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ALCOHOL: THEOLD RASCAL

IN NEWCLOTHES

J.IDÄNPÄÄN-HEIKKILÄ

Na tional Board ofHealth ,

Silta saarenkatu 18,00530 Helsinki 53, Finland

Introduction

The last five to ten years of alcohol research seem to prove that some of the

traditional myths about drinking - fears, as weil as wishes and claims - may in fact be

true.

Although alcohol abuse has been claimed to be the major cause ofcard iomyopathy

in the Western world , several studies have now raised the possibil ity that a moderate

alcohol con sumption may have a protective effect against ischaemic heart disease

death. Use of alcohol during pregnancy seems to increa se risks of abnormalities in

infants, a hypothesis which was already stated in the Bible, but has been proven in

studies during the last five years.

Some of these studies, and also the recent fmdings on the similarities between

alcohol and opiate addiction, will be reviewed .

The foetal alcohol syndrome

Alcohol is a smalI, easily diffusable moleeule that is equally distributed in the body

water. Therefore it crosses the placenta and reaches the foetus. This was reported for

thc first time by Nicloux (1899) who discovered that foetal alcohol concentrations

were qu ite similar to those in maternal blood. This was later confirmed in gas

chromatographie investigations (Idänpään-Heikkilä, Jouppila, Äkerblorn, Isoaho,

Kauppila & Koivisto, 1972) and the pattern of distribution of alcohol in placenta and

foetal organs (Figure I) was further studied by using total body autoradiography

(ldänpään-Heikkilä, Fritchie, Ho & McIsaac, 1971). Young foetuses have a low

cap acit y for the metabolism and elimination of alcohol. Alcohol dehydrogenase

activity in a two month old foetus is no more than 3-4% of adult activity

(Pikkarainen & Räih ä, 1967). The near-term foetus and the newborn eliminate

alcohol about two times more slowly than the mother (Figure 2).

In recent years there has been an increasing amount of evidence that consumption

ofalcohol by pregnant women can cause birth defects in their offspring. If'th is is true ,

it has taken thousands ofyears to con firm the hints which can be discovered from the

pages of the Bible (Book of Judges 13:3-5). Similarly it has taken more than two

thousand years to understand the motivation of the law in Carthage and Sparta

prohibiting the alcohol use by newly married couples to prevent conception during

ALCOHOL: THE OLD RASCAL IN NEW CLOTHES 361

intoxication. In England the College of Physicians called gin a 'cause of weak, feeble

and distempered children' and asked Parliament to enforce alcohol control (Witt i,

1978). Lemoine, Harousseau, Bortegru & Menuet (1967) and Jones, Smith, Ulleland

& Streissguth (1973) de scribed in the medical literature a typical foetal dy smorphic

condition which was later named 'the foetal alcohol syndrorne'.

Figure 1 Distribution of radioactivity (light areas) in monkey foetuses 15 minutes (A) and

90 minutes (B) after intravenous injection of ['4C]-ethanol to the mother. Abbreviations: ce,

cerebellum; b, blood; bm, bone rnarrow; gi, gastrointestinal tract; h, heart; hi, hippocarnpus;

ki, kidney; lg, lateral geniculate body; li, liver; lu, lung; pi, placenta; and th, thymus.

(Idänpään-Heikkilä eral., 1971).

Infusion Elimination ..

0;

.,- > 100 -I

OE 80 Mothe /

-§o

~o 60 r: c- Foetus

-gE 40 I

I

CD 20 I

240

Duration of Time after delivery

infusion (min) (min)

Figure 2 Placental transfer and elimination of infused ethanol in mother, foetus and

newborn infant. Bloodalcohollevels in mg 100mi-I(Idänpään-Heikkilä er al., 1972).

362 J.IDÄNPÄÄN-HEIKKILÄ

The syndrome consists of four anomalies: central nervous-system dysfunctions,

growth deficiencies, a characteristic cluster offacial abnormalities and various major

or minor malformations as described by Clarren & Smith (1978), (Table 1). The most

visible anomaly is the facial irregularities: short palpebral fissures, a hypoplastic

upper lip with thinned vermilion and diminished to absent philtrum. The face is

further altered by mid-facial and mandibular hypoplasia and sunken nasal bridge.

Table 1 Features ofthe foetal alcohol syndrome (Clarren & Smith, 1978).

Feature

CNS-dysfunction

1ntellectual

Neurological

Behavioural

Growth deficiency

Prenatal

Postnatal

Facialcharacteristics

Eyes

Nose

Maxilla

Mouth

Manifestation

Mild to moderate mental retardat ion

Microcephaly

Poor co-ordination, hypotonia

Irritability in infancy

Hyperactivity in childhood

More than 2 standard deviations below mean length

and weight

More than 2 standard deviations below mean length

and weight

Short palpebral fissures

Short, upturned

Hypoplastic philtrum

Hypoplastic

Thinned upper vermilion

Retrognathia in infancy

Micrognathia in adolescence

The first reported foetal alcohol syndromes were described in children of alcoholic

mothers (Lemoine et al., 1967). Since then more than 400 cases with the syndrome

have been analyzed and published in the United States and Europe. It has been

estimated that the frequency of the syndrome is between one and two live births per

1,000 with the frequency ofpartial expressions at perhaps three to five live births per

1,000 (Clarren & Smith, 1978). Kaminski, Rumeau-Rouquette & Schwartz (1976)

tried to quantitate the risk limit for alcohol use during pregnancy. A prospective

survey of more than 9,000 pregnant women showed that those who consumed

alcoholic beverages, in quantities more than the equivalent of 400 ml of wine/day,

during pregnancy had a higher risk ofan unfavourable outcome.

The increased risk among women with a moderate or high alcohol consumption

appeared to be limited to the beer drinkers, although the mean quantity of alcohol

consumed by beer drinkers was smaller than that consumed by wine drinkers. In this

study, wine drinking seemed to be safer than beer drin king.

Because ofthe widespread use ofalcohol, many questions need to be answered.

I) How much alcohol is it safe to drink?

2) Are there critical periods and ifso, at which stage in pregnancy is the risk greatest?

Is the first month of pregnancy, when many women are not yet aware of their

condition, especially sensitive?

3) Is steady consumption more risky than intermittent or episodic drinking?

4) Are the efTects of alcohol altered or potentiated by other concomitant factors such

as , cafTeine, smoking, minor tranquillizers and other drugs, nutrition, various

environmental agents and maternal age?

5) Are there difTerences between various kinds ofalcoholic beverages?

ALCOHOL: THE OLD RASCAL IN NEW CLOT HES 363

6) What is the mechanism of action: direct or indirect embryotoxicity of alcohol ,

indirect alteration in normal rnaternal-foetal interaction on piacental function , or

is alcohol's major metabolic product, acetaldehyde, responsible for the effects?

Meanwhile it may be wise to follow the advice by the US National Institute on

Alcohol Abuse and Alcoholism: the totally safe levels are unknown. The risk is

apparently established with the ingestion of 85 g of absolute alcohol, or about six

drinks per day. To avoid critical peaks ofblood alcohol concentration, two drinks a

da y ma y be the limit, even ifalcoholic beverages are used only once a week, month or

yea r.

Alcohol protects from coronary disease?

The role ofalcohol in cardiovascular diseases shows an interesting paradox. Alcohol

may cause cardiac arrhythmias and alcoholic cardiomyopathy but consumption of

alcohol has been shown to lower the incidence of coronary heart disease morbidity

and mortality.

Alcoholic cardiomyopathy is a well-known, though rare, sequel to chronic abuse

of alcohol (Brit. med . J., 1979). Alcohol seems to damage the ultrastructure of the

heart muscle. Similar microscopic changes have been demonstrated on skeletal

muscles in non-alcoholic healthy volunteers who con sumed alcohol during one

month. Once the asymptomatic phase has passed, the alcoholic heart muscle disease

may be detected c1inically and, if heavy alcohol use continues, the disease may

culminate in recurrent, acute episodes of myoglobinuria and irreversible, congestive

heart failure. Anal ysis of endomyocardial tissue sampies show increased creatinine

phosphokinase and lactic deh ydrogenase acti vit y in alcoholic heart disease in

comparison to congestive cardiom yopathy. The muscle damage is usually reversible

in the early phase, if the patient stops drinking. Between 1-2% of chronic alcoholics

develop heart failure and the prognosis is poor if high alcohol intake continues. In

addition , drinking worsens existing heart failure in patients who have congestive

cardiomyopathy or heart muscle disease due to some other aetiology.

There are three main risk factors for coronary heart disease: hypertension, high

serum cholesterol and cigarette smoking. According to present knowledge , alcohol

can be excluded from these risk factors and it ma y even decrease the risks. The

incidence of ischaemic heart disease is lower in people who drink alcohol than in

total abstainers. Klatsky, Friedman & Siegelaub (1977) reported (Kai ser Permanente

study) a statistically significant negative association between moderate alcohol

consumption and subsequent myocardial infarct in 464 patients. The same fmding

was made in the Framingham study (Stason , Neff, Miettinen & Jick, 1976) and an

even stronger negative correlation was found in middle-aged Japanese men in the

Honolulu heart study (Yano, Rhoads & Kagan, 1977). In thi s study, a significant

trend towards a lower incidence of ischaemic heart disease was shown, when alcohol

(up to 50 g per day) was consumed. Amounts over 50 g per day gave no definitie

answer. Light alcohol intake was found to have a negative association with fatal

myocardial infarctions, in a large group of cases and controls, in a study performed

by Hennekens, Ro sner & Cole (1978). In some earlier studies, the protective effect of

alcohol against ischaemic heart disease has been shown. Nevertheless, at present, the

protective hypothesis is more strongly supported than refuted in the medical

literature.

Yano et al. (1977) proposed that the protective effect was most evident if the

alcohol consumed was beer. Th is view was also supported by La Porte, Kuller &

Cresan (1979). St. Leger , Cochrane & Moore (1979) concluded that wine was more

likel y to have a protective effect against ischaemic heart disease . Wines are rich in

aromatic compounds and other trace components which ma y have an even more

364 J. IDÄNPÄÄN -HEIKKILÄ

important role than alcohol itself. The relati ve advantages of red, white or rose wine

were undecided. It was also speculated that wine drinkers were more relaxed and for

that reason might have a lower incidence of ischaemic heart disease. Neverth eless,

the study showed that death s from ischaemic heart disease, in eighteen developed,

countries were not strongly associated with such health service facto rs as docto r or

nurse den sity, but there was a strong and specific negative association between

ischaem ic heart disease deaths and alcohol (wine) consumption .

There is some evidence that the protective effect of alcohol may result from its

HDL-chole sterol increasing effects (Figure 3). Alcohol intake increases both serum

triglycerides (Taskinen & Nikkilä, 1977) and HDL-cholesterol and decreases the

LDL-cholesterol (Johansson & Medhus, 1974). The two later effects do protect from

coronary disease and the HDL-increase itself may be enough to expla in the

correlations.

• HOL - cnolesterot

... LO L - cholesterol

T /':,. Tolol cholesterol

2.0 o Tr igl yceri des 7.0 '~

-0

E 1.8 6.0 0

E E

E c: 1.6 5.0 c .2

• .2

lö C c '"

u 1.4 4.0

...----...--...--.( c '"

u

0 c: u 0

u

0 1. 2 .- ... 3.0 .-- 0 E E

.2'" .>: '"

0 Q. 1.0 2.0 a::

30 -90 120- 270 300 -600 > 600

Weekly olcohol consumption (mL)

Figure 3 The correlation between alcohol consumption and plasma-cholesterol (total), LDLcholesterol, HDL-cholesterol and triglycerides in American population according to Castelli,

Douyle, Gordon, Harnes, Hjortland, Hulley, Kagan & Zukel(1977), modi fied by Nikkilä (1979).

Alcohol , amines and dependence

One increasing field of alcohol research has concentrated on fmding links between

the biological, behavioural and biochemical effects ofalcohol. Many factors, psychological, social and genetic, may be the cause ofthe drinking problem ofan indi vidual

alcoholic. But drink ing also has some definitive pathological man ifestations,

dev iations ofnormal phy siology which all have biological mechan isms. It is therefore

necessary to study the biochemistry of alcoholism, alcohol-dependence, alcoholwithd rawal and the hang-over phenomenon.

Th ree areas of research which have given some interesting and promising results

have been selected for discussion.

I) The role of5-hydroxytryptamine (5HT) in alcohol drinking.