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Pethidine Facts

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

Description

Pethidine (meperidine) — also known as Demerol — is a synthetic opioid of the 4-phenylpiperidine class. It activates opioid receptors in the brain and spinal cord, suppressing pain while also blocking serotonin reuptake and sodium channels.

Subjective effects include pain suppression, euphoria, warmth, sedation, and reduced anxiety. The experience is a diffuse opioid calm with a mild activating edge — the heart beats faster and pupils dilate rather than constrict, reflecting the anticholinergic component.

Pethidine produces rapid physical dependence and carries high acute and chronic toxicity. Its defining danger is the breakdown product normeperidine, which accumulates with repeated dosing and causes seizures that cannot be reversed with naloxone[1] — a risk that grows with kidney impairment, old age, and use beyond 48 hours.[2]

Dose and durationby route · individual sensitivity varies

Oral(mg)
Threshold< 25 mgLight50 – 100 mgCommon100 – 200 mgStrong200 – 400 mgHeavy400+ mg

Starts in 30 – 60 minLasts 3 – 6 hoursAfter-effects 2 – 10 hours

Body and dependence

Acute toxicity
High
Chronic toxicity
High
Physical dependence
High
Psychological dependence
High
Withdrawal
Moderate · medical supervision
Compulsive redosing
High

Tolerance

Builds
Moderate
Fully resets after
10.5 days
Carries over to
morphine; fentanyl; oxycodone; hydromorphone; heroin; codeine; tramadol

Effectslikely at a common dose

Perception
none likely · 5 possible, including Visual acuity suppression, Spatial disorientation, Vestibular distortion
Body
Pupil constriction; Pain suppression; Body high; Sedation; +21 possible, including Respiratory depression, Nausea, Dizziness
Thinking
none likely · 13 possible, including Cognitive impairment, Decision impairment, Compulsive redosing urge
Feeling
none likely · 3 possible
Self
none likely · 4 possible, including Craving, Communication suppression
Time
none likely · 2 possible, including Temporal disorientation

Who shouldn't take it

Absolute
Severe renal impairment; MAOI use within 14 days; Duration of use exceeding 48 hours
Relative
Concurrent CNS depressant use; Seizure disorders; Concurrent SSRI use; Hepatic impairment; Concurrent CYP3A4 inhibitors; Pregnancy; Older adults (≥65 years); Sickle cell disease; Chronic cancer pain

Combinations62 recorded

Lethal (7)
Benzodiazepines, Barbiturates; GHB, Baclofen; GHB, GBL; Ibogaine; Ketamine; Local anesthetics; Tramadol
Dangerous (40)
Alpha-2 adrenergic receptor antagonist; Amphetamines; Anticholinergics; Antihistamines; Benzodiazepines; Buprenorphine, Kratom; Cannabis, THC; Clonidine, Guanfacine; Ephedrine, Pseudoephedrine; Gabapentin, Pregabalin; MAOIs; MDMA, Amphetamines; MDMA, MDA; Naltrexone; Nicotine; NRIs; SNRIs; SSRIs; Stimulants; THC; 5-HTP, Tryptophan; Antipsychotics; Atypical antipsychotics; Buspirone; and 16 more, see full page
Caution (10)
See full page: psychedex.org/substances/pethidine
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]
    ^Hershey LA (1983) Meperidine and central neurotoxicity. — Annals of Internal Medicine PMID:6838077
  2. [2]
    ^Preuss CV, et al. (2024) Meperidine - StatPearls (NCBI Bookshelf) Link
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