Picture of Morphine molecule

Morphine

Chemical Name:
(5a,6a)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
Classification:
Opiate
Primary Uses:
Analgesia
Brand Names:
Avinza, MSContin, Oramorph
Slang:
Morf, M, M.S.

General Information

In 1805, morphine was first extracted from opium by Friedrich Sertürner, who named the drug after the Greek god of dreams, Morpheus. By the 1830s, American physicians had implemented morphine into their practices, which helped mark the introduction of morphine as the universal painkiller. At this time, there were still no restrictions on the sale or manufacture of morphine, and anyone could buy the drug over-the-counter. Some over-the-counter elixirs which included morphine as an active ingredient were Mrs. Winslow's Soothing Syrup, Godfrey's Cordial, Children's Comfort, Mother Bailey's Quieting Syrup, Steedman's Teething Powders, Paregoric Elixir, and Hooper's Anodyne.

In 1853, a Scottish physician Alexander Wood invented the hypodermic syringe. This invention provided human beings with a very efficient method for administering drugs, but also set up the human race for tragedy resulting from intravenous opiate abuse. The use of injectable morphine during the American Civil War is thought to have caused the first wave of widespread addiction to injectable opiates. Morphine addiction was dubbed "soldier's disease." Some historians, however, disagree and believe morphine addiction became more of a problem after the war, as availability became widespread. Even so, both the use during the Civil War and increased availability contributed to the epidemic.

In 1874, an English chemist invented a new drug by adding an extra chemical group to morphine which allowed the drug to get to the brain faster. Heroin was born. As concern grew about widespread narcotic addiction, the government began to consider taking action. In 1906, the Pure Food and Drug Act was passed, requiring certain products be labeled accordingly; opiate-infused elixirs were included. Following the passage of this act, American's became more educated on the dangers of morphine and opium, and this subsequently caused many companies, who claimed their products to be "magic cure-alls," to go out of business. It would be almost ten more years until the use of any opiate-derivative for anything but medicinal purposes was forbidden. In 1914, the Harrison Narcotics Tax Act restricted doctors to prescribing opiates "in the course of his professional practice only." This meant doctors could only prescribe opiates for specific ailments and diseases, though not to addicts because addiction was not yet considered a "disease."1 2

Pharmacology & Pharmacokinetics

Morphine is a strong opioid analgesic and has a high binding affinity to the mu-, delta-, and kappa-opioid receptors. Its principle pharmacological effect is on the central nervous system and gastrointestinal tract. Common side effects due to its high binding affinity to mu-opioid receptors include euphoria, and respiratory depression. In some instances, however, morphine may cause the patient to feel dysphoric, which is thought to result from kappa-receptor binding. Vomiting, a somewhat common side effect of the drug, is a result of the stimulation of the chemoreceptor trigger zone; this same area can cause vomiting upon ingestion of a toxic substance.3

Orally-administered morphine is accompanied by extensive first-pass metabolism, with only about 40% reaching the central compartment. Inside the body, morphine is broken down into metabolites, the two primary being morphine-3-glucuronide and morphine-6-glucuronide. Morphine-6-glucuronide is present in smaller numbers (1-5%) compared with the former metabolite (55-75%), but it has greater analgesic effect. The half-life of oral morphine can be anywhere from 2-4 hours, with peak plasma concentrations occurring after about one hour.4 5

Legal Status

In the United States, this drug is a Schedule II substance, making it illegal to use or possess without a prescription. Schedule II substances, such as dextroamphetamine, morphine, oxycodone, and cocaine, meet the following criteria according to the Controlled Substances Act:

Side Effects

  • Pain relief
  • Euphoria or dysphoria
  • Mood changes
  • Reduced anxiety
  • Sedation
  • Itching
  • Nausea and vomiting
  • Decreased libido (sex drive)
  • Constipation
  • Facial flushing
  • Vertigo

Withdrawal

Withdrawal from morphine can begin in as little as a few hours to 24 hours after the last administration; however, many factors are at play including frequency of use, dosage, as well as body chemistry. Acute withdrawal symptoms peak between 48 and 72 hours, and are generally gone within a week; however, post-acute withdrawal syndrome (PAWS) can persist for weeks or months afterward. Opiate withdrawal is rarely fatal, though the outcome is largely dependent upon the user's health, whereas withdrawal from alcohol or benzodiazepines can easily result in death. Some of the symptoms of morphine withdrawal are listed below:

  • Cravings
  • Muscle/bone pain
  • Restlessness
  • Goose bumps
  • Involuntary leg/arm movements
  • Sweating
  • Insomnia
  • Nausea/vomiting
  • Depression

Sources

[1] Drew Pinsky, M.D., Marvin D. Seppala, M.D., Robert J. Meyers, Ph.D., John Gardin, Ph.D., William White, M.A., Stephanie Brown, Ph.D. When Painkillers Become Dangerous. Center City, Minnesota: Hazelden, 2004.
[2] Pelletier, Catherine E. Lange Smart Charts: Pharmacology. New York: Lange Medical Books/McGraw-Hill Companies, Inc., 2003.
[3] Cynthia Kuhn, Ph.D., Scott Swartzwelder, Ph.D., Wilkie Wilson, Ph.D. Buzzed: The Straight Facts About the Most Abused Drugs from Alcohol to Ecstacy. New York: W.W. Norton & Company, 2003. 175-192.
[4] MS-Contin (Morphine Sulfate Controlled-Release) Drug Information: Clinical Pharmacology. RxList. 2006. Accessed: November 14, 2006. Last Accessed: February 19, 2009.
[5] SL Collins et al. Peak plasma concentrations after oral morphine: a systematic review. Journal of Pain and Symptom Management 1998 16: 388-402.