History of Interventions in the Brain Using Psychotropic Substances

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Fantasies of intervening in the psyche and the use of psychotropic agents have a venerable history in mankind. Even in prehistoric times, substances like opium, cannabis, coca, peyote and alcohol were used, especially in the context of religious and magic rituals and other cultural practices. In ancient Greece, for example in the Hippocratic writings and the writings of Dioscourides and Galen, the use of opium was recommended for the treatment of pain and sleep disorders, particularly in women. Helleborus was the treatment of choice in psychiatric diseases. The Greek authors distinguished the black helleborus, a purgative, from the white helleborus, a substance which induced vomiting. Ancient Greek medical writings show that doctors believed psychiatric illnesses to have somatic foundations. They therefore tried to heal through the extraction of illness-inducing substances using emetics or purgatives. As can be seen, the concept of the so-called "biological psychiatry", meaning physical interventions in the psyche through somatic changes by means of pharmaceutical agents or other manipulations with an impact on the human brain, is a very old one. In the Middle Ages in Europe, cathartic methods using purgatives, emetics or phlebotomy retained some of their importance whilst different herbal extracts of plants with greater or lesser toxicity gained ascendance in the monastic medicine. Women collecting these plants and having some knowledge about their therapeutic effects often risked to be accused of witchcraft. The word "psycho-pharmacon" was introduced in 1584 by Reinhardus Lorichius of Hadarmar in the title of a book of prayers: "Medication for the soul".

The precursors of psychotherapy in the religious and monastic context became increasingly important in the conception of interventions in the psyche. Even as late as the 19th century, crude interventions such as cold baths or various mechanical machines, wheels and coercive chairs were recommended as treatment for psychiatric disorders (Schneider 1824). At the same time, the first chemical discoveries of psychotropic agents were being made, with the first descriptions of the active components of herbal plants like Morphine and Scopolamine. In 1826, sedation by bromides started the first era of modern sedatives. In the middle of the 19th century, Paraldehyde and Chloralhydrate (sedatives still currently in use) were developed. The famous psychiatric textbooks of Kraepelin in 1899 and Bleuler in 1916 showed a hapless polypharmacy in the pharmacological treatment of psychiatric diseases with a central concept of sedation. In 1903, the synthesis of the first barbituric acid (barbital) introduced a new era in psychopharmacology. Klaesi published his famous sleeping cures in 1920. The main focus of psychotropic intervention in these times was the treatment of agitation and aggression in severely disturbed psychiatric patients. No pharmacological treatment of mood disorders or other psychiatric symptoms such as hallucinations was as yet possible. Therefore other interventions based on Cardia-zol, insulin shocks or induced fever constituted the main focus of interest in somatic interventions in the psyche in the first half of the 20th century, until the effects of Lithium in the treatment of mania were discovered in 1949.

The idea of enhancing cognitive functioning also dates back far in ancient times. The stimulating plant Ephedra vulgaris was used by Chinese physicians such as Ma Huang over 500 years ago. The use of the Khat shrub Catha edulis in East Africa and the Middle East is relatively unchanged to the present day, where the custom of chewing leaves of the plant has been widespread for at least 700 years. Cathinone, the active ingredient, was only isolated in 1970.

It was not before 1880 that the active ingredient Ephedrine was isolated, finally leading to its characterisation in 1920. Ephedrine was widely used in the treatment of asthma. Increased efforts to search for a synthetic substitute led to the rediscovery of amphetamine that was synthesised 40 years before. Since then, many analogues of amphetamine have been developed and characterised, including the popular street drug, Methamphetamine, which was synthesised in 1912 in Darmstadt by Merck. During World War II, amphetamines came into use in the military as a means to keep pilots awake and vigilant during long flight hours. The first condition amphetamine was clinically used for was narcolepsy. Although not curative, it revolutionised therapy for this condition by making the patients relatively symptom free.

The use of stimulants in children dates back to 1937 when Bradley first used Benzedrine® and noted "a spectacular change in behaviour" along with "remarkably improved school performance". Ritalin®, which is used so often now, was first synthesised by L. Panizzon and named after his wife Marguerite (nicknamed "Rita"), who occasionally used it to improve her tennis performance. It was patented in 1950 and advertised by Ciba-Geigy thus: "it acts more carefully and longer than caffeine and amphetamines and does not involve habituation."

The story of the Coca plant Erythroxylon, which was used in South America 2000 years ago, seems comparable. The active ingredient Cocaine was first isolated in 1800, rapidly gaining popularity as an ingredient in tonic drinks such as Coca Cola and remaining popular until recent times. Its pharmacological use shifted from application as a local anaesthetic or a cure for a range of physical and psychological maladies (depression, indigestion, asthma, neurosis, syphilis and drug and alcohol addiction) to current practice of abuse as one of the most popular illicit street drugs in its various forms of powder, freebase and crack.

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