from Narcotic Drugs, by Anil Aggrawal,
Paperback, 8.5” x 5.5”.
National Book Trust, India,
A-5 Green Park, New Delhi-110 016.
Publication Date May 1995.
xvi+161 pages, ISBN 81-237-1383-5.
Price Rs. 46.00.

Chapter 3 Opium: the king of narcotics

Dr. Anil Aggrawal,
Professor of Forensic Medicine,
at the Maulana Azad Medical College,
New Delhi-110002
e-mail Dr Anil

Opium is consumed in a multitude of ways. Many people till the last century simply ate opium. With the discovery of its active constituent, morphine, in 1805 by Serturner, a way was opened by which the active constituents, rather than raw opium, could be directly taken. More opium alkaloids were discovered later. In 1817, the French chemist, Pierre Jean Bobiquet (1780-1840), isolated noscapine from opium and in 1832 he isolated yet another alkaloid codeine.

In 1835, another French chemist, Pierre Joseph Pelletier (1788- 1842), isolated thebaine from opium. In fact, since the discovery of morphine as an active constituent of opium, much scientific interest was aroused in alkaloids and any chemist worth his salt was extracting alkaloids from various plants. It was not out of mere curiosity; alkaloids were valuable drugs and it was far more effective to give the alkaloid itself than the plant. Pelletier joined forces with another Frenchman, a pharmacologist, Joseph Caventou (1795-1878), and between 1818 and 1820 both of them together isolated many alkaloids from different plants. Among them were quinine from cinchona, strychnine from Nux Vomica and caffeine from coffee. In 1848, Georg Merck (1815-1888), the German chemist, isolated papaverine from raw opium.

An important advance came about in 1853, when the French physician, Charles Gabriel Pravaz (1791-1853), invented the first practical metal syringe provided with a hollow needle. Known as the hypodermic syringe, it enabled doctors (and addicts too)to inject morphine directly underneath the skin or in the blood vessels. This produced a better and quicker effect than the ingestion of raw opium. Although as early as 1656, the English scientist Sir Christopher Wren(1632-1723), had succeeded in injecting drugs directly into a vein with the help of a hollow quill to which a small animal bladder was attached; this method never really caught on. A Scottish physician, Alexander Wood (1817-1884), was the first to inject morphine directly underneath the skin with the newly developed hypodermic syringe in the very same year that it was invented. (His wife became the first needle addict). His findings were published in 1855 and the whole world of medicine became aware of it. Soon afterwards, in the American Civil War (1861), morphine was widely administered to soldiers; not only to those wounded in battle to alleviate pain, but also to those suffering from dysentery. As a consequence, a large number of Civil War veterans returned to civilian life addicted to the drug, a condition euphemistically referred to as `army disease' or `soldier's illness'.


HEROIN: CURSE OF THE TWENTIETH CENTURY

By this time two facts had clearly emerged: morphine was undoubtedly a potent analgesic (a drug which suppresses pain and other bodily discomforts) and that it was an addictive drug. Thus, whenever morphine was used for killing pain for some length of time, say a month, the patient invariably became an addict. Addiction was a necessary evil, so to say. Scientists tried their hands at modifying the molecule of morphine. It was quite possible, they reasoned, that one part of the molecule was responsible for alleviation of pain, and some other for producing addiction. Could they remove, modify or alter the part responsible for producing addiction? In 1898, in an attempt to do so, the German chemist, Heinrich Dreser, treated morphine with an inexpensive and readily available chemical, called acetic anhydride, and produced a powerful chemical, diacetylmorphone. The drug imparted a sense of grandeur and made the user feel like a hero or heroine and that is why he called it heroin(without an `e' however). Most addicts these days take heroin.

However, at that time heroin was widely acclaimed as an answer to the problem of medical addiction. Leading scientists of his time agreed with Dreser that heroin was a potent non-addictive analgesic. Some even used heroin as a medicine for morphine addiction. However, heroin turned out to be a cruel disappointment. It proved to be an even more dangerous drug than morphine as far as addiction was concerned. It led to very strong addiction. The addict tends to languish as long as heroin is not given to him, but once the heroin is injected into his veins, he galvanises into action. It appears as if life has been infused into a corpse. Some addicts compare the sensation to that of a sexual orgasm! It is important to note here that heroin is not an `energiser'. A normal, healthy individual will not work better after an injection of heroin. An addict works better after an injection of heroin only because his capacity has already been severely compromised due to addiction. On the whole, the capacity of an addict after an injection is still far less than that of a normal person.

SMOKING OPIUM

Before the advent of the hypodermic needle (and even now at many remote places), opium was smoked. Smoking opium was called chandu or maddak and was prepared in a peculiar way in many of our villages. The raw or gum opium is placed in a pot and sufficient water added to cover it. This is boiled until the raw opium is dissolved into a liquid. The solution is then strained through a piece of fine gauze into another pot, thus separating twigs, pebbles and dirt from the raw product. Nothing is wasted and the strained impurities are again processed in order to recover the remainder of opium: the resultant solution is also strained into the container containing the first purified solution. When practically all of the raw opium has been thus separated from the impurities, the solution is brought to a boil over a low flame. After evaporation of the water, a thick black paste remains. This is called `prepared opium', `smoked opium', `cooked opium', chandu or maddak. About 100 gms of raw opium yield 75 gms of prepared opium.


ELABORATE RITUALS

Chandu is smoked in special wooden pipes. A bowl is attached to the pipe where opium smoulders and produces fumes which are lustily inhaled. The initial few puffs of the pipe create a feeling of euphoria. In China and many other parts of the world, opium dens are found where people can smoke opium in groups. These opium dens are more or less like modern bars with the difference that no alcohol is served in opium dens: only opium rules the roost. Although in the modern era, the hypodermic needle and heroin have replaced the pipe, opium smokers regard their vice as `decent' in comparison to the needle addicts. Sessions with the pipe continue ritualistically and the group of smokers who partake follow stated procedures. Such ceremonials are presided over by a `chef' one who is skilful at rolling and cooking the opium pills (made from chandu) and knows how to warm the pipe to the proper temperature.

Such ceremonials are followed more strictly in China than in any other part of the world. The smokers lie on their sides on the floor, rather than on mats while they `kick the gong around'(pass the pipe). The `proper' position, however, is to rest one's head on the abdomen of the next smoker. Each pill (yen pock) lasts from thirty seconds to three minutes and to satisfy the average smoker, six to ten pills must be prepared and consumed. The gathering occasions much conversation; real and imaginary exploits are recounted and elaborate tales recited by persons who ordinarily are quiet and reticent. Fumes from the burning opium condense in the bowl and the stem of the pipe as well as on the `gee rag' a piece of cloth which holds the bowl in position on the saddle of the pipe. This residue is known as yen shee or `opium dross' and is saved for its alkaloidal content. After the smoking session, this residue is scraped from the pipe and retained for future use, generally when the regular supply of opium is not available. `Opium dross' can be mixed with unsmoked opium or dissolved in wine or other alcoholic beverages. In solution form it can be drunk or injected into the body. This solution is referred to as yen shee suey and, though a poor substitute for cooked opium, it can sustain an addict when the real thing is not available.


CURBING OPIUM SMOKING

In our country, opium smoking assumed such monstrous dimensions, that the Government of Bengal had to pass the Bengal Opium Smoking Act in June 1933. It provided for the registration of the existing smokers who had to obtain a permit from the Excise Department. Anyone found smoking without a permit was prosecuted and on conviction had to undergo six months' imprisonment combined with paying a fine. As a result of the recommendation of the Opium Enquiry Committee in Bengal, the limit on the possession of opium by a person was reduced from 11 gm to just 3 to 4 gm. On purchase of an excess quantity, say upto 5 gm, one had to obtain a permit from the Excise Department. These permits were issued only on the certificate of a medical practitioner and in no case a quantity exceeding 5 gm was to be sold to any one consumer. Similar Acts were passed in Bihar and Uttar Pradesh. Now all these Acts have been replaced by a very wide ranging law, the Narcotic Drugs and Psychotropic Substances Act, 1985, which bars not only opium abuse, but other narcotics too.

These days raw opium is generally not available to an addict. Addicts can purchase heroin from shady dealers in small plastic bags containing about 100 mg of the powder. Heroin is a white crystalline powder, not unlike the common baking soda in appearance but is bitter in taste. It comes from illegal laboratories in almost pure form, but before reaching the addict, it passes through the hands of several shady dealers. Since their aim is to make money, they adulterate it with a similar looking substance. Common adulterants used are lactose (milk sugar), talcum powder or quinine. The rationale behind adding quinine is that it not only looks like heroin but tastes bitter too, just like heroin. Many inveterate addicts would test the `purity' of heroin by opening the plastic bag and putting a little powder on their tongue. If lactose or talcum powder had been added, they might detect the adulteration. Most addicts, however, do not care if their supply of heroin is adulterated or not. Some dealers add jaggery (or gur) to the powder, giving it a brownish appearance and that is why a slang name for street heroin is `brown sugar'. Street heroin is the final adulterated form of heroin which is made available to the addict. The origin of the name is self- explanatory. By the time, it reaches the street, it contains no more than 3 to 5 per cent heroin. Each intermediary agent who gets the powder adds an equal amount of adulterant to it. The process works something like this. The first dealer gets 100 per cent heroin. To about 28 gm of it, he would add 28 gm of lactose (or some other adulterant),making it 56 gm of 50 per cent heroin; second dealer will add 56 gm of lactose making it 112 gm of 25 per cent heroin. Thus, after passing through the hands of just five intermediate dealers (which is the average), the powder becomes 896 gm in quantity and only about 3 per cent in purity.

WAYS OF TAKING HEROIN

Heroin is self-administered by the addict in a number of ways: he can orally ingest it, sniff it, inject it beneath the skin (known as `skin-popping' because the skin is popped up and heroin injected), or inject it directly into a vein (known as `mainlining' because it is put in a main line, so to say). A number of poor people in our country take it by smoking (known as `chasing the dragon'). For this, a metal foil from an empty cigarette pack is taken and the white powder spread over it in the form of a straight line. The addict makes a straw from a paper and puts one end of it into his mouth (see diagram). The other end of the straw is kept a few millimetres away from one end of the powder line. A match is lit and the flame put beneath the foil. This vaporises some of the powder amd the addoct sucks in through the straw lustily. The flame is advanced along the line beneath the metal foil and at the same time the straw is advanced along the line above it, with the addict puffing furiously all the time. In this manner, the addict goes back and forth along the line, till all the powder is consumed. This peculiar way of inhaling the heroin smoke has given rise to the expression `chasing the dragon'. Some addicts keep a metal coin between their teeth and lips (see diagram). This is supposed to `catch' the impurities. When the addict is short of drug supply, this coin is scraped and whatever drug is recovered, is used.

The most popular method of heroin intake is, however, injection by a hypodermic needle. Consuming the drug by mouth or by sniffing does not give rise to as intense a pleasure as by injecting it directly into a vein. This is because the drug is broken down by the stomach juices. In addition, the veins carrying the drug from the stomach, first pass through the liver, where most of the remaining drug is broken down further. For this very reason, whenever doctors want to give morphine to their patients for medical reasons, they do so by injection. Heroin is taken by mouth or sniffed only by needleshy beginners; but, most of them later turn to the needle.


MECHANICS OF MAINLINING

One of the most amazing things in the dark and murky world of addicts is the mechanics of `mainlining'. For this the addicts use an elaborate paraphernalia, sometimes called `outfits', `works' or `toys', which include a variety of items. A spoon, wine bottle cap, or some similar device called a `cooker', is used for mixing and heating the heroin after being mixed with a small quantity of water. Sometimes the handle of the spoon is bent downwards and `doubled on itself' so that the hollow of the spoon will remain in level when kept on the table. The syringe, or `spike' as it is sometimes called, is either a commercially manufactured syringe or a home-made syringe consisting of an eye- dropper with a rubber suction device. The needle is then fitted to the eyedropper, which sometimes requires a `gasket' to ensure a proper fit. The gasket, also known as the `collar' or the `gaff', is a crude shim used to ensure a tight fit between the syringe and the needle. Many materials may be used to serve the purpose of a gasket, such as a scrap of paper, thread, rubber or tape but the favourite is a small strip of paper currency, tightly wrapped around the shank of the needle. Paper money is supposedly used because of its semi-repellency to water. When not in use, the needle is kept in a protective covering known as the `sheath'. It is generally made of a paper-book match cover, rolled and tied with a rubber band. The kit also includes a small ball of cotton, which is placed in the spoon. The heroin is drawn into the syringe through this cotton. This ball of cotton is supposed to filter out any `poison', but, ironically it is this very ball which adds dirt to the already dirty solution. Moreover, sometimes small cotton fibres get sucked in the syringe and are inadvertently injected into the vein. This is very dangerous because these cotton fibres get lodged in the lungs leading to serious propblems. The same dirty cotton is used again and again and what is quite amazing is that the adicts really believe that the cotton is filtering out the poison. In times of distress, when a fresh supply of the drug is not available, a typical addict will add this cotton to plain water and inject the resulting solution into his veins. Since the cotton becomes saturated with heroin through overuse, the resulting solution does give some relief to the addict. This practice is known as `shooting the cottons'.

The tourniquet or `tie-rag' is any article such as a necktie, towel or a belt that can be tied around the arm or leg to make the veins very prominent. This is a method which doctors use to given injections directly into the vein. The tourniquet is placed and tightened slightly above the elbow, so that veins in the front of the elbow become prominent. It is very easy to introduce a needle in the swollen vein. Those, who are unable to get hold of a hypodermic needle, tend to use things like the safety pin, sewing needle and even razor blades to make a hole in the vein and insert the eyedropper directly into the vein hole. On occasions, the addict might personalise the kit by making up a special leather or metal container. More often it is simply placed in an empty cigarette package, wrapped with a rubber band and hidden in the dirtiest corner of the addict's home. The reason for this is to take advantage of the fact that most investigators do not like to get their hands dirty during searches.


THE PROCEDURE EXTRAORDINAIRE

The addict begins the preparation for injection by emptying the contents of his satchet (known as `bindle' or `balloon'), into the `cooker'. After adding enough water to liquefy the substance, a heat source is placed at the bottom of the `cooker' and the substance is observed closely until the first bubble appears. The addict`s intention is to attain approximate body temperature. Then the solution from the `cooker' is drawn through a cotton ball into the syringe. Just at this moment, the tourniquet is applied above the elbow. Now the needle is inserted slowly into the vein until the blood can be seen coming into the eye-dropper. The rush of the blood in the dropper indicates that the vein has been successfully punctured. The drug is now pushed into the vein. Some addicts prefer to suck the blood back into the dropper three to four times in order to ensure that no trace of the drug remains in the dropper. This practice is known as `booting'. The effect of the injection is immediate and intense. Addicts describe it in various ways, ranging from a pleasant tingling sensation running up and down the limbs and settling in the abdominal region, to a sensation not unlike a sexual orgasm which tapers off into a feeling of lethargic well-being, resulting in a disregard for problems, and a total lack of a sense of responsibility. The condition is deeply desired by the addict and lasts for several hours following an injection.

An addict generally begins his career by injecting in the veins of the elbow. Due to repeated injections, however, the veins collapse and deteriorate and the addict is forced to move further down the forearm and then towards the back of the hand. As further deterioration takes place, the addict moves down to the feet and then upwards, travelling from the legs to the thighs and the groin area. Finally all these veins are scarred. A heroin addict can be spotted at once by just looking at the condition of his veins. When all the limb veins become scarred, some addicts start injecting the drug into the veins of the neck; some inject under the tongue and still others inject the drug into the dorsal vein of the penis. Female addicts are known to inject under the breasts. When all the veins of the body have become scarred, the desperate addict starts shooting in the chest, abdomen, buttocks, thighs; even in the webs between the fingers and the toes.


HOT SHOT

Sometimes an addict can get a sample of heroin, which is adulterated with a dangerous poison, strychnine. Its injection known as `hot shot' can cause quick death. `Hot shot' can also occur when an addict, used to injecting heroin of 3 to 5 per cent purity, gets a purer blend of the drug. Death can occur in this case, since the addict is not used to higher concentrations. If the addict is old and wise, he will first inject a small quantity of the heroin just to feel the effect. This is particularly important if the addict has a new supplier or is using an unknown brand of heroin. But if the addict is suffering badly from withdrawal symptoms, even an `old hand' will inject the whole drug quickly and may suffer death from a possible `hot shot'.


OPIUM DECOCTIONS

Some villagers boil opium in water, just as we boil tea leaves and prepare a decoction. This decoction is known as kasoomba or amalpani and contains about 5 per cent of opium. Kasoomba is sometimes offered to guests on festive occasions. An infusion of poppy capsules is also habitually drunk by some people in certain districts of Punjab and in parts of Rajasthan, especially Jaipur. Bhujri, a preparation made by frying green, unripe capsules in butter or ghee, is sometimes eaten by the addict villagers. A sweet known as halwa, prepared from the juice extracted from green poppy capsules, is also used. These preparations are basically used by villagers who have no access to elaborate equipment mentioned earlier.

Some opium-containing remedies were abused for addiction too. Two popular eighteenth century remedies containing opium were `Blackdrop' and `Paregoric'. `Blackdrop' was invented by Edward Runstall of Auckland and `Paregoric' by Le Mort of the University of Leyden. Another popular remedy in eighteenth century England was chlorodyne which contained chloroform, ether, morphia and Indian hemp. All the three drugs were used to soothe pain and to cure dysentery, but all the three caused addiction among the patients. Those who fell victims to these drugs behaved like morphinists (confirmed morphine addicts). Women were known to sell their husband's property and steal in order to obtain these drugs. These drugs were withdrawn from the market long before the twentieth century.


EFFECTS OF MORPHINE

Morphine produces a sense of emotional well being or contentment termed `euphoria'. It is the ability to produce euphoria which makes morphine (and its related drugs)one of the worst drugs of addiction. Rarely morphine may produce a sense of anxiety or fear termed `dyphoria'. Morphine is a potent suppressor of pain and of cough reflex. It also produces a vigorous spasm of the anal sphincter causing constipation. Morphine produces depression of respiration. An addict who has taken an overdose of opium, respires at a very low rate, about two to three beats per minute, while the normal respiratory rate is about eighteen beats per minute. It produces sedation in man (but excitement in the cat and the horse). It lowers the blood pressure and releases a hormone (antidiuretic hormone) which reduces the formation of urine. Because of these wide ranging effects on the human body, morphine is viewed as a valuable medicine by doctors. When an addict does not get his supply of opium (or morphine or heroin or any other related drug), he starts experiencing withdrawal symptoms which are very distressing. Withdrawal symptoms usually occur in three separate stages.

Stage 1 starts within four to six hours. In the beginning discomfort is more psychological than physical. Within eight to fourteen hours, restlessness, perspiring, runny eyes and nose, yawning and sneezing are experienced. These symptoms resemble that of a common cold. From fourteen to twenty-four hours, the symptoms increase and the addict experiences loss of appetite, slight body tremors, and a puckered appearance of the skin known as `goose flesh'. This causes the skin to take on the appearance of a plucked turkey, and hence the origin of the expression `going cold turkey'. This expression is used for addicts who are experiencing the first stage of withdrawal symptoms.

Stage 2 starts after twenty-four to thirty-six hours. The addict experiences insomnia (lack of sleep), vomiting, diarrhoea, weakness and depresssion, in addition to an intensification of the already present symptoms.

Stage 3 starts after forty-eight to seventy-eight hours. All the symptoms lead to severe muscular and stomach cramps and severe tremors and twitching. A rise in temperature and respiration rate ensues along with a worsening of the vomiting and diarrhoea. The involuntary twitching worsens. This is the source of origin for the term `kicking the habit'. After the addict has passed through all these stages, he feels as if he has gone through a state of `living hell'. Mainly to avoid this state, the addict keeps on taking morphine again and again.


THE RECEPTORS:

The mechanism of the action of morphine was not known till recent times. It now appears that there are special sites in our brain, called receptors, where morphine attaches and produces its actions. These receptors can best be conceptualized as locks, which can only be opened by specific keys. When the right key fits the lock, it opens the lock, and the symptoms flow out (Note to the Editor: A diagram may be placed here, depicting this analogy). Three different types of receptors (or locks) have been identified in the brain till now. True to the scientific tradition these receptors have been given names after the letters of the Greek alphabet. They are called µ (mu) receptors, (kappa receptors) and (delta) receptors. These names may sound somewhat incomprehensible, but they have an interesting origin. Certain drugs are known to attach themselves specifically to these receptors. The first letter of the drug, which was first shown to attach itself to these receptors, lends its name to these receptors. Thus morphine was first shown to attach itself to mu receptors. The first letter of the drug morphine is `m'. Thus these receptors could very well have been called the m-receptors. But the world of science has a tendency to name everything after the Greek letters( It is perhaps a tribute to the great Greek culture, which was one of the earliest cultures to start thinking scientifically). The equivalent of the letter m in Greek is µ. Thus these receptors came to be called the µ receptors. Similarly a drug known as Ketocyclazocine was first shown to attach itself to kappa receptors. The Greek equivalent for the English letter k is (kappa). Thus these receptors came to be known as kappa receptors.

Collectively these receptors are also known as opioid receptors - a Greek term, meaning opium like receptors. These are so called because in addition to morphine, several other drugs derived from opium can get attached here.

Stimulation of different receptors (or in our analogy, opening up of different locks) produces different symptoms. The molecule of morphine can attach itself to all these receptors, or in other words it has the key to all these locks. The attachment of morphine with any of the three receptors (and their subsequent stimulation) leads to a reduction in pain and lowering of the respiratory effort. Certain additional specific symptoms are produced by attachment of morphine and morphine like compounds to specific receptors. For instance the attachement of morphine to mu receptors produces additional sensations of elation and well-being (euphoria), and a tendency to addiction. Similarly attachment with kappa receptors leads to the additional symptoms such as constriction of pupils and sedation. Attachment to delta receptors leads to diminished movements of the bowels, thus producing constipation.

In recent years, scientists have come to know that µ receptors are in fact not just one entity, but two different entities. In other words, there are two different sub-types of µ receptors. These are called µ1 receptors and µ2 receptors. Stimulation of µ1 receptors results in suppression of pain, while the stimulation of µ2 receptors results in suppression of respiratory effort and a reduction in bowel movements.

Stimulation of various receptors and the symptoms produced by them can best be summarized in a table.

S.No. µ(mu) (kappa) (delta)
1. Reduction of pain Reduction of pain Reduction of pain
2. Suppression of respiratory effort Suppression of respiratory effort Suppression of respiratory effort
3. Sensations of elation and well-being(euphoria) Unpleasant sensations of anxiety or fear (dysphoria); Seeing unnatural and imaginary things (hallucinations) Emotional behaviour(also known technically as affective behaviour)
4. Constriction of pupils(known technically as miosis) Miosis --
5. Reduced movements of the bowel(responsible for constipation) -- Reduced movements of the bowel
6. Addiction (physical dependence) Addiction --

-- An interesting point can now be introduced at this stage. We have seen that morphine and several morphine like drugs attach themselves to these receptors and produce specific symptoms. There are certain other drugs, which do attach themselves to these receptors but do not produce any symptoms. Continuing with our old analogy, these drugs do have a similar looking key, and the key does fit the lock too, but somehow it fails to open the lock. The result is that such drugs not only do not produce any action, but they in fact block the receptors from being acted upon by the drugs which would have produced symptoms. This is an interesting situation, which can (and in fact is ) exploited by the doctors to treat a case of opium poisoning. But first let us be familiar with the names of these drugs. The former group of drugs which produces symptoms is known as "agonists" (from a Greek word meaning "I struggle". These drugs may be visualized as struggling to produce symptoms!). The latter group of drugs which attaches itself to the receptors, but does not produce any symptom, is known as "antagonists"(from a Greek word meaning "against I struggle". These drugs may be visualized as struggling against the drugs which produce symptoms!)

How can antagonists be used to counter the effects of agonists? Imagine a person has taken so much morphine that his respiration is severely depressed. His life is in danger because of this. But what is really going on in his body? If one had the means to look at the receptors in his brain, he would find that morphine molecules are sticking to the receptors and are producing the action of depressing his respiration. Morphine is destroyed by the body slowly, but as soon as some molecules are destroyed fresh molecules come and attach to those receptors. If the patient could be given an antagonistic drug, such as Naloxone, molecules of naloxone would get stuck to those receptors, but they would not produce any symptom. Not only that, these molecules, by attaching themselves to these receptors make them unavailable to morphine. And thus in the course of time the patient recovers.

There are certain other drugs which are called "partial agonists". These drugs do produce symptoms, but they are milder. Quite interestingly, a particular drug can be agonistic for one type of receptor, antagonistic for another and a partial agonist for the third type of receptor. For instance the drug Pentazocine (given to counter severe pain associated with surgery, burns and fractures), is antagonistic at the mu receptors, agonistic at kappa receptors, and partially agonistic at delta receptors. What this really means is that Pentazocine would attach itself to all receptors but would not produce any action specific to mu receptors and would produce only milder symptoms specific to delta receptors. Only at the Kappa receptors would it produce specific symptoms. Drugs which behave in this way are called "agonist-antagonists" (quite predictably so, because they act as agonists at some receptors and as antagonists at others). A table depicting the actions of the various morphine like drugs would make matters clearer.

S.No. Morphine like drug Behaviour at mu receptors Behaviour at kappa receptors Behaviour at delta receptors
1. Morphine Agonist Agonist Agonist
2. Nalorphine Antagonist Partial agonist Partial agonist
3. Pentazocine Antagonist Agonist Partial agonist
4. Nalbuphine Antagonist Agonist Agonist
5. Buprenorphine Partial agonist Antagonist (?)
6. Butorphanol Antagonist Agonist Agonist
7. Naloxone Antagonist Antagonist Antagonist

It is noteworthy that only one drug - Morphine - is agonistic at all the three receptors and only one drug- Naloxone - is antagonistic at all the three receptors. Thus naloxone is truly antagonistic to morphine and thus is very valuable in morphine poisoning. Previously Nalorphine was used in morphine poisoning but it is no more recommended. A reference to the above table would make the reason obvious.

Researchers have found a fourth type of receptor in the brain. It has been named the (sigma) receptor. A drug named SKF 10047 was first found to have an affinity for this receptor ( in fact the name sigma comes from the first letter of the drug). Stimulation of this centre produces unpleasant sensations(dysphoria) and hallucinations. The word hallucination comes from Latin alucinari, meaning "to wander in the mind". Hallucination refers to seeing, hearing or feeling things which do not exist. Thus a person having hallucinations may feel that some bugs were crawling over his skin, while in actuality there would be nothing.

Sigma receptor is however not considered a true opioid receptor because neither morphine nor naloxone attach here. It (the sigma receptor) is a lock for which neither morphine nor naloxone have a key. For a receptor to be a true opioid receptor, either morphine or naloxone must be able to attach themselves at it. However many morphine like drugs such as pentazocine and butorphanol do attach themselves to this receptor and produce unpleasant symptoms and thus it is useful to know that such a receptor does exist. Moreover certain other drugs such as PCP may also act through this receptor, as we shall see later.

It is now known that the human body produces its own set of morphine-like chemicals. These chemicals were discovered in the mid 1970s. Three distinct families have been discovered - enkephalins, endorphins and dynorphins. During severe injuies these chemicals are released and act as natural pain-killers. For quite somtime it was known that soldiers severely wounded in a war did not feel the pain as intensely as they should have-this always remained somewhat of a mystery. Now this phenomenon can be easily explained. You too may have experienced that after a severe injury, the pain subsides to a great extent, and is replaced by somewhat agreeable sensations. This is due to these endogenous morphine-like chemicals.


RELATIVES OF MORPHINE

We have encountered several relatives of morphine earlier, such as codeine, papaverine and heroin. A special mention must be made of etorphine, which once appeared in the Guinness Book of Records as `the most powerful pain relieving drug'. Its pain-relieving capability is 10,000 times that of morphine! It was originally prepared in the early 1960 from oripavine, which does not occur in the extract of the opium poppy. It is found in related plants- Papaver orientale and Papaver bracteatum. One of its interesting uses is immobilisation of large animals in zoos. It is administered by intravenous injections or in cases of dangerous animals on the tip of a dart fired from a crossbow. It is also used in general animal veterinary practice, particularly for horses and cattles.

Methadone is a related narcotic synthesised by the Germans during World War II, because of the unavailability of morphine. It was named Dolophine after Adolph Hitler (it thus became the first and the only narcotic to be named after a person. The name in turn gave rise to its slang name `dollys'). It was later used to minimise the discomforts of heroin withdrawal by being administered in small doses for about ten days a process termed detoxification. In the United States, next to heroin, methadone- the synthetic opiate is most responsible for addictions and is easily available in the street causing a major problem in its turn. Methadone is normally given as a substitute for heroin to reduce the severity of withdrawal symptoms in addicts undergoing treatment.

* * *
Dr Anil Aggrawal
Drugs on Stamps: Pictures
Chapter Two of Narcotic Drugs


Papaver somniferum - the opium poppy

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