Hydromorphone

Hydromorphone is an opioid of the morphinan class. Hydromorphone and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called 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. Hydromorphone is a hydrogenated ketone of morphine and thus is extremely similar in structure.

It is a derivative of morphine; to be specific, it is a hydrogenated ketone thereof. Comparatively, hydromorphone is to morphine as hydrocodone is to codeine—that is, also a semi-synthetic drug. Hydromorphone is made from morphine either by direct re-arrangement (made by reflux heating of alcoholic or acidic aqueous solution of morphine in the presence of platinum or palladium catalyst) or reduction to dihydromorphine (usually via catalytic hydrogenation), followed by oxidation with benzophenone in presence of potassium tert butoxide or aluminium tert butoxide (Oppenauer oxidation). The 6 ketone group may be replaced with a methylene group via the Wittig reaction to produce 6-Methylenedihydrodesoxymorphine, which is 80× stronger than morphine.^[3]

Hydromorphone is more soluble in water than morphine; therefore, hydromorphone solutions may be produced to deliver the drug in a smaller volume of water. The hydrochloride salt is soluble in three parts of water, whereas a gram of morphine hydrochloride dissolves in 16 ml of water; for all common purposes, the pure powder for hospital use can be used to produce solutions of virtually arbitrary concentration. When the powder appeared on the street, this very small volume of powder needed for a dose means that overdoses are likely for those who mistake it for heroin or other powdered narcotics, especially those that have been diluted prior to consumption.^[4]

Hydromorphone molecules exert their effects by binding to and activating the μ-opioid receptor as an agonist. This occurs due to the way in which opioids structurally mimic endogenous endorphins. Endorphins are responsible for analgesia, sedation, and cognitive euphoria along with physical euphoria. They can be released in response to pain, strenuous exercise, orgasm, or excitement. This mimicking of natural endorphins results in the drug's euphoric, analgesic (pain relief), and anxiolytic (anti-anxiety) effects.

The recreational effects of this compound, including cognitive euphoria and physical euphoria, occur because opioids structurally mimic endogenous endorphins which are naturally produced within the body and are also active on the μ-opioid receptor set in the brain. The way in which synthetic opioids such as heroin structurally mimic these natural endorphins results in their euphoric, pain relief and anxiolytic effects. This is because natural endorphins are responsible for reducing pain, causing sedation, and feelings of pleasure. The natural endorphins can be released in response to pain, strenuous exercise, orgasm, or general excitement.

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: Hydromorphone

Like most opioids, unadulterated hydromorphone does not cause many long-term complications other than psychological and physical dependence and constipation.^[5] The harmful or toxic aspects of hydromorphone's usage as a recreational substance are exclusively associated with not taking appropriate precautions in regards to its administration, overdosing, and using impure or adulterated batches of the substance.

Heavy dosages of hydromorphone can result in respiratory depression, leading onto fatal or dangerous levels of oxygen deprivation. This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors - this effect is proportional to the dosage of opiates consumed.

Hydromorphone 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 on their own vomit. 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).

Opioid overdoses can be fatal if not treated immediately by calling the local emergency medical services and administering an opioid antagonist such as naloxone to the overdosed user.

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 hydromorphone can be considered extremely 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 hydromorphone 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. Hydromorphone presents cross-tolerance with all other opioids, meaning that after the consumption of hydromorphone 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 physical tolerance to the depressant effects of the opioid.^[6] To account for this lack of tolerance, it is safer for a user that has been sober for an extended period of time to only dose a fraction of one's usual dosage when using again. It has also been found that the environment one is in can play a role in opioid tolerance.

In one 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] Because of the structral and chemical similarity of hydromorphone and heroin, it can be assumed that the same interaction between physical tolerance and the environment occurs in hydromorphone use.

Dangerous interactions

Hydromorphone is dangerous to use in combination with other depressants as many fatalities reported as overdoses are caused by interactions with other depressant drugs like alcohol or benzodiazepines, resulting in dangerously high levels of respiratory depression.^[8]

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^[9]. 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^[9]. 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.

• Austria: Hydromorphone 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]}
• Germany: Hydromorphone is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.^[10]
• Russia: Hydromorphone is a Schedule II controlled substance.^[11]
• Sweden: Hydromorphone is a prescription only medication.^[12]
• Switzerland: Hydromorphone is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.^[13]
• Turkey: Hydromorphone is a 'red prescription' only substance^[14] and illegal when sold or possessed without a prescription.^{[citation needed]}
• United Kingdom: Hydromorphone is a Class A, Schedule 2 drug in the United Kingdom.^[15]
• United States: Hydromorphone is a Schedule II Controlled Substance in the United States.^[16]

• Responsible use
• Safer injection guide
• Opioids
• Morphine
• Oxymorphone
• Naloxone

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