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Introduction to Morphine

Morphine is the main active compound in opium, the juice obtained from the seed pods of the poppy plant Papaver Somniferum, and has been widely used for millennia for means both medical and recreational. Its users range from medical patients with acute or chronic pain to occasional users of opiates, sometimes known as “chippers,” to habitual daily users. Daily users may be difficult to detect since as long as they have opiates, and maintain a regimen of good hygiene and nutrition, they may be completely functional members of society. The poppy plant, including its constituent morphine, has been used for millennia as a remedy for pain, as well as for recreational use. It naturally occurs throughout much of Asia, but can be cultivated in many places.

This drug is useful in medicine as a painkiller, antitussive, and for its smooth muscle constricting properties. It binds the mu-, and kappa-opioid receptors and the newly discovered nociceptin receptors in the brain and spinal cord and the delta-receptors in the brain, as well as mu-receptors in the intestinal tract. These receptors are normally binding sites for the endorphins and enkephalins, which are naturally occurring peptides (short sequences of amino acids) that are produced by the brain. There are, more fully, kappa-1, kappa-2 subtypes of the kappa-receptors, delta-1 and delta-2 subtypes of the delta-receptors and mu-1, mu-2, and mu-3 subtypes of the mu-receptors. Morphine resembles endorphins in its action as well since it functions as an analgesic and creates feelings of euphoria.

Although its state-sanctioned place is in the hospital or on prescription, its effects on mood are powerful enough to induce some people to run the risks involved with using it recreationally. These positive effects are accompanied by some side effects, such as sleepiness or drowsiness, blurred vision, constipation, and a decrease in appetite. With extended use, regardless of the underlying reasons, morphine produces in its user physical tolerance and addiction. Tolerance can be seen within 12-24 hours after an initial dose of morphine, and is defined by the user needing to take more of the drug to achieve the desired effect. Often, tolerance to the positive effects of analgesia and happiness will build first, leaving more undesired side effects untouched. This tolerance continues to build with repeated administration, and over weeks or months of daily use, morphine will produce both a physical and psychological addiction. Abrupt cessation of use will result in the classic opioid withdrawal which includes goose bumps, diarrhea, insomnia, physical pain, and cramps. The psychological addiction may include a dysphoria or unhappiness when the drug is not available or a feeling that morphine would be necessary in order to continue with daily functions.

History of Morphine

Although morphine has been used as a constituent of opium since before the beginning of recorded history, scientists did not begin to attempt to isolate opium's "active ingredient" until early in the eighteenth century. The first real breakthrough is generally credited to the German pharmacist's assistant Friedrich Wilhelm Adam Serturner. In 1906, Serturner published the results of his experiments, twenty of which dealt with what he termed "poppy acid." The compound isolated by Serturner in the course of his experiments would become known as the alkaloid morphine.[1]By experimenting with his alkaloid on animals, Serturner discovered that he had found opium's "principium somniferum," or sleep-making principle. He named his discovery "morphium" after the Greek god Morpheus, and we know it today as morphine. Serturner even took to experimenting on himself, passing through the various states of euphoria, depression and nausea, and warning of the dangers of the newly discovered substance..[1]

Morphine did not become popular for several years after its discovery, but by the early 1820's, it was commercially available in Western Europe and The US. The invention of the hypodermic syringe in the 1850's greatly increased morphine's popularity. Ironically, doctors initially thought that injecting morphine - as opposed to taking it orally - would curb its addictive properties, and morphine was even touted as a "cure" for opium addiction..[1]During the American Civil War, poppies were cultivated throughout the American South, and opium and morphine were regularly administered to soldiers for all types of ailment, from dysentery to battlefield wounds. As a result, many veterans became afflicted with the "soldier's disease," or opiate addiction..[1]As morphine use and addiction became more widespread, doctors became aware of the symptoms of opiate addiction and withdrawal, and warnings were published about the dangers of intravenous morphine use. Although opium addiction was still widespread among the lower classes, which could not afford hypodermic needles and medical attention from doctors, morphine became the focus of concerns about addiction, which became considered a medical issue in its own right around the turn of the twentieth century..[1]

During the latter half of the nineteenth century, an even more potent opiate was synethesized from morphine, and in 1898 Bayer began to mass-market it under the name heroin, derived from the german word for "heroic." Just as morphien had been used to treat opium addiction, heroin was thought to be a cure for morphine addiction.[1]The use of morphine and heroin brought the dangers of opiate addiction into sharp focus, and in 1914, the Harrison Narcotics Tax Act restricted morphine to medical use, and in 1924, the Heroin Act made that substance illegal, even in a medical context.[2] Within a relatively short span of time, opium, a substance that had been used since time immemorial, had been refined and synthesized into arguably one of the most dangerous drugs known to man, and modern drug prohibition had begun.

Using Morphine

Ways of Administration

Doses of morphine for controlling pain and other medical uses are generally smaller than recreational doses in opiate-naive patients, with analgesic effects often becoming apparent at 5 mg when injected, and IV drips of 15 mg per hour being sufficient to control pain. Oral therapeutic doses are commonly 10 mg pills, or 30 mg extended release pills. Recreational doses usually begin at 15-30 mg of oral morphine, but many users insufflate or inject morphine in order to attain a faster rush. Additionally, tolerance to morphine can build fast, even when leaving several days between use, so habituated users may use recreational doses large enough to kill a novice user. Preparations of morphine which are in the form of smokable opium, laudanum, or poppy tea, where morphine is one of the main, but not the only psychoactive constituent, are more difficult to gauge without the proper equipment, but the dosage of morphine is probably similar to those seen in pills. However, since morphine content can vary widely even from plant to plant in the same strain, extreme caution must be exercised by using obtaining their morphine from these sources, by starting with an extremely low amount and slowly titrating the dose upward to achieve the wanted effect. Morphine is taken up by the body very poorly when it is taken orally, with some estimations being that only 10-30% can be effectively taken up through the stomach and intestines, so this is another reason that recreational users often find alternate means of ingestion. Insufflation and rectal administration have about 60% bioavailability, and IV administration is close to 100%. Since morphine is soluble in water, all of these routes are effective and vary only by the fact that different types of cells in the body will take up morphine and dispense it into the blood more readily than others. Recreational users of morphine cross over all cultural and racial barriers historically, ranging from ancient Sumerians, to young adults with access to the drug, to pain patients who may deliberately up their own prescribed dosages for a rush, to medical professionals and others with easy access to this drug, to other adults of all walks of life seeking the euphoria of this opiate. Although its abuse is demonized in the media, many people with access to the pure product can lead normal lives with few apparent setbacks, except, of course, if their supply runs out. This is not to say morphine use is harmless, since users can easily overdose, and often increase their dosage over time, but much of the social harm seemingly caused by the drug may be more a product of its tight regulations and laws against recreational use rather than inherent dangers in the drug itself.

Effects of Morphine

Morphine constricts smooth muscles and increases the water uptake of cells from organs like the sphincter and intestines, which can make it useful in treating chronic diarrhea. Because of this, its use as an antidiarrheal agent is found often in third-world countries where poor sanitation can lead to gastrointestinal disorders [Please validate this Alfa. Morphine is not widely available in third world countries. Six countries consume 79% of the world's morphine (2005 estimate: International Narcotics Control Board)]. When morphine was first isolated and utilized by doctors, it was prescribed for other uses as well. These less common treatments include depression since there is a minority opinion that certain depressions may be due less to differences in serotonin levels, and more to inadequate levels of natural endorphins and enkephalins. While this is no longer a legitimate use for morphine due to its potential for abuse and addiction, the effect of such studies and ideas can be seen in more recent efforts to treat addiction with “safer”, less addictive synthetic opioids such as buprenorphine. Some mu-opioid receptors inhibit the cough reflex, and morphine was marketed early on in cough remedies as a powerful antitussive. While the non-narcotic dextromethorphan has, for the most part, filled this role today, a remnant of this early use of morphine can be seen in the use of codeine to treat coughs around the world. Characteristics of physicians’ enthusiasm for more newly-introduced drugs over old remedies, morphine had also been used as a treatment for opium addiction and in early studies on opium withdrawal, where it was revealed that injections of morphine would reverse withdrawal symptoms in both animals and man.

Combinations with Morphine

Since morphine use is fraught with peril in and of itself, combinations involving other drugs can be hazardous, and many are discouraged.

Combining morphine with other depressants, such as alcohol, benzodiazepines, or other opiates/opioids can often be dangerous or fatal since these combinations increase the risk of respiratory depression.

Combining morphine with stimulants such as amphetamines or cocaine can be fatal as well since contradictory messages will be sent to the heart and other organs. Morphine will have a tendency to slow the heart rate and breathing, while a stimulant will seek to increase these things. The result can be complications with the organs or overdose on one drug or the other as users attempt to up the dosage of one or both of these drugs in order to achieve different results. While co-administration of stimulants and morphine may be seen as pleasant by some, many users of morphine opt not to combine these due to the increased risk of harm or death.

In a clinical setting, morphine can be combined with antiemetics such as cyclizine in order to reduce nausea and vomiting.

Some studies have also been done where morphine was combined with gabapentin or dextromethorphan. These studies have shown that such combinations will increase the painkilling effect of morphine beyond what it can normally accomplish on its own without having to increase the dosage, which would help prevent patients’ tolerance from growing too rapidly. Interestingly, some recreational users combine low doses of dextromethorphan with morphine in order to increase the euphoric effects without requiring as much morphine. However, higher dosages of dextromethorphan can contribute to the risk of respiratory depression with morphine, and as such should be avoided.

Opiates and marijuana are sometimes combined, and some users report a synergy between the substances that is pleasant, but polypharmacy is a dangerous activity, and caution must be used when combining substances, and lower doses should be used than when the drugs are used on their own.

Different Uses for Morphine

Morphine is generally used in the medical community for several desired effects. It has a similar action to natural analgesic compounds in the brain, such as endorphins, which makes it an excellent drug for controlling pain. Pharmacologically, morphine is a mu-opioid, delta-opioid and kappa-opioid agonist. Binding at these receptors leads to a decrease in GABA inhibition, which is the brain’s usual means of controlling neural impulses. Additionally, it triggers an increase in excitatory dopamine activity in the brain’s reward centers, such as the nucleus accumbens, which leads to a “rush” or high reported by users. Morphine is effective at decreasing sensations of pain because it inhibits transmission from pain neurons in the peripheral nervous system, and also acts in the central nervous system to excite neurons in the dorsal horn, and other midbrain pathways. This leads to an effect of blocking pain signals in both branches of the nervous system, peripheral and central. Interestingly, morphine does not actually stop the transmission of pain signals from the body’s natural pain detectors, known as nociceptors. Instead, it is thought to uncouple the emotional or conscious acknowledgment of the pain; users of morphine often say that they can realize that the pain is still there, but that it no longer bothers them or that they can ignore it. Most commonly, doctors may give morphine to a patient in pain for a variety of reasons, ranging from anesthesia to post-surgery pain, to trauma pain after an accident. In most countries, only a doctor or medical professional may legally administer IV morphine. Doctors may prescribe morphine for pain, as well as to inhibit the cough reflex. This morphine comes in immediate release or extended release pills, depending on the nature of the pain to be treated.

Pharmacology of Morphine

LD50 (mg/kg) [1] :
Mice : 226-318 intravenously (hydrochloride)

Chemistry of Morphine

Column 1 Column 2
Systematic (IUPAC) name: (5[alpha],6[alpha])-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
Synonyms: morphium, morphia; morphine hemisulfate, Avinza, Dolcontin, Kadian, Kapanol, Morcap, Moscontin, MS Contin, MSIR, MST Continus, Oramorph, Sevredol (sulfate pentahydrate)
Molecular Formula: C17H19N3O, 2(C17H19N3O).5H2O (sulfate pentaydrate)
Molar mass: 285.34 g/mol, 321.80 g/mol (hydrochloride), 758.83 g/mol (sulfate pentahydrate)
CAS Registry Number: 57-27-2, 6009-81-0 (monohydrate), 52-26-6 (hydrochloride), 6211-15-0 (sulfate pentahydrate), 64-31-3 (sulfate anhydrous)
Melting Point: 253-254°C with decomposition, 200°C with decomposition (hydrochloride), 250°C with decomposition when anhydrous (sulfate pentahydrate)
Boiling Point: no data
Flash Point: no data
Solubility: Freebase : 1 g dissolves in about 5000 mL water, 1100 mL boiling water, 220 mL alcohol, 98 mL boiling alcohol, 6250 mL ether, 1220 mL chloroform, 114 mL amyl alcohol, 10 mL boiling methanol, 525 mL ethyl acetate; freely soluble in solutions of fixed alkalis and alkaline earth hydroxides, phenol, cresols; moderately soluble in mixture of chloroform with alcohols; slightly soluble in ammonia, benzene. Hydrochloride : 1 g dissolves in 17.5 mL water, 0.5 mL boiling water, 52 mL alcohol, 6 mL alcohol (60°C); slowly soluble in glycerol; insoluble in chloroform, ether. Sulfate pentahydrate : 1 g dissolves in about 15.5 mL water (25°C), 0.7 mL water (80°C), 565 mL alcohol, 240 mL alcohol (60°C); insoluble in chloroform, ether
Additional data: Freebase : density (20°C) 1.32, pKb (20°C) 6.13, pKa 9.85, pH of saturated solution 8.5. Sulfate pentahydrate : pKa 7.9, partition coefficient (octanol/water, at physiological pH) 1.42,
Notes: Freebase : small rhombic prisms or needles from dilute alcohol as the monohydrate, becomes anhydrous at 100°C. Hydrochloride : occurs as the trihydrate aspect : white flakes or crystalline powder; bitter taste; loses its water at about 100°C and becomes yellowish; protect from light. Sulfate pentahydrate : aspect : white fine odorless crystals or powder, or cubical masses; loses some H2O at room temperature, about 3 H2O at 100°C and the rest at 130°C; discolors on exposure to light; keep well closed and protected from light

The dangers of Morphine

There are many dangers associated with morphine use. The margin of safety of morphine compared to other drugs in its class is somewhat low, since doses two to three times that of an “effective” dose can prove fatal, especially in a person with little to no opiate/opioid tolerance. Although any opioid/opiate is potentially dangerous, many of the synthetic opioids require many more times the active dose in order to cause death. Morphine overdose causes death through respiratory depression. Most of the time, especially if another person is not present to administer CPR, any overdose will be fatal since the person will often be too incapacitated to send for help, or will actually be unconscious already.

Morphine is physically and psychologically addicting, and abrupt cessation of morphine after weeks to months of use will create the standard opiate withdrawal syndrome, characterized by diarrhea, goose bumps, depression, and insomnia. These symptoms often last 7-10 days, and many times habitual users will go back to using the drug during this period in order to avoid the withdrawal symptoms. These withdrawal symptoms can be fatal in laboratory animals, but are not generally fatal in healthy humans. While distinctly unpleasant and harrowing, there is a consensus among many users that it can be endured, and that the psychological addiction is more difficult to handle, since for months following detoxification there may be a sense of boredom with the world or outright depression. This is because the brain is slow to start producing adequate levels of endorphins again, which were not required during morphine use, but are at least in part needed in the absence of a drug in order to feel happiness.

Aside from the most serious side effect of morphine use, which is respiratory depression, there are many others, such as constipation, nausea, nightmares, lethargy, itchiness, and physical dependence over time. Other side effects of morphine use which are seen as being of lesser consequence include a temporary inability to ejaculate in males, and pupil constriction. All of these side effects, except for, of course, respiratory depression and death, are reversible with abstinence from the drug.

Producing Morphine

Forms of Morphine

Legal status of Morphine

Morphine is a controlled substance : 21 CFR 1308.12

United Nations



History of Morphine