Ethanol (alcohol) is, by far, the most commonly used and abused drug in modern society. In fact, alcohol is so commonly used it is seldom thought of as a drug at all, let alone a drug of abuse. Based on its frequency of use, it follows that the analysis of alcohol is the most frequently performed assay in forensic toxicology laboratories, both in the areas of postmortem toxicology and human performance toxicology. It also follows, then, that the results of these alcohol analyses are the most frequently employed laboratory results in criminal courts and the forensic toxicologist is frequently called on to provide an interpretation of these alcohol results.
The interpretation of alcohol results may range from determining its role in the cause of death in postmortem cases, differentiating antemortem alcohol consumption from postmortem alcohol production, to evaluating the effect of alcohol on driving performance in driving-while-intoxicated (DWI) cases. In general, however, the interpretation of alcohol results typically focuses more often on a discussion of its impairing effects on human performance, behavioral toxicity, than on its overt physiological toxicity. There are many factors that must be considered in the interpretation of alcohol results beyond its mere presence or the concentration at which it is found in a biological specimen.
The general effects of alcohol on human performance have been well established in both controlled scientific studies and epidemiological studies. These studies have allowed for the elucidation of a correlation between blood alcohol concentration (BAC) and performance effects. The degree and extent of impairment associated with a given blood alcohol concentration, however, may vary from that expected for a number of reasons. The level of impairment may be less than expected in individuals who have developed tolerance to the effects of alcohol. The level of impairment may be greater than expected in individuals who are naive to alcohol use, such as children and adolescents. The presence of other drugs may also alter the expected effects of alcohol on performance.
The forensic toxicologist may also be required to interpret the antemortem or perimortem effects of alcohol based on a postmortem alcohol concentration. A significant issue that must be considered in the interpretation of alcohol results under these conditions is whether the measured concentration truly reflects the alcohol concentration at the time of death. This issue is significant because both postmortem increases and decreases in alcohol concentration have been reported.
This section will discuss the effect each of these factors plays on the interpretation of alcohol results.


Ethanol is a short-chain aliphatic alcohol that is the natural product of sugar oxidation by yeast, a process referred to as fermentation. A small polar molecule, ethanol distributes throughout the total body water and, therefore, is found in all tissues and body fluids in proportion to their water content. As a pharmacologically active agent ethanol is classified as a central nervous system (CNS) depressant. Its mechanism as a CNS depressant may be through a direct action on the brain by dissolution of the molecule in the neuronal plasma membrane. This leads to a disruption of cellular functions by disordering the lipids of the cellular membrane. In addition, there is significant evidence for the existence of an ethanol receptor. This receptor is thought to be part of the y-aminobutyric acid (GABA) receptor complex, therefore, ethanol binding to the receptor enhances chloride ion movement into the cell. The mechanism for the reinforcing and mood-elevating effects of ethanol is unclear.
The behavioral effects of ethanol are consistent with a generalized central nervous system depression. The degree of depression and, hence, the degree or extent of impairment exhibits a dose-dependent relationship. The venous blood alcohol concentration and the breath alcohol concentration are also highly correlated with the type and extent of impairment associated with alcohol use. In general, venous blood or breath is sampled for analysis when the use of alcohol is suspected as the source of observed or measured impairment. The psychomotor impairment associated with alcohol use has been well documented in both laboratory studies and in actual driving studies, both closed-course and on-the-road driving. Although alcohol has been shown to impair a number of different tasks that rely on cognition and motor skills, the task of greatest interest and which most studies are directed towards measuring is the routine, yet complex psychomotor task of driving an automobile. Even laboratory studies that are designed to measure the most basic and simple behavioral tasks are utilized in an effort to understand how each element of the driving task, e.g. reaction time, tracking ability, divided attention, etc., is impaired by the use of alcohol.
The United States National Safety Council’s Committee on Alcohol and Drugs released a resolution in 1971 regarding alcohol impairment in which they stated that no individual, no matter what his previous experience with alcohol, is not unimpaired in his driving performance if his BAC is 0.08 gdl-1 or greater. Although the presence of impairment at the 0.08 g dl-1 blood alcohol level is generally accepted, a number of studies have demonstrated that the degree of impairment at this alcohol level can be highly variable between individuals. This variability is based on a number of factors including, but not limited to, the subject’s degree of experience with alcohol, whether their blood alcohol concentration is rising or falling, and their level of training and experience with the task on which they are tested. There are also a number of studies that suggest some behaviors may be impaired at blood alcohol concentrations as low as 0.02gdl-1. It is important to note that the type and degree of impairment is more variable between subjects at lower alcohol concentrations than it is at higher concentrations. Also, a greater proportion of people in any test population are impaired at higher blood alcohol concentrations, especially greater than 0.05gdl-1, than at blood alcohol concentrations below that level.
The general effects of alcohol on selected human performance measures are briefly summarized as follows. This summary is not a comprehensive review of every type of behavior affected by alcohol, but provides an overview of the types and degree of behavioral effects associated with alcohol consumption.
• A reduction in visual acuity and impaired peripheral vision has been documented at a BAC of 0.07g dl-1 and the extent of impairment increased with increasing BAC.
• Low doses of alcohol have been noted to decrease the subject’s sensitivity to taste and smell.
• A decrease in pain sensitivity is experienced at a BAC of 0.08 gdl-1 and increases with increasing concentration.
• An altered time sense, manifested as the slowing down of the passage of time, has been documented following low and moderate alcohol doses (BAC less than 0.08 gdl- 1).
• Choice Reaction Time (CRT) is impaired at concentrations of 0.05gdl-1. CRT is a motor performance test used to evaluate the integrity and function of motor pathways. Reaction time tasks typically use a button press in response to a critical stimulus to measure a subject’s latency to respond to that stimulus. CRT measures sensorimotor performance by selecting a single stimulus from among a number of alternatives. The task has both a recognition time component and a motor response component. The impairment measured consists of both an increased latency to respond to the stimulus and a decrease in the accuracy of the response.
• Tests of hand-eye coordination have measured deficits in performance at concentrations of 0.05 gdl-1 and greater.
• Performance on vigilance tasks has been shown to be impaired at a BAC of 0.06gdl-1. Vigilance tasks are tests of intellectual function and measure the ability to discriminate a specific signal from among a groupof choices. Such tasks provide a measure of an individual’s ability to recognize specific information. Impaired vigilance is probably a reflection of the drowsiness associated with alcohol consumption.
• An increase in body sway, as measured by the Romberg test and a laboratory-based performance device referred to as a wobble board, has been documented at a BAC of 0.05gdl-1. The body sway degrades to staggering and reeling as the blood alcohol concentration increases.
• The standardized field sobriety test (FST) employed by many law enforcement agencies is a battery of psychomotor performance tests that is utilized at the roadside to document the impairment of drivers suspected of DUI (driving under the influence)/ DWI. The three tests that constitute the standardized field sobriety test are the one leg stand (OLS), the walk and turn (WAT), and horizontal gaze nystagmus (HGN).
The OLS is a divided attention task with two distinct stages, instruction followed by balancing and counting. The Officer notes impairment by the number of errors, referred to as clues, made on the test. There are a maximum number of five clues on this test. If the individual tested scores two or more errors or is unable to complete the test there is a 65% predictability that the individual’s BAC is 0.10gdl-1 or greater.
The WAT is a divided attention task with two distinct stages, instruction and walking. There are a maximum number of nine clues on this test. If two or more clues are scored or the subject is unable to complete the test there is a 68% predictability that the individual’s BAC is 0.10 gdl-1 or greater.
The HGN test measures central nervous system motor pathway function. Nystagmus is a normal phenomenon that is not caused by alcohol, but is enhanced by alcohol. HGN is the most sensitive test in the FST battery to the impairing effects of alcohol. The officer observes the suspect’s eyes for the presence of smooth tracking and the onset of nystagmus. Studies have shown that the earlier that nystagmus occurs (the shorter the angle from directly in front of the subject) the greater the blood alcohol concentration. In fact, there appears to be a dose-response relationship between BAC and the angle of onset of nystagmus. There are a maximum number of six clues on the HGN, three per eye. If four or more clues are scored there is a 77% predictability that the individual’s BAC is 0.10gdl-1 or greater.
• Standard intelligence tests, such as the Wechsler Adult Intelligence test, have measured impaired cognition associated with alcohol use. This impairment increases with increasing dose.
• Most tests of driving skill, both on the road tests and driving simulators, show impairment at a BAC of 0.05 gdl-1. Epidemiological studies suggest an association between impaired driving performance and alcohol use. The majority of these studies show that 40%-60% of all fatally injured drivers have blood alcohol concentrations of 0.10 gdl-1 or greater and 30%-40% of those have a BAC in excess of 0.15gdl-1. It is important to note that a cause-and-effect relationship cannot be established by retrospective studies, therefore, it is not possible to state, based on these studies, that the presence of alcohol was the causitive factor in the accidents.
• The broad range of alcohol effects on behavior may be loosely categorized by BAC as follows:
- <0.05gdl-1 (low dose) - increased talkativeness, mild excitement, decreased attention, decreased inhibitions, and some minor motor skills impairment in some individuals;
- 0.05 – 0.10gdl-1 (moderate dose) - talkative, cheerful, loud, boisterous then sleepy, increased confidence, increased risk-taking, and impaired psychomotor skills (tracking, vigilance, divided attention, reaction time, etc.);
- 0.10 – 0.30gdl-1 (elevated dose) - nausea and vomiting may occur followed by lethargy, ataxia, slurred speech, diplopia, staggering gait, disorientation, and grossly impaired psy-chomotor skills;
- 0.30 – 0.50 gdl-1 (high dose) - stupor, visual impairment, marked decreased response to stimuli (even painful stimuli), and marked muscular incoordination. Coma and eventually death due to respiratory depression are generally accepted to occur at a BAC greater than 0.40 gdl- 1 in nonalcohol-dependent individuals. Note that highly tolerant individuals (e.g. chronic alcoholics) may not experience or appear to experience many of the more serious effects associated with high blood alcohol concentrations, but all individuals experience the cognitive and judgment impairing effects ofalco-hol at blood concentrations greater than 0.08 gdl- 1.
The general effects of alcohol on behavior in relation to a range of blood alcohol concentrations have been delineated in table format in a number of reference topics to facilitate an understanding of how BAC correlates to performance impairment.
• A large number of subjective tests have been used in association with the behavioral tasks described above. In these tasks the subject self-reports their mood, feelings, and impressions using a quantifiable scale, such as Self-rated Mood Scales, the Hopkins Symptom Checklist, the Cornell Medical Index, and other self-rated performance evaluations. These subjective tests indicate that with increasing BAC subjects typically feel elated, friendly and vigorous. As their BAC decreases after reaching its peak concentration they generally feel anger, depression and fatigue. Another common finding on such subjective tests is that subjects commonly underrate the extent of their psychomotor impairment.
Many of the tasks utilized in these studies show that behavioral tolerance may develop with repeated ethanol use. Tasks learned under the influence of alcohol are often performed better when repeated at that blood concentration than when performed in the absence of alcohol. Generally, the more complex the task the more significant the impairment measured at lower doses of alcohol. There is also a large between-study and between-subject variability in the type and extent of impairment noted. This is especially true when the blood alcohol concentration in subjects is below 0.08gdl-1. When interpreting the results of behavioral studies it is important to recognize that the reported results often refer only to some of the subjects tested and summary results typically are indicative of population tendencies and do not reflect absolute measures of behavioral effects.
In summary, even at low levels, ethanol disrupts performance and can interfere with complex activities such as driving. It generally causes feelings of happiness and reduces the ability of aversive events, such as pain, to control behavior. As the blood alcohol concentration increases the degree of impairment also increases and may eventually result in a loss of consciousness and finally death. The effects of alcohol on behavior are generally more pronounced and pleasurable while the blood alcohol levels are rising than while they are falling. There are also a number of behaviors that exhibit tolerance to the impairing effects of ethanol. This tolerance may be a consequence of both increased metabolism and learning.

A Brief History of Alcohol and the Law

The ability of alcohol to impair psychomotor performance and to produce behavioral changes has been well documented throughout history. The use and especially abuse of alcohol has always had a negative impact on society, however, the advent of the industrial age and the invention of the automobile have rendered these effects of even greater significance. As early as 1843 the New York Central Railroad prohibited employees to drink while on duty. In 1910 the New York City traffic code noted that the misuse of alcohol was a factor in traffic safety.
The increasing mechanization of American industry and the increasing use of automobiles was also accompanied by an ever-increasing awareness of safety issues, not only in factories, but also on the roads and in the home. The formation of the National Council for Industrial Safety in 1912, which became the National Safety Council in 1914 was a significant stepin the promotion of the safety movement in the United States. By 1924 the National Safety Council expanded its interests to include highway safety, and therefore, by implication, to the effects of alcohol on driving. The work of this organization has been continued and expanded by the National Highway Traffic Safety Administration (NHTSA).
The scientific support for this safety movement did not begin until the early 1920s when Professor Wid-mark, from the University of Lund in Sweden, developed a protocol for physicians to follow in the evaluation of drivers suspected of driving under the influence (DUI) of alcohol. From that point forward, the role of the scientist and scientific evidence gained a more and more important role in the relationship between alcohol and the law. The first law passed in the United States directed at drinking and driving was the Connecticut Motor Vehicle Law passed in 1924; that law stated that no one who has been drinking ought to be allowed to operate a motor vehicle. In 1935, Richard Holcomb and the Northwestern University Traffic Institute initiated a three-year study called the Evanston Study. This study reported on 270 drivers hospitalized after involvement in automobile accidents in Evanston, IL. The Evanston police tested 1750 drivers for their blood alcohol concentration and their breath alcohol concentration using Rolla Harger’s recently invented Drunkometer
over the same three-year period. In 1938, Holcomb reported that the chances of having an accident increased dramatically with the presence of any alcohol in the blood to the extent that each 0.02 gdl-1 rise in blood alcohol resulted in a doubling of the risk of accident.
The results of this study and the subsequent recommendations included in the joint 1938 statement issued by the Committee to Study Problems of Motor Vehicle Accidents (a special committee of the American Medical Association) and the Committee on Alcohol and Other Drugs formed the basis for the first legislation in the United States making DUI an offense. This legislation was passed in Indiana in March, 1939 and in Maine in April, 1939. The recommendations of these two committees also formed the basis for the Chemical Tests Section of the Uniform Vehicle Code published by the National Committee on Uniform Traffic Laws and Ordinances in 1946. In 1953, Implied Consent legislation was passed in New York State and was soon included in the Uniform Vehicle Code. Implied consent laws have subsequently been passed in all fifty States. The implied consent legislation provides that, as a condition precedent to being issued a driver’s license, an applicant agrees, by implication, to submit to a chemical test in any case in which he is suspected of DUI. Refusal to submit to the test results in the temporary loss of driving privileges.
In 1958, a Symposium on Alcohol and Road Traffic held at Indiana University issued a statement that a BAC of 0.05gdl-1 will definitely impair the driving ability of some individuals. As the BAC increases, a higher proportion of individuals will become impaired until a 0.10 gdl-1 is reached, at which point all individuals are definitely impaired. The Committee on Alcohol and Drugs in 1960 released a statement recommending that DUI laws be amended to reflect a 0.10 gdl-1 BAC as presumptive evidence of guilt; prior to this date, the presumptive concentration defined in most State laws was a 0.15gdl-1. The Uniform Vehicle Code was amended to reflect this recommendation in 1962.
The Grand Rapids Study, published in 1964 by Indiana University researchers, confirmed the results of the Evanston study and also stated that drivers with blood alcohol concentrations greater than 0.04 g dl-1 tend to have more single vehicle accidents that are also more severe than do sober drivers. Another significant finding from this study was that accident-related factors other than alcohol decreased in significance when the driver’s BAC was greater than 0.08gdl-1 and that accident involvement increased rapidly when the driver’s BAC was greater than 0.05 gdl-1. Drivers with BAC levels in the range 0.04-0.08 g dl-1 had a greater risk of accident involvement, but alcohol was not necessarily more significant than other risk factors.
The passage of the National Highway Safety Act in 1966 began the era of Federal intervention in the drinking and driving problem in earnest. The NHTSA, part of the newly created Department of Transportation, submitted a report to Congress in 1968 detailing how the problem of the drunken driver was being addressed. In 1971, NHTSA released a statement that no individual, no matter what his previous experience with alcohol, is not unimpaired in his driving performance if his BAC is 0.08 gdl-1 or greater. The last three decades have seen a continued proliferation of regulations and legislation concerning the drinking and driving problem. Although the legal limit for driving while impaired has remained at a 0.10 g dl-1 BAC in most states of the United States, a number of jurisdictions have begun to lower this limit to a 0.08gdl-1 BAC with some setting even lower limits for individuals younger than the legal drinking age. Law enforcement agencies have contributed to these efforts through the development and implementation of programs directed at reducing the number of impaired drivers through increased intervention and education.
The standardized field sobriety test and the drug evaluation and classification (DEC) program are two of the intervention programs that have been developed. The DEC program is primarily directed toward the training of police officers as drug recognition experts (DRE) in an effort to provide a mechanism for obtaining compelling evidence that a driver was impaired, specifically by a drug other than or in addition to alcohol, at the time of the stop. The FST, the individual components of which are described above (OLS, WAT, and HGN), is a series of pyschomotor tests used to measure impairment at the roadside following a traffic stop. The standardized field sobriety tests were developed in the 1970s through funding provided by NHTSA and have been standardized through laboratory studies and validated in field studies. Although drugs other than alcohol may impair the behaviors evaluated with the FST, the tasks have primarily been validated against a blood alcohol concentration of 0.1 gdl-1.

Alcohol Effects on Children and Adolescents

A large volume of data has been accumulated on the effects of ethanol on adults. Much of this information has been gathered from controlled scientific studies in which adult subjects were given a dose or multiple doses of ethanol and then asked to perform a task or series of tasks. Ethical considerations prevent the conducting of these types of experiments with children or adolescents. Although there are age restrictions in most countries for the legal consumption of ethanol, there have been a number of reports where children or adolescents have accidentally or intentionally consumed alcoholic beverages. These reports have indicated several things. For example, children appear to be more sensitive to the effects of ethanol than adults, that is, lower blood ethanol concentrations produce more significant toxicity in children than in adults. One study documenting this fact revealed that young teenagers were in a coma with positive pain reaction at an average blood ethanol concentration of 0.15gdl-1 and in a coma with no pain reaction at a blood ethanol concentration of 0.19gdl-1. These concentrations in adults would not be expected to produce a loss of consciousness.

Alcohol Tolerance

One of the most significant factors complicating the interpretation of blood ethanol concentration is the phenomenon of tolerance. Tolerance is a condition in which a decreased response to the effects of alcohol, or other drug, is acquired in the face of repeated exposure to alcohol or that other drug. The consequence of the development of tolerance is that it becomes necessary to successively continue to increase the dose of alcohol to achieve an equal pharmacological effect or duration of action. Tolerance may also be thought of as that condition in which a given dose of alcohol fails to produce the same effect or duration of action as a previous equivalent dose of alcohol. There are several types of tolerance as that phenomenon applies to ethanol.
Mellanby first described an acute tolerance to ethanol in 1919. Using dogs as his model, he showed that at a given blood ethanol concentration, intoxication was less severe during the descending portion of the blood ethanol concentration versus time curve than during the ascending portion. This acute tolerance to ethanol has become known as the ‘Mellanby effect’ and has subsequently been verified by a number of researchers. The Mellanby effect has been observed with tasks that measure psychomotor performance, cognitive performance, and on the subjective effects associated with alcohol use. The demonstration of acute tolerance depends on the range of blood ethanol concentrations studied and the tests employed to assess tolerance. Studies conducted to evaluate the development of acute tolerance have utilized the following experimental designs:
1. the measurement of the change in performance at the same blood ethanol concentration on the ascending and descending limbs of the blood ethanol concentration versus time curve;
2. the determination of the blood ethanol concentration at the onset of measurable impairment and when that impairment is no longer measurable;
3. the measurement of task performance when the blood ethanol concentration is maintained constant.
In addition to the development of acute tolerance to ethanol, there is also an acquired or chronic tolerance to ethanol. Acquired tolerance has been demonstrated by (1) comparing performance on specific tasks between light and heavy users of ethanol and (2) the development of experimentally acquired tolerance under laboratory conditions. A number of studies have demonstrated that heavy drinkers exhibit less alcohol-induced psychomotor impairment on the same tasks than light drinkers. It is less certain whether acquired tolerance develops to the impairing effects of ethanol on memory and cognitive function. A significant limitation to the development of a more comprehensive understanding of acquired tolerance is that controlled scientific studies of the effects of ethanol on behavior in human subjects are generally limited to blood ethanol concentrations no greater than 0.10gdl-1. Anecdotal reports, however, indicate that chronic alcoholics can have much higher blood ethanol concentrations without displaying overt symptoms of intoxication than can light drinkers.
Metabolic tolerance to ethanol also develops. Chronic alcoholics typically eliminate ethanol from the blood at higher rates than the occasional or social drinker does. The microsomal ethanol oxidizing system, which may become involved in ethanol metabolism at high blood alcohol concentrations and in chronic alcohol use, is inducible and may account for the increase in alcohol metabolism.

Drug Interactions with Ethanol

Another significant factor complicating the interpretation of ethanol concentrations is the co-administration of other drugs or chemicals. Alcohol can affect or be affected by other drugs both in terms of pharmacokinetics and pharmacodynamics. These interactions can be additive, synergistic, potentiating or antagonistic. An additive effect indicates that the total effect of a drug combination is the sum of the effects of the individual drugs. A synergistic effect means that the total effect of the drug combination is greater than the sum of the effects of the individual drugs. Potentiation is defined as an increase in the effect of a toxic substance acting simultaneously with a nontoxic substance. Antagonism refers to the canceling of effects of one drug by the simultaneous administration of another drug. The following is a summary of some of the major drug interactions with ethanol that have been characterized.


Amphetamines and other sympathomimetic amines may antagonize the depressant effects of ethanol, mainly by offsetting the fatigue produced by ethanol. Stimulants, in general, appear to diminish or negate the behavioral effects of ethanol on well-learned tasks, but have no impact on the impairing effects of alcohol on newly learned or unfamiliar behavioral tasks. The interactive toxic and behavioral effects of alcohol and stimulants are difficult to evaluate and may be dependent on a number of factors. Some of these factors are the relative dose of each drug, the relative time-frame of drug use, the complexity of the behavior being evaluated, the subject’s experience with that behavioral task, and the subject’s experience with or degree of tolerance to the drugs.


A number of studies have been performed documenting the combined effects of ethanol and benzodiaze-pines. Among the most significant interactions is the resultant increased blood diazepam concentration following the co-administration of ethanol. Although such an increase has not been evaluated with most benzodiazepines, it is very likely to occur based on the structural similarities among the various members of the benzodiazepine class of drugs. The N-dealkylation and hydroxylation phase I reactions of benzodiaze-pine metabolism are inhibited by acute doses of etha-nol. Benzodiazepines, however, do not affect alcohol dehydrogenase activity. Studies evaluating the behavioral effects of the combination of benzodiazepines and alcohol indicate an additive depressant effect on most measures of performance. In general, the behavioral effects of the benzodiazepines are very similar to those of ethanol and the two drugs in combination exacerbate the overt effects and apparent intoxication of each drug alone. Conversely, buspirone, a nonben-zodiazepine anxiolytic agent, does not potentiate the effects of low or moderate doses of ethanol.


A synergistic effect in CNS depression is seen when alcohol and barbiturates are co-administered. In general, the behavioral effects of the barbiturates are very similar to those of ethanol and the two drugs in combination exacerbate the overt effects and apparent intoxication of each drug alone. Acute ethanol intoxication inhibits barbiturate metabolism, thereby increasing barbiturate concentrations and increasing their associated toxicity.


The combined use of ethanol and cocaine results in the formation of a unique metabolite, cocaethylene, by means of a transesterification process that occurs in the liver. The half-life of cocaethylene is slightly longer than cocaine, it is more toxic than cocaine, but it exhibits the same type and degree of CNS stimulation as cocaine. Therefore, the overall toxicity due to cocaine is increased when it is used in combination with ethanol. Only a limited number of studies on the combined behavioral effects of cocaine, a CNS stimulant, and ethanol, a CNS depressant, have been conducted. The performance-enhancing effect of cocaine noted in most studies appears to be the result of the stimulant’s ability to reverse the effects of fatigue. Cocaine and ethanol interaction studies have shown that the addition of cocaine to ethanol does not enhance the impairing effects of ethanol on performance, but either attenuates the impairment resulting from ethanol consumption or leaves etha-nol-induced impairment unchanged. The performance-enhancing effect of cocaine in these studies has been measured to last for a number of hours, appears to occur only in well-learned behaviors, and is most significant in fatigued subjects.


Histamine-2 antagonists such as cimetidine and rani-tidine are commonly prescribed drugs used to treat peptic ulcer or excess stomach acid production. These drugs inhibit gastric alcohol dehydrogenase and, as a result, increase the bioavailability of ingested ethanol. These drugs also inhibit the cytochrome P450 micro-somal enzyme system, which could affect ethanol metabolism by the microsomal enzyme oxidizing system.


At high doses, cannabis acts like a hallucinogen, but at the low doses commonly used in North America, the drug is reported to cause a pleasurable high that may take several trials to experience and can usually be turned off at will. Most performance deficits associated with marijuana use appear to be due to a lack of motivation and an inability to attend to a task. The impairing effects are generally slight and measurable only in some of the individuals tested. The interaction of ethanol and marijuana is presumably additive, but is difficult to evaluate due to the high degree of inter-subject variability in the behavioral effects associated with marijuana use.


The opiates are CNS depressants that produce analgesia, euphoria, sedation, respiratory depression, mio-sis, nausea and emesis. When alcohol and members of the opiate class are co-administered the CNS depression and behavioral impairment are, at minimum, additive. Acute doses of ethanol also lead to the decreased hepatic metabolism of opiates such as methadone and propoxyphene. This inhibition results in an increase in the blood concentration of the parent drug and an associated increase in the behavioral and toxic effects of that drug. The administration of opiates, however, has no apparent effect on the metabolism of ethanol.

Tricyclic antidepressants

Tricyclic antidepressants increase catecholamine neurotransmitter concentrations in the synaptic junction by blocking their neuronal reuptake. Tricyclic antidepressants are extensively metabolized in the liver and the acute ingestion of ethanol inhibits this metabolism resulting in increased blood concentrations and a greater risk of toxicity. The tricyclic antidepressants exert a profound sedative effect that is additive to the sedating effects of ethanol.

Decreases in Ethanol Concentration

The interpretation of alcohol concentration is also complicated by the potential loss of alcohol from biological specimens in storage. There are three mechanisms by which this decrease in concentration may occur over time: (1) evaporation; (2) oxidation; and (3) microbial action.


Since ethanol is a volatile substance, evaporation loss from biological specimens may occur over time if the specimen is not collected and stored properly. Obviously, if the specimen container is improperly sealed ethanol will be lost from the sample. This is especially true if the specimen is stored at room temperature or a slightly elevated temperature. When a specimen is collected for subsequent alcohol analysis it is important that there be minimal air space (headspace) between the top of the specimen and the lid. If too large an air space exists, the vapor pressure of ethanol will allow the movement of ethanol from the specimen into the headspace, with the eventual release of the vapor when the container is opened.


The in vitro oxidation of ethanol to acetaldehyde has been reported. This process is oxyhemoglobin-mediated and uses oxygen in the blood and from the air that is in contact with the stored blood specimen. In general, the amount of ethanol loss is minimal and is limited to approximately 0.04gdl-1.

Microbial action

Certain microorganisms can use ethanol as a substrate for metabolism. This is an aerobic process that is facilitated by the volume of air in the headspace above the sample. Strains of the bacteria Serratia marcescens and Pseudomonas sp. have been isolated from blood specimens in which ethanol loss has been documented.

Increases in Ethanol Concentration

The interpretation of alcohol concentration is also complicated by the potential increase in alcohol concentration in stored biological specimens. An increase in alcohol concentration in specimens collected from living subjects typically occurs only during collection, but can occur prior to, during and subsequent to collection in postmortem specimens. There are two mechanisms by which an increase in concentration may occur: (1) contamination; and (2) postmortem ethanol formation.


Ethanol concentrations can be spuriously increased by external contamination of the specimen. Cleansing the collection site with an antiseptic containing ethanol is an obvious source of contamination. Alcohol-free antiseptics are available and should be used when collecting specimens for alcohol analysis. This is essentially the only way in which an increase in the ethanol concentration occurs in the specimens collected from living individuals. Although it is possible for bacterial colonies in the blood to produce ethanol as a byproduct of glucose metabolism healthy individuals do not have a sufficient number of bacterial colonies to produce measurable ethanol concentrations.
A number of additional sources for the possible external contamination by ethanol exist for postmortem specimens. In trauma cases for example, blood from the heart, a common site of postmortem blood collection, may be contaminated by stomach contents. If there is any residual ethanol remaining in the stomach contents, this will cause an artificial increase in the heart blood ethanol concentration when the stomach contents come in contact with the heart. In these cases, blood from a peripheral site, away from the site of trauma, should be collected and analyzed for ethanol.
Embalming fluid may also be a source of ethanol contamination if the specimens are not collected prior to embalming. If the issue of ethanol consumption arises after a body is embalmed, it is recommended that some of the embalming fluid be obtained and analyzed for the presence of ethanol to determine its contribution to the postmortem blood concentration, although most embalming fluids do not contain ethanol. Autopsy specimens may also be contaminated during collection if syringes are flushed with alcohol between sample collections and if the same syringe is used for the collection of specimens from different decedents. A large number of literature reports have documented these sources of ethanol contamination of biological specimens. Due to these reports, the incidence of external contamination has been significantly decreased owing to an increased awareness of the potential problems of using ethanol swabs, reusing syringes for sample collection, and the importance of collecting autopsy specimens prior to embalming.

Postmortem ethanol formation

A critical component in the interpretation of postmortem blood ethanol concentrations is the issue of whether the measured ethanol resulted from the consumption of alcoholic beverages before death or from the production of ethanol after death. A variety of aerobic and anaerobic bacteria, yeast and molds can, under proper conditions, produce ethanol. A number of substrates can be converted into ethanol by these microorganisms. Glucose is the primary substrate that may be converted into ethanol, therefore, any tissue with high concentrations of glucose or glycogen is susceptible to postmortem alcohol production. Blood, liver and muscle are examples of specimens with high sugar concentrations in which significant concentrations of ethanol attributed to postmortem formation have been measured. Conversely, urine and vitreous humor are ordinarily free of the combination of glucose and microorganisms necessary to produce ethanol and are, therefore, excellent samples for evaluating the role of postmortem ethanol formation. Other substrates for ethanol production include lactate, ribose and amino acids. The mechanism of ethanol production from sugar is glycolysis, which is the first stepin the normal breakdown of glucose.
Postmortem ethanol formation can occur in the body between death and specimen collection or can occur after the specimens are collected, but prior to analysis. The first condition is difficult to control since body recovery may be delayed for days or even weeks. The prevention of ethanol production after the specimens are collected can be accomplished by performing several simple procedures. Following collection, the specimens should be sent to the laboratory as soon as possible. At the time of collection blood specimens should be treated with a preservative and an anticoagulant. Sodium fluoride is the most common preservative and potassium oxalate is the most common anticoagulant used; both compounds are found in the gray topVacutainer® tube. The addition of 1-2% (w/v) is generally sufficient to inhibit most microbial activity. Specimens should also be refrigerated upon receipt by the laboratory and kept refrigerated until analysis. For long-term storage of the specimens following analysis, frozen storage is the preferred mechanism for preserving specimens and preventing ethanol formation.
There are a number of factors that can or should be considered when determining whether measured ethanol occurred due to antemortem consumption of alcohol or microbial activity: (1) the decedent’s drinking history; (2) notation of the signs of putrefaction; (3) the results of the analysis of multiple specimens; and (4) the production of volatile compounds in addition to ethanol.
Case history Witnessed drinking by the decedent prior to death is obviously significant. Although there is often an underestimation of the amount of ethanol consumed, the observation that the individual was drinking is usually reliable. Unfortunately, drinking history immediately prior to death is often unavailable, especially in the case of unattended deaths.
Signs of putrefaction Although conditions for a body to putrefy or decompose may vary tremendously, there are a number of common characteristics of a decomposed body. The most striking trait is the foul odor associated with the body. Bloating, discoloration, and skin slippage are also common features associated with decomposition. Insect infestation, such as maggots, is frequently present in decomposed bodies and is often helpful in ascertaining the length of time that an individual has been dead. When signs of putrefaction are present, postmortem production of ethanol must be considered as possible if not probable. Unfortunately, the amount of ethanol produced is highly variable between decedents; two bodies kept in the same conditions for the same length of time can produce widely different amounts of ethanol. This issue is further complicated if the individual had actually been drinking prior to death. In that scenario, the postmortem alcohol measured might be due to both antemortem consumption and postmortem formation.
Results of multiple specimen analysis When ethanol is absorbed by the body, it distributes according to the water content of each tissue or fluid. The greater the water content, the greater is the ethanol concentration in that tissue or fluid. Since the water content ofa fluid or tissue is relatively constant, once the ethanol has reached equilibrium, there is a predictable rela-tionshipbetween the ethanol concentration in the various tissues and fluids. Much of the work establishing these relationships has compared the ethanol concentration in blood to that of other fluids and tissues. For example, the vitreous humor and cere-brospinal fluid ethanol concentrations will typically be higher than the blood ethanol concentration after equilibrium has been reached. On the other hand, liver and brain will typically have lower ethanol concentrations than the blood ethanol concentration after equilibrium.
One advantage to postmortem toxicologic analysis is the availability of a wide variety of fluids and tissues that can be collected at autopsy. Since the analysis of ethanol in tissues is straightforward, multiple analyses for ethanol can readily be performed. The distribution of ethanol between these specimens can provide a strong indication as to whether the measured ethanol resulted from drinking or decomposition. For example, one approach to multiple specimen analysis is to analyze blood, vitreous humor and urine. In the postabsorptive phase of alcohol distribution, the vitreous humor to blood ethanol concentration ratio is about 1.2 and the urine to blood ethanol concentration ratio is about 1.3, although there are wide variations in these ratios. If the measured postmortem ethanol concentrations yield similar ratios to those established for these specimens, then it is reasonable to conclude that the measured ethanol resulted from drinking. Vitreous humor and urine are two specimens relatively resistant to the putrefactive process and thus, are not sites generally associated with postmortem ethanol formation. If the blood ethanol concentration is positive and the vitreous humor and urine ethanol concentrations are negative, this is a strong indication that the ethanol concentration in the blood is the result of decomposition. One study of postmortem alcohol production showed that a blood ethanol concentration of 0.01 gdl-1 was associated with a negative urine or vitreous humor ethanol concentration 46% of the time. When the blood ethanol concentration was 0.04 gdl- 1, this percentage decreased to 8%. These results support the analysis of multiple postmortem specimens to evaluate the role of postmortem alcohol production and the fact that urine and vitreous humor are excellent samples for this purpose.
A number of studies have been performed that describe the production of ethanol in postmortem blood. These studies can be summarized by the following conclusions.
1. When ethanol is produced postmortem, the ethanol concentration is usually less than 0.07gdl- 1.
2. Production of ethanol concentrations greater than 0.10gdl-1 has been reported.
3. The production of ethanol due to decomposition is variable and is dependent on the species of microorganism present, the available substrate, and the temperature and other environmental conditions.
Although urine has been shown to be generally immune to the effects of in vitro production of ethanol, several studies have indicated that the combination of glucose in the urine, a condition that often occurs in diabetics, and a Candida albicans infection can result in the production of large amounts of ethanol. Both components are required for ethanol production to occur and it will not occur in the absence of either the glucose or the microorganism. This can be demonstrated in the laboratory by performing serial analyses of the urine for ethanol over several days and observing the increase in ethanol concentration over time.
Production of other volatiles Microorganisms that produce ethanol may also be capable of producing other volatile substances, one of which is acetaldehyde. However, since acetaldehyde is also a metabolite of ethanol, its identification in biological specimens cannot be used as a marker for decomposition ethanol production. One other volatile commonly seen as a putrefactive product is n-propanol. n-Propanol is not identified in individuals drinking alcoholic beverages and, therefore, is a good marker for decomposition ethanol formation. One caution in the use of this alcohol as a marker of postmortem ethanol formation is that many laboratories use n-propanol as an internal standard for the analysis of ethanol by gas chromatography. Although the concentration of n-propanol added as an internal standard far exceeds the amount of n-propanol produced (generally <0.01 gdl-1 produced in blood) and, therefore, would not significantly affect the ethanol quantitation, the use of n-propanol as an internal standard would mask the presence of n-propanol in the specimen resulting from postmortem formation.
In vitro studies have identified other volatile substances that may be produced during the decomposition process. Volatiles that have been identified include acetone, isopropanol, n-butanol, t-butanol, isoamyl alcohol, and n-amyl alcohol. In a manner similar to ethanol formation, the specific volatile or volatiles produced is dependent on storage conditions.

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