|Summary sheet: Hydrocodone|
|Common names||Vicodin (with paracetamol), Zohydro ER (extended-release)|
|Routes of Administration|
Hydrocodone (commonly sold as Vicodin when combined with paracetamol) is a semi-synthetic opioid morphinan synthesized from codeine, one of the opioid alkaloids found in the opium poppy. It is a narcotic analgesic used orally as a cough suppressant, but also commonly taken orally for relief of moderate to severe pain. Those who take hydrocodone for recreational purposes report a sense of relaxation and euphoria, especially at higher doses.
Hydrocodone is prescribed predominantly within the United States, with the International Narcotics Control Board reporting that 99% of the worldwide supply in 2007 was consumed in the United States.
Like many opioids, such as dextropropoxyphene, hydrocodone is often combined with acetaminophen (paracetamol) to enhance analgesia and deter abuse. Acetaminophen overdoses and long-term use, often due to recreational use, can cause serious or fatal liver damage. Currently, the only brand of hydrocodone in the United States that does not have acetaminophen is Zohydro ER which comes in doses of up to 50mg.
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. The hepatic cytochrome P450 enzyme CYP2D6 converts it into hydromorphone, a more potent opioid.
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.
- Pain relief
- Physical euphoria - This particular substance can be considered as less intense in its physical euphoria when compared with that of morphine or heroin. The sensation itself can be described as extreme feelings of intense physical comfort, warmth and bliss which spreads throughout the body.
- Itchiness - This compound presents greater amounts of itchiness due to higher amounts of histamine release in comparison to other opioids.
- Respiratory depression - At low to moderate doses, this effect results in the sensation that breaths are slowed down mildly to moderately, but does not cause noticeable impairment. At high doses and overdoses, opioid-induced respiratory depression can result in a shortness of breath, abnormal breathing patterns, semi-consciousness, or unconsciousness. Severe overdoses can result in a coma or death without immediate medical attention.
- Sedation - At higher dosages, this compound can result in feelings of sedation but is considerably less sedating than that of oxycodone or heroin.
- Appetite suppression
- Cough suppression
- Decreased libido
- Decreased heart rate
- Difficulty urinating
- Stomach cramps
- Pupil constriction
- Orgasm suppression
- Cognitive euphoria - This particular substance can be considered as less intense in its cognitive euphoria when compared with that of morphine or diacetylmorphine (heroin) due to the upper limit of how much can be converted into its active form through metabolism. It is still, however, capable of extreme intensity and overwhelming bliss at heavier dosages with a low tolerance. The sensation itself can be described as powerful and overwhelming feeling of emotional bliss, contentment, and happiness.
- Anxiety suppression
- Compulsive redosing
- Dream potentiation
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Taking hydrocodone with grapefruit juice is believed to 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.
Toxicity and harm potential
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.
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.
Hydrocodone 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.
Tolerance and addiction 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.
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 one is in 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.
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
- Depressants (1,4-Butanediol, 2m2b, alcohol, barbiturates, benzodiazepines, GHB/GBL, methaqualone) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Stimulants - It is dangerous to combine hydrocodone, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of hydrocodone, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of hydrocodone will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only taking a certain amount of hydrocodone.
- Australia - In 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. Prior to this, no Austrian companies produced hydrocodone products, with dihydrocodeine, nicomorphine, and nicocodeine being more commonly used instead.
- Belgium - In Belgium, hydrocodone is no longer available for medical use.
- Canada - In 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 - In France, hydrocodone is no longer available for medical use. Hydrocodone is a prohibited narcotic.
- Germany - In Germany, hydrocodone is no longer available for medical use. Hydrocodone is listed under the Betäubungsmittelgesetz as a Suchtgift in the same category as morphine.
- Luxembourg - In 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 - In the Netherlands, hydrocodone is not available for medical use and is classified as a List 1 drug under the Opium Law.
- Sweden - Hydrocodone is no longer available for medical use in Sweden. The last remaining formula was deregistered in 1967.
- United Kingdom - In the 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. In some states, a Schedule II substance can be electronically prescribed if the doctor has the proper technology and an electronic signature license.
- Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- Karch, Steven B. (2008). Pharmacokinetics and pharmacodynamics of abused drugs. Boca Raton: CRC Press. pp. 55–56. ISBN 1-4200-5458-9.
- International Narcotics Control Board Report 2008. United Nations Pubns. 2009. p. 20. ISBN 9211482321. | https://books.google.co.uk/books?id=7iDhYnsYaocC&pg=PA20&hl=en#v=onepage&q&f=false
- Davis, Mellar P. (2005). "Hydrocodone". Opioids for cancer pain. Oxford UK: Oxford University Press. pp. 59–68. ISBN 0-19-852943-0. | https://books.google.co.uk/books?id=BK0WduGnx2kC&pg=PA59&lpg=PA59&dq=potency+of+hydrocodone&hl=en
- Prescription drug abuse: insight into the epidemic (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20686478
- Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
- Siegel, S., Hinson, R., Krank, M., & McCully, J. (1982). Heroin “overdose” death: contribution of drug-associated environmental cues. Science, 216(4544), 436–437. https://doi.org/10.1126/science.7200260