History of Morphine in Timeline

Morphine, an opiate derived from opium poppy latex, is primarily used as a pain reliever. It acts on the central nervous system to alleviate pain and modify pain perception. Various administration methods include oral, sublingual, inhalation, injection (muscle, subcutaneous, spinal), transdermal, and rectal suppository. Morphine effectively manages both acute and chronic pain, commonly used for myocardial infarction, kidney stones, and labor pain. Intravenous administration reaches peak effect in 20 minutes, oral in 60 minutes, lasting 3-7 hours. Long-acting morphine brands include MS Contin and Kadian, with generic versions also available. Repeated use can lead to physical and psychological dependence and tolerance.

1900: Dihydromorphine Synthesis

Around 1900, dihydromorphine was synthesized, marking a significant development in the field of opioid medications.

1914: Harrison Narcotics Tax Act

In 1914, the Harrison Narcotics Tax Act was passed in the US, making morphine a controlled substance and requiring a prescription for its possession.

1915: "Soldier's Disease"

The term "soldier's disease", referring to morphine addiction, first appeared in 1915. While it was previously believed that over 400,000 soldiers developed morphine addiction during the American Civil War, this is now disputed and potentially a fabrication.

1916: Oxycodone Synthesis

Oxycodone, another opioid analgesic, was synthesized in 1916.

1925: Morphine Structural Formula Determined and Poppy Straw Process Invented

In 1925, Robert Robinson determined the structural formula of morphine. In the same year, János Kabay invented a method for extracting morphine from poppy straw.

1930: Poppy Straw Process Announced

János Kabay's process for extracting morphine from poppy straw was announced in 1930.

1937: Pethidine Synthesis

Pethidine, a synthetic opioid analgesic, was invented in Germany in 1937.

1952: First Total Synthesis of Morphine

In 1952, Marshall D. Gates Jr. achieved the first total synthesis of morphine, a milestone that is still relevant today. Despite several other successful synthetic routes since then, it's thought that chemical synthesis is unlikely to be more cost-effective than natural extraction from the opium poppy.

1973: Total Synthesis of Morphine from Coal Tar

In 1973, a team at the National Institutes of Health (NIH) developed a method for total synthesis of morphine, codeine and thebaine from coal tar in response to a shortage of codeine-hydrocodone class cough suppressants.

1999: Heroin Detectability in Urine

A 1999 review estimated that low doses of heroin (which metabolizes into morphine) are detectable in standard urine tests for 1-1.5 days after use.

2000: Chronic Opioid Use and Cognitive Function

In 2000, a study on patients undergoing Chronic Opioid Analgesic Therapy (COAT) for severe, chronic pain found that regular opioid use doesn't seem to significantly impair driving abilities or general cognitive function. While COAT patients performed quickly on tasks requiring speed, they made more errors and showed slight impairments in visual memory, they demonstrated no major deficits in cognitive areas like visual-spatial perception, planning, or higher-order cognitive skills.

2000: Morphine's Pharmacological Profile

In Fall 2000, Jack DeRuiter from Auburn University's Department of Drug Discovery and Development highlighted the structural features of morphine that are important to its pharmacological profile.

2003: Discovery of Endogenous Morphine

In 2003, endogenous morphine was discovered to occur naturally in the human body.

2005: Global Morphine Consumption Disparity

A 2005 report highlighted the disparity in global morphine consumption, with wealthier nations consuming a disproportionately large share.

2006: Morphine for Acute Pulmonary Edema

A 2006 review found insufficient evidence to support the traditional use of morphine in treating acute pulmonary edema.

2009: Morphine Detectability in Urine

A 2009 review showed a 20 mg intravenous dose of morphine is detectable for 12-24 hours with a detection limit of 1 ng/ml. Similar results were observed with a detection limit of 0.6 ng/ml.

2013: Morphine's Effect on the Endocrine System

As of 2013, studies consistently show that morphine, like other opioids, frequently leads to hypogonadism and hormonal imbalances in chronic users of both genders. This dose-dependent side effect is present in both therapeutic and recreational users and can disrupt menstruation. While the impact of low-dose or short-term morphine use on the endocrine system remains unclear, it's suggested that the long-term effects may increase the risk of osteoporosis and bone fractures but are likely temporary.

2013: Morphine Production and Usage

In 2013, about 523 tons of morphine were produced globally. 45 tons were used for pain management, a 400% increase over the past two decades, mostly in developed countries. The majority of morphine, around 70%, was used in the production of other opioids.

June 2015: Biosynthesis of Morphine in Yeast

In June 2015, researchers successfully produced S-reticuline from sugar and converted R-reticuline to morphine in yeast, though the intermediate step remained unsolved.

August 2015: Complete Synthesis of Thebaine and Hydrocodone in Yeast

In August 2015, the first complete synthesis of thebaine and hydrocodone in yeast was achieved, but the process is still far from commercially viable.