Melancholia: Satan and his sugarcoated bullets

  Modern people often feel depressed, but few people feel sick because of it. So here comes the question: how to draw the line between melancholy and depression (scientific name depression)?
  To be honest, until today, every new edition of the Diagnostic and Statistical Manual of Mental Disorders refreshes the previous definition of “depression”. But as long as most of the descriptions are met, there is a high probability that it will be diagnosed as depression.
  Most of these symptoms are not new. In the Middle Ages, patients with all mental illnesses, including depression, were considered guilty of soul crimes and condemned by God. The patients’ bodies were filled with “evil black bile”, and it was Satan who appeared to show his power to mankind.
  In the nearly 500 years of post-modern medicine, the cognition of depression is still struggling, and its pathogenesis is still an unsolved mystery. So far, people have tried many ways to cheer themselves up – it is not difficult, but most of them are poisoned to quench thirst, more like Satan’s sugar-coated bullets.
wolf den tiger den

  The first time humans thought they had found a cure for depression was in the 18th century. A pharmacist assistant named F. Zeltina in North Rhine-Westphalia, Germany discovered that opium extracted from poppies has a strong anesthetic effect and can relieve pain, and then tried to extract the active ingredients that really have an anesthetic effect.
  Zeltina did it! In 1805, he named the alkaloid extracted from opium poppy and able to quickly enter deep sleep as “morphine” after the god of sleep in Greek mythology “Morphine”. Since then, the demon “Pain”, which has been entangled with human beings endlessly, has been subdued. As a kind of “mental pain”, depression seems to have ushered in a glimmer of light. Because there is often a vicious cycle between depression and physical pain, it was later discovered that the two share chemical messengers in the brain.
  No matter how unbearable the pain (whether it is physical or mental), people cannot refuse morphine—thereby losing the precious “voluntariness” in spirit. Especially on the battlefield, in order to allow soldiers to return to their positions as soon as possible, morphine was abused in large quantities. John Pemberton was such a soldier who was abused of morphine during the American Civil War. When he realized that he was addicted to morphine, he thought of a good way—to replace morphine with coca wine that was popular in Europe at that time.

  Throughout the 19th century, Coca-Cola enjoyed the reputation of “one sip of Coke, several times the happiness”, and was widely recommended to patients with depression.

coke inventor john pemberton


  The core ingredient of coca wine comes from an alkaloid “cocaine” purified from coca leaves, which not only has a refreshing effect, but also produces a pleasant hallucinogenic effect. In 1886, while giving up morphine with coca wine, John also improved the formula and synthesized a new drink, named “Coca-Cola”. Compared with the “sugar rush” of today’s carbonated drinks, the first generation of Coca-Cola is really on top.
  Throughout the 19th century, cocaine was widely used in surgical anesthesia, and Coca-Cola enjoyed the reputation of “one sip of Coke, several times the happiness”. It was widely recommended to patients with depression and became the first widely used antidepressant “drug”. Even, the American Neurological Association declared at the time: “A melancholy and silent person, who bears the deepest sorrow or sorrow, will stop crying and be happy under the influence of cocaine.” Even the psychologist Flo Ede also raved about taking cocaine, calling it a “magic substance”.
  At the same time when Coca-Cola became popular, Felix Hoffmann, a pharmacist at Bayer in Germany, continued to synthesize a substance with super antitussive and analgesic effects on the basis of morphine, and named it “heroin”. Means “hero”. Its scope of application soon expanded from the initial cough relief to the treatment of mental illnesses such as pain relief and anti-depression. As a result, the abuse of morphine quickly turned into the abuse of cocaine and heroin.
  However, with the emergence of cocaine and heroin addiction and side effects such as hallucinations and insomnia, the medical profession has to admit that drug research and promotion are indeed too hasty. After that, a series of decrees to prohibit or control the use were promulgated one after another. In 1903, Coca-Cola dropped cocaine from its formula, leaving only caffeine, a stimulant substance—almost non-addictive, but also ineffective against depression.
why worry

  Half a century after cocaine faded out, the first professional antidepressant drug “Isoniazid” was born in 1952. The inexplicable ecstasy of a group of tuberculosis patients taking the synthetic isoniazid drug to treat their lung ailments is once again a treasure trove for the melancholic. However, it has since been discontinued due to numerous side effects including liver damage.
  Fortunately, on another long and obstructed road, human beings’ resistance to depression has never stopped. In the 1960s, scientists first discovered that the concentration of serotonin (a monoamine neurotransmitter) in the cerebrospinal fluid of patients with depression was three times lower than that of normal people.


  Even today, Prozac is one of the most commonly used antidepressants.

  In a paper published in 1969, Carlson proposed that the level of serotonin in the brain is one of the factors affecting mood. So far, the long night of searching for the cause of depression has ushered in a ray of light. People began to believe that what made people sick was not purely psychological, but that depression also had a biological cause—the veil of “evil black bile” was lifted.
  The person who caught this ray of light was David Wang, a Chinese-American neurochemist from Eli Lilly and Company. He continued to experiment with the brain tissue of mice, and by separating the peripheral nerves of the mice that had taken synthetic drugs, he finally found a synthetic substance with high content that could prevent the recycle of serotonin—serotonin reuptake inhibitors. In this way, serotonin will stay longer between cells, and the concentration of serotonin in the brain will increase accordingly.

  In 1974, serotonin reuptake inhibitors first appeared in professional journals. At that time, it was estimated that the development of this new drug would cost 300 million U.S. dollars (about 1.2 billion U.S. dollars today), about 3-4 times the general R&D expenditure. But Lilly decided to take this step. David Wang and about 15 people from different fields, including chemists, medical scientists, pharmacists, and even experts from the marketing department, set up a special research and development team called “Lilly 110140” (Eli Lilly drug number).
  Since then, 12 years of clinical trials have confirmed that the biggest breakthrough of this drug lies in its safety and non-addiction. Since serotonin reuptake inhibitors are “selective” and will not affect the transmission of other nerve substances, they can also reduce the side effects of other drugs.
  In 1986, “Prozac” was first listed in Belgium. On December 29 of the following year, the US Food and Drug Administration officially approved Prozac. For those of you who feel like you’re dying of mental anguish, it’s a little belated, but there’s no better Christmas gift than this.
  As of 2001, when Prozac’s patents expired, its turnover reached $22 billion. Even today, Prozac is one of the most commonly used antidepressants. It made people believe for the first time that depression is curable and not ashamed to talk about it.

Nanaimo, Canada, September 1, 2021 Psychedelic shiitake mushrooms used to extract psilocybin and the resulting pills
Fantastic Voyage

  So, have humans defeated depression? not at all. The other side of the coin is this: For as many years as Prozac has been popular, so has controversy and doubts about Prozac.
  It was discovered early on that even though Prozac raised patients’ serotonin levels immediately, it took a while for the depressive symptoms to subside, and that nearly 50 percent of the patients didn’t respond at all. Although people still don’t understand the specific mechanism of serotonin’s action on brain nerves, it is clear that “serotonin” is not the only explanation for the pathology of depression. As for more, there is still no definite answer.
  The mystery is still unsolved, do you still take the medicine? eat! “Heal the scar and forget the pain” is human nature and the courage of civilization. A new trend is that hallucinogens, which have been banned since the last century, seem to be coming back. People always remember the happiness brought by morphine and cocaine, but at the same time, the experience of blood and tears always reminds human beings: when going to that mysterious place, be cautious.
  This time the protagonist is psilocybin extracted from psychedelic shiitake mushrooms. Vincent, a 61-year-old cancer subject, said that she thought life was meaningless, but within 6 hours after psilocybin injection, she saw a green and purple sea, rows of Egyptian ships and Russian dolls , a small, creamy white, animation-style crab leaps into view, as if there is still a humorous, beautiful side to life.
  Two recent studies in the United States show that nearly 80% of cancer patients become milder after using a small dose of psilocybin, their mental health and life satisfaction have also improved significantly, and they no longer feel the pain of the past. Positive mood persisted for more than 6 months.
  But do long-term use of such hallucinogens have side effects and addiction to the human body? After so many abuses of hallucinogens throughout history, it has finally been humbly acknowledged that even when doctors and patients feel that nothing is wrong, there are still some reactions that do not manifest in the moment. On the other hand, in the field of diagnosis and treatment of depression today, doctors usually guide patients to feel the contrast between taking the drug and stopping the drug, helping them to recognize their original self, and then handing over the choice of “whether to change their personality through drugs” to the patient. the patient himself.
  But whether it is Prozac or hallucinogens, “whether drugs can be used to change personality” has always been a huge controversy. Myths about depression are, in a way, myths about ourselves. For thousands of years, from theologians, psychologists, physiologists, to social ethicists, they have hypothesized, questioned, discovered, and subverted again and again, reminding human beings: We know so much about ourselves, but at the same time we still so little.
  The pain and despair of depression are the same in ancient and modern times, but at least today, no one will frivolously persuade people with depression: “Being a human being is the most important thing to be happy.” There are always some things that are more important than happiness.

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