Naloxone is an opioid antagonist medication that rapidly reverses the effects of opioid overdose. Sold under the brand name Narcan (among others), it has become one of the most important tools in the global response to the opioid overdose crisis. Naloxone works by competitively binding to mu-opioid receptors in the brain, displacing opioid molecules like heroin, fentanyl, and oxycodone, and effectively "switching off" their effects within minutes. It can restore breathing in someone who has stopped breathing due to an opioid overdose, making it a genuine lifesaver that has reversed hundreds of thousands of overdoses worldwide.
Naloxone has no abuse potential whatsoever. It does not produce euphoria, sedation, or any rewarding effects. In a person who has not taken opioids, administering naloxone produces essentially no noticeable effects at all. Because of its extraordinary safety profile and critical public health importance, naloxone has been made available over-the-counter (without a prescription) in the United States since 2023 and is widely distributed through harm reduction organizations, pharmacies, and community programs in many countries. It is on the WHO Model List of Essential Medicines.
The primary limitation of naloxone is its relatively short duration of action (30-90 minutes), which is shorter than most opioids. This means a person who has been revived from an overdose can potentially slip back into overdose once the naloxone wears off, particularly with long-acting opioids or large doses of fentanyl. This is why medical monitoring after naloxone administration is essential, and why calling emergency services is always the right move even after successful reversal.
Safety at a Glance
High Risk- Recognizing an Opioid Overdose
- Knowing the signs of opioid overdose can save a life. Look for:
- Toxicity: Naloxone has an exceptionally favorable safety profile and one of the widest therapeutic indices of any medication. T...
- Dangerous with: 1,4-Butanediol, 2-Fluorodeschloroketamine, 2M2B, 3-Cl-PCP (+82 more)
- Overdose risk: Naloxone IS the Overdose Treatment Naloxone is not a substance people overdose on -- it is the tr...
If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
Dosage
oral
insufflated
intramuscular
intravenous
Duration
oral
Total: 1 hrs – 2 hrsinsufflated
Total: 30 min – 1 hrsintramuscular
Total: 30 min – 1 hrsintravenous
Total: 30 min – 1 hrsHow It Feels
Naloxone is not used recreationally and does not produce a "high" or any desirable subjective effects. What a person experiences after receiving naloxone depends entirely on whether they have opioids in their system.
In opioid-naive individuals (people who have not recently taken opioids), naloxone administration produces virtually no subjective effects. Most people report feeling nothing at all. There may be mild, transient discomfort at the injection site if given IM or SC, or a brief stinging sensation in the nose with intranasal administration, but pharmacologically, it is essentially inert in someone without opioids on board.
In opioid-dependent individuals, naloxone precipitates acute withdrawal syndrome, which is intensely unpleasant. Within minutes, the person may experience severe body aches, profuse sweating, goosebumps (piloerection), abdominal cramping, nausea, vomiting, diarrhea, agitation, anxiety, irritability, rapid heart rate, runny nose, tearing of the eyes, yawning, and restlessness. The severity of precipitated withdrawal is proportional to the degree of physical dependence and the dose of naloxone. This experience is extremely distressing but not life-threatening on its own.
In someone being revived from an overdose, the experience is typically abrupt and disorienting. The person may go from unconsciousness to wakefulness within minutes. They are often confused, agitated, frightened, and sometimes combative. Many people do not remember taking the overdose or understand what is happening. Some express anger at having their high reversed. Nausea and vomiting are common. This is why it is important for those administering naloxone to be prepared to explain calmly what happened and to position the person in the recovery position in case they vomit.
Subjective Effects
The effects listed below are based on the Subjective Effect Index (SEI), an open research literature based on anecdotal reports and personal analyses. They should be viewed with a healthy degree of skepticism. These effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects.
Physical Effects
Physical(9)
- Dehydration— A state of insufficient bodily hydration manifesting as persistent thirst, dry mouth, and physical d...
- Diarrhea— Diarrhea is the occurrence of frequent, loose, or watery bowel movements as a side effect of certain...
- Excessive yawning— Involuntary, repeated yawning that occurs far more frequently than normal and often without the usua...
- Nausea— An uncomfortable sensation of queasiness and stomach discomfort that may or may not lead to vomiting...
- Pain relief— A suppression of negative physical sensations such as aches and pains, ranging from dulled awareness...
- Physical fatigue— Physical fatigue is a state of bodily exhaustion characterized by reduced energy, diminished capacit...
- Pupil dilation— A visible enlargement of the pupil diameter (mydriasis) that can range from subtle widening to drama...
- Sedation— A state of deep physical and mental calming that manifests as a progressive desire to remain still, ...
- Temperature regulation disruption— Impaired thermoregulation causing unpredictable fluctuations between feeling hot and cold, with risk...
Cognitive & Perceptual Effects
Pharmacology
Mechanism of Action
Naloxone is a competitive antagonist at mu-, kappa-, and delta-opioid receptors, with its highest affinity for the mu-opioid receptor. It works by binding to these receptors without activating them, physically displacing opioid agonists (heroin, fentanyl, morphine, oxycodone, etc.) from the receptor binding site. Because naloxone has a higher binding affinity than most opioid agonists, it effectively outcompetes them and blocks their effects. This is a pure antagonist action -- naloxone has zero intrinsic activity at opioid receptors, meaning it cannot produce opioid-like effects regardless of dose.
Onset and Duration by Route
The speed of onset depends heavily on the route of administration. Intravenous (IV) naloxone is the fastest, producing effects within 1-2 minutes. Intramuscular (IM) injection takes approximately 3-5 minutes. Intranasal administration (the Narcan nasal spray formulation most commonly carried by laypeople and first responders) has an onset of 8-13 minutes. Subcutaneous injection falls somewhere between IM and IV at roughly 3-5 minutes. The duration of action for all routes is approximately 30-90 minutes, though this varies with the dose administered and individual metabolism.
Pharmacokinetics
Naloxone is extensively metabolized in the liver primarily through glucuronidation by UGT2B7, producing naloxone-3-glucuronide as the major metabolite. Its plasma half-life is approximately 30-90 minutes (averaging around 60-70 minutes in most studies), which is notably shorter than the half-life of most opioid agonists. Oral bioavailability is extremely low (roughly 2-5%) due to extensive first-pass hepatic metabolism, which is why it is administered parenterally or intranasally rather than by mouth. The volume of distribution is 2-5 L/kg, indicating good tissue penetration. Naloxone crosses the blood-brain barrier rapidly, which accounts for its fast onset of action.
Clinical Considerations
The short half-life relative to most opioids is the single most important pharmacological consideration. Heroin has a half-life of roughly 2-6 hours, methadone 15-60 hours, and fentanyl analogues can persist for hours. This mismatch means naloxone can wear off while significant opioid concentrations remain, causing "renarcotization" -- the return of opioid overdose symptoms after initial successful reversal. This is why redosing may be necessary and why 911 should always be called. With the emergence of fentanyl and its ultra-potent analogues, multiple doses of naloxone are frequently required for successful reversal.
Detection Methods
Standard Drug Panel Inclusion
Naloxone is an opioid antagonist that is not detected on any standard drug panel. It is not a substance of abuse and has no psychoactive effects when taken alone. Naloxone is included in combination products (e.g., Suboxone) as an abuse-deterrent. Drug testing for naloxone is not performed in workplace, clinical, or forensic settings under normal circumstances.
Urine Detection
Naloxone is detectable in urine for approximately 6 to 24 hours after parenteral administration. It undergoes rapid hepatic glucuronidation, and the primary urinary metabolite is naloxone-3-glucuronide. The very short half-life (30 to 90 minutes) limits the detection window. Detection of naloxone in urine is occasionally performed in overdose investigation or compliance monitoring contexts to verify Suboxone use versus buprenorphine-only diversion.
Blood and Saliva Detection
Blood concentrations of naloxone are detectable for only 2 to 6 hours after intramuscular or intranasal administration due to the short half-life. Extended-release formulations (Vivitrol uses naltrexone, not naloxone) are not applicable. Oral fluid testing is not used for naloxone.
Hair Follicle Detection
Hair testing for naloxone is not commercially available and is not clinically relevant. The compound has no abuse potential.
Confirmatory Testing
LC-MS/MS can detect and quantify naloxone in biological specimens when specifically requested. This is primarily relevant in forensic toxicology (overdose death investigations) or compliance monitoring for buprenorphine/naloxone combination products.
Reagent Testing
Reagent testing is not applicable to naloxone. The compound is encountered exclusively in pharmaceutical formulations (nasal spray, injectable, sublingual film) with clear labeling and is not subject to adulteration or substitution concerns.
Interactions
| Substance | Status | Note |
|---|---|---|
| 1,4-Butanediol | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| 2-Fluorodeschloroketamine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 2M2B | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| 3-Cl-PCP | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 3-HO-PCE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 3-HO-PCP | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 3-MeO-PCE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 3-MeO-PCMo | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 3-MeO-PCP | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| 4-MeO-PCP | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Acetylfentanyl | Dangerous | Compounding respiratory depression and overdose risk |
| Alcohol | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Atropa belladonna | Dangerous | Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure |
| Baclofen | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Benzodiazepines | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Bromazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Buprenorphine | Dangerous | Compounding respiratory depression and overdose risk |
| Cake | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Carisoprodol | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Clonazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Clonazolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Clonidine | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Codeine | Dangerous | Compounding respiratory depression and overdose risk |
| Datura | Dangerous | Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure |
| Deschloroetizolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Deschloroketamine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Desomorphine | Dangerous | Compounding respiratory depression and overdose risk |
| Dextromethorphan | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Dextropropoxyphene | Dangerous | Compounding respiratory depression and overdose risk |
| Diazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Diclazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Dihydrocodeine | Dangerous | Compounding respiratory depression and overdose risk |
| Diphenhydramine | Dangerous | Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure |
| Diphenidine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Ephenidine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Eszopiclone | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Ethylmorphine | Dangerous | Compounding respiratory depression and overdose risk |
| Etizolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| F-Phenibut | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Fentanyl | Dangerous | Compounding respiratory depression and overdose risk |
| Flualprazolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Flubromazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Flubromazolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Flunitrazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Flunitrazolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Gabapentin | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Gaboxadol | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| GBL | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| GHB | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Grayanotoxin | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Harmala alkaloid | Dangerous | Risk of serotonin syndrome and severe respiratory depression; potentially fatal |
| Heroin | Dangerous | Compounding respiratory depression and overdose risk |
| HXE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Hydrocodone | Dangerous | Compounding respiratory depression and overdose risk |
| Hydromorphone | Dangerous | Compounding respiratory depression and overdose risk |
| Inhalants | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Ketamine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Kratom | Dangerous | Compounding respiratory depression and overdose risk |
| Lorazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| MAOI | Dangerous | Risk of serotonin syndrome and severe respiratory depression; potentially fatal |
| Memantine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Mephenaqualone | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Methadone | Dangerous | Compounding respiratory depression and overdose risk |
| Methaqualone | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Methoxetamine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Methoxphenidine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Metizolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Midazolam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Mirtazapine | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Morphine | Dangerous | Compounding respiratory depression and overdose risk |
| MXiPr | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Myristicin | Dangerous | Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure |
| Nicotine | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Nifoxipam | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Nitrous | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| O-Desmethyltramadol | Dangerous | Compounding respiratory depression and overdose risk |
| O-PCE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Oxycodone | Dangerous | Compounding respiratory depression and overdose risk |
| Oxymorphone | Dangerous | Compounding respiratory depression and overdose risk |
| PCE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| PCP | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Peganum harmala | Dangerous | Risk of serotonin syndrome and severe respiratory depression; potentially fatal |
| Pentobarbital | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Pethidine | Dangerous | Compounding respiratory depression and overdose risk |
| Phenobarbital | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| SAMe | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| 2-Aminoindane | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 2-FA | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 2-FEA | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 2-FMA | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 2,5-DMA | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 1,3-Butanediol | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
| 1B-LSD | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
| 1cP-AL-LAD | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
| 1cP-LSD | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
| 1cP-MiPLA | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
History
Discovery and Development
Naloxone was synthesized in 1961 by Mozes J. Lewenstein and Jack Fishman while working at Sankyo Company (now Daiichi Sankyo) in Japan. The compound was part of a systematic effort to develop opioid antagonists by modifying the structure of oxymorphone. Lewenstein and Fishman discovered that replacing the N-methyl group of oxymorphone with an allyl group produced a pure antagonist with no agonist activity -- a critical breakthrough that distinguished naloxone from earlier mixed agonist-antagonists like nalorphine.
Regulatory History
Naloxone was patented in 1961 and first approved by the U.S. Food and Drug Administration (FDA) in 1971 under the brand name Narcan, manufactured by Endo Laboratories. For decades, it was used primarily in hospital and ambulance settings as an injectable medication. Its role was largely limited to clinical use by healthcare professionals for intraoperative opioid reversal and emergency overdose treatment.
The Overdose Crisis and Expanding Access
The dramatic escalation of opioid overdose deaths in the United States beginning in the late 1990s (first from prescription opioids, then heroin, then illicit fentanyl) transformed naloxone from a niche hospital drug into a major public health tool. Key milestones:
- 2014: Evzio, the first naloxone auto-injector designed for layperson use, was approved by the FDA.
- 2015: The FDA approved Narcan Nasal Spray (4mg intranasal formulation), making naloxone far more accessible to non-medical users. This was a turning point -- nasal administration requires no needles and minimal training.
- 2016-2020: Numerous states passed standing order laws allowing pharmacies to dispense naloxone without an individual prescription. Community distribution programs expanded rapidly.
- 2023: The FDA approved Narcan Nasal Spray for over-the-counter (OTC) sale without a prescription, making it as accessible as any drugstore product. RiVive (3mg intranasal naloxone) was also approved OTC the same year.
Jack Fishman's Legacy
Jack Fishman, who died in 2013, lived to see his compound become one of the most consequential medications of the 21st century. He received relatively little public recognition during his lifetime despite naloxone saving an estimated tens of thousands of lives annually by the 2010s. The opioid overdose reversal agent he helped create has been administered millions of times worldwide.
Harm Reduction
Recognizing an Opioid Overdose
Knowing the signs of opioid overdose can save a life. Look for:
- Breathing: Slow, shallow, irregular, or completely stopped. This is the most dangerous sign. Gurgling or snoring sounds (the "death rattle") indicate airway obstruction.
- Skin: Blue or grayish lips, fingertips, or face (cyanosis). Pale, clammy skin.
- Pupils: Pinpoint (extremely small) pupils, even in dim light.
- Responsiveness: Cannot be woken by loud voice or sternal rub (knuckles firmly rubbed on the breastbone). Limp body.
- Pulse: Slow or absent heartbeat.
If someone is showing these signs, act immediately. You cannot "wait and see" with a potential opioid overdose -- minutes matter.
How to Administer Narcan Nasal Spray
- Call 911 first (or have someone else call while you administer naloxone). Even if naloxone works, the person needs medical monitoring.
- Open the package and remove the nasal spray device. Do not prime or test it.
- Tilt the person's head back slightly to open the airway.
- Insert the nozzle into one nostril until your fingers touch the bottom of the person's nose.
- Press the plunger firmly to deliver the full dose. Each device delivers one spray -- do not attempt to split the dose.
- If no response in 2-3 minutes, administer a second dose in the other nostril. With fentanyl, a second or even third dose is often needed.
After Administering Naloxone
- Put the person in the recovery position (on their side with the top knee bent forward) to prevent choking if they vomit.
- Stay with the person until emergency services arrive. Naloxone wears off in 30-90 minutes, and the overdose can return.
- Be prepared for the person to be confused, agitated, or upset when they wake up. They may not understand what happened. Speak calmly and explain that they had an overdose and you gave them medicine.
- Do not let the person use more opioids after being revived. Their tolerance has been effectively reset by the naloxone, and using their usual dose could cause another overdose.
- Do not leave the person alone even if they seem fine. The opioid may outlast the naloxone.
Carrying Naloxone
If you or anyone you know uses opioids -- even prescribed ones -- carry naloxone. Many pharmacies dispense it without a prescription. Harm reduction organizations often provide free naloxone kits with training. Many states have standing orders that allow any pharmacy to dispense naloxone to anyone who asks.
Good Samaritan Laws
Most US states (and many other jurisdictions) have Good Samaritan laws that provide legal protection to people who call 911 to report an overdose and/or administer naloxone. These laws typically protect both the person who called and the person who overdosed from drug possession charges. Check your local laws, but do not let fear of legal consequences stop you from calling for help -- a life is more important.
Toxicity & Safety
Naloxone has an exceptionally favorable safety profile and one of the widest therapeutic indices of any medication. There is no established lethal dose in humans, and massive overdoses of naloxone have been administered without fatality.
General Safety
In opioid-naive individuals, naloxone is remarkably well-tolerated even at doses far exceeding therapeutic ranges. It has no abuse potential, no dependence liability, and does not produce respiratory depression, sedation, or other dangerous effects. The FDA has stated that naloxone is safe enough for over-the-counter use by untrained laypeople, a designation that speaks to its extraordinary safety margin.
Precipitated Withdrawal
The primary adverse effect of naloxone is the precipitation of acute opioid withdrawal in physically dependent individuals. While intensely unpleasant, precipitated withdrawal from naloxone is very rarely fatal on its own. The main risks associated with precipitated withdrawal are:
- Aspiration: Vomiting while semi-conscious can lead to aspiration pneumonia. This is why recovery position is important.
- Dehydration: Severe vomiting and diarrhea can cause dehydration, particularly in already compromised individuals.
- Cardiovascular stress: Rapid sympathetic activation can stress the heart, particularly in individuals with pre-existing cardiac conditions.
Rare Adverse Events
- Pulmonary edema: Non-cardiogenic pulmonary edema has been reported in rare cases following naloxone administration, typically in the context of overdose reversal. The mechanism is not fully understood and may relate to the sudden release of catecholamines upon reversal.
- Cardiac arrhythmias: Extremely rare, generally associated with pre-existing cardiac disease and the sympathetic surge of precipitated withdrawal.
- Seizures: Very rare and typically associated with mixed overdoses involving other substances.
Important Context
The risks of NOT administering naloxone during a suspected opioid overdose vastly outweigh any risks of giving it. Opioid overdose kills by stopping breathing. Brain damage from oxygen deprivation begins within 3-5 minutes. Naloxone's potential side effects are temporary and manageable; untreated opioid overdose is frequently fatal. When in doubt, give naloxone.
Addiction Potential
Naloxone is not addictive and has no abuse potential. It produces no euphoria, no rewarding effects, and no physical dependence. It is classified as a non-scheduled medication in the United States, meaning the DEA does not consider it a substance of abuse.
Overdose Information
Naloxone IS the Overdose Treatment
Naloxone is not a substance people overdose on -- it is the treatment for opioid overdose. Understanding when and how to use it is critical.
When to Use Naloxone
Administer naloxone if you suspect an opioid overdose. Signs include:
- Unresponsiveness (cannot be woken by voice or sternal rub)
- Slow, shallow, or stopped breathing
- Blue or gray lips and fingertips
- Pinpoint pupils
- Gurgling or snoring sounds
- Limp body
When in doubt, give naloxone. It will not harm someone who is not overdosing on opioids. If the person is unconscious from a non-opioid cause, naloxone simply will not do anything. There is no downside to administering it when unsure.
Multiple Doses and Fentanyl
The rise of illicitly manufactured fentanyl and its analogues (carfentanil, fluorofentanyl, etc.) has changed the naloxone landscape significantly. Because fentanyl is extremely potent and often present in large doses in illicit supplies:
- A single dose of naloxone may not be sufficient. Fentanyl's high receptor affinity and the large quantities present in street drugs can overwhelm a single 4mg intranasal dose.
- Be prepared to give 2-3 doses spaced 2-3 minutes apart.
- Continue rescue breathing between doses if you are trained in CPR. Breathe for the person until the naloxone takes effect.
- Fentanyl analogues like carfentanil may require even higher total naloxone doses. Hospital settings may use continuous IV naloxone infusion for these cases.
After Reversal
Even after successful naloxone reversal, the person must be monitored because:
- Renarcotization: Naloxone's duration (30-90 min) is shorter than most opioids. The person can slip back into overdose as naloxone wears off.
- With fentanyl patches or extended-release formulations, opioid release continues for hours. Multiple waves of renarcotization are possible.
- The person's tolerance has been pharmacologically reset by the naloxone. If they use opioids again immediately after, even their "usual" dose can be fatal.
Emergency Services
Always call 911, even if naloxone appears to have worked. The person needs professional medical assessment. Paramedics can provide additional naloxone, monitor for renarcotization, check for complications (aspiration, hypoxia-related brain injury), and transport to a hospital if needed.
Dangerous Interactions
The combinations listed below may be life-threatening. Independent research should always be conducted to ensure safety when combining substances.
Severe respiratory depression risk; leading cause of polydrug overdose
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Severe respiratory depression risk; leading cause of polydrug overdose
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Compounding respiratory depression and overdose risk
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding respiratory depression and overdose risk
Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Compounding respiratory depression and overdose risk
Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding respiratory depression and overdose risk
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding respiratory depression and overdose risk
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Risk of serotonin syndrome and severe respiratory depression; potentially fatal
Compounding respiratory depression and overdose risk
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Compounding respiratory depression and overdose risk
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Risk of serotonin syndrome and severe respiratory depression; potentially fatal
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding respiratory depression and overdose risk
Severe respiratory depression risk; leading cause of polydrug overdose
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding respiratory depression and overdose risk
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Compounding respiratory depression and overdose risk
Compounding respiratory depression and overdose risk
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Risk of serotonin syndrome and severe respiratory depression; potentially fatal
Severe respiratory depression risk; leading cause of polydrug overdose
Compounding respiratory depression and overdose risk
Severe respiratory depression risk; leading cause of polydrug overdose
Severe respiratory depression risk; leading cause of polydrug overdose
Tolerance
| Full | Not applicable — opioid antagonist |
| Half | N/A |
| Zero | N/A |
Cross-tolerances
Legal Status
Throughout the world, naloxone is not considered a controlled substance. It is a prescription drug in most countries.
Australia: In Australia, naloxone is considered an over the counter drug and is available at most pharmacies
Canada: In Canada, naloxone kits are distributed at many emergency rooms, clinics, and some pharmacies.
Germany:** Naloxone is a prescription medicine, according to Anlage 1 AMVV.
Switzerland: Preparations containing only naloxone are listed as "Abgabekategorie B" pharmaceuticals, which require a prescription to obtain.
Turkey: Naloxone is only sold as an addictive to buprenorphine to deter abuse, which is prescription only.
United States: At a federal level, naloxone is a prescription drug. Many states have programs that make naloxone over the counter and available at request at most pharmacies. In the United States, most jurisdictions have programs to deploy naloxone to law enforcement and fire and rescue services.
United Kingdom: In the United Kingdom, naloxone is considered a prescription drug, but drug services can supply it without a prescription. And anyone can use it to save a life in an emergency.
Responsible use
Safer injection guide
Naloxone (Wikipedia)
Naloxone (Erowid Vault)
Naloxone (TiHKAL / Isomer Design)
Combatting America's Opioid Crisis: Heroin's Antidote (Vice)
Tips (6)
Carry naloxone if you or anyone you know uses opioids, even prescribed ones. Many pharmacies dispense Narcan without a prescription, and harm reduction organizations often provide free kits with training. You never know when you might be the person who saves a life.
Most US states have Good Samaritan laws that protect you from drug possession charges when you call 911 for an overdose. Do not let fear of legal consequences stop you from calling -- a person's life is always more important. Check your state's specific protections.
Check the expiration date on your naloxone regularly and replace it when expired. Expired naloxone may still have some effectiveness in an emergency (better than nothing), but the potency degrades over time. Many harm reduction programs will exchange expired kits for free.
Naloxone wears off in 30-90 minutes, but most opioids last much longer. After reversing an overdose, the person can slip back into overdose as the naloxone wears off. Always call 911 and stay with the person even after they wake up.
With fentanyl and its analogues now dominant in the street supply, a single dose of naloxone may not be enough. Carry at least two doses. If the first dose does not produce a response within 2-3 minutes, administer a second dose in the other nostril. Some fentanyl overdoses require three or more doses.
Free naloxone training is available from local health departments, harm reduction organizations, and many pharmacies. Training typically takes 15-30 minutes and covers recognizing an overdose, administering naloxone, rescue breathing, and recovery position. You do not need medical training to save a life with naloxone.
Community Discussions (12)
Further Reading
References (4)
- Opioid receptors — Pasternak & Pan Annual Review of Pharmacology (2013)paper
- PubChem: Naloxone
PubChem compound page for Naloxone (CID: 5284596)
pubchem - Naloxone - TripSit Factsheet
TripSit factsheet for Naloxone
tripsit - Naloxone - Wikipedia
Wikipedia article on Naloxone
wikipedia