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Naloxone Facts

Opioid; Substituted morphinan; Mu-opioid receptor antagonist

Description

Naloxone is a semi-synthetic opioid antagonist of the morphinan class. It blocks opioid receptors in the brain without activating them, physically displacing opioids from their binding sites and reversing overdose-induced respiratory failure.[1][2]

Subjective effects include no perceptible change in opioid-naive individuals — any increase in pain sensitivity falls below conscious awareness. In opioid-dependent individuals, the experience is defined by abrupt reversal: consciousness returns within minutes, but with distress more intense than ordinary withdrawal because receptor occupancy shifts instantaneously.[3]

Naloxone produces no dependence and carries negligible direct toxicity.[2] The risks come from reversal itself: abrupt opioid removal can cause cardiovascular stress and, rarely, fluid in the lungs,[4] and the short duration means overdose may return if the opioid outlasts it.[5][6]

Dose and durationby route · individual sensitivity varies

Oral(mg)
Threshold< 4 mgLight4 – 8 mgCommon8 – 16 mgStrong16 – 28 mgHeavy28+ mg

Starts in 5 – 15 minLasts 1 – 2 hoursAfter-effects 1 – 12 hours

Body and dependence

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

Tolerance

Builds
None
Fully resets after
Not recorded

Effectslikely at a common dose

Perception
none likely · 2 possible
Body
Nausea; Diarrhea; Excessive sweating; Pupil dilation; Restlessness; +20 possible, including Temperature dysregulation, Vomiting, Dehydration sensation
Thinking
none likely · 4 possible, including Confusion
Feeling
Anxiety; Dysphoria; +6 possible, including Anhedonia, Depression, Emotional lability
Self
Craving; +3 possible, including Social disconnection

Who shouldn't take it

Absolute
Hypersensitivity to naloxone
Relative
Cardiovascular disease; Known opioid dependence (non-life-threatening context)

Combinations60 recorded

Dangerous (10)
Anticholinergics; Benzodiazepines, Barbiturates; Ketamine, DXM, PCP; Opioids; SNRIs; Antipsychotics; GHB, GBL; Ibogaine; MAOIs; SSRIs
Caution (32)
See full page: psychedex.org/substances/naloxone
Not graded (18)
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]
    ^Khan S, Tyson AS, Ranjbar M, et al. (2025) Structural snapshots capture nucleotide release at the mu-opioid receptor — Nature doi:10.1038/s41586-025-09677-6
  2. [2]
    ^abSaari TI, Strang J, Dale O (2024) Clinical Pharmacokinetics and Pharmacodynamics of Naloxone — Clinical Pharmacokinetics doi:10.1007/s40262-024-01355-6
  3. [3]
    ^Martinez S, Jones JD, Dunn KE, et al. (2026) Evidence of heterogeneity in the opioid withdrawal syndrome: Spontaneous and precipitated withdrawal — Pharmacology, Biochemistry, and Behavior doi:10.1016/j.pbb.2026.174153
  4. [4]
    ^Elkattawy S, Alyacoub R, Ejikeme C, Noori MAM, Remolina C (2021) Naloxone induced pulmonary edema — Journal of Community Hospital Internal Medicine Perspectives doi:10.1080/20009666.2020.1854417
  5. [5]
    ^Clayton J, Kozell LB, Eshleman AJ, et al. (2026) Slow Dissociation of Nitazenes from the µ-Opioid Receptor Underlies the Challenge of Overdose Reversal — bioRxiv doi:10.64898/2026.04.14.718203
  6. [6]
    ^Skolnick P, Paavola J, Heidbreder C (2024) Synthetic opioids have disrupted conventional wisdom for treating opioid overdose — Drug and alcohol dependence reports doi:10.1016/j.dadr.2024.100268
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