Several factors which do not in themselves cause alcohol hangover are known to influence its severity. These factors include personality, genetics, health status, age, sex, associated activities during drinking such as smoking, the use of other drugs, physical activity such as dancing, as well as sleep quality and duration.

- Genetics: alleles associated with aldehyde dehydrogenase (ALDH) and flushing phenotypes (alcohol flush reaction) in Asians are known genetic factors that influence alcohol tolerance and the development of hangover effects. Existing data shows that drinkers with genotypes known to lead to acetaldehyde accumulation are more susceptible to hangover effects. The fact that about 25% of heavy drinkers claim that they have never had a hangover is also an indication that genetic variation plays a role in individual differences of hangover severity.

- Age: some people experience hangovers as getting worse as one ages. This is thought to be caused by declining supplies of alcohol dehydrogenase, the enzyme involved in metabolizing alcohol. Although it is actually unknown whether hangover symptoms and severity change with age, research shows that drinking patterns change across ages, and heavy drinking episodes that may result in hangover are much less often experienced as age increases.

- Sex: at the same number of drinks, women are more prone to hangover than men, and this is likely explained by sex differences in the pharmacokinetics of alcohol. Women attain a higher blood alcohol concentration (BAC) than men at the same number of drinks. At equivalent BACs, men and women appear to be indistinguishable with respect to most hangover effects.

- Cigarette smoking: acetaldehyde which is absorbed from cigarette smoking during alcohol consumption is regarded as a contributor to alcohol hangover symptoms.

Studies show that alcohol hangover is associated with a decrease in blood glucose concentration (less than 70 ml/dl), but the relationship between blood glucose concentration and hangover severity is unclear. Also known as insulin shock, hypoglycemia can lead to coma or even death.

A bad trip (drug-induced temporary psychosis or psychedelic crisis) is a disturbing experience typically associated with use of one or more of various hallucinogens of types including psychedelics, such as LSD, mescaline, psilocybin, and DMT, dissociatives, such as dextromethorphan, and phencyclidine, and deliriants, such as Salvinorin A (the active chemical of "Salvia divinorum").

The manifestations can range from feelings of vague anxiety and alienation to profoundly disturbing states of unrelieved terror, ultimate entrapment, or complete loss of self-identity. Psychedelic specialists in the therapeutic community do not necessarily consider unpleasant experiences as threatening or negative, instead focusing on their potential to greatly benefit the user when properly resolved. Bad trips can be exacerbated by the inexperience or irresponsibility of the user or the lack of proper preparation and environment for the trip, and are reflective of unresolved psychological tensions triggered during the course of the experience.

It is suggested that, at a minimum, such crises be managed by preventing the individual from harming oneself or others by whatever means necessary up to and including physical restraint, providing the patient with a safe and comfortable space, and supervising the intake until all effects of the drug have completely worn off.

The effects of psychedelics vary widely from one individual to the next, and from one experience to the next. Sometimes individuals under the influence of such drugs do not understand that they have taken a drug and believe that they will never return to their ordinary, sober perception. In cases where the individual cannot be kept safe, hospitalization may be useful, though the value of this practice for individuals not mentally ill is disputed by proponents of the investigative or recreational use of psychoactive compounds. Psychosis is exacerbated in individuals already suffering from this condition.

Alcohol dependence is not prerequisite to blackouts (either en bloc or fragmentary). Students in one study who reported blackouts were demographically similar to other drinking students. Importantly, however, students reporting blackouts drank more, and had other symptoms of alcoholic drinking, even though they did not fall into the alcoholic range on the Michigan Alcoholism Screening Test (MAST). Half of the students reported having had a blackout during their drinking careers, which closely followed other research findings.

In another study 25% of healthy college students reported being familiar with alcoholic blackouts. 51% of the students reported that they had had at least one blackout. Blackouts were reported during activities such as spending money (27%), sexual conduct (24%), fighting (16%), vandalism (16%), unprotected intercourse (6%), and driving a car (3%). So a significant number of students were engaged in a range of possibly hazardous activities during blackouts.

Of 545 individuals in another study, 161 (29.5%) reported driving drunk, 139 (25.5%) reported a regretted sexual situation, 67 (12.3%) reported unprotected sex, 60 (11%) reported having damaged property, 55 (10.1%) reported getting into a physical fight, and 29 (5.3%) reported injuring someone while under the influence of alcohol in the past 6 months.

Pregaming (also pre-drinking or pre-loading) is the process of getting drunk prior to going out socializing, typically done by college students and young adults in the United States and Europe, in a manner as cost-efficient as possible, with hard liquor and cheap beer consumed while in small groups.

Although pregaming is typically done before a night out, it can also precede other activities, like attending a college football game, large party, social function, or another activity where possession of alcohol may be limited or prohibited. The name "pregaming" spread from the drinking that took place during tailgating before football games to encompass similar drinking periods.

Other terms for the practice are pre-partying, prinking and (in Europe) prefunking.

Pregaming has been associated with binge drinking and other dangerous activities, leading some universities to attempt to crack down on the practice. Government agencies at both the state and federal level have studied the problems created by pregaming.

The furtive nature of pregaming and bingeing can lead to massive quick consumption, acute alcohol poisoning, hospitalization, and death.

A 2012 study of more 250 Swiss students indicated that those who "pre-loaded" ended up consuming more total alcohol over the night (seven drinks rather than four) and engaged in riskier behavior. They had a 24% chance of reporting negative consequences from drinking (such as injury, unprotected sex, and unplanned drug use), compared to 18% chance for those who did not pre-drink.

Alcohol intoxication, also known as drunkenness among other names, is a physiological condition that may result in psychological alterations of consciousness. Drunkenness is induced by the ingestion or consumption of alcohol in a living body. Alcohol intoxication is the result of alcohol entering the bloodstream faster than it can be metabolized by the body. Metabolism results in breaking down the ethanol into non-intoxicating byproducts.

Some effects of alcohol intoxication, such as euphoria and lowered social inhibition, are central to alcohol's desirability as a beverage and its history as one of the world's most widespread recreational drugs. Despite this widespread use and alcohol's legality in most countries, many medical sources tend to describe any level of alcohol intoxication as a form of poisoning due to ethanol's damaging effects on the body in large doses. Some religions consider alcohol intoxication to be a sin.

Symptoms of alcohol intoxication include euphoria, flushed skin, and decreased social inhibition at lower doses, with larger doses producing progressively severe impairments of balance, and decision-making ability as well as nausea or vomiting from alcohol's disruptive effect on the semicircular canals of the inner ear and chemical irritation of the gastric mucosa.

Sufficiently extreme levels of blood-borne alcohol may result in coma or death.

Research indicates that some users of alcohol, particularly those with a history of blackouts, are predisposed to experience blackouts more frequently than others. One such study indicated a link between prenatal exposure to alcohol and vulnerability towards blackouts, in addition to the oft-cited link between this type of exposure and alcoholism. Alternatively, another study has indicated that there appears to be a genetic predisposition towards blacking out, suggesting that some individuals are made to be susceptible to alcohol-related amnesia.

From a neurobiological perspective, central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission has been shown to modulate both alcohol consumption and impulsivity. Some variations in 5-HT neurotransmission may thus contribute to a risk of AD (alcohol dependence), especially the forms of AD associated with a high level of impulsivity 2.

As the extracellular concentration of 5-HT is regulated by the activity of the 5-HT transporter (5-HTT), the gene SLC6A4 encoding this protein represents an important potential candidate gene for AD risk. Using a meta-analysis approach, Feinn et al. found evidence for an association of the short allele of the 5-HTTLPR (SLC6A4) with AD, but the overall effect size estimated by odd ratios was found weak. As expected in a complex condition like alcohol dependence, the disagreement in the association between AD and 5-HTTLPR likely reflects the impossibility for a single genetic determinant to explain the whole of the risk.

Aside from chemical components which may cause a predisposition to alcohol dependence and blackouts, expectations of alcohol use may predispose drinkers toward alcoholism and blackouts. In a study of 123 college students significant correlations were found between students’ alcohol expectancies, level of alcohol abuse, and blackout history. The students who experienced blackouts (38.6%) had much higher positive alcohol expectancies than those without blackouts. Positive and negative expectancies were positively correlated among the no-blackout group, but negatively correlated among the blackout group.

Excited delirium occurs most commonly in males with a history of serious mental illness or acute or chronic drug abuse, particularly stimulant drugs such as cocaine and MDPV. Alcohol withdrawal or head trauma may also contribute to the condition.

A majority of fatal case involved men.

People with excited delirium commonly have acute drug intoxication, generally involving PCP, methylenedioxypyrovalerone (MDPV), cocaine, or methamphetamine. Other drugs that may contribute to death are antipsychotics.

Alcohol is metabolized by a normal liver at the rate of about 8 grams of pure ethanol per hour. 8 grams or is one British standard unit. An "abnormal" liver with conditions such as hepatitis, cirrhosis, gall bladder disease, and cancer is likely to result in a slower rate of metabolism.

Ethanol is metabolised to acetaldehyde by alcohol dehydrogenase (ADH), which is found in many tissues, including the gastric mucosa. Acetaldehyde is metabolised to acetate by acetaldehyde dehydrogenase (ALDH), which is found predominantly in liver mitochondria. Acetate is used by the muscle cells to produce acetyl-CoA using the enzyme acetyl-CoA synthetase, and the acetyl-CoA is then used in the citric acid cycle.

Ethanol's acute effects are due largely to its nature as a central nervous system depressant, and are dependent on blood alcohol concentrations:

- 20–79 mg/dL: Impaired coordination and euphoria

- 80–199 mg/dL – Binge drinking: Ataxia, poor judgement, labile mood. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines the term "binge drinking" as a pattern of drinking that brings a person's blood alcohol concentration (BAC) to 0.08 g/dL or above.

- 200–299 mg/dL: Marked ataxia, slurred speech, poor judgement, labile mood, nausea and vomiting

- 300–399 mg/dL: Stage 1 anaesthesia ("blackout"), memory lapse, labile mood

- 400+ mg/dL: Respiratory failure, coma

As drinking increases, people become sleepy, or fall into a stupor. After a very high level of consumption, the respiratory system becomes depressed and the person will stop breathing. Comatose patients may aspirate their vomit (resulting in vomitus in the lungs, which may cause "drowning" and later pneumonia if survived). CNS depression and impaired motor co-ordination along with poor judgment increases the likelihood of accidental injury occurring. It is estimated that about one-third of alcohol-related deaths are due to accidents and another 14% are from intentional injury.

In addition to respiratory failure and accidents caused by effects on the central nervous system, alcohol causes significant metabolic derangements. Hypoglycaemia occurs due to ethanol's inhibition of gluconeogenesis, especially in children, and may cause lactic acidosis, ketoacidosis, and acute renal failure. Metabolic acidosis is compounded by respiratory failure. Patients may also present with hypothermia.

The pathophysiology of excited delirium has been unclear, but likely involves multiple factors. These may include positional asphyxia, hyperthermia, drug toxicity, and/or catecholamine-induced fatal cardiac arrhythmias.

In order to maintain high-quality performance, some musicians take chemical substances. Some musicians take drugs or alcohol to deal with the stress of performing. As a group they have a higher rate of substance abuse. The most common chemical substance which is abused by pop musicians is cocaine, because of its neurological effects. Stimulants like cocaine increase alertness and cause feelings of euphoria, and can therefore make the performer feel as though they in some ways ‘own the stage’. One way in which substance abuse is harmful for a performer (musicians especially) is if the substance being abused is aspirated. The lungs are an important organ used by singers, and addiction to cigarettes may seriously harm the quality of their performance. Smoking causes harm to alveoli, which are responsible for absorbing oxygen.

Street children in many developing countries are a high risk group for substance misuse, in particular solvent abuse. Drawing on research in Kenya, Cottrell-Boyce argues that "drug use amongst street children is primarily functional – dulling the senses against the hardships of life on the street – but can also provide a link to the support structure of the ‘street family’ peer group as a potent symbol of shared experience."

Ideas of reference and delusions of reference describe the phenomenon of an individual's experiencing innocuous events or mere coincidences and believing they have strong personal significance. It is "the notion that everything one perceives in the world relates to one's own destiny".

In psychiatry, delusions of reference form part of the diagnostic criteria for psychotic illnesses such as schizophrenia, delusional disorder, bipolar disorder (during the elevated stages of mania), as well as schizotypal personality disorder. To a lesser extent, it can be a hallmark of paranoid personality disorder. Such symptoms can also be caused by intoxication, especially with hallucinogens or stimulants like methamphetamine.

Having a particular genetic variant (A-allele of ADH1B rs1229984) is associated with non-drinking and lower alcohol consumption. This variant is also associated with favorable cardiovascular profile and a reduced risk of coronary heart disease compared to those without the genetic variant, but it is unknown whether this may be caused by differences in alcohol consumption or by additional confounding effects of the genetic variant itself.

Females demonstrated a higher average rate of elimination (mean, 0.017; range, 0.014-0.021 g/210 L) than males (mean, 0.015; range, 0.013-0.017 g/210 L). Female subjects on average had a higher percentage of body fat (mean, 26.0; range, 16.7-36.8%) than males (mean, 18.0; range, 10.2-25.3%).

People who engage in polypharmacy and other hypochondriac behaviors are at an elevated risk of death from CDI. Elderly people are at the highest risk of CDI, because of having many age-related health problems requiring many medications combined with age-impaired judgment, leading to confusion in taking medications.

Combined drug intoxication (CDI), also known as multiple drug intake (MDI) or lethal polydrug/polypharmacy intoxication, is an unnatural cause of human death. CDI is often confused with drug overdose, but it is a completely different phenomenon. It is distinct in that it is due to the simultaneous use of multiple drugs, whether the drugs are prescription, over-the-counter, recreational, or some other combination. Alcohol can exacerbate the symptoms and may directly contribute to increased severity of symptoms. The reasons for toxicity vary depending on the mixture of drugs. Usually, most victims die after using two or more drugs in combination that suppress breathing, and the low blood oxygen level causes brain death.

The CDI/MDI phenomenon seems to be becoming more common in recent years. In December 2007, according to Dr. John Mendelson, a pharmacologist at the California Pacific Medical Center Research Institute, deaths by combined drug intoxication were relatively "rare" ("one in several million"), though they appeared then to be "on the rise". In July 2008, the Associated Press and CNN reported on a medical study showing that over two decades, from 1983 to 2004, such deaths have soared. It has also become a prevalent risk for older patients.

Acute intoxication, such as binge drinking and alcoholism, are known potent risk factors for suicide. Binge drinking is also associated with an increased risk of unplanned sex, unprotected sex, unplanned pregnancies, and an increased risk of HIV infection. 10 percent of women and 19 percent of men have reported being assaulted as a result of alcohol. Males who drink more than 35 units of alcohol per week report being physically hurt as a result of alcohol, and 15 percent report physically hurting others as a result of their drinking. Almost 16 percent of binge drinkers report being taken advantage of sexually, and 8 percent report taking advantage of another person sexually as a result of alcohol within a 1-year period. Heavy drinkers cause approximately 183,000 rapes and sexual assaults, 197,000 robberies, 661,000 aggravated assaults, and 1.7 million simple assaults each year. Binge drinking has been associated with high odds of divorce, spousal abuse, and poor job performance. Binge drinking can cause adverse effects on the body including effects on blood homeostasis and its circadian variation, cardiac rhythm, ischaemic heart disease, blood pressure, white blood cell activity, female reproductive hormone levels as well as adverse effects on the fetus. There is also evidence from animal studies that binge drinking causes brain damage. Binge drinking has been associated with lower abdominal pain in women. Ketoacidosis can occur in individuals who chronically abuse alcohol and have a recent history of binge drinking. Alcohol affects brain development quite significantly especially during adolescence when the brain is still developing. The main lobes that are involved in decision making and complex thought processes are undergoing their final development phase during adolescence and binge drinking can negatively stunt the growth of these frontal lobes.

Studies have shown that those who fall into minorities due to either their gender identity or sexual orientation (such as those that identify as LGBT), are more prone to depression.

Another theory is that there may be shared risk factors that can lead to both substance abuse and mental illness. Mueser hypothesizes that these may include factors such as social isolation, poverty, lack of structured daily activity, lack of adult role responsibility, living in areas with high drug availability, and association with people who already misuse drugs.

Other evidence suggests that traumatic life events, such as sexual abuse, are associated with the development of psychiatric problems and substance abuse.

Depressed mood can be the result of a number of infectious diseases, nutritional deficiencies, neurological conditions and physiological problems, including hypoandrogenism (in men), Addison's disease, Cushing's syndrome, hypothyroidism, Lyme disease, multiple sclerosis, Parkinson's disease, chronic pain, stroke, diabetes, and cancer.

As demonstrated by the chart below, numerous studies have examined factors which mediate substance abuse or dependence. In these examples, the predictor variables lead to the mediator which in turn leads to the outcome, which is always substance abuse or dependence. For example, research has found that being raised in a single-parent home can lead to increased exposure to stress and that increased exposure to stress, not being raised in a single-parent home, leads to substance abuse or dependence. The following are some, but by no means all, of the possible mediators of substance abuse.

As demonstrated by the chart below, numerous studies have examined factors which moderate substance abuse or dependence. In these examples, the moderator variable impacts the level to which the strength of the relationship varies between a given predictor variable and the outcome of substance abuse or dependence. For example, there is a significant relationship between psychobehavioral risk factors, such as tolerance of deviance, rebelliousness, achievement, perceived drug risk, familism, family church attendance and other factors, and substance abuse and dependence. That relationship is moderated by familism which means that the strength of the relationship is increased or decreased based on the level of familism present in a given individual.

Examples of mediators and moderators can be found in several empirical studies. For example, Pilgrim et al.’s hypothesized mediation model posited that school success and time spent with friends mediated the relationship between parental involvement and risk-taking behavior with substance use (2006). More specifically, the relationship between parental involvement and risk-taking behavior is explained via the interaction with third variables, school success and time spent with friends. In this example, increased parental involvement led to increased school success and decreased time with friends, both of which were associated with decreased drug use. Another example of mediation involved risk-taking behaviors. As risk-taking behaviors increased, school success decreased and time with friends increased, both of which were associated with increased drug use.

A second example of a mediating variable is depression. In a study by Lo and Cheng (2007), depression was found to mediate the relationship between childhood maltreatment and subsequent substance abuse in adulthood. In other words, childhood physical abuse is associated with increased depression, which in turn, in associated with increased drug and alcohol use in young adulthood. More specifically, depression helps to explain how childhood abuse is related to subsequent substance abuse in young adulthood.

A third example of a mediating variable is an increase of externalizing symptoms. King and Chassin (2008) conducted research examining the relationship between stressful life events and drug dependence in young adulthood. Their findings identified problematic externalizing behavior on subsequent substance dependency. In other words, stressful life events are associated with externalizing symptoms, such as aggression or hostility, which can lead to peer alienation or acceptance by socially deviant peers, which could lead to increased drug use. The relationship between stressful life events and subsequent drug dependence however exists via the presence of the mediation effects of externalizing behaviors.

An example of a moderating variable is level of cognitive distortion. An individual with high levels of cognitive distortion might react adversely to potentially innocuous events, and may have increased difficulty reacting to them in an adaptive manner (Shoal & Giancola, 2005). In their study, Shoal and Giancola investigated the moderating effects of cognitive distortion on adolescent substance use. Individuals with low levels of cognitive distortion may be more apt to choose more adaptive methods of coping with social problems, thereby potentially reducing the risk of drug use. Individuals with high levels of cognitive distortions, because of their increased misperceptions and misattributions, are at increased risk for social difficulties. Individuals may be more likely to react aggressively or inappropriately, potentially alienating themselves from their peers, thereby putting them at greater risk for delinquent behaviors, including substance use and abuse. In this study, social problems are a significant risk factor for drug use when moderated by high levels of cognitive distortions.

Binge drinking is also associated with strokes and sudden death. Binge drinking increases the risk of stroke by 10 times. In countries where binge drinking is commonplace, rates of sudden death on the weekend in young adults and middle aged people increase significantly. The withdrawal phase after an episode of binge drinking is particularly associated with ischaemic stroke as well as subarachnoid haemorrhage and intracerebral haemorrhage in younger men. In individuals with an underlying cardiac disorder a binge on alcohol increases the risk of silent myocardial ischaemia as well as angina. Binge drinking has negative effects on metabolism, lipid profile, blood coagulation and fibrinolysis, blood pressure and vascular tone and is associated with embolic stroke and acute myocardial infarction. Due to these risks experts believe that it is extremely important to warn people of the risks of binge drinking. Binge-drinking by people otherwise considered to be light drinkers is associated with an increased risk of cardiovascular problems and . Binge drinking increases cardiovascular toxicity due to its adverse effects on the electrical conduction system of the heart and the process of atherothrombosis. Excessive alcohol consumption is responsible for an average of 80,000 deaths in the U.S. each year and $223.5 billion in economic costs in 2006. More than half of these deaths and three-quarters of the economic costs are due to binge drinking (≥4 drinks for women; ≥5 drinks for men, per occasion).