to dehydration and electrolyte imbalances, each of which could exacerbate certain side effects and damage the brain.  Anyone who vomits after ingesting this substance combination should seek emergency medical attention.

Note: Realize that the aforestated list of reactions to the combination of Xanax and alcohol may be incomplete.  Anyone with questions regarding side effects and/or adverse reactions resulting from Xanax and alcohol is encouraged to seek professional medical attention.  If you’re aware of effects that may occur as a result of ingesting this combination that weren’t listed, be sure to report and describe them in the comments section below.

Variables that influence Xanax and Alcohol effects

There are a multitude of variables that can influence the particular physiologic reactions that a person experiences after ingesting Xanax with alcohol, as well as their respective severities.  Such variables may include: respective dosages (of Xanax and alcohol); administration details (e.g. latency between ingestion); other substances utilized (e.g. dietary supplements, prescription medications, etc.); tolerance to either substance; and individual-specific factors (e.g. age, body composition, medical conditions, etc.).  If contemplating the variance in physiologic reactions attributable to the co-ingestion of Xanax and alcohol, these influential variables warrant analysis.

  1. Dosages of each

The extent to which Xanax and alcohol alter the physiology of a particular user will be determined by the dosages of each substance.  Assuming tolerance is equal among users, most would agree that ingesting lower doses of Xanax and alcohol [in combination] would yield a less substantial shift away from baseline (homeostatic) physiology as compared to ingestion of high doses.  Knowing this, it is fair to suggest that persons who ingest lower doses of Xanax and alcohol [in combination] will probably exhibit: less intoxication (and pleasurable effects), fewer side effects, and less severe side effects – than those who ingest high dosages.  In other words, the physiologic reaction to half bottle of tequila and a Xanax bar will be greater than the physiologic reaction to a small glass of white wine and a subtherapeutic dose of Xanax.

  • Low doses: When administered as a substance combination, if the respective dosages of Xanax and alcohol are low, the likelihood of severe adverse reactions and/or interaction effects are minimized – as compared to higher dosages. Not only are lower doses of each substance easier for the body to efficiently absorb and distribute, but low doses place a less significant burden upon the liver and kidneys implicated in metabolism and excretion.  This reduces odds of hepatic and/or renal dysfunction resulting from this substance combination, and also decreases odds of interactions resulting from pharmacokinetic processes.  In addition to more efficient pharmacokinetics at low doses, the degree to which physiology is modulated by substance pharmacodynamics is less significant.  Specifically, lower doses of Xanax and alcohol exert less of an effect upon neurochemical receptors (e.g. GABA-A) and yield less CNS depression – than high doses.  Overall, it’s reasonable to suspect that most healthy adults who ingest low doses of this substance combination (Xanax plus alcohol) probably won’t endure serious adverse reactions.
  • High doses: When high dosages of Xanax and alcohol are ingested as a substance combination, the likelihood of deleterious reactions substantially increases. Simultaneous ingestion of high-dose Xanax and alcohol results in less efficient pharmacokinetic processes such as absorption, metabolism, and excretion – of each substance.  As a result, each substance will remain in systemic circulation for a longer period than at lower doses, leading to a prolonged duration over which the user remains intoxicated and/or endures adverse reactions.  Moreover, because large doses of Xanax and alcohol will have been ingested together, a greater quantity of each drug will necessitate metabolism and excretion, thereby placing a greater burden upon the liver and kidneys, respectively, which increases risk of hepatotoxicity, nephrotoxicity, and other pharmacokinetic interactions.  Ingestion of Xanax and alcohol at high doses also yields more substantial physiologic modulation as a result of pharmacodynamics.  In other words, interaction with neurochemical targets (e.g. GABA(A) receptors, Gly receptors, NMDA receptors, et al.) will be more significant at higher doses, ultimately generating more significant CNS depression.  Overall, it’s reasonable to suspect that anyone who ingests high doses of this substance combination (Xanax plus alcohol) is at major risk of enduring serious adverse reactions (e.g. respiratory depression, respiratory failure, vomiting, and/or death).

Xanax to Alcohol ratio:  Not everyone who mixes Xanax with alcohol will ingest dosages [of each substance] that are of equivalent physiologic potency.  For example, at one extreme, an individual may ingest a mega-dose of Xanax along with a small amount of alcohol.  In this case, because a large quantity of Xanax was ingested with a small amount of alcohol, it’s reasonable to assume that the user’s physiology is subject to greater influence from the Xanax, yielding a greater number of Xanax-related side effects.

As another example, at the opposite extreme, an individual may get “hammered” drunk and ingest a micro-dose of Xanax.  In this case, because a large quantity of alcohol was ingested with a small amount of Xanax, it’s reasonable to assume that the user’s physiology would be under greater influence of the alcohol, yielding more alcohol-related side effects.  Moreover, if dosages of Xanax and alcohol [in the combination] were of relatively equal physiologic potency, the number of side effects (and their respective severities) may be evenly attributable to each substance.

That said, because the pharmacokinetics and pharmacodynamics of each substance differ, and physiology of persons who administer this substance combination will vary, it’s impossible to estimate the dosage at which the physiologic effect of one substance [in the combination] would supersede that of the other.  If attempting to approximate dosage equivalency in terms of physiologic potency, one might hypothesize that the effect of 0.25 mg Xanax is akin to the effect of alcohol found within a standard can of beer (14 grams).  Assuming this hypothesis were reliable, anyone ingesting 0.50 mg Xanax with 2 cans of beer would incur relatively equal physiologic modulation from each substance.

Furthermore, anyone ingesting 1 mg Xanax with 1 can of beer would incur greater physiologic modulation from Xanax, and anyone ingesting 0.25 mg Xanax with 4 cans of beer would incur greater physiologic modulation from alcohol.  If alcohol was more potent in the combination, enzymes implicated in its metabolism (e.g. ADH) and neurochemical targets implicated in its action (e.g. NMDA receptors) will be affected more than if Xanax was more potent.  Finally, if doses of each substance are high and of relatively equal physiologic potency, likelihood of interaction effects and/or synergistically-mediated side effects will increase.

Note: Know that the aforestated hypothetical dosing equivalencies should not be considered accurate.  As an attempt to accurately estimate the physiologic potency of Xanax and alcohol, you’d need to undergo individualized physiologic testing.  That said, even if this testing were conducted, it would still be challenging to compare Xanax and alcohol dosages due to slight variation in pharmacodynamics and significant variation in pharmacokinetics.

  1. Administration specifics

Details associated with the administration of Xanax and alcohol may influence effects and/or reactions attributable to ingestion of this substance combination.  Administration details to consider as potentially influencing reactions to Xanax and alcohol include: administration timing (e.g. morning), administration rate (i.e. speed), food / water intake (fullness and hydration), and time between ingestions (i.e. latency).  A person who administers this substance combination in the evening at a slow rate after eating a full meal and hydrating may exhibit noticeably different reactions than if he/she administered the substance combination rapidly in the morning on an empty stomach.

  • Fullness / Hydration: The degree to which a person is full [of food] and hydrated [with water] while administering Xanax and alcohol could affect reactions to this substance combination. It is known that the administration Xanax plus alcohol on an empty stomach tends to induce a more potent physiologic response than ingestion on a full stomach – or ingestion with food.  When the stomach is empty, Xanax and alcohol are rapidly absorbed and metabolized, yielding a more potent and/or quicker onset of intoxication.  Moreover, an empty stomach increases likelihood of gastric irritation resulting from either substance.  If ingested on a full stomach, this substance combination will undergo slower absorption and metabolism, yielding a less potent and/or slower onset of intoxication.  Furthermore, having food in the stomach can help absorb excess production of stomach acid to reduce gastrointestinal side effects.  The degree to which a person is hydrated prior to ingestion of this substance combination may also influence physiologic reactions.  For example, someone who’s dehydrated may find that Xanax plus alcohol exacerbate dehydration-related effects (e.g. fever, vomiting, etc.) and undergo slower systemic elimination due to lack of hydration.  Oppositely, someone who’s well-hydrated may avert severe effects attributable to dehydration and may eliminate each substance quicker.  In brief, Xanax and alcohol may be more tolerable among persons who are full and hydrated – as compared to those who are fasted and/or dehydrated.  To get extra technical, one might consider the elapsed time since food and/or beverage ingestion, as well as macronutrient and micronutrient compositions of food and/or beverages.
  • Ingestion latency: The amount of time that elapses between the respective ingestion of Xanax and alcohol can influence physiologic reactions to this substance combination. Someone who ingests Xanax and alcohol simultaneously will likely exhibit more substantial physiologic reactions and be more susceptible to interaction effects than if there were latency (or a time gap) between ingestions.  As a general rule of thumb, the greater the ingestion latency, the lower the likelihood of interaction effects resulting from this substance combination.  This is because increased time between administration of Xanax and alcohol yields less overlap in pharmacokinetic processes (absorption, metabolism, and elimination) and pharmacodynamic effects.  In other words, with some latency between ingestion of Xanax and alcohol, one of the substances will have undergone [partial or full] metabolism [and possibly some elimination] before the second is introduced.
  • Time of day: The time of day at which an individual ingests the combination of Xanax and alcohol may also influence the severity of side effects and/or adverse reactions that occur.  This is because production of neurotransmitters and hormones shifts throughout the day in accordance with circadian biology.  For most individuals, the endogenous production of CNS activators (e.g. cortisol) is highest in the morning – yielding CNS arousal, whereas the endogenous production of CNS depressants (e.g. melatonin) is highest in the evening – yielding CNS depression.  Knowing that Xanax and alcohol promote CNS depression, and that CNS function is likely to be more depressed in the evening [in accordance with circadian biology], it’s possible that nighttime ingestion of this substance combination yields increased CNS depression as compared to morning or afternoon ingestion [of an equivalent dose].  For this reason, one might speculate that individuals who ingest Xanax plus alcohol in the evening may be at [slightly] increased risk of side effects and/or adverse reactions attributable to excessive CNS depression (e.g. respiratory failure) as compared to morning or afternoon users.
  • Rate of administration: The rate at which an individual administers Xanax and alcohol may also influence onset and/or significance of intoxication, side effect severity, and likelihood of adverse reactions. When administered rapidly, such as by chugging a beer [in 30 seconds] after taking 0.5 mg Xanax, a greater quantity of Xanax and alcohol enter systemic circulation simultaneously, which may: expedite onset and/or bolster significance of intoxication and increase risk of severe side effects and/or adverse reactions – as compared to slower rates of administration.  When administered slowly, such as by sipping a beer over a 30-minute duration and dividing 0.5 mg Xanax into doses of 0.25 mg to be taken once every 30 minutes, a lesser quantity of Xanax and alcohol enter systemic circulation simultaneously, which could: prolong onset and/or reduce significance of intoxication and decrease risk of severe side effects and adverse reactions – as compared to faster rates of administration.  It should be stated that, because Xanax is manufactured in pill format, most users will administer Xanax at a rapid rate via swallowing an entire pill rather than bothering with dividing up dosages.  That said, rate of alcohol consumption may be subject to significant variation among users of this substance combination.
  • Mode of administration: The modality by which Xanax and alcohol are administered may also influence physiologic reactions to this substance combination. Certain modes of administration will induce greater and/or more rapid onset of intoxication and/or more severe side effects and/or adverse reactions – as compared to others.  This is because mode of administration dictates pharmacokinetics and bioavailability of each substance.  Someone who administers Xanax via intranasal insufflation and alcohol via intravenous injection may exhibit a noticeably different physiologic reaction to this substance combination than had he/she administered each substance orally.  Although Xanax and alcohol are traditionally administered orally, examples of other alternative administration modalities include: intranasal, intravenous, subcutaneous, rectal, etc.
  • Xanax format: The format of Xanax ingested along with alcohol may have a significant impact upon the duration over which you are intoxicated and/or the side effects that you experience. Xanax is manufactured in two distinct formats, including: immediate-release (IR) and extended-release (XR).  The immediate-release (IR) format is rapidly absorbed with a duration of effect ranging from 2 to 4 hours.  The extended-release (XR) format of Xanax is absorbed at a slower rate with a duration of effect ranging from 8 to 12 hours.  Considering these format differences, it’s reasonable to suspect quicker onset of intoxication among persons who administer immediate-release (IR) formats and longer duration of intoxication among persons who administer extended-release (XR) formats – along with alcohol.
  1. Co-administered substances

Anyone who administers additional substances with the combination of Xanax and alcohol may exhibit different physiologic responses than had they refrained from administration of additional substances.  Additional substances might include things like: dietary supplements, over-the-counter (OTC) medications, pharmaceutical medications, illicit drugs, etc.  If these additional substances were administered on the same day as Xanax and alcohol, there’s a chance that they could: alter pharmacokinetics; potentiate or attenuate physiologic responses; and/or induce unwanted side effects of their own.

  • Pharmacokinetic interactions: If additional substances are administered with the combination of Xanax and alcohol, there’s a chance that they might modulate pharmacokinetics of Xanax and/or alcohol to provoke an interaction effect. It is known that Xanax undergoes metabolism via CYP3A4 whereas alcohol undergoes metabolism via ADH, ALDH, CYP2E1, and catalase. In the event that an additional substance is administered [with Xanax plus alcohol] that interacts with CYP3A4, ADH, ALDH, CYP2E1, or catalase – it may significantly alter rate of Xanax or alcohol metabolism.  For example, administration of a CYP3A4 inhibitor like clarithromycin would impair Xanax metabolism and may potentiate and/or prolong its effect, whereas administration of a CYP3A4 inducer like rifampicin would enhance Xanax metabolism and may reduce the duration of its effect.  With regard to alcohol, administration of an acetaldehyde dehydrogenase (ADH) inhibitor like Fomepizole will potentiate its intoxicating effect.  Moreover, even if additional substances don’t interact with enzymes implicated in the metabolism of Xanax or alcohol, they may increase hepatic and renal burden – and risk of hepatotoxicity and nephrotoxicity.  Administration of additional substances could also affect absorption and distribution of Xanax and alcohol.
  • Physiologic effect (potentiation vs. attenuation): Any substances administered with Xanax and alcohol might potentiate or attenuate their pharmacodynamic actions and/or cumulative effect upon CNS function. For example, someone who ingests the supplement “kava” (a GABA receptor modulator) prior to administration of Xanax and alcohol may exhibit a synergistic GABAergic effect and greater CNS depression as compared to someone who doesn’t.  In this case, side effects attributable to GABAergic transmission and CNS depression may become more numerous and/or extreme.  Oppositely, someone who ingests a GABA(A) receptor antagonist like flumazenil may exhibit less significant GABAergic enhancement from Xanax and alcohol.  In this case, side effects attributable to GABAergic transmission and corresponding CNS depression may be less noticeable.  That said, substances need not directly interact with the pharmacodynamic actions of Xanax and alcohol to alter physiologic responses to the combination.  Knowing that Xanax and alcohol downregulate CNS activity, it’s reasonable to suspect that co-administered CNS activators (e.g. psychostimulants) will reduce CNS depression and corresponding side effects [from Xanax and alcohol], whereas co-administered CNS de-activators (e.g. sedatives) will amplify CNS depression and corresponding side effects.
  • Side effects: Not all substances ingested with Xanax and alcohol will induce interaction effects or modulate CNS activation, however, some might provoke side effects distinct from those attributable to Xanax and/or alcohol. Certain individuals might assume that all side effects experienced while under the influence of Xanax and/or alcohol are attributable to Xanax and/or alcohol – without suspecting that a co-administered substance might be culpable.  For example, someone who administers a dietary supplement along with Xanax and alcohol may develop a headache and assume that the headache was caused by Xanax and/or alcohol or an interaction effect, when in reality, the dietary supplement was the sole inducer.  In any regard, some individuals should expect significantly more side effects if they ingest another substance with Xanax and alcohol.

Note: In some cases, the administration of an additional substance may not alter physiologic responses to the combination of Xanax and alcohol.  For this reason, it should not be assumed that a substance you’ve used with Xanax and alcohol is affecting physiologic responses to this combination.  That said, the greater the number of substances administered with Xanax and alcohol, the increased odds of experiencing an interaction effect.  Moreover, in the event that a substance is administered that interacts with Xanax or alcohol, the dosing of that particular substance will determine the significance of the interaction effect.  If you have a question about the risk of an interaction effect, consult a medical professional.

  1. Preexisting Tolerance

The degree to which an individual exhibits physiologic tolerance to alprazolam (Xanax) and/or alcohol will influence the magnitude of a user’s physiologic reaction to these substances.  Lower tolerance in respect to the dosages of each substance administered will yield a more substantial physiologic response whereby likelihood of severe side effects and/or adverse reactions is increased.  Higher tolerance in respect to the dosages of each substance administered will yield a less substantial physiologic response whereby likelihood of side effects and/or adverse reactions is reduced.

  • Zero tolerance: First-time users of Xanax and alcohol will exhibit zero physiologic tolerance and will be prone to a more substantial physiologic response to each substance in the combination.  Specifically, first-time users will not exhibit pharmacokinetic-related adaptations which allow for more efficient metabolism and elimination of each substance, nor will they exhibit neuroadaptations which reduce the significance of psychoactive effects induced by each substance.  As a result, substance-naïve individuals or persons without tolerance will be at greatest risk of serious adverse reactions attributable to slow metabolism and/or elimination, as well as from greater potency of psychoactive effect plus magnitude of CNS depression.
  • Moderate tolerance: Persons who administer Xanax and alcohol on a somewhat-regular basis will exhibit some degree of tolerance prior to ingestion of the combination. Their body will have adapted in ways that promote more efficient metabolism and elimination of each substance.  These adaptations should minimize risk of hepatotoxicity and/or nephrotoxicity as compared to someone devoid of preexisting tolerance.  Moreover, some neuroadaptation will have occurred such that neurochemistry will be less sensitive to the psychoactive effect of each substance.  For this reason, less significant: CNS depression, intoxication, and side effects should be expected among someone with moderate tolerance as compared to a first-time user.
  • High tolerance: Individuals who administer Xanax and alcohol frequently may exhibit high physiologic tolerance to each substance. High physiologic tolerance that occurs after frequent Xanax and alcohol ingestion will result in the upregulation and/or downregulation of enzymes to enhance the efficiency of substance metabolism and elimination.  Furthermore, high physiologic tolerance will also result in upregulation and/or downregulation of neurotransmitter receptor sites in the brain such that the psychoactive effect of Xanax and alcohol become less significant.  This considered, most would expect less intoxication, fewer side effects, and decreased odds of adverse reactions [relative to dosage] among persons with high tolerance.

It must be mentioned that some individuals may exhibit high physiologic tolerance to one substance in the combination (e.g. Xanax), but low physiologic tolerance to the other (e.g. alcohol).  If this is the case, it’s logical to suspect that the greater the dosage administered of the substance to which a person exhibits less tolerance, the more significant its effect will be upon physiology.  In other words, someone with a high tolerance to Xanax and a low tolerance to alcohol who administers this substance combination will likely exhibit a greater number of alcohol-mediated side effects and/or adverse reactions as compared to Xanax-mediated side effects.

That said, because Xanax and alcohol exhibit significant overlap in pharmacodynamic actions, it’s likely that persons who’ve developed tolerance to one substance will exhibit cross-tolerance for the other.  Specifically, both Xanax and alcohol function principally via positive allosteric modulation of the GABA(A) receptor to enhance GABAergic transmission.  As a result, neuroadaptation [within the GABA(A) receptor complex] as a result of high tolerance to one substance may reduce the significance of psychoactive effect, intoxication, and side effects induced by the other.

Still, it is important to note that some degree of cross-tolerance does not indicate an identical overlap in physiologic tolerance.  Someone with high tolerance to Xanax and low tolerance to alcohol will have incurred enzymatic changes that promote efficient metabolism and elimination of Xanax, but not alcohol.  Moreover, this individual will also exhibit sensitivity to pharmacodynamic actions of alcohol that do not occur from Xanax (e.g. NMDA receptor antagonism, Gly receptor antagonism, and 5-HT3 receptor agonism).

Based on the fact that the pharmacodynamics of Xanax are relatively limited to GABA(A) receptor modulation, it’s reasonable to hypothesize that someone with a high tolerance to alcohol (which exerts similar action upon GABA(A) receptors as Xanax) and low tolerance to Xanax would experience less significant physiologic reactions after ingesting the combination than someone with a high tolerance to Xanax and low tolerance to alcohol.  This is because the individual with a high tolerance to alcohol and low tolerance to Xanax would’ve exhibited neuroadaptations equipped to handle the action of Xanax upon GABA(A) receptors, but the person with a high tolerance to Xanax and low tolerance to alcohol would not exhibit neuroadaptations equipped to handle secondary actions of alcohol upon NMDA, Gly, and 5-HT3 receptors.

That said, there’s no substantial overlap in the enzymes implicated in the metabolism of Xanax and alcohol.  For this reason, anyone who exhibits high tolerance to one substance in the combination and low tolerance to the other may struggle with efficient metabolism and excretion of the substance to which they exhibit low tolerance.  This could prolong intoxication, bolster intoxication, and/or increase risk of hepatic and/or renal dysfunction.

It’s also necessary to underscore that the degree to which tolerance influences reactions to the co-administration of Xanax and alcohol is relative to the dose.  To explain, let’s assume the combination of Xanax (0.5 mg) and alcohol (14 grams) were assigned to 3 individuals, each with different levels of tolerance: zero tolerance, moderate tolerance, and high tolerance.  Relative to the aforestated dose (0.5 mg Xanax and 14 grams alcohol), the person with zero tolerance would probably exhibit the most severe side effects and intoxication (due to zero physiologic adaptation), whereas the individual with high tolerance would probably exhibit the fewest side effects and would be least intoxicated (due to more substantial physiologic adaptation).

If relativity of dosing is disregarded, we could hypothesize that individuals with high tolerance may be increasingly prone to severe side effects and/or adverse reactions for numerous reasons.  Perhaps the individuals with high tolerance have incurred deleterious long-term physiologic adaptations from regular ingestion of each substance, or perhaps those with high tolerance may constantly test the limits of safe dosing thresholds – putting them at increased risk of severe adverse reactions from Xanax and alcohol.  Oppositely, without considering tolerance relative to dose, one might assume that persons with low tolerance would have incurred zero deleterious physiologic adaptations and may be more risk averse in terms of testing the limits of safe dosing thresholds, thereby minimizing their chances of severe intoxication and/or adverse reactions.

  1. Individual factors

In addition to variables such as: dosage, preexisting tolerance, administration details, and/or usage of other substances – individual-specific factors can significantly influence how someone reacts to the co-ingestion of Xanax and alcohol.  Important individual-specific factors to consider as influencing reactions to this substance combination include: age, genetics, medical conditions, physical attributes, and sex.  It is differences in the aforestated individual factors that often explain why multiple individuals will experience different side effects and/or adverse reactions despite similarities in dosing, tolerance, administration details, etc.  Below is a list of individual-specific factors that may help explain your particular reaction to Xanax and alcohol.

  • Age: The age of a person who ingests Xanax and alcohol may influence their physiologic reaction to this substance combination. Some research suggests that the half-life of Xanax is prolonged among elderly men as compared to younger male adults.  Because elderly men seem to eliminate Xanax at a slower rate than average, elderly men may incur the greatest degree of intoxication and/or the most prolonged intoxication from Xanax [within the substance combination], putting them at increased risk of severe side effects as compared to younger adults.  Additionally, it is known that elderly individuals (regardless of sex) metabolize alcohol at a slower rate than younger adults due to age-related impairment of enzyme function (e.g. ADH, CYP2E1, etc.).  Impaired metabolism and elimination of Xanax and alcohol increases susceptibility to adverse reactions to this substance combination among elderly users.  Elderly individuals are also more likely than younger adults to: use medications for age-related medical conditions, exhibit impaired organ function (e.g. brain, liver, kidneys), and exhibit poorer water distribution – each of which may further increase risk of adverse reactions to Xanax and alcohol.  Comparatively, young adults tend to metabolize and eliminate Xanax and alcohol efficiently, putting them at decreased risk of an adverse reaction to this substance combination.  Although pediatrics may eliminate Xanax and alcohol quicker than adults, the CNS of pediatrics will be underdeveloped and their body size will be smaller (on average) such that their risk of adverse reactions from ingestion of this substance combination.  In terms of age, young healthy adults should be least susceptible to adverse reactions from Xanax and alcohol due to the attainment of peak physical and CNS development (compared to children), and lack of degeneration (as evidenced in elderly).
  • Genetics: The genetic and epigenetic expression of an individual who ingests Xanax and alcohol can have a significant impact on how they respond to these substances. Among the most important genes to discuss in terms of influencing physiologic reactions to Xanax and alcohol are those encoding for enzymes implicated in metabolism of each substance.  Xanax undergoes hepatic metabolism primarily via CYP3A4, whereas alcohol undergoes metabolism via ADH (alcohol dehydrogenase), ALDH (aldehyde dehydrogenase), CYP2E1, and catalase.  Because expression of genes encoding for the aforementioned enzymes will be subject to individual variation, the rate and degree of Xanax and alcohol metabolism will vary among users.  Rate and degree of metabolism [as mediated by genetics] will determine the significance and duration of intoxication, as well as a person’s risk of adverse reactions.  In addition to genes involved in substance metabolism, it’s also necessary to consider genes that encode for homeostatic neurochemistry of the user.  Someone with a particular set of genes may exhibit a homeostatic neurochemical signature that makes him/her more prone to potent psychoactive effects from Xanax and alcohol – as compared to an individual with notably different genes and a markedly different homeostatic neurochemical signature.  Another possibility is that certain individuals exhibit genes that expedite detox from Xanax and/or alcohol whereby homeostasis is reestablished at a faster pace following ingestion of this substance combination compared to others.  Also worth mentioning is that epigenetic expression may influence the significance of effect exerted upon the CNS by Xanax and alcohol.
  • Medical conditions: Preexisting medical conditions and/or history of a particular medical condition may also influence how a person responds to Xanax and alcohol. Anyone with a medical condition is likely at increased risk of experiencing severe side effects or adverse reactions following the ingestion of this substance combination.  For example, someone with hepatic impairment may be unable to efficiently metabolize Xanax and alcohol, putting him/her at risk of hepatotoxicity, prolonged intoxication, and other adverse reactions – following ingestion of this combination.  Another example might involve someone with a history of low blood pressure who exhibits an additional blood pressure decrease and faints following the administration of Xanax and alcohol.  It’s also reasonable to consider that symptoms of a preexisting medical condition may be exacerbated by the effects of Xanax and/or alcohol – or vice-versa.  For example, someone with a history of major depressive disorder (MDD) may experience a notable worsening of depression, resulting in suicidal ideation – after using this substance combination.  Furthermore, persons with medical conditions may be prone to more severe side effects from Xanax and alcohol as a result of medications used for treatment – each of which might provoke unwanted interactions via pharmacokinetics or potentiation of CNS effects.  Examples of medical conditions that might significantly increase risk of adverse reactions to these substances include: cardiac disorders, gastrointestinal disorders, hormone imbalances, and neuropsychiatric disorders.
  • Physical attributes: The physical attributes of persons who ingest Xanax and alcohol may influence the extent to which they become intoxicated and side effect severity. Specific physical attributes to consider include: body size (height and weight) and body composition (fat and muscle).  In terms of body size, larger individuals (taller and heavier) can generally tolerate greater quantities of Xanax and alcohol with fewer and/or less severe side effects than smaller individuals (shorter and lighter).  In other words, someone with a height of 7-feet and weight of 300 lbs. will probably experience a less substantial physiologic reaction to 0.25 mg Xanax plus 1 beer – as compared to someone with a height of 5-feet and weight of 120 lbs.  This is primarily due to the fact that larger individuals exhibit increased distributional volume of each substance, and thus, may be slightly less intoxicated based on their size.  In terms of body composition, persons with high muscle / low fat should tolerate Xanax and alcohol better than persons with low muscle / high fat.  This is because both alprazolam (Xanax) and alcohol are hydrophilic, meaning they have an affinity for water stores within the body.  Since muscle mass harbors more water than fat, individuals with high muscle / low fat may be prone to less intoxication than individuals with low muscle / high fat.
  • Sex: It’s reasonable to suspect that sex may also influence physiologic effects resulting from co-ingestion of Xanax and alcohol. There’s some research showcasing slower systemic elimination of Xanax in elderly males as compared to elderly females.  Other research suggests that Xanax may modulate activity within the HPA (hypothalamic-pituitary-adrenal) axis to a greater extent in females as compared to males.  Additionally, preliminary evidence indicates that the rate of alcohol metabolism may differ in females from that of males.  It is also known that, on average, males have larger bodies with more muscle and less fat compared to females, making them less prone to significant intoxication and side effects from Xanax and alcohol.  Moreover, statistical data indicate that females are at higher risk (up to 100-fold) for incurring adverse reactions to alcohol compared to males.  All sex-specific differences considered, most would expect females to exhibit highest risk of adverse reactions from the ingestion of Xanax and alcohol as compared to males who ingest an equivalent dose.

Why would anyone mix Xanax and alcohol?

Some may wonder why an individual would ever ingest Xanax and alcohol, especially when this combination of CNS depressants could lead to serious adverse reactions (e.g. respiratory failure) and may prove fatal.  Nonetheless, in most cases, persons who ingest Xanax and alcohol simultaneously are doing so to experience a potent intoxication and/or for the sake of self-experimentation.  In other cases, individuals may unintentionally ingest one substance while under the influence of the other – perhaps unaware of a potential interaction.  Though less common, a small percentage of individuals may intentionally ingest high doses of Xanax and alcohol as a suicide attempt.

  1. Intoxication (i.e. “High): Most individuals who administer Xanax and alcohol together do so with the intent of experiencing profound intoxication (mediated predominantly by the upregulation of GABAergic transmission) and characterized by CNS depression. Individuals who utilize Xanax with alcohol for intoxication may exhibit: a history of drug abuse, a thrill-seeking or addictive personality type, and/or a preexisting mental illness. Some may seek the intoxication from Xanax and alcohol as a thrill, whereas others may seek the intoxication as a means of escaping from an undesirable state of consciousness (e.g. high anxiety).
  2. Experimentation: A subset of individuals may administer Xanax with alcohol as a form of self-experimentation or consciousness exploration. These individuals may simply want to know how they feel, think, and act while under the influence of two psychoactive substances simultaneously – especially as compared to each as a standalone. Moreover, those who administer this substance combination as an experiment may attempt to avoid excessive intoxication and avert potentially dangerous adverse reactions that occur at high doses.
  3. Mistake: Certain persons may have been drinking and taken a Xanax because they either: assumed that most of the alcohol was cleared from systemic circulation at the time of Xanax ingestion – or forgot that they had been drinking. Others may have taken a Xanax and initiated drinking because they either: assumed that Xanax was cleared from systemic circulation at the time of alcohol ingestion – or forgot they had taken a Xanax (this may be more likely with the XR version). In these cases, the simultaneous ingestion of Xanax and alcohol was a mistake or done unintentionally.
  4. Suicide attempt: Unfortunately, some persons will intentionally ingest high doses of Xanax with alcohol as a suicide attempt. These individuals will probably end up extremely intoxicated and will be at serious risk for adverse reactions, as well as incurring permanent physiologic damage. Most attempting suicide with this drug combination exhibit an unmanaged neuropsychiatric disorder (e.g. major depression) and would be better served seeking emergency psychiatric care.

Note: It should also be mentioned that certain individuals may ingest Xanax and alcohol together intentionally, possibly under the wrongful assumption that mixing the two substances is safe.  This probably occurs when patients are uninformed of interactions by a medical professional and/or fail to assess interactions prior to initiation of Xanax.

Mixing Xanax and Alcohol: Overview of the Scientific Literature

In the scientific literature, there are toxicological overviews and case reports in which the combination of Xanax and alcohol is discussed.  Additionally, multiple experiments were conducted in the 1990s in which the physiologic effect of Xanax plus alcohol was studied in healthy volunteers.  Based on the data, it’s reasonable to suspect that the ingestion of this substance combination increases risk of death and yields more substantial cognitive impairment than the standalone ingestion of either substance.  Included below are brief summaries of some articles in which the combination of Xanax and alcohol were mentioned.

2014: Circumstances and toxicology of sudden or unnatural deaths involving alprazolam.

Darke, Torok, and Duflou (2014) sought to investigate sudden or unnatural deaths presented to the New South Wales Department of Forensic Medicine (DOFM) between 1997 and 2012.  At the time, researchers noticed that the number of unnatural deaths had increased from just 3 [in 1997] to 86 [in 2012].  One reason for the stark increase in unnatural deaths from 1997 to 2012 was an increased usage of alprazolam (Xanax).

As of 1997 alprazolam was implicated in no deaths, however, in 2012 alprazolam was implicated in 58 deaths (4.5% of annual cases).  Among persons who experienced unnatural deaths in which alprazolam was causally implicated, toxicological assays revealed median alprazolam concentrations of ~0.08 mg/L.  It was further noted that 37.4% of fatalities exhibited alprazolam levels exceeding 0.1 mg/L.

Researchers documented that ~95% of unnatural deaths involving alprazolam revealed ingestion of other substances, including alcohol.  Around 34.5% of investigated deaths were attributable to the co-ingestion of alcohol along with alprazolam.  Researchers concluded that unnatural toxicity-mediated deaths involving alprazolam occur mostly among persons with a history of alcohol and/or drug problems, indicating that co-ingestion of alprazolam and alcohol can be fatal.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/24629629

1999: Fatal overdose of tramadol and alprazolam.

A case of death by overdose involving Xanax and alcohol was reported by Michaud, Augsburger, Romain, et al. (1999).  This particular case involved a 30-year-old female with a history of major depression who had ingested a cocktail of Xanax, alcohol, and tramadol at undetermined dosages.  Toxicological blood samples detected 0.21 mg/L Xanax, 1.29 g/kg alcohol, and 38.3 mg/L tramadol.  This case highlights the fact that co-administration of Xanax and alcohol may lead to death by overdose.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/10643652

1993: The combination of alprazolam and alcohol on behavioral aggression.

Bond and Silveira (1993) conducted a study in which they assessed the combined effect of alprazolam and alcohol on aggressive behavior.  A total of 48 individuals characterized as “moderate social drinkers” were recruited for the study, divided into four groups, and assigned to receive one of the following combinations:  alprazolam (1 mg) + alcohol (0.5 g/kg); alprazolam (1 mg) + placebo drink; placebo capsule + alcohol (0.5 g/kg); or placebo capsule + placebo drink.

Ratings of mood, intoxication status, and breath alcohol concentrations were collected at intervals of: 90, 150, and 210 minutes post-alprazolam ingestion – and 45, 105, and 165 minutes post-alcohol ingestion.  At the 105-minute interval post-ingestion, participants engaged in a competitive reaction time task in which additional physiological measures were collected.  Results from the study indicated that all active treatments (alprazolam + alcohol; alprazolam + placebo; alcohol + placebo) significantly increased sedation and intoxication in participants.

Among recipients of alprazolam plus alcohol, slight reductions in the stress response were observed on physiological measures collected during the competitive reaction time task – as compared to recipients of other combinations.  That said, recipients of alprazolam plus alcohol exhibited greater aggression during the competitive reaction time task compared to other groups.  These results suggest that persons under simultaneous influence of Xanax and alcohol may behave more aggressively, unpredictably, and/or dangerously than individuals under the standalone influence of either substance.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/8410962

1990: Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers.

Linnoila, Stapleton, Lister, et al. (1990) were among the first to investigate the effect of alprazolam plus alcohol upon physiology.  The aforementioned researchers conducted a study in which they assigned healthy male volunteers to receive either: alprazolam plus alcohol, diazepam plus alcohol, standalone alcohol, standalone diazepam, standalone alprazolam, or a placebo.  While under the influence of these substances, participants underwent assessments designed to measure cognitive and psychomotor function.

Assessments revealed that a large dose of standalone alprazolam (2 mg) significantly impaired cognitive function as evidenced by compromised abilities on information processing (verbal and nonverbal) and memory tests.  Standalone alprazolam also reduced blood pressure, but did not affect heart rate nor concentrations of plasma norepinephrine.  Comparatively, the combination of alprazolam plus alcohol led to more significant impairment on a subset of tests, suggesting greater physiologic intoxication.

Intriguingly, researchers did not find evidence to support a synergistic effect resulting from co-ingestion of alprazolam and alcohol.  That said, the dosages of each substance may have been too for a synergistic effect to have been observed from co-administration.  Further research is warranted before a synergistic effect between Xanax and alcohol can be dismissed.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/2276384

What to do if you mix Xanax with alcohol…

Anyone who ingests Xanax and alcohol simultaneously is at risk of experiencing severe adverse reactions, permanent long-term complications, and death.  For this reason, all individuals under the influence of Xanax plus alcohol are encouraged to contact emergency medical services.  Emergency medical services should be able to effectively treat preexisting adverse reactions and minimize risk of death.  In addition to receiving professional medical care, other strategies that may effectively reduce risk of deleterious reactions include: avoiding substances that may potentiate effects of Xanax and alcohol, bolstering food intake and/or hydration, and/or administering attenuators.  Prior to implementing any of these strategies, it is necessary to confirm safety and hypothesized utility with a medical professional.

  1. Medical attention: If you’ve ingested Xanax and alcohol together or discover someone who has, it is recommended to contact emergency medical services (e.g. dial 911) as soon as possible and inform them of this ingestion. Although you may be hesitant to contact them, this step could be the difference between life and death – especially among persons who ingested high doses of each substance and/or have preexisting medical conditions [that make them prone to adverse reactions]. Emergency medical services will send professionals to assess your physiologic reaction to the combination of Xanax and alcohol.  These professionals will be trained to recognize, diagnose, treat, and/or prevent adverse reactions.  Moreover, even if no serious adverse reactions occur, it’s better to err on the side of safety than to risk incurring permanent long-term complications or end up dead.
  2. Avoid substances: After you’ve contacted emergency medical services, it is recommended to avoid administering additional substances (dietary supplements, pharmaceutical drugs, illicit drugs, etc.) while awaiting professional help. Many people mistakenly assume that they have a safe “home remedy” or supplement for counteracting the effects of Xanax and/or alcohol toxicity, however, these may prove to be ineffective or downright dangerous. Certain substances can potentiate CNS depression resulting from Xanax and alcohol such that they increase respiratory depression, respiratory failure, coma, and/or death.  Examples of such substances might include:  barbiturates, benzodiazepines, nonbenzodiazepines, and opiates/opioids.  Unless you’ve received medical approval to administer a substance for the treatment of Xanax and/or alcohol toxicity, abstain from administration.
  3. Food + hydration: For some individuals, it may be helpful to increase food intake and/or hydration following the ingestion of Xanax and alcohol. Increasing food intake may slow the absorption of unabsorbed Xanax and/or alcohol, thereby delaying metabolism of each substance, onset of intoxication, and possibly the degree of resulting intoxication.  Moreover, foods supply glucose and various micronutrients which may prevent certain adverse reactions resulting from alcohol-induced imbalances.  Basic foods such as saltine crackers can even help absorb excess stomach acid [resulting from alcohol intake] to minimize gastrointestinal-mediated side effects.  In addition to ramping up food intake in the immediate aftermath of ingesting Xanax and alcohol, certain individuals may benefit from increasing fluid intake.  Alcohol is known to induce dehydration and/or electrolyte imbalances, each of which may provoke and/or exacerbate unwanted reactions among users of Xanax and alcohol.  By ingesting more fluids, especially those containing electrolytes, it may be possible to attenuate and/or counteract a subset of adverse reactions to Xanax and alcohol.
  4. Consider attenuators: After emergency medical services are informed of Xanax and alcohol co-ingestion, certain individuals with preexisting medical knowledge and/or access to medically-accepted treatments for Xanax and/or alcohol toxicity may want to inquire whether it’s safe and recommended to administer such substances. Usually the administration of an attenuator should be reserved for extreme medical emergencies in which someone may be at risk of dying prior to the arrival of emergency medical personnel. An example of an attenuator that may prove useful in preventing serious adverse reactions from Xanax is the drug Flumazenil, a competitive benzodiazepine receptor antagonist.  While it’s unlikely that someone would happen to have Flumazenil on hand, if they do, it may require urgent administration to counteract the effects of Xanax.  Moreover, because Xanax and alcohol each induce CNS depression, certain substances that upregulate CNS function might be helpful for attenuating excessive CNS depression.  That said, never ingest any additional substance without professional medical guidance – even if suspected to be safe or helpful.
  5. Adjust body positioning: Anyone who’s seriously intoxicated as a result of Xanax and alcohol could pass out, experience respiratory depression or failure, choke on their vomit, and die. To reduce likelihood that someone will suffocate and/or choke on their vomit before the arrival of medical professionals, it is recommended to adjust the positioning of their body. If the person is still conscious, help them get situated in a comfortable position such that they are seated or lying down (to prevent fainting) while receiving good airflow (to prevent hypoxia and/or CO2 toxicity).  If the person is passed out or unconscious, it is recommended to perform the Bacchus Maneuver.

Have you ever mixed Xanax and Alcohol?

If you’ve ever ingested Xanax with alcohol, feel free to discuss your experience in the comments section below.  Following the co-ingestion of Xanax and alcohol, what were the most prominent effects, side effects, and/or adverse reactions that you experienced and how long did each last?  If you were to rate the magnitude of these effects and/or reactions on a scale from 1 to 10 (with “1” being negligible and “10” being extreme) what numeric rating would you assign to each?

To help others get a better understanding of your experience, mention the respective dosages of Xanax and alcohol that were ingested (e.g. 0.5 mg Xanax with 14 grams of alcohol).  If you exhibited tolerance to either substance, rate your tolerance as either: low, moderate, or high.  Also provide some personal details that may have influenced your physiologic response to this substance combination such as your: age, body size/composition, genetic expression (in regards to substance metabolism), medical conditions, and whether you used other substances (e.g. dietary supplements, medications, etc.) along with this combination.

For general reference, mention your motive for ingesting the combination of Xanax and alcohol such as:  honest mistake, intoxication, sleep enhancement, etc.  To clarify, note whether Xanax and alcohol were administered simultaneously or if one was administered before the other.  If one substance was administered prior to the other, approximately how much time had elapsed between the administration of each?  Looking back on your experience, do you regret ingesting Xanax with alcohol? (Elaborate).  Are you planning to ingest the combination again in the future? (If so, why?).

Overall, it is important to underscore that the simultaneous ingestion of Xanax and alcohol is associated with a high risk of serious adverse reactions.  For certain individuals and/or at specific dosages, this substance combination could induce respiratory depression, respiratory failure, coma, and death.  Anyone with questions or concerns regarding the ingestion of Xanax, alcohol, or their combination should contact a medical professional.

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