Morphine is a pain medication of the opiate variety which is found
naturally in a number of plants and animals. It acts directly on
the central nervous system (CNS) to decrease the feeling of pain.
It can be taken for both acute pain and chronic pain. It is
frequently used for pain from myocardial infarction and during
labour. It can be given by mouth, by injection into a muscle, by
injecting under the skin, intravenously, into the space around the
spinal cord, or rectally. Maximum effect is around 20 minutes
when given intravenously and 60 minutes when given by mouth,
while duration of effect is 3–7 hours. Long-acting
formulations also exist.
Potentially serious side effects include a decreased respiratory
effort and low blood pressure.
Morphine has a high potential for
addiction and abuse. If the dose is reduced after long-term use,
withdrawal may occur. Common side effects include drowsiness,
vomiting, and constipation. Caution is advised when used during
pregnancy or breast feeding, as morphine will affect the baby.
Morphine was first isolated between 1803 and 1805 by Friedrich
Sertürner. This is generally believed to be the first isolation of
an active ingredient from a plant. Merck began marketing it
commercially in 1827.
Morphine was more widely used after the
invention of the hypodermic syringe in 1853–1855. Sertürner
originally named the substance morphium after the Greek god of dreams,
Morpheus, as it has a tendency to cause sleep.
The primary source of morphine is isolation from poppy straw of the
opium poppy. In 2013, approximately 523 kilograms (1,153 pounds)
of morphine were produced. Approximately 45 kilograms (99 lb)
were used directly for pain, a four-time increase over the last twenty
years. Most use for this purpose was in the developed world.
About 70 percent of morphine is used to make other opioids such as
hydromorphone, oxymorphone, and heroin. It is a Schedule
II drug in the United States, Class A in the United Kingdom,
and Schedule I in Canada. It is on the World Health Organization's
List of Essential Medicines, the most effective and safe medicines
needed in a health system.
Morphine is sold under many trade
1 Medical uses
1.2 Shortness of breath
Opioid use disorder
3 Adverse effects
3.2 Hormone imbalance
3.3 Effects on human performance
3.4 Reinforcement disorders
3.4.3 Dependence and withdrawal
5.1.1 Gene expression
5.1.2 Effects on the immune system
5.2.1 Absorption and metabolism
5.2.3 Detection in body fluids
6 Natural occurrence
6.1 Human biosynthesis
6.2 Biosynthesis in the opium poppy
9 Precursor to other opioids
11 Society and culture
11.1 Legal status
11.2 Non-medical use
11.3 Slang terms
11.4 Trade names
11.5 Access in developing countries
13 External links
Two capsules (5 mg & 10 mg) of morphine sulfate
Morphine is used primarily to treat both acute and chronic severe
pain. It is also used for pain due to myocardial infarction and for
labor pains. Its duration of analgesia is about three to seven
However, concerns exist that morphine may increase mortality in the
setting of non ST elevation myocardial infarction.
also traditionally been used in the treatment of acute pulmonary
edema. A 2006 review, though, found little evidence to support
this practice. A 2016 Cochrane review concluded that morphine is
effective in relieving cancer pain. Side-effects of nausea and
constipation are rarely severe enough to warrant stopping
Shortness of breath
Morphine is beneficial in reducing the symptom of shortness of breath
due to both cancer and noncancer causes. In the setting of
breathlessness at rest or on minimal exertion from conditions such as
advanced cancer or end-stage cardiorespiratory diseases, regular,
low-dose sustained-release morphine significantly reduces
breathlessness safely, with its benefits maintained over time.
Opioid use disorder
Morphine is also available as a slow-release formulation for opiate
substitution therapy (OST) in Austria, Bulgaria, and Slovenia, for
addicts who cannot tolerate either methadone or buprenorphine.
Relative contraindications to morphine include:
respiratory depression when appropriate equipment is not available
Although it has previously been thought that morphine was
contraindicated in acute pancreatitis, a review of the literature
shows no evidence for this.
Adverse effects of opioids
Common and short term
Decreased sex drive
Loss of appetite
Impaired sexual function
Decreased testosterone levels
Opioid-induced abnormal pain sensitivity
Increased risk of falls
A localized reaction to intravenous morphine caused by histamine
release in the veins
Like loperamide and other opioids, morphine acts on the myenteric
plexus in the intestinal tract, reducing gut motility, causing
constipation. The gastrointestinal effects of morphine are mediated
primarily by μ-opioid receptors in the bowel. By inhibiting gastric
emptying and reducing propulsive peristalsis of the intestine,
morphine decreases the rate of intestinal transit. Reduction in gut
secretion and increased intestinal fluid absorption also contribute to
the constipating effect. Opioids also may act on the gut indirectly
through tonic gut spasms after inhibition of nitric oxide
generation. This effect was shown in animals when a nitric oxide
precursor, L-arginine, reversed morphine-induced changes in gut
Opioid § Hormone imbalance
Clinical studies consistently conclude that morphine, like other
opioids, often causes hypogonadism and hormone imbalances in chronic
users of both sexes. This side effect is dose-dependent and occurs in
both therapeutic and recreational users.
Morphine can interfere with
menstruation in women by suppressing levels of luteinizing hormone.
Many studies suggest the majority (perhaps as much as 90%) of chronic
opioid users have opioid-induced hypogonadism. This effect may cause
the increased likelihood of osteoporosis and bone fracture observed in
chronic morphine users. Studies suggest the effect is temporary. As of
2013[update], the effect of low-dose or acute use of morphine on the
endocrine system is unclear.
Effects on human performance
Most reviews conclude that opioids produce minimal impairment of human
performance on tests of sensory, motor, or attentional abilities.
However, recent studies have been able to show some impairments caused
by morphine, which is not surprising, given that morphine is a central
nervous system depressant.
Morphine has resulted in impaired
functioning on critical flicker frequency (a measure of overall CNS
arousal) and impaired performance on the
Maddox wing test (a measure
of deviation of the visual axes of the eyes). Few studies have
investigated the effects of morphine on motor abilities; a high dose
of morphine can impair finger tapping and the ability to maintain a
low constant level of isometric force (i.e. fine motor control is
impaired), though no studies have shown a correlation between
morphine and gross motor abilities.
In terms of cognitive abilities, one study has shown that morphine may
have a negative impact on anterograde and retrograde memory, but
these effects are minimal and transient. Overall, it seems that acute
doses of opioids in non-tolerant subjects produce minor effects in
some sensory and motor abilities, and perhaps also in attention and
cognition. It is likely that the effects of morphine will be more
pronounced in opioid-naive subjects than chronic opioid users.
In chronic opioid users, such as those on Chronic
Therapy (COAT) for managing severe, chronic pain, behavioural testing
has shown normal functioning on perception, cognition, coordination
and behaviour in most cases. One 2000 study analysed COAT patients
to determine whether they were able to safely operate a motor vehicle.
The findings from this study suggest that stable opioid use does not
significantly impair abilities inherent in driving (this includes
physical, cognitive and perceptual skills). COAT patients showed rapid
completion of tasks that require speed of responding for successful
Rey Complex Figure
Rey Complex Figure Test) but made more errors than
controls. COAT patients showed no deficits in visual-spatial
perception and organization (as shown in the WAIS-R Block Design Test)
but did show impaired immediate and short-term visual memory (as shown
Rey Complex Figure
Rey Complex Figure Test – Recall). These patients showed
no impairments in higher order cognitive abilities (i.e., planning).
COAT patients appeared to have difficulty following instructions and
showed a propensity toward impulsive behaviour, yet this did not reach
statistical significance. It is important to note that this study
reveals that COAT patients have no domain-specific deficits, which
supports the notion that chronic opioid use has minor effects on
psychomotor, cognitive, or neuropsychological functioning.
Morphine by Santiago Rusiñol
Morphine is a highly addictive substance. In controlled studies
comparing the physiological and subjective effects of heroin and
morphine in individuals formerly addicted to opiates, subjects showed
no preference for one drug over the other. Equipotent, injected doses
had comparable action courses, with no difference in subjects'
self-rated feelings of euphoria, ambition, nervousness, relaxation,
drowsiness, or sleepiness. Short-term addiction studies by the
same researchers demonstrated that tolerance developed at a similar
rate to both heroin and morphine. When compared to the opioids
hydromorphone, fentanyl, oxycodone, and pethidine/meperidine, former
addicts showed a strong preference for heroin and morphine, suggesting
that heroin and morphine are particularly susceptible to abuse and
Morphine and heroin were also much more likely to produce
euphoria and other positive subjective effects when compared to these
other opioids. The choice of heroin and morphine over other
opioids by former drug addicts may also be because heroin (also known
as morphine diacetate, diamorphine, or diacetyl morphine) is an ester
of morphine and a morphine prodrug, essentially meaning they are
identical drugs in vivo.
Heroin is converted to morphine before
binding to the opioid receptors in the brain and spinal cord, where
morphine causes the subjective effects, which is what the addicted
individuals are seeking.
Several hypotheses are given about how tolerance develops, including
opioid receptor phosphorylation (which would change the receptor
conformation), functional decoupling of receptors from G-proteins
(leading to receptor desensitization), μ-opioid receptor
internalization or receptor down-regulation (reducing the number of
available receptors for morphine to act on), and upregulation of the
cAMP pathway (a counterregulatory mechanism to opioid effects) (For a
review of these processes, see Koch and Hollt.) CCK might mediate
some counter-regulatory pathways responsible for opioid tolerance.
CCK-antagonist drugs, specifically proglumide, have been shown to slow
the development of tolerance to morphine.
Dependence and withdrawal
Opioid dependence and
Cessation of dosing with morphine creates the prototypical opioid
withdrawal syndrome, which, unlike that of barbiturates,
benzodiazepines, alcohol, or sedative-hypnotics, is not fatal by
itself in neurologically healthy patients without heart or lung
Acute morphine withdrawal, along with that of any other opioid,
proceeds through a number of stages. Other opioids differ in the
intensity and length of each, and weak opioids and mixed
agonist-antagonists may have acute withdrawal syndromes that do not
reach the highest level. As commonly cited[by whom?], they are:
Stage I, 6 h to 14 h after last dose: Drug craving, anxiety,
irritability, perspiration, and mild to moderate dysphoria[citation
Stage II, 14 h to 18 h after last dose: Yawning, heavy
perspiration, mild depression, lacrimation, crying, headaches, runny
nose, dysphoria, also intensification of the above symptoms, "yen
sleep" (a waking trance-like state) [clarification needed]
Stage III, 16 h to 24 h after last dose:
nose) and increase in other of the above, dilated pupils, piloerection
(goose bumps – a purported origin of the phrase, 'cold turkey,' but
in fact the phrase originated outside of drug treatment), muscle
twitches, hot flashes, cold flashes, aching bones and muscles, loss of
appetite, and the beginning of intestinal cramping
Stage IV, 24 h to 36 h after last dose: Increase in all of
the above including severe cramping and involuntary leg movements
("kicking the habit" also called restless leg syndrome), loose stool,
insomnia, elevation of blood pressure, moderate elevation in body
temperature, increase in frequency of breathing and tidal volume,
tachycardia (elevated pulse), restlessness, nausea
Stage V, 36 h to 72 h after last dose: Increase in the
above, fetal position, vomiting, free and frequent liquid diarrhea,
which sometimes can accelerate the time of passage of food from mouth
to out of system, weight loss of 2 kg to 5 kg per 24 h,
increased white cell count, and other blood changes
Stage VI, after completion of above: Recovery of appetite and normal
bowel function, beginning of transition to postacute and chronic
symptoms that are mainly psychological, but may also include increased
sensitivity to pain, hypertension, colitis or other gastrointestinal
afflictions related to motility, and problems with weight control in
either direction
In advanced stages of withdrawal, ultrasonographic evidence of
pancreatitis has been demonstrated in some patients and is presumably
attributed to spasm of the pancreatic sphincter of Oddi.
The withdrawal symptoms associated with morphine addiction are usually
experienced shortly before the time of the next scheduled dose,
sometimes within as early as a few hours (usually 6 h to
12 h) after the last administration. Early symptoms include
watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria,
sweating, and in some cases a strong drug craving. Severe headache,
restlessness, irritability, loss of appetite, body aches, severe
abdominal pain, nausea and vomiting, tremors, and even stronger and
more intense drug craving appear as the syndrome progresses. Severe
depression and vomiting are very common. During the acute withdrawal
period, systolic and diastolic blood pressures increase, usually
beyond premorphine levels, and heart rate increases, which have
potential to cause a heart attack, blood clot, or stroke.
Chills or cold flashes with goose bumps ("cold turkey") alternating
with flushing (hot flashes), kicking movements of the legs ("kicking
the habit") and excessive sweating are also characteristic
symptoms. Severe pains in the bones and muscles of the back and
extremities occur, as do muscle spasms. At any point during this
process, a suitable narcotic can be administered that will
dramatically reverse the withdrawal symptoms. Major withdrawal
symptoms peak between 48 h and 96 h after the last dose and
subside after about 8 to 12 days. Sudden withdrawal by heavily
dependent users who are in poor health is very rarely fatal. Morphine
withdrawal is considered less dangerous than alcohol, barbiturate, or
The psychological dependence associated with morphine addiction is
complex and protracted. Long after the physical need for morphine has
passed, the addict will usually continue to think and talk about the
use of morphine (or other drugs) and feel strange or overwhelmed
coping with daily activities without being under the influence of
morphine. Psychological withdrawal from morphine is usually a very
long and painful process.[unreliable medical source] Addicts often
suffer severe depression, anxiety, insomnia, mood swings, amnesia
(forgetfulness), low self-esteem, confusion, paranoia, and other
psychological disorders. Without intervention, the syndrome will run
its course, and most of the overt physical symptoms will disappear
within 7 to 10 days including psychological dependence. A high
probability of relapse exists after morphine withdrawal when neither
the physical environment nor the behavioral motivators that
contributed to the abuse have been altered. Testimony to morphine's
addictive and reinforcing nature is its relapse rate. Abusers of
morphine (and heroin) have one of the highest relapse rates among all
drug users, ranging up to 98% in the estimation of some medical
A large overdose can cause asphyxia and death by respiratory
depression if the person does not receive medical attention
Overdose treatment includes the administration of
naloxone. The latter completely reverses morphine's effects, but may
result in immediate onset of withdrawal in opiate-addicted subjects.
Multiple doses may be needed.
The minimum lethal dose of morphine sulfate is 120 mg, but in
case of hypersensitivity, 60 mg can bring sudden death. In
serious drug dependency (high tolerance), 2000–3000 mg per day
can be tolerated.
Morphine is the prototypical opioid and is the standard against which
other opioids are tested. It interacts predominantly with the
μ–δ-opioid (Mu-Delta) receptor heteromer. The μ-binding
sites are discretely distributed in the human brain, with high
densities in the posterior amygdala, hypothalamus, thalamus, nucleus
caudatus, putamen, and certain cortical areas. They are also found on
the terminal axons of primary afferents within laminae I and II
(substantia gelatinosa) of the spinal cord and in the spinal nucleus
of the trigeminal nerve.
Morphine is a phenanthrene opioid receptor agonist – its main
effect is binding to and activating the μ-opioid receptors in the
central nervous system. Its intrinsic activity at the μ-opioid is
heavily dependent on the assay and tissue being tested; in some
situations it is a full agonist while in others it can be a partial
agonist or even antagonist. In clinical settings, morphine exerts
its principal pharmacological effect on the central nervous system and
gastrointestinal tract. Its primary actions of therapeutic value are
analgesia and sedation. Activation of the μ-opioid receptors is
associated with analgesia, sedation, euphoria, physical dependence,
and respiratory depression.
Morphine is also a κ-opioid and δ-opioid
receptor agonist, κ-opioid's action is associated with spinal
analgesia, miosis (pinpoint pupils) and psychotomimetic effects.
Opioid is thought to play a role in analgesia. Although
morphine does not bind to the σ-receptor, it has been shown that
σ-agonists, such as (+)-pentazocine, inhibit morphine analgesia, and
σ-antagonists enhance morphine analgesia, suggesting downstream
involvement of the σ-receptor in the actions of morphine.
The effects of morphine can be countered with opioid antagonists such
as naloxone and naltrexone; the development of tolerance to morphine
may be inhibited by
NMDA antagonists such as ketamine or
dextromethorphan. The rotation of morphine with chemically
dissimilar opioids in the long-term treatment of pain will slow down
the growth of tolerance in the longer run, particularly agents known
to have significantly incomplete cross-tolerance with morphine such as
levorphanol, ketobemidone, piritramide, and methadone and its
derivatives; all of these drugs also have
NMDA antagonist properties.
It is believed that the strong opioid with the most incomplete
cross-tolerance with morphine is either methadone or dextromoramide.
Studies have shown that morphine can alter the expression of a number
of genes. A single injection of morphine has been shown to alter the
expression of two major groups of genes, for proteins involved in
mitochondrial respiration and for cytoskeleton-related proteins.
Effects on the immune system
Morphine has long been known to act on receptors expressed on cells of
the central nervous system resulting in pain relief and analgesia. In
the 1970s and '80s, evidence suggesting that opioid drug addicts show
increased risk of infection (such as increased pneumonia,
tuberculosis, and HIV/AIDS) led scientists to believe that morphine
may also affect the immune system. This possibility increased interest
in the effect of chronic morphine use on the immune system.
The first step of determining that morphine may affect the immune
system was to establish that the opiate receptors known to be
expressed on cells of the central nervous system are also expressed on
cells of the immune system. One study successfully showed that
dendritic cells, part of the innate immune system, display opiate
Dendritic cells are responsible for producing cytokines,
which are the tools for communication in the immune system. This same
study showed that dendritic cells chronically treated with morphine
during their differentiation produce more interleukin-12 (IL-12), a
cytokine responsible for promoting the proliferation, growth, and
differentiation of T-cells (another cell of the adaptive immune
system) and less interleukin-10 (IL-10), a cytokine responsible for
promoting a B-cell immune response (B cells produce antibodies to
fight off infection).
This regulation of cytokines appear to occur via the p38 MAPKs
(mitogen-activated protein kinase)-dependent pathway. Usually, the p38
within the dendritic cell expresses
TLR 4 (toll-like receptor 4),
which is activated through the ligand LPS (lipopolysaccharide). This
causes the p38 MAPK to be phosphorylated. This phosphorylation
activates the p38 MAPK to begin producing IL-10 and IL-12. When the
dendritic cells are chronically exposed to morphine during their
differentiation process then treated with LPS, the production of
cytokines is different. Once treated with morphine, the p38 MAPK does
not produce IL-10, instead favoring production of IL-12. The exact
mechanism through which the production of one cytokine is increased in
favor over another is not known. Most likely, the morphine causes
increased phosphorylation of the p38 MAPK. Transcriptional level
interactions between IL-10 and IL-12 may further increase the
production of IL-12 once IL-10 is not being produced. This increased
production of IL-12 causes increased T-cell immune response.
Further studies on the effects of morphine on the immune system have
shown that morphine influences the production of neutrophils and other
cytokines. Since cytokines are produced as part of the immediate
immunological response (inflammation), it has been suggested that they
may also influence pain. In this way, cytokines may be a logical
target for analgesic development. Recently, one study has used an
animal model (hind-paw incision) to observe the effects of morphine
administration on the acute immunological response. Following hind-paw
incision, pain thresholds and cytokine production were measured.
Normally, cytokine production in and around the wounded area increases
in order to fight infection and control healing (and, possibly, to
control pain), but pre-incisional morphine administration
(0.1 mg/kg to 10.0 mg/kg) reduced the number of cytokines
found around the wound in a dose-dependent manner. The authors suggest
that morphine administration in the acute post-injury period may
reduce resistance to infection and may impair the healing of the
Absorption and metabolism
Morphine can be taken orally, sublingually, bucally, rectally,
subcutaneously, intranasally, intravenously, intrathecally or
epidurally and inhaled via a nebulizer. As a recreational drug, it is
becoming more common to inhale ("Chasing the Dragon"), but, for
medical purposes, intravenous (IV) injection is the most common method
Morphine is subject to extensive first-pass
metabolism (a large proportion is broken down in the liver), so, if
taken orally, only 40% to 50% of the dose reaches the central nervous
system. Resultant plasma levels after subcutaneous (SC), intramuscular
(IM), and IV injection are all comparable. After IM or SC injections,
morphine plasma levels peak in approximately 20 min, and, after
oral administration, levels peak in approximately 30 min.
Morphine is metabolised primarily in the liver and approximately 87%
of a dose of morphine is excreted in the urine within 72 h of
Morphine is metabolized primarily into
morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) via
glucuronidation by phase II metabolism enzyme UDP-glucuronosyl
transferase-2B7 (UGT2B7). About 60% of morphine is converted to M3G,
and 6% to 10% is converted to M6G. Not only does the metabolism
occur in the liver but it may also take place in the brain and the
kidneys. M3G does not undergo opioid receptor binding and has no
analgesic effect. M6G binds to μ-receptors and is half as potent an
analgesic as morphine in humans.
Morphine may also be metabolized
into small amounts of normorphine, codeine, and hydromorphone.
Metabolism rate is determined by gender, age, diet, genetic makeup,
disease state (if any), and use of other medications. The elimination
half-life of morphine is approximately 120 min, though there may
be slight differences between men and women.
Morphine can be stored in
fat, and, thus, can be detectable even after death.
Morphine can cross
the blood–brain barrier, but, because of poor lipid solubility,
protein binding, rapid conjugation with glucuronic acid and
ionization, it does not cross easily. Diacetylmorphine, which is
derived from morphine, crosses the blood–brain barrier more easily,
making it more potent.
Main article: Extended-release morphine
There are extended-release formulations of orally administered
morphine whose effect last longer, which can be given once per day.
Brand names for this formulation of morphine include Avinza,
Kadian, MS Contin and Dolcontin. For constant pain, the
relieving effect of extended-release morphine given once (for
Kadian) or twice (for MS Contin) every 24 hours is roughly the
same as multiple administrations of immediate release (or "regular")
Extended-release morphine can be administered together
with "rescue doses" of immediate-release morphine as needed in case of
breakthrough pain, each generally consisting of 5% to 15% of the
24-hour extended-release dosage.
Detection in body fluids
Morphine and its major metabolites, morphine-3-glucuronide and
morphine-6-glucuronide, can be detected in blood, plasma, hair, and
urine using an immunoassay.
Chromatography can be used to test for
each of these substances individually. Some testing procedures
hydrolyze metabolic products into morphine before the immunoassay,
which must be considered when comparing morphine levels in separately
Morphine can also be isolated from whole blood
samples by solid phase extraction (SPE) and detected using liquid
chromatography-mass spectrometry (LC-MS).
Ingestion of codeine or food containing poppy seeds can cause false
A 1999 review estimated that relatively low doses of heroin (which
metabolizes immediately into morphine) are detectable by standard
urine tests for 1-1.5 days after use. A 2009 review determined
that, when the analyte is morphine and the limit of detection is
1 ng/ml, a 20 mg intravenous (IV) dose of morphine is
detectable for 12–24 hours. A limit of detection of 0.6 ng/ml
had similar results.
See also: Opium
A freshly-scored opium poppy seedpod bleeding latex.
Morphine is the most abundant opiate found in opium, the dried latex
extracted by shallowly scoring the unripe seedpods of the Papaver
Morphine is generally 8–14% of the dry weight of
opium, although specially bred cultivars reach 26% or produce
little morphine at all (under 1%, perhaps down to 0.04%). The latter
varieties, including the 'Przemko' and 'Norman' cultivars of the opium
poppy, are used to produce two other alkaloids, thebaine and
oripavine, which are used in the manufacture of semi-synthetic and
synthetic opioids like oxycodone and etorphine and some other types of
drugs. P. bracteatum does not contain morphine or codeine, or other
narcotic phenanthrene-type, alkaloids. This species is rather a source
of thebaine. Occurrence of morphine in other
Papaveraceae, as well as in some species of hops and mulberry trees
has not been confirmed.
Morphine is produced most predominantly early
in the life cycle of the plant. Past the optimum point for extraction,
various processes in the plant produce codeine, thebaine, and in some
cases negligible amounts of hydromorphone, dihydromorphine,
dihydrocodeine, tetrahydro-thebaine, and hydrocodone (these compounds
are rather synthesized from thebaine and oripavine).
In the brain of mammals, morphine is detectable in trace steady-state
concentrations. The human body also produces endorphins, which are
chemically related endogenous opioid peptides that function as
neuropeptides and have similar effects as morphine.
This section needs expansion. You can help by adding to it. (October
Morphine is an endogenous opioid in humans that can be synthesized by
and released from various human cells, including white blood
cells. CYP2D6, a cytochrome P450 isoenzyme, catalyzes the
biosynthesis of morphine from codeine and dopamine from tyramine along
the biosynthetic pathway of morphine in humans. The morphine
biosynthetic pathway in humans occurs as follows:
L-tyrosine → para-tyramine or
L-DOPA → dopamine →
(S)-norlaudanosoline → (S)-reticuline → 1,2-dehydroretinulinium
→ (R)-reticuline → salutaridine → salutaridinol → thebaine →
neopinone → codeinone → codeine → morphine
Norlaudanosoline (also known as tetrahydropapaveroline) can also
be synthesized from
3,4-dihydroxyphenylacetaldehyde (DOPAL), a
L-DOPA and dopamine. Urinary concentrations of
endogenous codeine and morphine have been found to significantly
increase in individuals taking
L-DOPA for the treatment of Parkinson's
Biosynthesis in the opium poppy
Morphine biosynthesis in the opium poppy
Morphine is biosynthesized in the opium poppy from the
tetrahydroisoquinoline reticuline. It is converted into salutaridine,
thebaine, and oripavine. The enzymes involved in this process are the
salutaridine synthase, salutaridine:NADPH 7-oxidoreductase and the
codeinone reductase. Researchers are attempting to reproduce the
biosynthetic pathway that produces morphine in genetically engineered
yeast. In June 2015 the S-reticuline could be produced from sugar
and R-reticuline could be converted to morphine, but the intermediate
reaction could not be performed. In August 2015 the first complete
synthesis of thebaine and hydrocodone in yeast were reported, but the
process would need to be 100,000 times more productive to be suitable
for commercial use.
Chemical structure of morphine. The benzylisoquinoline backbone is
shown in green.
Same structure as a three-dimensional perspective drawing.
Morphine is a benzylisoquinoline alkaloid with two additional ring
closures. It has:
A rigid pentacyclic structure consisting of a benzene ring (A), two
partially unsaturated cyclohexane rings (B and C), a piperidine ring
(D) and a tetrahydrofuran ring (E). Rings A, B and C are the
phenanthrene ring system. This ring system has little conformational
Two hydroxyl functional groups: a C3-phenolic OH (pKa 9.9) and a
An ether linkage between C4 and C5,
Unsaturation between C7 and C8,
A basic, tertiary amine function at position 17,
5 centers of chirality (C5, C6, C9, C13 and C14) with morphine
exhibiting a high degree of stereoselectivity of analgesic action.
Most of the licit morphine produced is used to make codeine by
methylation. It is also a precursor for many drugs including heroin
(3,6-diacetylmorphine), hydromorphone (dihydromorphinone), and
oxymorphone (14-hydroxydihydromorphinone); many morphine derivatives
can also be manufactured using thebaine or codeine as a starting
material. 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
group produces a compound some 1,443 times more potent than morphine,
stronger than the
Bentley compounds such as etorphine (M99, the
Immobilon tranquilliser dart) by some measures.
The structure-activity relationship of morphine has been extensively
studied. As a result of the extensive study and use of this molecule,
more than 250 morphine derivatives (also counting codeine and related
drugs) have been developed since the last quarter of the 19th century.
These drugs range from 25% the analgesic strength of codeine (or
slightly more than 2% of the strength of morphine) to several thousand
times the strength of morphine, to powerful opioid antagonists,
including naloxone (Narcan), naltrexone (Trexan), diprenorphine
(M5050, the reversing agent for the Immobilon dart) and nalorphine
(Nalline). Some opioid agonist-antagonists, partial agonists, and
inverse agonists are also derived from morphine. The
receptor-activation profile of the semi-synthetic morphine derivatives
varies widely and some, like apomorphine are devoid of narcotic
Morphine and most of its derivatives do not exhibit optical isomerism,
although some more distant relatives like the morphinan series
(levorphanol, dextorphan and the racemic parent chemical dromoran) do,
and as noted above stereoselectivity in vivo is an important issue.
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 that 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 or 2 on the
morphine carbon skeleton.
The methyl group that 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
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
Attachment, removal or modification of functional groups to positions
3 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
Structure and properties
Index of refraction, nD
Step 1: 8.21
at 25 °C
Step 2: 9.85
at 20 °C
0.15 g/L at 20 °C
190 °C sublimes
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, sulfate, tartrate, and
citrate; less commonly methobromide, hydrobromide, hydroiodide,
lactate, chloride, and bitartrate and the others listed below.
Morphine diacetate, which is another name for heroin, is a Schedule I
controlled substance, so it is not used clinically in the United
States; it is a sanctioned medication in the
United Kingdom and in
Canada and some countries in Continental Europe, its use being
particularly common (nearly to the degree of the hydrochloride salt)
in the United Kingdom.
Morphine meconate is a major form of the
alkaloid in the poppy, as is morphine pectinate, nitrate, sulphate,
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, more rarely sodium morphenate takes
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.
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
current, 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 that is no longer in common
use; and pseudomorphine, an alkaloid that exists in opium, form as
degradation products of morphine.
The salts listed by the
United States Drug Enforcement Administration
for reporting purposes, in addition to a few others, are as follows:
Select forms of morphine as 'morphiniums' or N-protonated cations of
morphine, i.e. ionic salts & chemical form with freebase
Salt or drug
Free base conversion ratio
Morphine hydrobromide (2 H2O)
Morphine hydrochloride (3 H2O)
Morphine hydriodide (2 H2O)
Morphine meconate (5 H2O)
Morphine phosphate (1⁄2 H2O)
Morphine phosphate (7 H2O)
Morphine sulfate (5 H2O)
Morphine tartrate (3 H2O)
Morphine dinicotinate HCl (Nicomorphine)
Morphine total synthesis
The first morphine total synthesis, devised by Marshall D. Gates, Jr.
in 1952, remains a widely used example of total synthesis. Several
other syntheses were reported, notably by the research groups of
Rice, Evans, Fuchs, Parker, Overman,
Mulzer-Trauner, White, Taber, Trost, Fukuyama,
Guillou, and Stork. It is "highly unlikely" that a chemical
synthesis will ever be able to compete with the cost of producing
morphine from the opium poppy.
First generation production of alkaloids from licit latex-derived
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 extracted at least six to ten
times, 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. The somewhat similar Gregory process was developed in the
United Kingdom during the Second World War, which begins with stewing
the entire plant, in most cases save the roots and leaves, in plain or
mildly acidified water, then proceeding through steps of
concentration, extraction, and purification of alkaloids.[citation
needed] Other methods of processing "poppy straw" (i.e., dried pods
and stalks) use steam, one or more of several types of alcohol, or
other organic solvents.
The poppy straw methods predominate in Continental Europe and the
British Commonwealth, with the latex method in most common use in
India. The latex method can involve either vertical or horizontal
slicing of the unripe pods with a two-to five-bladed knife with a
guard developed specifically for this purpose to the depth of a
fraction of a millimetre and scoring of the pods can be done up to
five times. An alternative latex method sometimes used in China in the
past is to cut off the poppy heads, run a large needle through them,
and collect the dried latex 24 to 48 hours later.
In India, opium harvested by licensed poppy farmers is dehydrated to
uniform levels of hydration at government processing centers, and then
sold to pharmaceutical companies that extract morphine from the opium.
However, in Turkey and Tasmania, morphine is obtained by harvesting
and processing the fully mature dry seed pods with attached stalks,
called poppy straw. In Turkey, a water extraction process is used,
while in Tasmania, a solvent extraction process is used.[citation
Opium poppy contains at least 50 different alkaloids, but most of them
are of very low concentration.
Morphine is the principal alkaloid in
raw opium and constitutes roughly 8–19% of opium by dry weight
(depending on growing conditions). Some purpose-developed strains
of poppy now produce opium that is up to 26% morphine by
weight. A rough rule of thumb to determine the
morphine content of pulverised dried poppy straw is to divide the
percentage expected for the strain or crop via the latex method by
eight or an empirically determined factor, which is often in the range
of 5 to 15. The Norman strain of P. Somniferum, also
developed in Tasmania, produces down to 0.04% morphine but with much
higher amounts of thebaine and oripavine, which can be used to
synthesise semi-synthetic opioids as well as other drugs like
stimulants, emetics, opioid antagonists, anticholinergics, and
smooth-muscle agents.
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.
Most morphine produced for pharmaceutical use around the world 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
Precursor to other opioids
Morphine is a precursor in the manufacture in a large number of
opioids such as dihydromorphine, hydromorphone, hydrocodone, and
oxycodone as well as codeine, which itself has a large family of
Morphine is commonly treated with acetic
anhydride and ignited to yield heroin. Throughout Europe there is
growing acceptance within the medical community of the use of slow
release oral morphine as a substitution treatment alternative to
methadone and buprenorphine for patients not able to tolerate the
side-effects of buprenorphine and methadone. Slow-release oral
morphine has been in widespread use for opiate maintenance therapy in
Austria, Bulgaria, and Slovakia for many years and it is available on
a small scale in many other countries including the UK. The
long-acting nature of slow-release morphine mimics that of
buprenorphine because the sustained blood levels are relatively flat
so there is no "high" per se that a patient would feel but rather a
sustained feeling of wellness and avoidance of withdrawal symptoms.
For patients sensitive to the side-effects that in part may be a
result of the unnatural pharmacological actions of buprenorphine and
methadone, slow-release oral morphine formulations offer a promising
future for use managing opiate addiction. The pharmacology of heroin
and morphine is identical except the two acetyl groups increase the
lipid solubility of the heroin molecule, causing heroin to cross the
blood–brain barrier and enter the brain more rapidly in injection.
Once in the brain, these acetyl groups are removed to yield morphine,
which causes the subjective effects of heroin. Thus, heroin may be
thought of as a more rapidly acting form of morphine.
Illicit morphine is rarely produced from codeine found in
over-the-counter cough and pain medicines. This demethylation reaction
is often performed using pyridine and hydrochloric acid.
Another source of illicit morphine comes from the extraction of
morphine from extended-release morphine products, such as MS-Contin.
Morphine can be extracted from these products with simple extraction
techniques to yield a morphine solution that can be injected. As
an alternative, the tablets can be crushed and snorted, injected or
swallowed, although this provides much less euphoria but retains some
of the extended-release effect, and the extended-release property is
why MS-Contin is used in some countries alongside methadone,
dihydrocodeine, buprenorphine, dihydroetorphine, piritramide,
levo-alpha-acetylmethadol (LAAM), and special 24-hour formulations of
hydromorphone for maintenance and detoxification of those physically
dependent on opioids.
Another means of using or misusing morphine is to use chemical
reactions to turn it into heroin or another stronger opioid. Morphine
can, using a technique reported in New Zealand (where the initial
precursor is codeine) and elsewhere known as home-bake, be turned into
what is usually a mixture of morphine, heroin, 3-monoacetylmorphine,
6-monoacetylmorphine, and codeine derivatives like acetylcodeine if
the process is using morphine made from demethylating codeine.
Since heroin is one of a series of 3,6 diesters of morphine, it is
possible to convert morphine to nicomorphine (Vilan) using nicotinic
anhydride, dipropanoylmorphine with propionic anhydride,
dibutanoylmorphine and disalicyloylmorphine with the respective acid
anhydrides. Glacial acetic acid can be used to obtain a mixture high
in 6-monoacetylmorphine, niacin (vitamin B3) in some form would be
precursor to 6-nicotinylmorphine, salicylic acid may yield the
salicyoyl analogue of 6-MAM, and so on.
The clandestine conversion of morphine to ketones of the hydromorphone
class or other derivatives like dihydromorphine (Paramorfan),
desomorphine (Permonid), metopon, etc. and codeine to hydrocodone
(Dicodid), dihydrocodeine (Paracodin), etc. is more involved,
time-consuming, requires lab equipment of various types, and usually
requires expensive catalysts and large amounts of morphine at the
outset and is less common but still has been discovered by authorities
in various ways during the last 20 years or so.
Dihydromorphine can be
acetylated into another 3,6 morphine diester, namely
diacetyldihydromorphine (Paralaudin), and hydrocodone into thebacon.
An opium-based elixir has been ascribed to alchemists of Byzantine
times, but the specific formula was lost during the Ottoman conquest
Constantinople (Istanbul). Around 1522,
reference to an opium-based elixir that he called laudanum from the
Latin word laudare, meaning "to praise" He described it as a potent
painkiller, but recommended that it be used sparingly. In the late
eighteenth century, when the
East India Company
East India Company gained a direct
interest in the opium trade through India, another opiate recipe
called laudanum became very popular among physicians and their
Morphine was discovered as the first active alkaloid extracted from
the opium poppy plant in December 1804 in Paderborn, Germany, by
Friedrich Sertürner. In 1817 Sertürner reported experiments
in which he administered morphine to himself, three young boys, three
dogs, and a mouse; all four people almost died. Sertürner
originally named the substance morphium after the Greek god of dreams,
Morpheus, as it has a tendency to cause sleep.
The drug was first marketed to the general public by Sertürner and
Company in 1817 as a pain medication, and also as a treatment for
opium and alcohol addiction. It was first used as a poison in 1822
Edme Castaing of
France was convicted of murdering a
patient. Commercial production began in Darmstadt,
1827 by the pharmacy that became the pharmaceutical company Merck,
with morphine sales being a large part of their early growth.[citation
needed] In the 1850s Alexander Wood reported that he had injected
morphine into his wife Rebecca as an experiment. The myth goes that
this killed her because of respiratory depression, but she
outlived her husband by ten years.
Later it was found that morphine was more addictive than either
alcohol or opium, and its extensive use during the American Civil War
allegedly resulted in over 400,000 sufferers from the "soldier's
disease" of morphine addiction. This idea has been a subject of
controversy, as there have been suggestions that such a disease was in
fact a fabrication; the first documented use of the phrase "soldier's
disease" was in 1915.
Diacetylmorphine (better known as heroin) was synthesized from
morphine in 1874 and brought to market by
Bayer in 1898.
approximately 1.5 to 2 times more potent than morphine weight for
weight. Due to the lipid solubility of diacetylmorphine, it can cross
the blood–brain barrier faster than morphine, subsequently
increasing the reinforcing component of addiction. Using a
variety of subjective and objective measures, one study estimated the
relative potency of heroin to morphine administered intravenously to
post-addicts to be 1.80–2.66 mg of morphine sulfate to
1 mg of diamorphine hydrochloride (heroin).
Advertisement for curing morphine addiction, ca. 1900
An ampoule of morphine with integral needle for immediate use. Also
known as a "syrette". From WWII. On display at the Army Medical
Morphine became a controlled substance in the US under the Harrison
Narcotics Tax Act of 1914, and possession without a prescription in
the US is a criminal offense.
Morphine was the most commonly abused
narcotic analgesic in the world until heroin was synthesized and came
into use. In general, until the synthesis of dihydromorphine (ca.
1900), the dihydromorphinone class of opioids (1920s), and oxycodone
(1916) and similar drugs, there were no other drugs in the same
efficacy range as opium, morphine, and heroin, with synthetics still
several years away (pethidine was invented in
Germany in 1937) and
opioid agonists among the semi-synthetics were analogues and
derivatives of codeine such as dihydrocodeine (Paracodin),
ethylmorphine (Dionine), and benzylmorphine (Peronine). Even today,
morphine is the most sought after prescription narcotic by heroin
addicts when heroin is scarce, all other things being equal; local
conditions and user preference may cause hydromorphone, oxymorphone,
high-dose oxycodone, or methadone as well as dextromoramide in
specific instances such as 1970s Australia, to top that particular
list. The stop-gap drugs used by the largest absolute number of heroin
addicts is probably codeine, with significant use also of
dihydrocodeine, poppy straw derivatives like poppy pod and poppy seed
tea, propoxyphene, and tramadol.
The structural formula of morphine was determined by 1925 by Robert
Robinson. At least three methods of total synthesis of morphine from
starting materials such as coal tar and petroleum distillates have
been patented, the first of which was announced in 1952, by Dr.
Marshall D. Gates, Jr.
Marshall D. Gates, Jr. at the University of Rochester. Still, the
vast majority of morphine is derived from the opium poppy by either
the traditional method of gathering latex from the scored, unripe pods
of the poppy, or processes using poppy straw, the dried pods and stems
of the plant, the most widespread of which was invented in
1925 and announced in 1930 by Hungarian pharmacologist János
In 2003, there was discovery of endogenous morphine occurring
naturally in the human body. Thirty years of speculation were made on
this subject because there was a receptor that, it appeared, reacted
only to morphine: the μ3-opioid receptor in human tissue. Human
cells that form in reaction to cancerous neuroblastoma cells have been
found to contain trace amounts of endogenous morphine.
Society and culture
In Australia, morphine is classified as a Schedule 8 drug under the
variously titled State and Territory Poisons Acts.
In Canada, morphine is classified as a Schedule I drug under the
Controlled Drugs and Substances Act.
In France, morphine is in the strictest schedule of controlled
substances, based upon the December 1970 French controlled substances
In Germany, morphine is a verkehrsfähiges und verschreibungsfähiges
Betäubungsmittel listed under Anlage III (the equivalent of CSA
Schedule II) of the Betäubungsmittelgesetz.
In Switzerland, morphine is similarly scheduled to Germany's legal
classification of the drug.
In Japan, morphine is classified as a narcotic under the Narcotics and
Psychotropics Control Act (麻薬及び向精神薬取締法, mayaku
oyobi kōseishinyaku torishimarihō).
In the Netherlands, morphine is classified as a List 1 drug under the
In the United Kingdom, morphine is listed as a Class A drug under the
Misuse of Drugs Act 1971
Misuse of Drugs Act 1971 and a Schedule 2 Controlled Drug under the
Misuse of Drugs Regulations 2001.
In the United States, morphine is classified as a Schedule II
controlled substance under the
Controlled Substances Act
Controlled Substances Act with a main
Administrative Controlled Substances Code Number (ACSCN) of
Morphine pharmaceuticals in the US are subject to
annual manufacturing quotas; morphine production for use in extremely
dilute formulations and its production as an intermediate, or chemical
precursor, for conversion into other drugs is excluded from the US
Internationally (UN), morphine is a Schedule I drug under the Single
Convention on Narcotic Drugs.
Example of different morphine tablets
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.[medical citation needed]
Animal and human studies and clinical experience back up the
contention that morphine is one of the most euphoric drugs known, and
via all but the IV route heroin and morphine cannot be distinguished
according to studies because heroin is a prodrug for the delivery of
systemic morphine. Chemical changes to the morphine molecule yield
other 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, etc. used
clinically in many countries of the world but in many cases also
produced illicitly in rare instances.[medical citation needed]
In general, non-medical use of morphine 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, 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 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 divert 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.[medical
Morphine is also available in a paste that 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 present in many batches
of illicit heroin as the result of incomplete acetylation.[medical
Informal names for morphine include: Cube Juice, Dope, Dreamer, Emsel,
First Line, God's Drug, Hard Stuff, Hocus, Hows, Lydia, Lydic, M, Miss
Emma, Mister Blue, Monkey, Morf, Morph, Morphide, Morphie, Morpho,
Mother, MS, Ms. Emma, Mud, New Jack Swing (if mixed with heroin),
Sister, Tab, Unkie, Unkie White, and Stuff.
MS Contin tablets are known as misties, and the 100 mg
extended-release tablets as greys and blockbusters. The "speedball"
can use morphine as the opioid component, which is combined with
cocaine, amphetamines, methylphenidate, or similar drugs. "Blue
Velvet" is a combination of morphine with the antihistamine
tripelennamine (Pyrabenzamine, PBZ, Pelamine) taken by injection, or
less commonly the mixture when swallowed or used as a retention enema;
the name is also known to refer to a combination of tripelennamine and
dihydrocodeine or codeine tablets or syrups taken by mouth. "Morphia"
is an older official term for morphine also used as a slang term.
"Driving Miss Emma" is intravenous administration of morphine.
Multi-purpose tablets (readily soluble hypodermic tablets that can
also be swallowed or dissolved under the tongue or betwixt the cheek
and jaw) are known, as are some brands of hydromorphone, as Shake
& Bake or Shake & Shoot.
Morphine can be smoked, especially diacetylmorphine (heroin), the most
common method being the "Chasing The Dragon" method. To perform a
relatively crude acetylation to turn the morphine into heroin and
related drugs immediately prior to use is known as AAing (for Acetic
Anhydride) or home-bake, and the output of the procedure also known as
home-bake or, Blue
Heroin (not to be confused with Blue Magic heroin,
or the linctus known as Blue
Morphine or Blue Morphone, or the Blue
Velvet mixture described above).
Morphine is marketed under many different brand names in various parts
of the world.
Access in developing countries
Although morphine is cheap, people in poorer countries often do not
have access to it. According to a 2005 estimate by the International
Narcotics Control Board, six countries (Australia, Canada, France,
Germany, the United Kingdom, and the United States) consume 79% of the
world’s morphine. The less affluent countries, accounting for 80% of
the world's population, consumed only about 6% of the global morphine
supply. Some countries[which?] import virtually no morphine, and
in others[which?] the drug is rarely available even for relieving
severe pain while dying.
Experts in pain management attribute the under-distribution of
morphine to an unwarranted fear of the drug's potential for addiction
and abuse. While morphine is clearly addictive, Western doctors
believe it is worthwhile to use the drug and then wean the patient off
when the treatment is over.
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Wikimedia Commons has media related to Morphine.
Wikinews has related news: 2005 Afghan opium harvest begins
U.S. National Library of Medicine: Drug Information
Morphine bound to proteins in the PDB
The Periodic Table of Videos
The Periodic Table of Videos (University of
Intravenous morphine loading (Vimeo) (YouTube) – A short
education video teaching health professionals the main points about
intravenous loading of analgesics, in particular morphine.
Papaverrubine B (O-methyl-porphyroxine)
Papaverrubine C (epiporphyroxine)
(Phenanthrenes. Includes opioids)
Papaverrubine D (porphyroxine)
Analgesics (N02A, N02B)
Codeine# (+paracetamol, +aspirin)
Hydrocodone (+paracetamol, +ibuprofen, +aspirin)
Oxycodone (+paracetamol, +aspirin, +ibuprofen, +naloxone, +naltrexone)
Aspirin (acetylsalicylic acid)# (+paracetamol/caffeine)
Wintergreen (methyl salicylate)
Local anesthetics (e.g., cocaine, lidocaine)
Tricyclic antidepressants (e.g., amitriptyline#)
Tricyclic antidepressants (e.g., amitriptyline#)
‡Withdrawn from market
§Never to phase III
Opioid receptor agonists (opioids) (e.g., morphine, heroin,
hydrocodone, oxycodone, opium, kratom)
α2δ subunit-containing voltage-dependent calcium channels blockers
(gabapentinoids) (e.g., gabapentin, pregabalin, phenibut)
AMPA receptor antagonists (e.g., perampanel)
CB1 receptor agonists (cannabinoids) (e.g., THC, cannabis)
Dopamine receptor agonists (e.g., levodopa)
Dopamine releasing agents (e.g., amphetamine, methamphetamine, MDMA,
Dopamine reuptake inhibitors (e.g., cocaine, methylphenidate)
GABAA receptor positive allosteric modulators (e.g., barbiturates,
benzodiazepines, carbamates, ethanol (alcohol) (alcoholic drink),
inhalants, nonbenzodiazepines, quinazolinones)
GHB (sodium oxybate) and analogues
Glucocorticoids (corticosteroids) (e.g., dexamethasone, prednisone)
nACh receptor agonists (e.g., nicotine, tobacco, arecoline, areca nut)
Nitric oxide prodrugs (e.g., alkyl nitrites (poppers))
NMDA receptor antagonists (e.g., DXM, ketamine, methoxetamine, nitrous
oxide, phencyclidine, inhalants)
Orexin receptor antagonists (e.g., suvorexant)
See also: Recreational drug use
Opioid receptor modulators
Agonists (abridged; see here for a full list): 3-HO-PCP
Papaver somniferum (opium)
Dynorphin B (rimorphin)
Leumorphin (dynorphin B-29)
Salvinorin A (salvia)
Salvinorin B ethoxymethyl ether
Salvinorin B methoxymethyl ether
Tricyclic antidepressants (e.g., amitriptyline, desipramine,
Nociceptin (orphanin FQ)
Enkephalinase inhibitors: Amastatin
Propeptides: β-Lipotropin (proendorphin)
Kyotorphin (met-enkephalin releaser/degradation stabilizer)
See also: Receptor/signaling modulators • Signaling peptide/protein
Glycine receptor modulators
Positive modulators: Alcohols (e.g., brometone, chlorobutanol
(chloretone), ethanol (alcohol), tert-butanol (2M2P), tribromoethanol,
Barbiturates (e.g., pentobarbital, sodium thiopental)
Dihydropyridines (e.g., nicardipine)
Ginseng constituents (e.g., ginsenosides (e.g., ginsenoside-Rf))
Glutamic acid (glutamate)
Neuroactive steroids (e.g., alfaxolone, pregnenolone (eltanolone),
pregnenolone acetate, minaxolone, ORG-20599)
Tropeines (e.g., atropine, bemesetron, cocaine, LY-278584,
Volatiles/gases (e.g., chloral hydrate, chloroform, desflurane,
diethyl ether (ether), enflurane, halothane, isoflurane,
methoxyflurane, sevoflurane, toluene, trichloroethane (methyl
Endocannabinoids (e.g., 2-AG, anandamide (AEA))
Quinolines (e.g., 4-hydroxyquinoline, 4-hydroxyquinoline-3-carboxylic
acid, 5,7-CIQA, 7-CIQ, 7-TFQ, 7-TFQA)
Negative modulators: Amiloride
Benzodiazepines (e.g., bromazepam, clonazepam, diazepam,
Dihydropyridines (e.g., nicardipine, nifedipine, nitrendipine)
Ginkgo constituents (e.g., bilobalide, ginkgolides (e.g., ginkgolide
A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide M))
Neuroactive steroids (e.g., 3α-androsterone sulfate, 3β-androsterone
sulfate, deoxycorticosterone, DHEA sulfate, pregnenolone sulfate,
Opioids (e.g., codeine, dextromethorphan, dextrorphan, levomethadone,
levorphanol, morphine, oripavine, pethidine, thebaine)
Picrotoxin (i.e., picrotin and picrotoxinin)
Tropeines (e.g., bemesetron, LY-278584, tropisetron, zatosetron)
See here instead.
GABA receptor modulators
GABAA receptor positive modulators
Ionotropic glutamate receptor modulators
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