The poppy is an ornamental plant with beautiful flowers. When greedy individuals extract juice from its fruit to produce opium, the gorgeous flowers become the "source of evil." Nevertheless, large-scale opium addiction and abuse only occurred among Chinese who smoked pure opium paste with specially designed pipe and lamp. Maybe it is so ritualistic and cumbersome that opium in other regions was often consumed orally, and it is less addictive. What truly made opium an international addictive drug were the discovery of morphine and heroin.
Abuse and addiction: extracting morphine from raw opium
People have always been curious about what substance made raw opium so potent and miraculous. In 1804, German pharmacist Friedrich Sertürner successfully extracted the pure active ingredient from this ancient medicine for the first time. Now we know that raw opium contains about 50 alkaloids. But the most common are Morphine, Noscapine, and Codeine. Among them, morphine content is about 4-20%.
Because morphine is a completely pure substance, it is far more anesthetic and sedative than raw opium or poppy pods. Its original purpose was also to relieve pain, but doctors soon found that patients felt euphoria within a few minutes after injection, much shorter than the half an hour of oral administration. The American Civil War was a hotbed for morphine abuse and addiction. At that time, the dosage of morphine had not been standardized. Doctors often increased the dose so that the wounded could quickly get out of pain. After the war, many retired veterans became dependent on it. Doctors and pharmaceutical distributors were driven by profit, and promoted the benefits of morphine to patients. Experts even proposed the notion that it was "more advanced and safer than opiate." Therefore, the toxicity and side effects of morphine could not be properly understood by the European and American public, and people were more actively trying it. In 1900, the number of drug addicts in the United States reached about hundreds of thousands.
Semi-synthetic drugs: heroin is modified morphine
Some wanted to modify morphine chemically to create an ideal substitute that would be non-addictive and highly effective for pain relief. In 1874, British chemist Alder Wright successfully synthesized diacetylmorphine from boiling acetic anhydride and morphine in a laboratory at St. Mary's Hospital in London. However, animal experiments showed that injected rabbits and dogs became extremely weak and drowsy, and even breathing and heartbeat were suppressed. It seemed a poison with no medical value.
23 years later, Bayer researcher Hoffmann attempted to acetylate less addictive codeine to create a morphine substitute. But he accidentally got a more potent acetylated morphine. For commercial gain, Bayer announced that it was a safe alternative to morphine without fully studying its pharmacology. Bayer also gave it a catchy brand name, "Heroin," and spared no effort in promoting it on the international market. Articles about heroin's quick and non-addictive effect were published in mainstream medical journals in Europe and America. In newspapers, posters, and brochures, heroin was advertised by more than ten languages with powerful slogans about its heroic and side-effect-free potency as painkillers to attract doctors and patients. Free heroin samples were even given to doctors.
However, within just a few years, numerous reports emerged about heroin addiction and its damaging effects on mental and physical health. Many patients could not quit it at all after taking it. Their digestive and nervous systems suffered severe damage to result in emaciated addicts. But it was too late—the demon is out of the bottle and put it back is impossible. It became the most dangerous drug of the 20th century.
Addictive opioids: opium, morphine, heroin are similar to endorphin
The opioid receptors in the brain were discovered by scientists in the 1970s. They certainly were not designed for exogenous opioids. Scientists hypothesized that some unknown substance would be synthesized by us to bind with these receptors. A few years later, a polypeptide with similar function was isolated and named endorphin. Once the brain receives pain signals, the body releases endorphins to bind with opioid receptors in the spinal cord to stop pain reaching to brain. There are also such receptors in brain that not only suppress pain but also promote dopamine release to please and satisfy you. Stress hormones such as cortisol are also reduced by activated opioid receptors to achieve relaxation.
Morphine is an alkaloid that has a structure very different from endorphins but can also bind to opioid receptors for pleasure and pain relief. Orally administered morphine is first detoxified in liver to reduce its potency. If they are injected into the bloodstream, they directly penetrate the blood-brain barrier and bind with opioid receptors. Addicts experience an unparalleled euphoria within minutes that oral consumption cannot compare to. Heroin is metabolized into morphine, but the acetylated hydroxyl groups are more hydrophobic, and it enters brain faster and in greater amounts. Therefore, it is several times more potent and addictive than morphine.
However, cells have multiple mechanisms to desensitize receptors, which serves as a protection for avoiding continued activation. Even short-term use of opioids will alter cell communication pathways. Phosphorylated opioid receptors prevent signals from transmitting towards downstream. They are more likely to trigger endocytosis, and then they are digested by lysosomes. Long-term smoking or injection not only downregulates gene expression to reduce opioid receptors but also synthesizes more enzymes to break down morphine. At the same time, the nervous system becomes more excitable to counteract the inhibition from opioids. Eventually, addicts must increase the dosage or change methods (oral → smoking → injection) to achieve the original euphoria. Once they stop using, withdrawal symptoms become very intense. The balance result from opioid is broken: excitation suddenly takes dominance to result in anxiety, rapid heartbeat, sweating, tearing, etc.; addicts will also suffer from torture caused by daily joints friction and organs collision. It is said that this feeling is like countless ants gnawing at bones and skin.