Oxycodone

Oxycodone, or dihydro hydroxy codeinone, is an opioid of the morphinan class. Oxycodone 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.

Oxycodone, 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 oxycodone lacks the double bond on that ring found in codeine. Oxycodone also shares the 3-methoxy substitution found in codeine; however, it contains an additional hydroxy group at R₁₄. Oxycodone is analogous to the other morphinans including dihydrocodeine, heroin, ethylmorphine, and codeine.

Oxycodone produces effects that are typical of μ-opioid agonists, suggesting a pharmacological similarity to more traditional opioids, such as codeine and morphine. These compounds exert their effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement.

In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations. Specifically in diabetic mice, the κ-opioid receptor appears to be involved in the direct pain relief caused by oxycodone,^[5] while in nondiabetic mice, the μ1-opioid receptor seems to be primarily responsible for these effects.^[6]

Metabolism

Oxycodone has 3 metabolites: noroxycodone (CYP3A4/5), oxymorphone (CYP2D6), and 6α-/6β-oxycodol (6-Ketoreduction). Of these, oxymorphone is the active one. Anywhere from 5-19% of oxycodone is metabolized to oxymorphone, the rest being mostly noroxycodone (45-70%) and 6-oxycodols (~2-14%). Grapefruit juice inhibits CYP3A4 activity, allowing more oxycodone to be metabolized into oxymorphone which potentiates oxycodone.^[7]

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

Anecdotal reports which describe the effects of this compound within our experience index include:

• Experience: 80 mg Oxycodone (Oral/Insufflated) - My Highest Dose

Additional experience reports can be found here:

• Erowid Experience Vaults: Oxycodone

Oxycodone has a low toxicity relative to dose. As with all opioids, long-term effects can vary but can include diminished libido, apathy, and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

As with other opioids, the chronic use of oxycodone can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of oxycodone develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. 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). Oxycodone presents cross-tolerance with all other opioids, meaning that after the consumption of oxycodone 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.^[8] 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.^[9]

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^[10]. 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^[10]. 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.

Oxycodone is subject to international conventions on narcotic drugs. In addition, oxycodone is subject to national laws that differ by country. The 1931 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs of the League of Nations included oxycodone.^[11] The 1961 Single Convention on Narcotic Drugs of the United Nations, which replaced the 1931 convention, categorized oxycodone in Schedule I.^[12]

• Australia: Oxycodone is in Schedule I (derived from the Single Convention on Narcotic Drugs) of the Commonwealth's Narcotic Drugs Act 1967.^[13] In addition, it is in Schedule 8 of the Australian Standard for the Uniform Scheduling of Drugs and Poisons ("Poisons Standard"), meaning it is a "controlled drug... which should be available for use but require[s] restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence".^[14]
• Austria: Oxycodone is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).^{[citation needed]}
• Canada: Oxycodone is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA).^[15]
• Germany: The drug is in Appendix III of the Narcotics Act (Betäubungsmittelgesetz or BtMG).^[16] The law allows only physicians, dentists, and veterinarians (Ärzte, Zahnärzte und Tierärzte) to prescribe oxycodone and the federal government to regulate the prescriptions (e.g., by requiring reporting).^[16]
• Hong Kong: Oxycodone is regulated under Part I of Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.^[17]
• Russia: Oxycodone is a Schedule II controlled substance.^[18]
• Singapore: Oxycodone is listed as a Class A drug in the Misuse of Drugs Act of Singapore, which means offences in relation to the drug attract the most severe level of punishment. A conviction for unauthorized manufacture of the drug attracts a minimum sentence of 10 years of imprisonment and corporal punishment of five strokes of the cane, and a maximum sentence of life imprisonment or 30 years of imprisonment and 15 strokes of the cane.^[19] The minimum and maximum penalties for unauthorized trafficking in the drug are respectively five years of imprisonment and five strokes of the cane, and 20 years of imprisonment and 15 strokes of the cane.^[20]
• Switzerland: Oxycodone is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.^[21]
• Turkey: Oxycodone is a 'red prescription' only substance^[22] and illegal when sold or possessed without a prescription.^{[citation needed]}
• UK: Oxycodone is a Class A drug under the Misuse of Drugs Act.^[23]
• USA: Oxycodone is a Schedule II controlled substance.^[24]

• Responsible use
• Extraction of opioids from painkiller products
• Depressants
• Codeine
• Naloxone

• Oxycodone (Wikipedia)
• Oxycodone (Erowid Vault)
• Oxycodone (TiHKAL / Isomer Design)
• Oxycodone (DrugBank)
• Oxycodone (Drugs-Forum)