Study guide: History of Opioid Medicine

📋 Course Outline

1. Pain and Drug Terminology
2. Dependence and Addiction
3. Opium from Prehistory to Antiquity
4. Religious and Philosophical Views
5. Pain Relief and Early Anesthesia
6. Morphine Extraction and Isolation
7. Morphine Derivatives and Receptors
8. Opioid Misuse and Social Control
9. Opioid Regulation and Medical Use
10. Overdose Risks and Clinical Balance

📅 Key Dates

1. 2000 BCA cylinder seal associated with the veterinarian Urlugaledinna records the first therapeutic use of opium at Sumer.
2. 1805-1817Sertürner identified morphine, called principium somniferum, through chemical, animal-pharmacology, and clinical work.
3. 1822The Formulaire de Magendie described morphine acetate, sulfate, and hydrochloride salts.
4. 1840Velpeau declared that avoiding pain by artificial means was an impossible chimera.
5. 1846The first general anesthetic was administered in Boston, beginning a contentious and gradual adoption of anesthesia.
6. 1874Wright discovered heroin, a semisynthetic morphine derivative.
7. 1911-1912The Hague Convention initiated controls on the production, trade, and use of opium, morphine, and cocaine.
8. 17/12/1914The Harrison Law prohibited nonmedical use of cocaine, opium, and morphine.
9. 12 juillet 1916The French law criminalized social use, trade, and fraudulent possession of poisonous substances, reserving legal use to highly supervised medicine.
10. 1948A decree confirmed the 1916 regulations and classified substances into three tables: poisonous substances, narcotics, and dangerous substances.

📖 1. Pain and Drug Terminology

🔑 Key Concepts & Definitions

• Pain: An unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
• Opium: The substance obtained by dehydrating the juice of the poppy.
• Alkaloid: A chemically pure, pharmacologically active substance extracted from plants or living organisms, such as atropine, morphine, or cocaine.

★ Must-know

📌 Analgesia is the relief of pain, whereas anesthesia is the abolition of all sensation.

📌 Opiates are opium-derived substances, including morphine and chemically related derivatives, whereas opioids are synthetic or endogenous molecules that act on opioid receptors but have structures very different from morphine.

Further detail

• Anesthesia comprises:
  • narcosis
  • analgesia
  • muscle relaxation

💡 Memory Hook

Analgesia reduces pain; anesthesia abolishes sensation.

📖 2. Dependence and Addiction

🔑 Key Concepts & Definitions

• Dependence: OMS - A powerful or compulsive desire to use a psychoactive substance, a concept that can also extend to activities such as gambling, video games, or sex.
• Withdrawal: The physiological syndrome of unpleasant effects that follows stopping substance use.
• Tolerance: The need to increase the quantity of a substance at each renewed use to obtain the desired effect.

📝 Essential Points

• The five indicators are:
  • impaired control of starting, stopping, or regulating use
  • physiological withdrawal
  • tolerance
  • abandonment of other interests as time spent obtaining, using, or recovering from the substance increases
  • continued use despite manifest harm

💡 Memory Hook

Tolerance and withdrawal can sustain continued substance use.

📖 3. Opium from Prehistory to Antiquity

★ Must-know

• Archaeological traces of opium use date back about 7,000 years, and poppy seeds and capsules have been found in European Neolithic settlements dating to 5000 BC.

Further detail

• In ancient Egypt, opium was used as an analgesic and sedative, including to prevent babies from crying.

• In the Odyssey, Homer describes opium in the 8th century BC as calming anger and making pain forgotten. - Homère, Odyssée, 13e siècle avant

• Theophrastus describes opium harvesting as extracting poppy latex by making incisions in the capsule. - Théophraste, Historia Plantarum

• Hippocrates recommended poppy juice for uterine illnesses and recognized its constipating and hypnotic effects.

📖 4. Religious and Philosophical Views

★ Must-know

• In medieval Christianity, pain was treated as divinely willed and expiatory, and the Church prohibited analgesics; physicians who used opium could be excommunicated.

📌 The Buddhist view distinguishes physical pain, which offers little scope for action, from mental pain, which can be acted upon and transcended.

Further detail

• The Jewish approache raises whether people may intervene to relieve divinely willed illness and emphasizes treating through prayer in practice.

• Plato considered pain inseparable from pleasure. - Platon, 428-348 av J.-C.

• Blaise Pascal accepted or even sought pain and regarded illness as the Christian's natural state.

💡 Memory Hook

Some traditions treat pain as divinely given; Buddhism distinguishes physical and mental pain.

📖 5. Pain Relief and Early Anesthesia

★ Must-know

• Analgesia was not accepted for surgery before the 19th century or for obstetrics before the 20th century.

Further detail

• In 1847, Magendie argued that loss of consciousness was degrading and that a courageous person should not tolerate it.

📖 6. Morphine Extraction and Isolation

★ Must-know

• Morphine production purifies opium, a natural mixture of active poppy substances, to isolate morphine as its principal and most powerful analgesic substance.

Further detail

• Sertürner introduced the name morphium, later changed to morphine by Gay-Lussac, and Meissner classified morphine among the alkaloids.

• Robiquet discovered codeine in 1832, and Merck discovered papaverine in 1848.

📖 7. Morphine Derivatives and Receptors

★ Must-know

📌 An opioid agonist binds to opioid receptors and triggers a biological response, whereas an antagonist binds to receptors and prevents that response.

• The three receptor types are:
  • mu
  • delta
  • kappa

Further detail

• Heroin is 10 times more active than morphine and fentanyl is 100 times more active than morphine.

📌 The exogenous opioid system includes morphine, codeine, methadone, and heroin and is associated with analgesia and addiction, whereas the endogenous system includes proenkephalin, prodynorphin, and pro-opiomelanocortin and is associated with pain, pleasure, and stress.

💡 Memory Hook

Agonists activate opioid receptors; antagonists block their activation.

📖 8. Opioid Misuse and Social Control

📝 Essential Points

• The cited literary depictions are:

  • Thomas de Quincey's The Confessions of an English Opium-Eater
  • Baudelaire's Les Paradis Artificiels
  • Arthur Conan Doyle's The Adventures of Sherlock Holmes

• Between 1900 and 1912, heroin addiction increased sharply in the United States, and heroin was successively described as useless, dangerous, and proscribed as a medicine.

📖 9. Opioid Regulation and Medical Use

🔑 Key Concepts & Definitions

• Opioid substitution: Treatment using medicines such as methadone or buprenorphine, which have longer half-lives and reduce intoxication and physiological withdrawal effects.

📝 Essential Points

• In 1999, France replaced narcotics prescription books with secure prescriptions and regulated prescription duration according to the substance.

• In 1976, morphine solution from the Saint Christopher Hospital entered France after having been proposed in London a few years earlier.

• The 1987 WHO pain scale was intended to regulate analgesic use according to pain intensity, alongside broader opioid prescribing and dispensing. - OMS

• Morphine can be administered orally, by injection including patient-managed pumps, or transdermally through patches.

📖 10. Overdose Risks and Clinical Balance

★ Must-know

• The course reports 15,500 US prescription-painkiller overdose deaths in 2009, 33,000 in 2015, and 65,000 in 2018. - CDC, prescription painkiller overdoses, 1990 jusqu’à nos

📌 Opioid consumption does not itself constitute trafficking, dependence is a disease, and substitution medicines are not equivalent to illicit drugs; however, high doses, long treatments, powerful medicines, and short half-lives can increase dependence, overdose, and mortality risks.

Further detail

• In France, deaths from heroin overdose fell sharply between 1995 and 2005 following the introduction of substitution medicines.

• In the course's account of US overdose deaths, methadone is involved in 30% of cases, and more than half of deaths involve prescribed medicines.

• The reported sources are:

  • 55% from a relative or friend
  • 17.3% by medical prescription
  • 11.4% purchased from a relative or friend
  • 4.8% taken from a relative or friend
  • 4.4% purchased from a stranger
  • 7.1% from other sources

💡 Memory Hook

A medicine is not automatically a trafficked drug, but no opiate is harmless.

📊 Synthesis Tables

Opioid Receptor Actions

Exogenous and Endogenous Opioid Systems