opiates and opioid drugs Opium is a crude extract of the seed capsules of the poppy, Papaver somniferum, which contains the opiate alkaloids morphine and codeine. Opioid drugs are synthetic derivatives that act in a similar manner to morphine. The earliest written records of the profound recreational and medicinal effects of opium date from approximately 4000 bc. There is also considerable reference to these effects in Greek and Roman mythology. In the late seventeenth century the physician Thomas Sydenham wrote:
‘Amongst the remedies it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium.’The recreational use of opium was popularized in the early nineteenth century by such writers as Thomas De Quincey (Confessions of an English Opium Eater) and Samuel Taylor Coleridge (Kubla Khan).

Morphine, named after Morpheus, the Greek god of dreams, is the prototypic opioid drug. Heroin, a close structural analogue of morphine, is more lipid-soluble than morphine and rapidly penetrates the brain. This accounts for reports that the euphoric experience (often referred to as the ‘rush’ or ‘buzz’) following heroin administration is more intense. In attempts to exploit the desired therapeutic effects of morphine, but to avoid its unwanted effects (see below), a vast number of opioid drugs have been designed, synthesized, and tested. Some have been introduced into clinical practice. After centuries of research and drug development, and despite the undesired responses they evoke in man, morphine and heroin still remain major therapeutic agents in the treatment of severe pain states.

Both the naturally occurring plant-derived opiates and the opioid drugs exert their profound actions on the body by interacting with specific membrane receptor proteins on nerve cells (described as acting as agonists at these receptors). So also do the body's internally generated endorphins. There are three well-documented forms of these receptors, which are referred to by the Greek letters m, s, and k. In addition, a new, closely related receptor, the ORL1 receptor, has recently been identified. Each of these receptors binds drugs in a specific manner and the binding of the drug to the receptor evokes a change in nerve cell activity. The different profile of responses mediated by the different receptors results from their differing distributions throughout the central nervous system. Most of the therapeutically useful opioid drugs produce their effects by acting as agonists at the m receptor, although some also have activity at the k receptor. The therapeutic potential of the d receptor awaits exploitation. Antagonist drugs such as naloxone can block the actions of opioid agonists. Such antagonists are useful in the treatment of opioid overdose.

Opioid agonist drugs produce a number of therapeutic responses. Pain relief (analgesia) results from inhibitory actions in the spinal cord and in the brain. Whilst opiates are long-established as generally useful in suppressing severe pain, there are some pain states, such as trigeminal neuralgia, in which they or the opioid drugs are often ineffective. Opioids used to be referred to as narcotic drugs because they induce sleep. Opioids cause profound constipation and can be used to treat severe states of diarrhoea. However, the constipating effect of opioids is undesired in the treatment of pain, especially if the drug is administered over a prolonged period. Codeine and some other agents are used as cough suppressants, but this action may not be mediated through the classical opioid receptors. In the treatment of pain states associated with terminal illness, opioid-induced euphoria would appear to be of potential benefit, but there is some controversy over whether opioids induce even mild euphoria in patients suffering from severe, chronic pain.

Unfortunately opioid agonist drugs also have a number of unwanted actions. They depress respiration and this is usually the cause of death in overdose. Some individuals experience nausea and vomiting. Opioids can cause itching, by releasing histamine from mast cells. Also blood pressure may fall, heart rate may slow, and bronchoconstriction may be produced especially at high doses. Constriction of the pupils is a characteristic effect that can be used to diagnose opioid overdose, since other agents that induce coma more commonly dilate them.

On repeated administration, the degree of effect induced by opioids declines, as the person becomes tolerant. This means that to obtain the same level of response the dose of the drug has to be increased. The intense euphoria that results from opioid administration, especially following intravenous injection, smoking, or sniffing, is the reason opioids are abused (taken for non-medicinal purposes). This results in the development of psychological dependence, which is manifest as craving for the drug. Such craving can last for many months after the last drug experience. Opioid-induced euphoria results mainly from an enhanced release of the neurotransmitter dopamine from dopaminergic neurons that terminate in the region of the forebrain known as the nucleus accumbens. Other euphoric agents, such as nicotine and cocaine, also enhance dopamine release at this site, but by different mechanisms. Opioids also induce physical dependence. On cessation of drug administration or on administration of an opioid antagonist, physical dependence is manifest by a withdrawal or abstinence syndrome characterized by fever, sweating, nausea, diarrhoea, insomnia, muscle cramps, and erection of hairs. This piloerection causes the goose pimples that explain the origin of the term ‘cold turkey’, and the muscle cramps have given rise to the term ‘kicking the habit’. However, patients in severe pain do not appear to develop marked tolerance or physical dependence on opioids.

In summary, the site of action of opiates, which are the derivatives of plant-derived opium, and of the drugs that have been synthesized to imitate their effects, has been shown to be at specific cell membrane receptors, hence named opioid receptors, which also bind the body's own endorphins. All these agents may therefore be known generally as opioids.

Graeme Henderson

o·pi·ate • adj. / ˈōpē-it; -ˌāt/ relating to, resembling, or containing opium: the use of opiate drugs. ∎ fig., dated causing drowsiness or a dulling of the senses.• n. / ˈōpē-it; -ˌāt/ a drug with morphinelike effects, derived from opium. ∎ fig. a thing that soothes or stupefies.• v. / -ˌāt/ [tr.] [often as adj.] (opiated) impregnate with opium.PHRASES: the opiate of the masses (or people) something regarded as inducing a false and unrealistic sense of contentment among people.

opiate (oh-piăt) n. one of a group of drugs derived from opium. Synthetic drugs with similar effects are called opioids, a term often used to include both the natural and synthetic drugs. This group includes morphine, codeine, diamorphine (heroin), methadone, and buprenorphine. They depress the central nervous system and are used to relieve moderate to severe pain and suppress coughing. Side-effects include drowsiness, nausea and vomiting, constipation, and depression of breathing; prolonged use can lead to tolerance and dependence.

opiate One of a group of drugs derived from opium, an extract of the poppy plant Papaver somniferum that depresses brain function (a narcotic action). Opiates include morphine and its synthetic derivatives, such as heroin and codeine. They are used in medicine chiefly to relieve pain, but the use of morphine and heroin is strictly controlled since they can cause drug dependence and tolerance.

opiate containing opium, narcotic XVI; sb. XVII. — medL. opiātus; see OPIUM, -ATE2.