Opioid drug used in pain relief Hydrocodone, also known as dihydrocodeinone, is a semi-synthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically, it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with homatropine methylbromide to relieve cough. It is also available by itself in a long-acting form sold under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug: in the United States, it is classified as a Schedule II Controlled Substance.
Common side effects include dizziness, sleepiness, nausea, and constipation. Serious side effects may include low blood pressure, seizures, QT prolongation, respiratory depression, and serotonin syndrome. Rapidly decreasing the dose may result in opioid withdrawal. Use during pregnancy or breastfeeding is generally not recommended. Hydrocodone is believed to work by activating opioid receptors, mainly in the brain and spinal cord. Hydrocodone 10mg is equivalent to about 10mg of morphine by mouth.
Hydrocodone was patented in 1923, while the long-acting formulation was approved for medical use in the United States in 2013. It is most commonly prescribed in the United States, which consumed 99% of the worldwide supply as of 2010. In 2018, it was the 402nd most commonly prescribed medication in the United States, with more than 400,000 prescriptions. Hydrocodone is a semi-synthetic opioid, converted from codeine or less often from thebaine. Production using genetically engineered yeasts has been developed but is not used commercially.
Safety at a Glance
High Risk- It is strongly recommended that one use harm reduction practices when using this drug.
- Australia: Hydrocodone is a Schedule 8 (S8) or controlled drug.
- Toxicity: Hydrocodone has not been shown to be toxic and is physically benign at reasonable dosages. As with all opioids, long-...
- Dangerous with: 3-Cl-PCP, 3-HO-PCE, 3-HO-PCP, 3-MeO-PCE (+43 more)
- Overdose risk: fatal at heavy dosages. Like most opioids, unadulterated hydrocodone at appropriate dosages does ...
If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
Dosage
oral
Duration
oral
Total: 4 hrs – 8 hrsHow It Feels
Hydrocodone is the quintessential American opioid, and its subjective character reflects a kind of middle-ground warmth that feels both familiar and satisfying. The onset begins twenty to forty minutes after oral administration, a gathering heat that starts in the stomach and radiates outward with a steadiness that feels almost engineered. There is a moment -- usually around the thirty-minute mark -- when the warmth crosses a threshold and becomes unmistakable, a whole-body flush that announces the compound has arrived in earnest.
The peak is characterized by a warm, enveloping euphoria that strikes a balance between the dreamy abstraction of morphine and the clear-headed comfort of codeine. The body becomes heavy and relaxed, muscles releasing their grip with a sigh of pharmacological relief. There is a distinct physical pleasure to the experience -- not merely the absence of pain but an active sensation of comfort, as though every nerve ending has been individually reassured. The skin feels warm to the touch. An itch may develop on the nose, the scalp, the inner forearms -- the signature histamine release of opioid receptor activation, unpleasant in theory but woven so thoroughly into the warm fabric of the experience that scratching it becomes its own minor pleasure.
Emotionally, hydrocodone produces a buoyant contentment that approaches genuine happiness. Worries do not merely recede; they are gently escorted offstage by a warm usher who promises they can return later. Conversation becomes easier, warmer, more generous. There is a talkativeness that distinguishes hydrocodone from more sedating opioids -- an impulse to connect, to share, to engage with the people around you from a position of unearned but convincing well-being. Music sounds richer. Food tastes better. The world takes on the soft, golden quality of a late afternoon in autumn.
The peak holds for three to four hours, a generous plateau that allows ample time to settle into the warmth and appreciate its contours. Nausea may surface, particularly on an empty stomach, and constipation develops as reliably as the euphoria itself. The drowsiness is present but not overwhelming -- a warmth that invites rest without demanding it, leaving you free to drift between activity and pleasant stillness as the mood carries you.
The comedown is gentle and extended. The warmth fades slowly, like the last light of sunset draining from the sky. There is a brief period of mild melancholy as the euphoria departs, a recognition that something pleasant has ended, but it lacks the harsh, clawing quality of stronger opioids' withdrawal. What remains is a comfortable drowsiness that slides easily into sleep, and mornings after hydrocodone often arrive with a faint, pleasant memory of warmth that has almost but not entirely dissipated.
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(11)
- Constipation— A slowing or cessation of bowel movements resulting in difficulty passing stool, commonly caused by ...
- Diarrhea— Diarrhea is the occurrence of frequent, loose, or watery bowel movements as a side effect of certain...
- Headache— A painful sensation of pressure, throbbing, or aching in the head that can range from a dull backgro...
- Increased heart rate— A noticeable acceleration of heartbeat that can range from a subtle awareness of one's pulse to a fo...
- Motor control loss— A distinct decrease in the ability to control one's physical body with precision, balance, and coord...
- 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...
- Respiratory depression— A dangerous slowing and shallowing of breathing that can progress from barely noticeable reductions ...
- Sedation— A state of deep physical and mental calming that manifests as a progressive desire to remain still, ...
- Seizure— Uncontrolled brain electrical activity causing convulsions and loss of consciousness -- a life-threa...
- Spontaneous physical movements— Spontaneous physical movements are involuntary, seemingly random yet patterned body movements — twit...
Cognitive & Perceptual Effects
Cognitive(5)
- Amnesia— A complete or partial inability to form new memories or recall existing ones during and after substa...
- Anxiety— Intense feelings of apprehension, worry, and dread that can range from a subtle background unease to...
- Anxiety suppression— A partial to complete suppression of anxiety and general unease, producing a calm, relaxed mental st...
- Depression— A persistent state of low mood, emotional numbness, hopelessness, and diminished interest or pleasur...
- Sleepiness— A progressive onset of drowsiness, heaviness, and the desire to sleep that pulls the individual towa...
Pharmacology
The euphoria, anxiety suppression and pain relief effects appear to stem from the way in which opioids mimic endogenous endorphins. Endorphins are responsible for analgesia (reducing pain), causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or excitement. This mimicking of natural endorphins results in the drug's effects. It acts primarily on μ-opioid receptors, with about six times lesser affinity to δ-opioid receptors.
In the liver, hydrocodone is transformed into several metabolites. It has a serum half-life that averages 3.8 hours. The hepatic cytochrome P450 enzyme CYP2D6 converts it into hydromorphone, a more potent opioid.
Taking hydrocodone with grapefruit juice may enhance its psychoactive effects. It is hypothesized that the CYP3A4 inhibitors in grapefruit juice may interfere with the metabolism of hydrocodone, although there has been no research into this issue.
Hydrocodone has not been shown to be toxic and is physically benign at reasonable dosages. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. Some people may also have an allergic reaction to hydrocodone, such as the swelling of skin and rashes.potentially fatal at heavy dosages.
Like most opioids, unadulterated hydrocodone at appropriate dosages does not cause many long-term complications other than dependence and constipation. Outside of the extremely powerful addiction and physical dependence, the harmful or toxic aspects of opioid usage are exclusively associated with not taking the necessary precautions in regards to its administration, overdosing and using impure products. Hydrocodone commonly being mixed with acetaminophen (paracetamol) however can complicate the drug’s safety profile due to acetaminophen’s toxicity on the liver.
Heavy dosages of hydrocodone can result in respiratory depression, leading onto fatal or dangerous levels of anoxia (oxygen deprivation). This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors proportional to the dosage consumed. When hydrocodone is paired with acetaminophen however (as is the case with many pharmaceutical preparations of hydrocodone), liver toxicity or even acute liver failure becomes a significant risk, especially if mixed with alcohol; on top of hydrocodone and alcohol’s already heightened risk for possibly inducing dangerous levels of respiratory depression.
Hydrocodone (on its own) can also cause nausea and vomiting; a significant number of deaths attributed to opioid overdose are caused by aspiration of vomit by an unconscious victim. This is when an unconscious or semi-conscious user who is lying on their back vomits into their mouth and unknowingly suffocates. It can be prevented by ensuring that one is lying on their side with their head tilted downwards so that the airways cannot be blocked in the event of vomiting while unconscious (also known as the recovery position). In case of overdose, it is advised to administer a dose of naloxone intravenously or intramuscularly to reverse the effects of opioid agonism.
It is strongly recommended that one use harm reduction practices when using this drug.
As with other opiate-based painkillers,moderately addictive and is capable of causing both physical and psychological dependence. When physical dependence has developed, withdrawal symptoms may occur if a person suddenly stops their usage. Most of these symptoms (like with other opioids) are somatic in their manifestation.with prolonged use, including therapeutic effects. This results in users having to administer increasingly large doses to achieve the same effects. The rate at which this occurs develops at different rates for different effects with tolerance to the constipation-inducing effects developing particularly slowly. After that,3 - 71 - 2 weeks to be back at baseline (in the absence of further consumption). Hydrocodone presents cross-tolerance with Cross-all opioids, meaning that after the consumption of hydrocodone all opioids will have a reduced effect.
The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance. To account for this lack of tolerance, it is safer to only dose a fraction of one's usual dosage if relapsing. It has also been found that the environment in which one uses the substance can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment.
Australia:** Hydrocodone is a Schedule 8 (S8) or controlled drug.
Austria:** Hydrocodone is regulated in Austria in the same fashion as in Germany (see below) under the Austrian Suchtmittelgesetz (SMG). Since 2002, it has been available in the form of German products and those produced elsewhere in the European Union under Article 76 of the Schengen Treaty.
Belgium:** Hydrocodone is no longer available for medical use.
Canada:** Hydrocodone is a Schedule I controlled substance and is available by prescription only. Hydrocodone is prescribed alone as well as in proprietary combinations, typically with an NSAID or paracetamol.
France:** Hydrocodone is no longer available for medical use. Hydrocodone is a prohibited narcotic.
Germany:** Hydrocodone is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.
Luxembourg:** - Hydrocodone is available by prescription under the name Biocodone. Prescriptions are more commonly given for use as a cough suppressant (antitussive) rather than for pain relief (analgesic).
The Netherlands:** Hydrocodone is not available for medical use and is classified as a List 1 drug under the Opium Law.
Russia:** Hydrocodone is a Schedule I controlled substance.
Sweden:** Hydrocodone is no longer available for medical use in Sweden. The last remaining formula was deregistered in 1967.
Switzerland: Hydrocodone is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.
United Kingdom:** Hydrocodone is not available for medical use and is listed as a Class A drug under the Misuse of Drugs Act 1971. Various formulations of dihydrocodeine, a weaker opioid, are frequently used as an alternative.
United States:** As of October 6, 2014, all hydrocodone products are now designated as Schedule II controlled substances. They are no longer Schedule III narcotics. Prescriptions can no longer have refills and a handwritten paper script must be obtained for each fill.
Responsible use
Opioid
Dihydrocodeine
Heroin
Hydrocodone (Wikipedia)
Hydrocodone (Erowid Vault)
Hydrocodone (Isomer Design)
Hydrocodone (DrugBank)
Hydrocodone (Drugs.com)
Detection Methods
Standard Drug Panel Inclusion
Hydrocodone is a semi-synthetic opioid that is detected on standard opiate immunoassay panels, though detection is less reliable than for morphine and codeine. Some 5-panel immunoassays at the 2000 ng/mL cutoff may miss hydrocodone because the assay antibodies have lower affinity for hydrocodone compared to morphine. At the lower 300 ng/mL cutoff commonly used in clinical and pain management settings, detection is more reliable. Expanded opioid panels and hydrocodone-specific immunoassays are available and widely used.
Urine Detection
Hydrocodone is detectable in urine for approximately 2 to 4 days. It is metabolized primarily to hydromorphone (via CYP2D6) and norhydrocodone (via CYP3A4). Both the parent drug and these metabolites may be targeted in urine testing. The presence of hydromorphone as a metabolite is expected in hydrocodone users and does not indicate separate hydromorphone use.
Blood and Saliva Detection
Blood concentrations of hydrocodone are detectable for approximately 12 to 24 hours. Oral fluid testing can detect hydrocodone for 24 to 36 hours and is increasingly used in pain management compliance monitoring.
Hair Follicle Detection
Hair follicle testing can detect hydrocodone for up to 90 days. Most expanded hair testing panels include hydrocodone as a specific analyte alongside codeine and morphine.
Confirmatory Testing
GC-MS and LC-MS/MS can distinguish hydrocodone from other opioids and quantify both parent drug and metabolites. The ratio of hydrocodone to hydromorphone in urine is used clinically to assess compliance with prescribed hydrocodone versus diversion of hydromorphone.
Reagent Testing
Marquis reagent produces a purple color with hydrocodone, though the intensity may be less than with morphine. Mecke reagent produces a blue-green color. Mandelin reagent shows a grey-brown reaction. These reactions are consistent with the semi-synthetic opiate class.
Interactions
| Substance | Status | Note |
|---|---|---|
| 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 |
| Alcohol | Dangerous | — |
| Atropa belladonna | Dangerous | Compounding CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure |
| Benzodiazepines | Dangerous | — |
| Cake | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| 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 |
| Diclazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| 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 |
| Etizolam | 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 |
| Gaboxadol | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| GBL | Dangerous | — |
| GHB | Dangerous | — |
| Harmala alkaloid | Dangerous | Risk of serotonin syndrome and severe respiratory depression; potentially fatal |
| HXE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Inhalants | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Ketamine | Dangerous | — |
| Lorazepam | Dangerous | Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths |
| Memantine | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Mephenaqualone | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| 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 |
| MXiPr | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| Naloxone | Dangerous | Compounding respiratory depression and overdose risk |
| Nicotine | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| Nifoxipam | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| O-PCE | Dangerous | Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration |
| PCE | 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 |
| Phenobarbital | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| SAMe | Dangerous | Severe respiratory depression risk; leading cause of polydrug overdose |
| 3-FMA | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 4-MMC | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| 8-Chlorotheophylline | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| Adrafinil | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| Benzydamine | Caution | Stimulants mask opioid sedation, increasing overdose risk when the stimulant wears off |
| Nitrous | Uncertain | — |
| PCP | Uncertain | — |
| 1,3-Butanediol | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
| 25E-NBOH | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
| 2C-T | Low Risk & No Synergy | No significant pharmacological interaction; opioids may slightly dull the psychedelic experience |
History
Hydrocodone belongs to the opioid class of substances, which has a history spanning thousands of years from the ancient use of opium poppy to modern synthetic and semi-synthetic analogues.
The isolation of morphine from opium in 1804 by Friedrich Sertürner marked the beginning of modern opioid pharmacology. Subsequent developments included the synthesis of heroin (diacetylmorphine) in 1874, the development of numerous semi-synthetic and fully synthetic opioids throughout the 20th century, and the identification of endogenous opioid receptors and peptides in the 1970s.
The opioid crisis of the early 21st century, driven largely by overprescription of pharmaceutical opioids and the subsequent emergence of illicit fentanyl and its analogues, represents one of the most significant public health challenges in modern history. This crisis has fundamentally reshaped discussions around opioid prescribing, addiction treatment, and harm reduction policy.
Hydrocodone exists within this complex pharmacological and social context, with its history shaped by its development, clinical utility, and the broader dynamics of opioid use and regulation.
Harm Reduction
It is strongly recommended that one use harm reduction practices when using this drug.
As with other opiate-based painkillers,moderately addictive and is capable of causing both physical and psychological dependence. When physical dependence has developed, withdrawal symptoms may occur if a person suddenly stops their usage. Most of these symptoms (like with other opioids) are somatic in their manifestation.with prolonged use, including therapeutic effects. This results in users having to administer increasingly large doses to achieve the same effects. The rate at which this occurs develops at different rates for different effects with tolerance to the constipation-inducing effects developing particularly slowly. After that,3 - 71 - 2 weeks to be back at baseline (in the absence of further consumption). Hydrocodone presents cross-tolerance with Cross-all opioids, meaning that after the consumption of hydrocodone all opioids will have a reduced effect.
The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance. To account for this lack of tolerance, it is safer to only dose a fraction of one's usual dosage if relapsing. It has also been found that the environment in which one uses the substance can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment.
- Australia:** Hydrocodone is a Schedule 8 (S8) or controlled drug.
- Austria:** Hydrocodone is regulated in Austria in
Toxicity & Safety
Hydrocodone has not been shown to be toxic and is physically benign at reasonable dosages. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. Some people may also have an allergic reaction to hydrocodone, such as the swelling of skin and rashes. It is potentially fatal at heavy dosages.
Like most opioids, unadulterated hydrocodone at appropriate dosages does not cause many long-term complications other than dependence and constipation. Outside of the extremely powerful addiction and physical dependence, the harmful or toxic aspects of opioid usage are exclusively associated with not taking the necessary precautions in regards to its administration, overdosing and using impure products. Hydrocodone commonly being mixed with acetaminophen (paracetamol) however can complicate the drug’s safety profile due to acetaminophen’s toxicity on the liver.
Heavy dosages of hydrocodone can result in respiratory depression, leading onto fatal or dangerous levels of anoxia (oxygen deprivation). This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors proportional to the dosage consumed. When hydrocodone is paired with acetaminophen however (as is the case with many pharmaceutical preparations of hydrocodone), liver toxicity or even acute liver failure becomes a significant risk, especially if mixed with alcohol; on top of hydrocodone and alcohol’s already heightened risk for possibly inducing dangerous levels of respiratory depression.
Hydrocodone (on its own) can also cause nausea and vomiting; a significant number of deaths attributed to opioid overdose are caused by aspiration of vomit by an unconscious victim. This is when an unconscious or semi-conscious user who is lying on their back vomits into their mouth and unknowingly suffocates. It can be prevented by ensuring that one is lying on their side with their head tilted downwards so that the airways cannot be blocked in the event of vomiting while unconscious (also known as the recovery position). In case of overdose, it is advised to administer a dose of naloxone intravenously or intramuscularly to reverse the effects of opioid agonism.
It is strongly recommended that one use harm reduction practices when using this drug.
Dependence and abuse potential
As with other opiate-based painkillers, the chronic use of hydrocodone can be considered moderately addictive and is capable of causing both physical and psychological dependence. When physical dependence has developed, withdrawal symptoms may occur if a person suddenly stops their usage. Most of these symptoms (like with other opioids) are somatic in their manifestation.
Tolerance to many of the effects of hydrocodone develops with prolonged use, including therapeutic effects. This results in users having to administer increasingly large doses to achieve the same effects. The rate at which this occurs develops at different rates for different effects with tolerance to the constipation-inducing effects developing particularly slowly. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Hydrocodone presents cross-tolerance with all opioids, meaning that after the consumption of hydrocodone all opioids will have a reduced effect.
The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance. To account for this lack of tolerance, it is safer to only dose a fraction of one's usual dosage if relapsing. It has also been found that the environment in which one uses the substance can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment.
Dangerous interactions
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
Stimulants - Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest.
Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.
DXM - Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.
PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.
Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present.
Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.
Addiction Potential
moderately addictive
Overdose Information
fatal at heavy dosages.
Like most opioids, unadulterated hydrocodone at appropriate dosages does not cause many long-term complications other than dependence and constipation. Outside of the extremely powerful addiction and physical dependence, the harmful or toxic aspects of opioid usage are exclusively associated with not taking the necessary precautions in regards to its administration, overdosing and using impure products. Hydrocodone commonly being mixed with acetaminophen (paracetamol) however can complicate the drug’s safety profile due to acetaminophen’s toxicity on the liver.
Heavy dosages of hydrocodone can result in respiratory depression, leading onto fatal or dangerous levels of anoxia (oxygen deprivation). This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors proportional to the dosage consumed. When hydrocodone is paired with acetaminophen however (as is the case with many pharmaceutical preparations of hydrocodone), liver toxicity or even acute liver failure becomes a significant risk, especially if mixed with alcohol; on top of hydrocodone and alcohol’s already heightened risk for possibly inducing dangerous levels of respiratory depression.
Hydrocodone (on its own) can also cause nausea and vomiting; a significant number of deaths attributed to opioid overdose are caused by aspiration of vomit by an unconscious victim. This is when an unconscious or semi-conscious user who is lying on their back vomits into their mouth and unknowingly suffocates. It can be prevented by ensuring that one is lying on their side with their head tilted downwards so that the airways cannot be blocked in the event of vomiting while unconscious (also known as the recovery position). In case of overdose, it is advised to administer a dose of naloxone intravenously or intramuscularly to reverse the effects of opioid agonism.
It is strongly recommended that one use harm reduction practices when using this drug.
- Dependence and abuse potentia
Dangerous Interactions
The combinations listed below may be life-threatening. Independent research should always be conducted to ensure safety when combining substances.
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 CNS depression with anticholinergic effects; risk of cardiac events and respiratory failure
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; 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
Severe respiratory depression; this combination is the leading cause of prescription drug overdose deaths
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
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
Risk of serotonin syndrome and severe respiratory depression; potentially fatal
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
Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
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
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
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
Risk of serotonin syndrome and severe respiratory depression; potentially fatal
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
Tolerance
| Full | with prolonged use |
| Half | 3 - 7 days |
| Zero | 1 - 2 weeks |
Cross-tolerances
Legal Status
Australia:** Hydrocodone is a Schedule 8 (S8) or controlled drug.
Austria:** Hydrocodone is regulated in Austria in the same fashion as in Germany (see below) under the Austrian Suchtmittelgesetz (SMG). Since 2002, it has been available in the form of German products and those produced elsewhere in the European Union under Article 76 of the Schengen Treaty.
Belgium:** Hydrocodone is no longer available for medical use.
Canada:** Hydrocodone is a Schedule I controlled substance and is available by prescription only. Hydrocodone is prescribed alone as well as in proprietary combinations, typically with an NSAID or paracetamol.
France:** Hydrocodone is no longer available for medical use. Hydrocodone is a prohibited narcotic.
Germany:** Hydrocodone is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.
Luxembourg:** - Hydrocodone is available by prescription under the name Biocodone. Prescriptions are more commonly given for use as a cough suppressant (antitussive) rather than for pain relief (analgesic).
The Netherlands:** Hydrocodone is not available for medical use and is classified as a List 1 drug under the Opium Law.
Russia:** Hydrocodone is a Schedule I controlled substance.
Sweden:** Hydrocodone is no longer available for medical use in Sweden. The last remaining formula was deregistered in 1967.
Switzerland: Hydrocodone is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.
United Kingdom:** Hydrocodone is not available for medical use and is listed as a Class A drug under the Misuse of Drugs Act 1971. Various formulations of dihydrocodeine, a weaker opioid, are frequently used as an alternative.
United States:** As of October 6, 2014, all hydrocodone products are now designated as Schedule II controlled substances. They are no longer Schedule III narcotics. Prescriptions can no longer have refills and a handwritten paper script must be obtained for each fill.
Responsible use
Opioid
Dihydrocodeine
Hydrocodone (Wikipedia)
Hydrocodone (Erowid Vault)
Hydrocodone (Isomer Design)
Hydrocodone (DrugBank)
Hydrocodone (Drugs.com)
Experience Reports (2)
Tips (10)
Constipation from Hydrocodone is universal with regular opioid use. Start a fiber supplement and stool softener proactively. Severe opioid-induced constipation can cause bowel obstruction which is a surgical emergency.
The most dangerous time in opioid use is after a period of abstinence. If you have been clean for days or weeks, your tolerance has dropped significantly. Taking your previous dose after a break is how most relapse-related overdoses occur. Always restart at a fraction of your previous dose.
Most hydrocodone comes combined with acetaminophen (Vicodin, Norco). Acetaminophen is severely hepatotoxic above 4000mg per day, and the threshold is lower if you drink alcohol. If you are taking multiple hydrocodone pills recreationally, calculate your total acetaminophen dose. Liver failure from APAP is agonizing and often fatal without a transplant.
The brain changes from chronic opioid use are not necessarily permanent. Neuroplasticity allows for significant recovery, especially in younger users. Research shows measurable improvement in reward circuitry and emotional regulation after 12-18 months of sustained abstinence. It gets better.
Opioid tolerance and cross-tolerance are complex with Hydrocodone. Switching between different opioids requires careful dose conversion. Do not assume equivalent effects at standard conversion ratios; start lower than calculated.
For someone with no opioid tolerance, 5-10mg hydrocodone produces noticeable effects. Starting with 5mg and waiting at least 90 minutes before considering more is the safer approach. Do NOT take 30-40mg as a starting dose — this level of recklessness with opioids is how people end up in the emergency room or worse.
Community Discussions (12)
See Also
References (4)
- Opioid receptors — Pasternak & Pan Annual Review of Pharmacology (2013)paper
- PubChem: Hydrocodone
PubChem compound page for Hydrocodone (CID: 5284569)
pubchem - Hydrocodone - TripSit Factsheet
TripSit factsheet for Hydrocodone
tripsit - Hydrocodone - Wikipedia
Wikipedia article on Hydrocodone
wikipedia