Hydrocodone

Hydrocodone, or 3-methyl-dihydromorphinone, is an opioid of the morphinan class. Hydrocodone and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called a phenanthrene. A fourth nitrogen-containing ring is fused to the phenanthrene at R₉ and R₁₃, with the nitrogen member looking at R₁₇ of the combined structure. This structure is called morphinan.

Hydrocodone, along with other morphinans, contains an ether bridge between two of its rings, connecting R₄ and R₅ through an oxygen group. It contains a carbonyl group bound at R₆ and a methyl group located on the nitrogen atom at R₁₇. The carbon-oxygen double bond of the carbonyl saturates the benzene ring it is bonded with, thus hydrocodone lacks the double bond on that ring found in codeine.

Hydrocodone also shares the 3-methoxy substitution found in codeine; the two differ only from their R₆ substituents. Hydrocodone is analogous to the other morphinans including dihydrocodeine, heroin, ethylmorphine, codeine, and oxycodone.

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.^[4] 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,^[5] although there has been no research into this issue.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that 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. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

• Erowid Experience Vaults: Hydrocodone

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.^[6] 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.^[7]

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^[8]. 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^[8]. 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.

• Australia: Hydrocodone is a Schedule 8 (S8) or controlled drug.^{[citation needed]}
• 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.^{[citation needed]}
• Belgium: Hydrocodone is no longer available for medical use.^{[citation needed]}
• 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.^{[citation needed]}
• France: Hydrocodone is no longer available for medical use. Hydrocodone is a prohibited narcotic.^{[citation needed]}
• Germany: Hydrocodone is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.^[9]
• 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).^{[citation needed]}
• The Netherlands: Hydrocodone is not available for medical use and is classified as a List 1 drug under the Opium Law.^{[citation needed]}
• Russia: Hydrocodone is a Schedule I controlled substance.^[10]
• Sweden: Hydrocodone is no longer available for medical use in Sweden. The last remaining formula was deregistered in 1967.^{[citation needed]}
• Switzerland: Hydrocodone is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.^[11]
• 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.^{[citation needed]}
• United States: As of October 6, 2014, all hydrocodone products are now designated as Schedule II controlled substances.^[12] They are no longer Schedule III narcotics. Prescriptions can no longer have refills and a handwritten paper script must be obtained for each fill.^{[citation needed]}

• Responsible use
• Opioid
• Codeine
• Dihydrocodeine
• Oxycodone
• Heroin

• Hydrocodone (Wikipedia)
• Hydrocodone (Erowid Vault)
• Hydrocodone (Isomer Design)
• Hydrocodone (DrugBank)
• Hydrocodone (Drugs.com)