Morphine

(4R,4aR,7S,7aR,12bS)-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol

Overview

Morphine belongs to Opioids.

Key safety note: Morphine is a strong opioid and its central danger is dose-dependent respiratory depression, which is the usual mechanism of opioid death: the risk is greatest in opioid-naïve people, at higher doses, and above all when it is combined with other CNS depressants (other opioids, benzodiazepines, alcohol, gabapentinoids), which act synergistically on breathing.^[6]^[5]

Effects

Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.

Pain relief, a warm relaxation and, especially by injection, euphoria and a sense of calm detachment. Drowsiness and clouded thinking.
Physical signs: pinpoint pupils, slowed breathing, itch and flushing (histamine release), nausea/vomiting and constipation.
With regular use: tolerance to euphoria and analgesia (but not to constipation), physical dependence, and an unpleasant flu-like withdrawal on stopping.

Dosing & duration

Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral (immediate- and modified-release), intravenous, intramuscular, subcutaneous and spinal (epidural/intrathecal): clinician-prescribed and titrated. Figures below are clinical context, NOT a recreational guide.. Morphine is a prescription strong opioid. Dosing is individualised and titrated to effect and tolerance by clinicians, with very different doses in opioid-naïve versus opioid-tolerant patients. There is no safe recreational dose: the amount that produces euphoria in a naïve person overlaps with the amount that stops their breathing, and the danger multiplies with any other depressant (alcohol, benzodiazepines, other opioids). Equianalgesic reference: ~30 mg oral morphine ≈ 10 mg IV morphine. Have naloxone available. Never use alone.

Dose ranges

Oral IR (opioid-naïve adult, clinical)

≈5–10 mg every 4 h, titrated

IV (opioid-naïve adult, clinical)

≈2–5 mg, titrated by a clinician

Equianalgesic reference

≈30 mg oral ≈ 10 mg IV

Duration

onset

IV ≈5–10 min, oral IR ≈30–60 min

total

IR analgesia ≈3–4 h (modified-release ≈12–24 h)

after effects

Sedation/constipation may persist. Withdrawal on cessation after regular use

Chemical & Physical Properties

Formula	C17H19NO3
Molar mass	285.34 g/mol
State	Solid
Melting point	255 °C
Boiling point	190 °C (sublimes)
Density	1.32 g/cm³ at 20 °C
Vapor pressure	Not reported
pKa	8.18
LogP	0.87
Solubility	149 mg/L (at 20 °C), In water, 1.49×10² mg/L at 20 °C, Insoluble in water
Refractive index	Not reported

Identifiers & Synonyms

CAS	57-27-2
CAS (enantiomer)
PubChem CID	5288826
InChIKey	BQJCRHHNABKAKU-KBQPJGBKSA-N
InChI	InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1
SMILES	CN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)O)O[C@H]3[C@H](C=C4)O

Synonyms

(-)-Morphine
Morphia
Roxanol
MS Contin
Oramorph

Pharmacodynamics & Biochemistry

Morphine is the prototypical opioid: the main analgesic alkaloid of the opium poppy (Papaver somniferum) and the reference against which other opioids are compared. It is a μ-opioid receptor (MOR) agonist (a full agonist in most systems, though measured intrinsic activity is assay-dependent), with weaker activity at the κ- and δ-opioid receptors. Activating these Gi/Go-coupled receptors closes voltage-gated calcium channels, opens potassium channels and lowers cyclic AMP, reducing neuronal excitability and neurotransmitter release along pain pathways. This produces analgesia together with the characteristic opioid effects: euphoria and sedation, pinpoint pupils (miosis), suppression of cough and of the brainstem respiratory drive, slowed gut motility (constipation), nausea and histamine release (itch, flushing). Respiratory depression, a reduced ventilatory response to CO₂, is the effect that kills in overdose, and it is reversible by the antagonist naloxone. Morphine is glucuronidated in the liver by UGT2B7 to two main metabolites: morphine-6-glucuronide (M6G), which is itself an active μ-opioid analgesic and accumulates in renal impairment, and morphine-3-glucuronide (M3G), which does not bind opioid receptors and is analgesically inactive but may contribute to neuroexcitation (hyperalgesia, myoclonus) at high exposures. Oral morphine has low, variable bioavailability (less than 40% reaching systemic circulation according to the oral-tablet label) because of extensive first-pass metabolism, and an effective half-life of roughly 2–4 hours.

Biological targets

Binding & functional measurements

Target	Measurement	Species
μ-opioid receptor	Ki 1.2 nM	Human
κ-opioid receptor	Ki 24 ± 2.3 nM	Human
δ-opioid receptor	Ki 140 ± 18 nM	Human
δ-opioid receptor	Ki 50 ± 0.60 nM	Guinea pig
δ-opioid receptor	EC50 668 ± 65 nM Emax 109 ± 14%	Human
δ-opioid receptor	Ki 217 ± 19 nM	Rat
κ-opioid receptor	Ki 113 ± 9.0 nM	Guinea pig
κ-opioid receptor	EC50 710 ± 23 nM Emax 76.1 ± 2%	Human
μ-opioid receptor	Ki 2.0 ± 0.30 nM	Guinea pig
μ-opioid receptor	EC50 34 ± 5.1 nM Emax 89 ± 17%	Human
μ-opioid receptor	Ki 6.5 ± 0.74 nM	Rat

Pharmacokinetics

Bioavailability	Less than 40% oral, with substantial variability
T_max	Not reported
Half-life	≈2–4 h effective half-life after IV administration
V_d	≈3–4 L/kg
Protein binding	≈30–35%
Metabolism	hepatic glucuronidation to M3G (~50%) and M6G (~5–15%) via UGT2B7. Minor sulfation and demethylation
Excretion	primarily renal. ≈10% excreted unchanged in urine

Toxicology & Safety

Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

200 mg/kg (mouse, i.p.)

Morphine is a strong opioid and its central danger is dose-dependent respiratory depression, which is the usual mechanism of opioid death: the risk is greatest in opioid-naïve people, at higher doses, and above all when it is combined with other CNS depressants (other opioids, benzodiazepines, alcohol, gabapentinoids), which act synergistically on breathing. Overdose (pinpoint pupils, unconsciousness, slow/absent breathing) is a medical emergency reversible with naloxone. With repeated use, tolerance and physical dependence develop, and stopping abruptly causes an opioid withdrawal syndrome (agitation, aches, sweating, gastrointestinal upset, craving) that is highly unpleasant but not usually life-threatening. Common effects include constipation (which does not abate with tolerance), nausea, sedation, itch and urinary retention. M6G (an active metabolite) and M3G accumulate in renal impairment, so lower doses are needed there. It should not be used with MAOIs, and caution is required in respiratory disease, head injury and the elderly. Non-medical injection adds infection and overdose risk. Never use alone.^[6]^[5]

Legal Status

Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.

US: Schedule II. UK: Class A. DE: BtMG Anlage III

Interactions & Contraindications

Drug interactions

Benzodiazepines, Alcohol, Opioids, Gabapentinoids (gabapentin, pregabalin) Synergistic respiratory depression and sedation, including with sedating antihistamines. The leading cause of opioid death.^[6]

MAOIs Risk of severe reactions, so avoid.^[6]

Other serotonergic drugs Potential (uncommon) serotonin toxicity at high combined exposure.^[6]

Contraindications

Significant respiratory depression or acute severe asthma without monitoring.^[5]

Paralytic ileus or gastrointestinal obstruction^[5]

Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent (within 14 days) MAOI use.^[6]

Head injury or raised intracranial pressure raised intracranial pressure or head injury.^[5]

Kidney or liver impairment severe impairment (active M6G/M3G accumulation), and caution in the elderly.^[5]

Combining with alcohol or other CNS depressants^[5]

Usage & Context

A first-line strong opioid analgesic for moderate-to-severe acute pain (e.g. after surgery, trauma, myocardial infarction), cancer pain and palliative care, and for the relief of breathlessness in end-of-life care. Given orally (immediate- and modified-release), by injection (IV/IM/subcutaneous) and spinally.
The reference opioid against which the potency of all others is set, and the standard from which morphine milligram equivalents (MME) are calculated for safe prescribing.
Also used non-medically for its euphoria. It is the archetypal drug of the opioid class and a benchmark in addiction and overdose. Diamorphine (heroin) is a more lipophilic pro-drug that is de-acetylated to morphine.

Sources & Evidence

Further Information

More in this subclass