Heroin in the brain

In 1972 brain researchers from Johns Hopkins University made a puzzling discovery that would illuminate scientists' understanding of drug addiction.  They found that the human brain's neurons had specific receptor sites for opiate drugs: opium, heroin, codeine and morphine. But then there was the obvious question. Why would nature put in our brains a receptor for a plant? After all, humans beings didn't evolve over millions of years eating opium or shooting heroin. The scientists reasoned there must be some other function for these receptors sites. They soon figured out that the active ingredient in all these opiates - morphine - had a chemical structure similar to endorphins, a class of chemicals present in the brain . Endorphins are feel-good chemicals naturally-manufactured in the brain when the body experiences pain or stress. They are called the natural opiates of the body. Endorphins flood the space between nerve cells and usually inhibit neurons from firing, thus creating an analgesic effect. On a lower level they can excite neurons as well. When endorphins do their work, the organism feels good, high, or euphoric, and feels relief from pain [analgesia]. Logically, endorphin levels go up when a person exercises, goes into labor, or is stressed out. Although they seem to be triggered by stress, endorphins can do more than relieve pain, they actually make us feel good. Like an evil twin, the morphine molecule locks onto the endorphin-receptor sites on nerve endings in the brain and begins the succession of events that leads to euphoria or analgesia.  This imposter is more powerful than the body's own endorphins because the organism can actually control how much of the feel-good chemical hits the brain. Since we are all pleasure-seeking organisms, the motivation to self-administer such a drug is easy to understand. The drawback, of course, is addiction.
	The first intravenous injection of heroin can be extremely unpleasant, causing vomiting and nausea. Often this experience is enough to scare someone away, but social and psychological pressures may motivate a person to keep trying. After a few more uses, the beneficial effects are obvious. Some users have distinguished between the "rush" and the "high." The rush lasts only one or two minutes and is said to be caused by the injected heroin bathing the brain before it gets distributed by the bloodstream and changed into a more useable form of morphine. The rush is often described as a heightened sexual orgasm, and a great relief of tension, which pervades the abdomen. After the rush, the high lasts for four or five hours and is caused by the morphine diffusing from the bloodstream into the brain. It is described as a warm, drowsy, cozy state. Addicts report a profound sense of satisfaction, as though all needs were fulfilled. There is also a pleasant state of mild dizziness that is not as impairing as alcohol's effects, and a sense of 'distancing' or apathy toward whatever is going on in the environment. Some addicts lose the effect of euphoria, and use heroin only for relief of unpleasant withdrawal symptoms. Since all opiates produce cross-tolerance, the use of codeine, opium or morphine can relieve the withdrawal symptoms of heroin.
	The mechanism of addiction is still not fully understood. Generally speaking, addiction is a socially-derived word that refers to a person's compulsive use of a drug in spite of being harmed by it. Dependence and tolerance are conditions that can lead to addiction. Dependence occurs when, after a constant supply of the opiate, the brain shows adaptation, or a change in its circuitry. When that drug is taken away, neurons that have long been inhibited start pumping out neurotransmitters again. This imbalance of chemicals in the brain interacts with the nervous system to produce the classic opiate withdrawal symptoms: nausea, muscle spasms, cramps, anxiety, fever, diarrhea. Tolerance, another poorly understood phenomenon, describes the need for a drug user to administer larger and larger doses of the drug to achieve the same psychoactive effect. A general hypothesis says that when the body's chemical equilibrium is upset, as in habitual drug-taking, the body sets up oppositional processes to restore itself. More of the drug is needed to overcome these efficient corrective processes. Tolerance occurs with regular use of almost all psychoactive drugs.
	It is not surprising that other drugs of abuse mimic or interfere with naturally-occurring neurotransmitters as well. Nicotine for example mimics a common neurotransmitter in the brain called acetylcholine which affects skeletal and heart muscle function. Cocaine and amphetamines cause an abundance of another neurotransmitter, dopamine, to stay in the cleft between nerve cells, stimulating them. The active ingredient in marijuana, THC, is mildly hallucinogenic and probably interacts with many chemical pathways.
	The opiates like heroin are the drugs that cause the most classic set of withdrawal symptoms. About eight to twelve hours after the last heroin use, an addict's eyes begin to tear and he/she starts to experience flu-like symptoms: sneezing, weakness, depression, muscle cramps, nausea, vomiting, diarrhea. The symptoms increase in severity over two to three days. Within a week to 10 days the illness is over. The phrase 'cold turkey' probably comes from the appearance of goose bumps all over the body, which resembles a plucked turkey. Muscle spasms in the legs produce kicking movements, and this may be the derivation of the expression 'kick the habit.' In contrast to opiates, cocaine withdrawal is much less dramatic, characterized by sleep disturbances and depression. Some researchers believe that no real withdrawal syndrome exists for cocaine, marijuana, amphetamines, and hallucinogens, since withdrawal symptoms appeared to be psychological rather than physical. At the opposite end of the spectrum are alcohol and barbiturates (downers). For reasons not fully understood by scientists, withdrawal from alcohol and barbiturates, both central nervous system depressants, can be fatal.
	By the turn of the century, the habit-forming properties of opium were well known. In an effort to eliminate the addictiveness of morphine, German pharmacists tinkered with its molecular structure. They invented a derivative called diacetylmorphine. The Bayer Company named it heroin and marketed it as less-addicting and less toxic alternative to morphine. Heroin turned out to be 2 to 3 times more potent than morphine. It was in fact an already-metabolized version of morphine, so heroin had a more direct route to the brain than morphine itself. By the late 1920s heroin was the most widely abused opiate.
	Edythe D. London, PhD., Director, National Institute of Drug Addiction Brain Imaging CenterEncyclopedia of Drugs & Alcohol, Jerome Jaffe, editor The Hardest Drug by John Kaplan Introduction to Psychopharmacology