Ethanol

ETHANOL (a.k.a. ethanol / ethyl or grain alcohol (CH₃CH₂OH)) : a primary alcohol existing as a transparent, colorless, volatile, flammable liquid, miscible with water, methanol, ether, chloroform and acetone; it is formed by microbial fermentation of carbohydrates or by synthesis from ethylene
Epidemiology : lifetime prevalence of alcohol abuse and alcohol addiction (alcoholism) in USA is 5-10% for men and 3-5% for women. According to a new report from the World Health Organization (WHO), the harm caused by alcohol nearly equals that from smoking. Add in the social consequences of drinking, including wrecked families and lost days at work, which were excluded from the WHO report, and alcohol should arguably be the greater concern. Although a handful of researchers still question the idea that moderate drinking is beneficial, the consensus from epidemiological studies is that alcohol can improve health if taken in small doses - primarily by reducing the risk of heart attacks in older people. Bombarded by stories in the media portraying the medicinal effects of moderate consumption - but with no consistent message on what defines moderation - too many of us like to take much more than one drink, many valuing alcohol as a social lubricant and reliever of stress. The health benefits of alcohol are largely limited to a few individuals : since 1970, studies from all over the world have shown that moderate alcohol intake - 1-2 drinks a day - lowers the risk of coronary heart disease by 20-30% for older men and women^ref. Today, the idea that moderate drinking can be beneficial to health is well established. But in the 1980s and 1990s, some sceptics suggested that this effect might be a statistical mirage^ref. Teetotallers, they argued, include ex-alcoholics, the elderly and ill. So the apparent health benefits of moderate drinking could in fact be an artefact. Some epidemiologists still wonder whether abstainers' relatively poor health is linked to some factor not directly related to their rejection of alcohol. But more recent epidemiological analyses have adjusted, so far as is possible, for confounding effects, and still find health benefits from moderate drinking^ref1,
ref2. They are backed by studies showing that alcohol benefits the body by boosting levels of 'good' cholesterol and blood proteins that are signs of a healthy heart^ref.

Another issue that has mostly been laid to rest is that wine is better than beer or spirits - a phenomenon labelled the 'French paradox' because it was thought to explain why citizens of this nation tend to escape heart disease despite an artery-clogging diet. Among many studies contradicting this idea, one of Czech beer drinkers found that those who imbibed four to nine litres each week had the lowest risk of heart disease, compared with those who drank more or less^ref. The remaining debate is over what constitutes a healthy pattern of drinking. Seven drinks a week can be supped one per day with dinner or downed together in a Friday night. The weight of studies suggests that binge drinking in this way does not protect from heart disease in the same way as spreading it out over several days^ref. Even small amounts of alcohol increase the risk of injury and boost the chances of developing about 60 diseases, including several cancers, liver cirrhosis and neuropsychological disorders. When these are fed into the epidemiological equation, only men over the age of 45 and women over 55 seem to lower their overall health risks by moderate drinking^ref. Translated into guidelines for sensible drinking, this means that a middle-aged teetotal man, with high cholesterol or a family history of heart disease, would probably benefit by including a single drink a day with dinner. He might, however, achieve the same or better payback by starting to exercise or adopting a healthier diet. And for older people already following an exemplary lifestyle, the benefit reaped from a daily drink is probably marginal. Those in their 20s and 30s, meanwhile, may start accruing heart benefits from a daily drink, but at this age the threat of accidental injury equals the negligible risk from heart disease, so even moderate drinking seems to offer little payback. Another difficulty in conveying advice on healthy alcohol consumption is the lack of a standard definition for 'a drink'. The alcohol content of any drink varies with its volume and alcohol concentration, so that guidelines advocating a 'moderate' intake are often inconsistent within and between countries : a December 2003 report from the International Center for Alcohol Policies in Washington DC revealed that a 'standard' drink in Britain contains 8 grams of ethanol, in the United States it contains 14 g and in Japan 19.75 g. After a 1991 edition of the US TV programme 60 Minutes on the health benefits of wine, trade magazines reported a hike in the next month's wine sales of more than 40%. In part, the soft ride given to alcohol may be linked to the fact that the media and other influential sectors of society (politicians) tend to be drinkers. The alcohol industry has also tried hard to disseminate the virtues of its products. In the mid-1990s, the US wine industry proposed bottle labels advertising the health benefits of moderate drinking. Some labels appeared but were quickly abandoned when the US Bureau of Alcohol, Tobacco, Firearms and Explosives provisionally banned such statements in 1999. Industry representatives argue that they promote responsible drinking by broadcasting or contributing to public-health campaigns. At the same time, they acknowledge that the medical evidence on alcohol's health benefits has helped them persuade policy-makers of their product's appeal. > 75% of US healthcare providers did not define moderation in accordance with national guidelines. Internationally, the highest disease load attributable to alcohol is found in the heavy-drinking former socialist countries of Eastern Europe and in Latin America. Rich developed countries have the next biggest problem, with public-health experts being especially worried about binge drinking among the young. Trends differ from country to country - consumption is rising in Britain, for instance, but falling in France and Italy. In most developing countries, alcohol consumption is still relatively low, but it is climbing steeply, particularly in Asia, driven by economic growth and aggressive marketing.

In Britain - where overall alcohol consumption has risen by 50% since 1970. More forceful measures to curb consumption, e.g. raising the minimum legal drinking age, cutting the number of liquor shops, and restricting advertising and the hours during which drink can be sold work. Perhaps unsurprisingly, the price of alcohol has a very powerful influence on total consumption.

The 1985 Mikhail Gorbachev's government move to clamp down on the production of illegal alcohol slashed consumption from 14.2 to 10.5 litres of pure alcohol per person per year - and is estimated to have cut the number of alcohol-related deaths from accidents, poisoning and violence by 11% over 5 years^ref. But in present-day Russia, alcohol consumption and related mortality have climbed back to pre-1985 levels. In a one-party state the Soviet leaders didn't have to worry too much about a public backlash. But few democratic politicians are keen to impose higher taxes on alcohol and restrict its sale - there are few votes to be gained, and many potentially to be lost, from such actions : the key to success, the academy's report argued, will be to make the public more aware that measures to restrict the sale of alcohol and increase its price can relieve the unwanted consequences of excessive drinking, including violent crime. Sometimes problems have to escalate before WHO is convinced to do something drastic against industry. The Dietary Guidelines for Americans, published by the US government, recommends < 1 drink a day for women and 2 for men (1 drink is defined as 12 ounces (355 ml) of beer, 5 ounces (148 ml) of wine or 1.5 ounces (44 ml) of spirits). For young people, drinking even a small amount of alcohol could increase the chances of developing heart disease. The finding contrasts with the widely held view that drinking in moderation - around 2 drinks per day for men and one for women - can help protect against heart disease. Researchers are confident that this holds true for people who are over about 55 and at risk of heart disease. But they are unclear whether the health benefits of alcohol begin to accrue early in life - or exactly what alcohol is doing in the body to produce its beneficial effects. Using data from an ongoing study on heart disease, the hearts of > 3,000 people aged 33-45 years were probed using a CAT scanner. They searched for one of the earliest signs of heart disease - a hardening of coronary arteries - and then matched this up with information collected between 1985 and 2001 on how much each person drank. The more a person imbibed, the greater their likelihood of showing artery hardening. Those who had > 14 drinks per week, for example, were twice as likely to have artery problems than those who drank < 6. This result is at odds with a commonly found pattern in other studies on alcohol and heart disease, in which those who drink moderately have a lower risk of problems than both teetotallers and those who drink heavily^ref. The finding implies that drinking alcohol early in life does not rack up gradual benefits that will protect drinkers later on. Instead, it backs the idea that a slug of liquor protects against heart disease in older people in a different way: by having almost immediate effects. It may, for example, cut the risk of a blood clot forming and choking off an artery. Binge drinking, defined as > 5 drinks at one time, is harmful. Indeed, the researchers found it difficult to tell whether younger people who drank more were harming their arteries because of the total quantity they drank or because they tended to drink in binges. Both probably contribute. The study is one of the first and largest to look in detail at the effects of alcohol on a young age group, in which the signs of impending cardiovascular problems are difficult to pick up. Most research has concentrated on older groups in which scientists can track more easily how many are struck by disease. Public-health experts already believe that young drinkers gain little by drinking at a young age. Any positive effects on the heart are thought to be outweighed by the increased risk of cancer, accidents and injuries. It might not be a good thing to recommend any alcohol. It will be difficult to pin down at what age the benefits of alcohol start to outweigh the risks. It could be done by examining those who take up drinking later in life, but very few people do this. Meanwhile, public-health experts recognize that young people are unlikely to give up drinking because of seemingly remote risks of disease. So they say that standard advice still holds: if you are going to drink, do so in moderation.
Aetiology : GABRG3

SNPs are linked with the risk of becoming an alcoholic. A gene that helps flies deal with stress also makes them tolerant to repeated alcohol intake : humans probably have a similar gene, which could help to explain some cases of alcoholism and possibly even lead to a treatment. High alcohol tolerance, the ability to resist the effects of alcohol after continued drinking, is one of the factors that can lead to alcohol dependence and addiction : highly tolerant people tend to drink more than others simply because they don't get the same kick from a given dose. Both tolerance and the tendency to develop alcoholism are known to be partly inherited. But only a few of the genes responsible have been identified. Because genetic studies in humans are difficult, Ulrike Heberlein's team at the University of California in San Francisco turned to the fruit fly Drosophila melanogaster. To measure ethanol tolerance in flies, the researchers placed the flies in a column containing several platforms. When they were exposed to ethanol vapour, the flies tended to lose their balance and fall off their platform to the next one down, until they finally landed with a drunken bump at the bottom of the column. The sooner the flies hit the bottom, the drunker they were. The researchers checked the ethanol tolerance of tens of thousands of flies whose genomes had been damaged at random locations. Normal flies took about 20 minutes to reach the bottom of the column. When the researchers exposed the same flies to a repeated dose of ethanol 4 hours later, the flies had developed a tolerance against the ethanol and took 8 minutes longer to hit the bottom. But mutants lacking a gene dubbed hangover reached the bottom of the column just 23 minutes after exposure to the second dose : this indicates that hangover mutants have a lower tolerance^ref. The mutant flies also died younger and coped less well than normal flies with other kinds of stress, such as excessive heat. The hangover gene codes for a type of protein that turns on other genes. Humans have many genes like this, making it likely that one of them is equivalent to hangover.It might turn on genes that activate the cellular response to stress. Humans probably have the equivalent gene : a similar gene is switched on in mice when they are given alcohol. It's nice to see that these things seem to be parallel in different organisms. Hangover is the second known gene responsible for ethanol tolerance. In 2000 Heberlein's group showed that a gene for a neurotransmitter called octopamine, which helps flies memorize rewarding experiences, is also important^ref. Flies lacking both these genes have almost no alcohol tolerance. Such genes could be used to help identify people at risk of becoming alcoholics. The ultimate goal is to identify potential drug targets to treat alcoholism. Once you understand how tolerance works, you can potentially interfere with it pharmacologically^ref.
Pathogenesis : absorption (80% in duodenum and jejunum; 20% in stomach and colon; faster during starvation, accelerated gastric emptying (water, cholinergic drugs, hypoglycemia, gastroresection, ..), CO₂-added drinks and if 15 < ethanol < 30%, slower during sugar-rich meals, physical or mental effort, hypothermia); ethanol ==
1) ==+ NAD⁺ alcohol dehydrogenase (ADH)

==> NADH + H⁺ +
2) ==+ NADP⁺ + FAD + H⁺ + MEOS==>NADP⁺ + H⁺ + FADH₂ + cyt P450 +
3) ==+ 2O₂^- + 2 H⁺ + SOD== H₂O₂ + O₂ == + 2H₂O₂catalase==> 2H₂O + O₂ +
4) ==+ OH^- ==> CH₃CHOH ==>

acetaldehyde

aldehyde dehydrogenase

₂

oxidase

₂

acetic acid

₂

Such reactions occur mainly in liver (85-90%), but also in monocytes, histiocytes, myocytes and gastric cells (less expressed in females). R.O.S. produced in 3) and 4) cause peroxidation in membrane lipids, alteration in mitochondria (=> megamitochondria

), alterations in microtubules (=> ballooned cells (showable by Masson trichromic staining

) and eosinophilic Mallory bodies

(detected by van Gieson staining

)). Protein adducts are immunogen and cause hypersensitivities => fibrosis : perisinusoidal => perivenular => pericellular (a₁-FP-producing rosette of 7÷8 cells arranged in 2 strands). A normal dose of alcohol is metabolized mainly by ADH (90%), MEOS (8%) and SOD+catalase (2%). During chronic intoxication alcohol is metabolized mainly by ADH (50%) and MEOS (50%). 8% of absrobed ethanol is conjugated to glucuronic acid. 2% is eliminated through respiration, urine and skin. While ethanol concentration in expirated air is proportional to alcoholemia, alcoholuria is not.
Toxicity relates to V/Dt, ADH3*1, ALDH2*1, HLA-A1, HLA-B40 and overactive SLO-1 / BK (a potassium channel that regulates nerve firing in Caenorhabditis elegans). In vitro, ethanol stimulates adenosine signaling by inhibiting SLC29A1 / type 1 equilibrative nucleoside transporter (ENT1)

, whereas chronic ethanol exposure downregulates ENT1. In vivo ENT1 has a physiological role in ethanol-mediated behaviors and decreased A₁ adenosine receptor function promotes alcohol consumption^ref
Roughly 80% of alcohol-dependent individuals report smoking tobacco regularly : the combined effects of alcohol dependence and chronic smoking are associated with greater regional brain damage than chronic alcoholic drinking or smoking alone, an effect most prominent in the frontal lobes. Cigarette smoking, independent of alcohol consumption, also has adverse effects on neuronal viability and cell membranes in the midbrain and on cell membranes of the cerebellar vermis, and associated with lower N-acetylaspartate levels in lenticular nuclei and thalamus^ref
Clearance : pulmonary, renal, and cutaneous
TLV : 1,000 ppm
Ethanol content in different drinks :

spumants : 4-7 g/dl
beer : 5 g/dl
wine : 10 g/dl
superalcoholics : 40 g/dl

Favorable effects : resveratrol in wine may inhibit oxidation of LDLs => reduced rissk of acute myocardial infarction (AMI)

^ref (RDA 35-40 g/day for males and 23-28 g/day for females)
Symptoms & signs :

acute abuse : alcohol is metabolized mainly by ADH (75%) and MEOS (25%); grading according to alcoholemia :

< 0.5 g/L : subclinical grade, no alterations in chronic abusers
0.5-1 g/L : drunkenness, increased loquacity and euphoria, pleasant effects, no alterations in chronic abusers
1-1.5 gL : more marked effects, impaired light and sound perception, self confidence and disinhibition, delayed reflexes (the most dangerous stage). No alterations in chronic abusers
1.5-2.5 g/L : easy sleepiness, sleep up to stuporous sleep, severe disorders of equilibrium; only alterations of motory and emotional equilibrium in chronic abusers
2.5-4 g/L : acute pancreatitis , staggering gait , hyperkinetic arrhythmias , cerebellar ataxia , alcoholic tremor , orthostatic systemic arterial hypotension , suppression of inhibitory (=> initial euphoria ) and then excitatory systems (depression ), anterograde amnesia ("blackouts"), toxic coma . Zieve syndrome : hypercholesterolemia, hepatosplenomegaly, fatty infiltration of the liver, hemolytic anemia , and hypertriglyceridemia following the ingestion of large amounts of ethanol. Sleepiness and slowing in chronic abusers
> 5 g/L : death due to respiratory paralysis. Coma in chronic abusers

chronic abuse : alcohol is metabolized mainly by ADH (50%) and MEOS (50%)

obesity (7 calorie per gram)
nervous system

coticopontocerebellar stage :

heart

alcoholic myopathy (decreased contractility => increased HR and CO => arrhythmias and CHF)
alcoholic myocarditis => alcoholic cardiomyopathy

metabolic cataract
digestive apparatus

hemorrhagic gastritis and esophagitis => gastric atrophy => anorexia => protein-calorie malnutrition => alcoholic neuropathy / beriberi , Wernicke's encephalopathy + Korsakoff dementia or psychosis
chronic pancreatitis
micronodular liver steatosis => alcoholic hepatitis (Laënnec disease) => liver cirrhosis => esophageal varices
increase in digestive mucosal permeability
hyperperistalsis

cancers

esophageal squamous cell carcinoma (ESCC) (RR = 10)
cardias cancer
pancreatic cancer
breast cancer
colorectal cancer

blood : microcytic (iron-deficiency) or macrocytic (megaloblastic due to folate and vitamin B12 deficiency) anemia , cytoplasmic vacuolization of erythroid progenitors, reduced heme synthesis due to mitochondrial damage, direct inibition of HSC, thrombocytopenia , leukopenia
impotentia coeundi , drop of libido

abuse in pregnants => fetal alcohol syndrome (FAS)
withdrawal : irritability, delirium tremens ,epilepsy

Laboratory examinations : approximately 20% of patients seen in clinical practice have an underlying alcohol-use disorder^ref

acute abuse :

alcoholemia : alcohol assumption curve is quite linear and decreases begins after 30' (different curves for assumption with empty or full stomach, with greater effects in the first case)

indirect methods

alcohol in expirated air (Alco-test^®) : a reagent turns green in presence of ethanol (false positivity to ketone bodies). Mouth washing is recommended beofre examination as sometimes ethanol is administered by people offering first aids to consciousless patients.
alcoholuria

direct methods

Winnik method : microdiffusion in Conway cell
colorimetric method : oxidation to acetaldehyde by alcohol dehydrogenase
gas-chromatography (GC) : 0.5 mL blood + 2 mL picric acid (deproteinizing agent for 10') + propanol (internal standard with known concentration). After deproteinization the sample is centrifuged and divided into 2 parts : 1 mL overnatant is aspirated and injected into the GC => [ethanol]_sample = [ethanol]_standard x AUC_ethanol / AUC_propanol

chronic abuse :

conventional biomarkers are known to lack sensitivity and specificity^{ref1,
ref2,
ref3}

increased enzyme markers (gGT, ALT and AST)
increased MCV
increased C-reactive protein (CRP)

	MCV, µL	gGT, U/L	AST, U/L	ALT, U/L
alcohol abusers (n = 111)	99	92	51	47
teetotalers (n = 50)	91 (P <0.05)	25 (P <0.0001)	22 (P <0.005)	9 (P <0.0001)
sensitivity	0.3	0.64	0.47	0.53
specificity	0.92	0.86	0.95	0.93

carbohydrate-deficient transferrin (CDT) / desialotransferrin in serum and CSF due to disturbed liver synthesis^{ref1,
ref2,
ref3,
ref4}. Normal human transferrin (Tf), produced mainly in hepatocytes, occurs in several isoforms as a result of differences in glycosylation^ref. Tf has 2 asparagine-linked N-glycosylation sites, both usually occupied by oligosaccharides^ref. These N-glycan chains are composed of N-acetylglucosamine, mannose, galactose, and sialic acid^ref1,
ref2. The 2 N-glycan chains of Tf show bi-, tri-, and tetraantennary branchings, each terminating with a negatively charged sialic acid residue^ref. Tf is theoretically a group of isoforms with 0 to 8 sialic acid residues per molecule^ref. The isoelectric points of these isoforms range from 5.2 to 5.9^ref, and their molecular masses vary from 75.37 to 79.61 kDa^ref. Without any chronic alcohol abuse, the relative distribution of transferrin isoforms is usually as follows: tetrasialotransferrin 75%, pentasialotransferrin 15%, trisialotransferrin 5%, disialotransferrin <2%, and mono- and asialotransferrin <1% each.

^ref

^{ref1,
ref2,
ref3}

^ref1,
ref2

^ref

^TM

^ref

^ref1,
ref2

^ref

CDG Ia

^ref

^ref1,
ref2

asialotransferrin : when measured by capillary zone electrophoresis (CZE)^ref1,
ref2, it is present in 92% of alcohol abusers and absent in 95% of moderate alcohol consumers. The structure of asialotransferrin can be heterogeneous, with incomplete N-glycans (lack of all terminal sialic acid molecules but presence of remnant carbohydrate chains) or with a complete lack of the N-glycans : there is evidence (obtained by two independent analytical methods) of the complete lack of both N-glycans in at least some of the asialotransferrin molecules that are present in serum after chronic alcohol abuse^{ref1,
ref2,
ref3}. In this case, the analyte asialotransferrin is clearly defined and does not allow individual interpretation. is present in only trace amounts (<0.5% of total transferrin)^ref, under physiologic conditions. Asialotransferrin represents the transferrin isoform with the most distinct increase after chronic alcohol abuse. Serum asialotransferrin increases by 219–250%, monosialotransferrin by only 28–58%, and disialotransferrin by 148–225%^ref. Asialotransferrin (pI = 5.9) differs from tetrasialotransferrin (pI = 5.4) by 0.5 pH units. This is of major importance because tetrasialotransferrin is the quantitatively most important (non-CDT) isoform (64–80% of total transferrin). Disialotransferrin as the most important CDT isoform differs from tetrasialotransferrin by only 0.2 pH units and trisialotransferrin by only 0.1 pH units. As a result, coanalysis of small amounts of this non-CDT isoform can cause overestimation of CDT. So the analysis of asialotransferrin should be more robust against pH variations compared with CDT analysis, where slight pH differences can cause coelution or cofocusing of CDT and non-CDT isoforms^{ref1,
ref2,
ref3}. Monosialotransferrin (isoelectric point 5.8), which is anodically next to asialotransferrin, is usually absent^ref or is present in only very small amounts [<0.9% of total transferrin^ref]. Under conditions of complete transferrin-Fe³⁺ saturation, there is no transferrin isoform cathodically next to asialotransferrin. Thus, significant cofocusing or coelution of asialotransferrin with other transferrin isoforms, especially non-CDT isoforms, is unlikely. As an analyte, asialotransferrin can simplify the production of a specific antibody for a direct assay. With a complete lack of both transferrin N-glycans^{ref1,
ref2,
ref3}, the structure of asialotransferrin is different from the structure(s) of the non-CDT isoforms. Thus, there is the possibility of raising a specific antibody that binds strongly to the analyte (asialotransferrin), e.g., to an epitope near or at the original point of attachment of the carbohydrate chain(s). The availability of such an antibody against asialotransferrin would make a direct assay (without microcolumn fractionation of asialotransferrin from the other transferrin isoforms, as is currently needed for CDT and non-CDT fractionation by most of the commercial CDT assays) more probable. This would be an important step toward automation of CDT (or, more precisely, asialotransferrin) analysis^ref
monosialotransferrin
disialotransferrin :

measured by capillary zone electrophoresis (CZE)^ref :

a specificity and sensitivity for discriminating excessive from moderate alcohol consumers of 0.75 at a cutoff of 0.7% of total transferrin
sum (asialo- + disialotransferrin) at a threshold of 1.2% had a sensitivity of 0.73 and a specificity of 0.92
trisialotransferrin values did not distinguish between the two populations

measured by an assay combining anion-exchange minicolumn chromatography with immunoturbidimetry (%CDT)^ref :

cutoff	sensitivities	specificities
2.6%	0.77	0.74
2.8%	0.67	0.83
3%	0.63	0.90

^ref1,
ref2

^ref

HPLC sensitivity of 52% and a specificity of 98% for differentiation between moderate and heavy drinkers at a 1.8% cutoff^ref. This discrepancy may be attributed in part to the partial overlapping of disialo- and trisialo-Tf observed in HPLC methods when asialo-Tf is present^ref

Alcohol Use Disorders Identification Test (AUDIT) questionnaire score > 8; higher AUDIT scores seem associated with greater severity of alcohol misuse, and scores >12 are characteristic of alcohol dependence^ref

Antidipsotropic therapy :

naltrexone
oxazepam
vitamin B₁ / thiamine
hydroelectrolyte therapy
suicide substrate inhibitors of both cytosolic and mitochondrial aldehyde dehydrogenase cause the blood acetaldehyde concentration to rise to 5-10 times above the level achieved when ethanol is given alone, causing alarming symptoms (face flushing, pulsating headache, nausea and vomiting, sweating, vertigo, syncope). Further they inhibit hepatic microsomal DMEs and thereby interfere with the metabolism of phenytoin , chlordiazepoxide , barbiturates , and other drugs. Never administer until the patient has abstained from alcohol for > 12 hours. Similar effects are caused by coprine, 7-aminocephalosporanic acid, cyanamide, sulfonylureas , metronidazole , certain cephalosporins , and the ingestion of animal charcoal.
calcium acamprosate / N-acetylhomotaurine (Campral^®, Aotal^®, Zulex^®) is a mGluRI 5 antagonist and a weak NMDA receptors antagonist
5-HT₃ antagonists
sodium 4-hydroxybutyrate (GHB) (Alcover^®) (sweet withdrawal, contraindicated with severe organic or mental diseases, pregnancy or lactation, drug dependence)
benzodiazepine use can cause excessive depression

Illegal and surrogate alcohol products consumed in Estonia. The initial source of information was a series of visits made in August 2005 to a soup kitchen in central Tartu, Estonia. Individuals were asked for brief details of their personal circumstances, what they normally drank, and in addition they were asked to bring samples of the substances they usually consumed. In other cases, the substances identified were purchased by the investigators or from informal contacts in northeastern part of Estonia, an area that is well known for illegal alcohol consumption. Samples were tested for chemical contents. We identified a range of alcohol-containing substances that are consumed, although, not intended for consumption. These comprised medicinal products, after-shaves, illegally produced spirits, and fire-lighting fuel. The medicinal compounds contained, on average, 67% ethanol by volume; the after-shaves contained slightly less. Both were typically pure, with a few containing detectable quantities of isoamyl alcohol. The illegally produced alcohol contained, on average, 43% ethanol by volume, ranging from 32-53%. However, many also contained detectable quantities of long chain alcohols. These substances are half the price or less of commercial vodka, with fire lighting fuels especially inexpensive. Conclusions: There is in Estonia a range of alcohol-containing substances easily available at low cost. Some contain substantially higher concentrations of ethanol than commercial spirits and others also contain toxic long chain alcohols^ref