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Promethazine Facts

Depressant; Sedative; Phenothiazine; Histamine H1 receptor antagonist

Description

Promethazine — also sold as Phenergan — is a synthetic antihistamine of the phenothiazine class. It blocks histamine signaling in the brain, producing the heavy sedation characteristic of first-generation antihistamines.[1]

Subjective effects include heavy drowsiness, dry mouth, visual acuity suppression, thought deceleration, and emotional suppression.[2] The experience is one of thick, physically weighted sedation — more cognitively impairing than benzodiazepines, with a distinctly drying, anticholinergic character.

Promethazine produces no established physical dependence, but carries two FDA black box warnings: fatal respiratory depression in children under 2, and severe tissue damage from injection.[3] In adults, the dominant danger is combination use — it amplifies opioid respiratory depression and compounds heart rhythm risk.[4][5]

Dose and durationby route · individual sensitivity varies

Oral(mg)
Threshold< 5 mgLight12.5 – 25 mgCommon25 – 50 mgStrong50 – 100 mgHeavy100+ mg

Starts in 20 – 60 minLasts 4 – 8 hoursAfter-effects 6 – 12 hours

Body and dependence

Acute toxicity
Moderate
Chronic toxicity
Moderate
Physical dependence
Negligible
Psychological dependence
Low
Withdrawal
None recorded
Compulsive redosing
Negligible

Tolerance

Builds
Moderate
Fully resets after
Not recorded
Carries over to
diphenhydramine; chlorpheniramine; hydroxyzine; doxylamine; other first-generation H1 antihistamines; muscarinic antagonists

Effectslikely at a common dose

Perception
none likely · 8 possible, including Visual acuity suppression, Vestibular distortion, Spatial disorientation
Body
Sedation; Physical fatigue; Nausea suppression; Dry mouth; Bodily heaviness; Motor control impairment; +10 possible, including Dizziness, Abnormal heartbeat, Heart rate perception changes
Thinking
Focus suppression; Cognitive impairment; Thought deceleration; Cognitive fatigue; Decision impairment; Analysis suppression; Information processing suppression; +8 possible, including Memory suppression, Language suppression, Confusion
Feeling
none likely · 3 possible, including Empathy suppression
Self
none likely · 4 possible, including Communication suppression, Social disconnection
Time
none likely · 2 possible, including Temporal disorientation

Who shouldn't take it

Absolute
Comatose patients; Promethazine or phenothiazine hypersensitivity; Children under 2 years; Intra-arterial or subcutaneous injection
Relative
Concurrent QT-prolonging medications; Lower respiratory tract disease; Seizure disorders; Concurrent MAOI use; Hepatic impairment; Elderly patients; Narrow-angle glaucoma; Prostatic hypertrophy or bladder obstruction; Bone marrow suppression history

Combinations60 recorded

Dangerous (30)
Amphetamines; Anticholinergics; Antihistamines; Atypical antipsychotics; Benzodiazepines, Barbiturates; Buprenorphine, Kratom; DXM; GHB, Baclofen; GHB, GBL; Lithium; MDMA, MDA; Naltrexone; Opioids; Alpha-2 adrenergic receptor antagonist; Benzodiazepines; Clonidine, Guanfacine; Ephedrine, Pseudoephedrine; Ibogaine; Local anesthetics; MAOIs; MDMA, Amphetamines; NDRIs (Wellbutrin); NRIs; NSAIDs; and 6 more, see full page
Caution (25)
See full page: psychedex.org/substances/promethazine
Not graded (5)
Not listed never means safe.

Seek help immediately if

No emergency profile is recorded for this substance. Not recorded never means no risk.

988 Suicide & Crisis LifelineFireside Project: 62-FIRESIDE

Version r1 · Not medical advice

References

  1. [1]
    ^IUPHAR/BPS Guide to Pharmacology (2024) Promethazine Receptor Binding Data — IUPHAR/BPS Guide to Pharmacology Link
  2. [2]
    ^Paule MG, Chelonis JJ, Blake DJ, Dornhoffer JL (2004) Effects of drug countermeasures for space motion sickness on working memory in humans. — Neurotoxicology and teratology PMID:15451046
  3. [3]
    ^New England Journal of Medicine (Staff) (2005) Boxed Warning Added to Promethazine Labeling for Pediatric Use — New England Journal of Medicine Link
  4. [4]
    ^Miuli A, Stigliano G, Lalli A, et al. (2020) "Purple Drank" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications. — Journal of psychoactive drugs doi:10.1080/02791072.2020.1797250
  5. [5]
    ^Ali Z, Ismail M, Khan F, Sajid H (2021) Association of H1-antihistamines with torsade de pointes: a pharmacovigilance study of the food and drug administration adverse event reporting system. — Expert opinion on drug safety doi:10.1080/14740338.2021.1846717
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