Morphine is a benzylisoquinoline alkaloid with two additional ring closures.

Most of the licit morphine produced is used to make codeine by methylation. It is also a precursor for many drugs including heroin (diacetylmorphine), hydromorphone, and oxymorphone. Replacement of the N-methyl group of morphine with an N-phenylethyl group results in a product that is 18 times more powerful than morphine in its opiate agonist potency. Combining this modification with the replacement of the 6-hydroxyl with a 6-methylene produces a compound some 1,443 times more potent than morphine, stronger than the Bentley compounds such as etorphine.

The structure-activity relationship of morphine has been extensively studied. The structural formula of morphine was determined in 1925 and confirmed in 1952 when two methods of total synthesis were also published. As a result of the extensive study and use of this molecule, more than 200 morphine derivatives (also counting codeine and related drugs) have been developed since the last quarter of the 19th Century. These drugs range from 25 per cent the strength of codeine or a little over 2 per cent of the strength of morphine, to several hundred times the strength of morphine to several powerful opioid antagoinsts including naloxone (Narcan), naltrexone (Trexan), and nalorphine (Nalline) for human use and also among the strongest antagonists known, such as diprenorphine (M5050), the reversing agent in the Immobilon large animal tranquilliser dart kit; the tranquilliser is another ultra-potent morphine derivative/structural analogue, viz., etorphine (M99). Morphine-derived agonist-antagonist drugs have also been developed. Elements of the morphine structure have been used to create completely synthetic drugs such as the morphinan family (levorphanol, dextromethorphan and others) and other groups which have many members with morphine-like qualities. The modification of morphine and the aforementioned synthetics has also given rise to non-narcotic drugs with other uses such as emetics, stimulants, antitussives, anticholinergics, muscle relaxants, local anaesthetics, general anaesthetics, and others.

Most semi-synthetic opioids, both of the morphine and codeine subgroups, are created by modifying one or more of the following:

  • Halogenating or making other modifications at positions 1 and/or 2 on the morphine carbon skeleton.
  • The methyl group which makes morphine into codeine can be removed or added back, or replaced with another functional group like ethyl and others to make codeine analogues of morphine-derived drugs and vice versa. Codeine analogues of morphine-based drugs often serve as prodrugs of the stronger drug, as in codeine and morphine, hydrocodone and hydromorphone, oxycodone and oxymorphone, nicocodeine and nicomorphine, dihydrocodeine and dihydromorphine, etc.
  • Saturating, opening, or other changes to the bond between positions 7 and 8, as well as adding, removing, or modifying functional groups to these positions; saturating, reducing, eliminating, or otherwise modifying the 7-8 bond and attaching a functional group at 14 yields hydromorphinol; the oxidation of the hydroxyl group to a carbonyl and changing the 7-8 bond to single from double changes codeine into oxycodone.
  • Attachment, removal or modification of functional groups to positions 3 and/or 6 (dihydrocodeine and related, hydrocodone, nicomorphine); in the case of moving the methyl functional group from position 3 to 6, codeine becomes heterocodeine which is 72 times stronger, and therefore six times stronger than morphine
  • Attachment of functional groups or other modification at position 14 (oxymorphone, oxycodone, naloxone)
  • Modifications at positions 2, 4, 5 or 17, usually along with other changes to the molecule elsewhere on the morphine skeleton. Often this is done with drugs produced by catalytic reduction, hydrogenation, oxidation, or the like, producing strong derivatives of morphine and codeine.

Both morphine and its hydrated form, C17H19NO3H2O, are sparingly soluble in water. In five liters of water, only one gram of the hydrate will dissolve. For this reason, pharmaceutical companies produce sulfate and hydrochloride salts of the drug, both of which are over 300 times more water-soluble than their parent molecule. Whereas the pH of a saturated morphine hydrate solution is 8.5, the salts are acidic. Since they derive from a strong acid but weak base, they are both at about pH = 5; as a consequence, the morphine salts are mixed with small amounts of NaOH to make them suitable for injection.

A number of salts of morphine are used, with the most common in current clinical use being the hydrochloride, sulphate, tartrate, acetate, citrate; less commonly methobromide, hydrobromide, hydroiodide, lactate, chloride, and bitartrate and the others listed below. Morphine meconate is a major form of the alkaloid in the poppy, as is morphine pectinate, nitrate and some others. Like codeine, dihydrocodeine and other, especially older, opiates, morphine has been used as the salicylate salt by some suppliers and can be easily compounded, imparting the therapeutic advantage of both the opioid and the NSAID; multiple barbiturate salts of morphine were also used in the past, as was/is morphine valerate, the salt of the acid being the active principle of valerian. Calcium morphenate is the intermediate in various latex and poppy-straw methods of morphine production. Morphine ascorbate and other salts such as the tannate, citrate, and acetate, phosphate, valerate and others may be present in poppy tea depending on the method of preparation. Morphine valerate produced industrially was one ingredient of a medication available for both oral and parenteral administration popular many years ago in Europe and elsewhere called Trivalin (not to be confused with the curremt, unrelated herbal preparation of the same name) which also included the valerates of caffeine and cocaine, with a version containing codeine valerate as a fourth ingredient being distributed under the name Tetravalin.

Closely related to morphine are the opioids morphine-N-oxide (genomorphine) which is a pharmaceutical which is no longer in common use; and pseudomorphine, an alkaloid which exists in opium, form as degradation products of morphine.


A Hungarian chemist, János Kabay, found and internationally patented a method to extract morphine from poppy straw. In the opium poppy the alkaloids are bound to meconic acid. The method is to extract from the crushed plant with diluted sulfuric acid, which is a stronger acid than meconic acid, but not so strong to react with alkaloid molecules. The extraction is performed in many steps (one amount of crushed plant is at least six to ten times extracted, so practically every alkaloid goes into the solution). From the solution obtained at the last extraction step, the alkaloids are precipitated by either ammonium hydroxide or sodium carbonate. The last step is purifying and separating morphine from other opium alkaloids. Opium poppy contains at least 40 different alkaloids, but most of them are of very low concentration. Morphine is the principal alkaloid in raw opium and constitutes ~8-19% of opium by dry weight (depending on growing conditions) . In the 1950s and 1960s, Hungary supplied nearly 60% of Europe's total medication-purpose morphine production. To this day, poppy farming is legal in Hungary, but poppy farms are limited by law to 2 acres (8,100 m2). It is also legal to sell dried poppy in flower shops for use in floral arrangements.It was announced in 1973 that a team at the National Institutes of Health in the United States had developed a method for total synthesis of morphine, codeine, and thebaine using coal tar as a starting material. A shortage in codeine-hydrocodone class cough suppressants (all of which can be made from morphine in one or more steps, as well as from codeine or thebaine) was the initial reason for the research.

The UN Office On Drugs & Crime Bulletin On Narcotics, issue II of 1952, describes the process which led to the final determination of the structural formula of morphine in 1925 and the invention of two methods of total synthesis of morphine.

Most morphine produced for pharmaceutical use around the world, for example a little under 50 per cent of opium licitly produced by the latex method, is actually converted into codeine as the concentration of the latter in both raw opium and poppy straw is much lower than that of morphine; in most countries the usage of codeine (both as end-product and precursor) is at least equal or greater than that of morphine on a weight basis and codeine is by far the most commonly-used opioid in the world. Whilst strains of poppies have been engineered to produce much higher yields of the other useful opioid pharmaceutical precursors thebaine and oripavine, no known strain of P. somniferum will produce more codeine than morphine under most or all possible conditions. The poppy straw process of producing licit(lawful) opioid alkaloids generally yields more codeine but an equal or somewhat smaller thebaine yield.

Extraction and detection

Morphine can be isolated from whole blood samples by solid phase extraction (SPE) and detected using liquid chromatography-mass spectrometry (LC-MS).

Illicit use

The euphoria, comprehensive alleviation of distress and therefore all aspects of suffering, promotion of sociability and empathy, "body high", and anxiolysis provided by narcotic drugs including the opioids can cause the use of high doses in the absence of pain for a protracted period, which can impart a morbid craving for the drug in the user. Being the prototype of the entire opioid class of drugs means that morphine has properties that may lend it to misuse. Morphine addiction is the model upon which the current perception of addiction is based.

Animal and human studies and clinical experience back up the contention that morphine is one of the most euphoric of drugs, and via all but the IV route heroin and morphine cannot be distinguished according to studies. Chemical changes to the morphine molecule yield other powerful euphorigenics such as dihydromorphine, hydromorphone (Dilaudid, Hydal) and oxymorphone (Numorphan, Opana) as well as the latter three's methylated equivalents dihydrocodeine, hydrocodone and oxycodone respectively; in addition to heroin, there are dipropanoylmorphine, diacetyldihydromorphine and other members of the 3,6 morphine diester category like nicomorphine and other similar semi-synthetic opiates like desomorphine, hydromorphinol &c. used clinically in many countries of the world but in many cases also produced illicitly in rare instances.

Misuse of morphine generally entails taking more than prescribed or outside of medical supervision, injecting oral formulations, mixing it with unapproved potentiators such as alcohol, cocaine, and the like, and/or defeating the extended-release mechanism by chewing the tablets or turning into a powder for snorting or preparing injectables. The latter method can be every bit as time-consuming and involved as traditional methods of smoking opium. This and the fact that the liver destroys a large percentage of the drug on the first pass impacts the demand side of the equation for clandestine re-sellers, as many customers are not needle users and may have been disappointed with ingesting the drug orally. As morphine is generally as hard or harder to ert than oxycodone in a lot of cases, morphine in any form is uncommon on the street, although ampoules and phials of morphine injection, pure pharmaceutical morphine powder, and soluble multi-purpose tablets are very popular where available.

Morphine is also available in a paste which is used in the production of heroin which can be smoked by itself or turned to a soluble salt and injected; the same goes for the penultimate products of the Kompot (Polish Heroin) and black tar processes. Poppy straw as well as opium can yield morphine of purity levels ranging from poppy tea to near-pharmaceutical grade morphine by itself or with all of the more than 50 other alkaloids. It also is the active narcotic ingredient in opium and all of its forms, derivatives, and analogues as well as forming from breakdown of heroin and otherwise being present in many batches of illicit heroin as the result of incomplete acetylation.

See also