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Codeine Facts

Opioid; Depressant; Substituted morphinan; Mu-opioid receptor agonist

Description

Codeine (3-methylmorphine) is a naturally-occurring opioid of the morphinan class. Codeine itself binds opioid receptors only weakly;[1] it is morphine that suppresses pain and produces the sedation and warmth characteristic of opioids.

Subjective effects include pain suppression, sedation, mild euphoria, anxiolysis, a sense of diffuse warmth, and cognitive slowing. The overall experience is a quieter version of morphine — gentle and tranquil — but its intensity varies dramatically between individuals based on how efficiently genetics convert codeine to morphine.[2]

Codeine produces moderate physical and psychological dependence, and its main toxicity risk is respiratory depression driven by morphine.[3] The defining danger is genetic: people who convert codeine to morphine unusually fast can experience life-threatening effects from standard doses — a trait present in up to 18% of some populations.[4]

Dose and durationby route · individual sensitivity varies

Oral(mg)
Threshold< 15 mgLight30 – 60 mgCommon60 – 120 mgStrong120 – 200 mgHeavy200+ mg

Starts in 30 – 45 minLasts 3 – 6 hoursAfter-effects 2 – 4 hours

Body and dependence

Acute toxicity
Moderate
Chronic toxicity
Moderate
Physical dependence
Moderate
Psychological dependence
Moderate
Withdrawal
Mild
Compulsive redosing
Moderate

Tolerance

Builds
Moderate
Fully resets after
10 days
Carries over to
morphine; heroin; oxycodone; hydrocodone; fentanyl; tramadol; dihydrocodeine

Effectslikely at a common dose

Perception
Sleep-transition hallucinations; +4 possible, including Spatial disorientation, Vestibular distortion, Visual haze / noise
Body
Pain suppression; Tactile euphoria; Sedation; Constipation; Pupil constriction; Bodily heaviness; Body high; Breathing alteration; Muscle relaxation; Physical fatigue; +15 possible, including Respiratory depression, Nausea, Dizziness
Thinking
Thought deceleration; Cognitive fatigue; Cognitive impairment; Focus suppression; Information processing suppression; +8 possible, including Analysis suppression, Decision impairment, Compulsive redosing urge
Feeling
Anxiety suppression; Euphoria; +1 possible
Self
none likely · 4 possible, including Communication suppression, Craving
Time
none likely · 2 possible, including Temporal disorientation

Who shouldn't take it

Absolute
CYP2D6 ultrarapid metabolizer status; Children under 12 years; Post-tonsillectomy/adenoidectomy
Relative
Respiratory insufficiency; Hepatic impairment; Renal impairment; Breastfeeding

Combinations62 recorded

Lethal (6)
Benzodiazepines, Barbiturates; GHB, Baclofen; GHB, GBL; Ketamine; Local anesthetics; Tramadol
Dangerous (39)
Antihistamines; Benzodiazepines; Buprenorphine, Kratom; Cannabis, THC; Gabapentin, Pregabalin; MDMA, Amphetamines; Naltrexone; NRIs; Stimulants; THC; 5-HTP, Tryptophan; Alpha-2 adrenergic receptor antagonist; Amphetamines; Anticholinergics; Antipsychotics; Atypical antipsychotics; Buspirone; Caffeine; Cannabis; CBD; Dopamine agonists; DXM; Ephedrine, Pseudoephedrine; Glutamate modulator; and 15 more, see full page
Caution (12)
See full page: psychedex.org/substances/codeine
Not graded (5)
Not listed never means safe.

Seek help immediately if

  • Unresponsive / can't be woken, even to a firm sternal rub
  • Slow, shallow, or stopped breathing
  • Pinpoint pupils
  • Blue/grey lips, fingertips, or skin (cyanosis)
  • Limp body; pale, clammy skin
  • Choking or gurgling sounds ("death rattle")
  • Slow, erratic, or absent pulse

What to do

  1. Try to wake them — shout their name, firm sternal rub
  2. Call emergency services immediately
  3. Administer naloxone if available
  4. Give rescue breaths (or CPR if there is no pulse)
  5. Place them in the recovery position
  6. Stay with them; re-dose naloxone every 2–3 minutes if there is no response
Reversal agent
Naloxone (Narcan) — opioid antagonist. May require repeated doses; its effect can wear off before the opioid does.

With prompt naloxone and rescue breathing, reversal is usually rapid. Because naloxone can wear off before the opioid — especially with long-acting opioids (methadone) or high-potency ones (fentanyl) — a period of monitoring is needed even after the person revives.

988 Suicide & Crisis LifelineFireside Project: 62-FIRESIDE

Version r1 · Not medical advice

References

  1. [1]
    ^Volpe DA, McMahon Tobin GA, Mellon RD, et al. (2011) Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs — Regulatory Toxicology and Pharmacology doi:10.1016/j.yrtph.2010.12.007
  2. [2]
    ^Eddy NB, Friebel H, Hahn KJ, Halbach H (1968) Codeine and its alternates for pain and cough relief. I. Codeine, exclusive of its antitussive action — Bulletin of the World Health Organization PMID:4972938
  3. [3]
    ^Frost J, Helland A, Nordrum IS, Slordal L (2012) Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths — Forensic Science International doi:10.1016/j.forsciint.2012.01.019
  4. [4]
    ^Kim TD, Kwak JS, Shin JG, et al. (2025) CYP2D6 genotyping in a Korean cohort: comparative analysis with Asian, Caucasian, and African populations — Pharmacogenomics doi:10.1080/14622416.2025.2565993
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