Fatal overdose may occur when opiates are combined with other depressants such as benzodiazepines, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1] It is strongly discouraged to combine these substances, particularly in common to heavy doses.



U-47700[2] is a synthetic opioid substance of the benzamide chemical class that produces analgesic, relaxing, sedating and euphoric effects when administered.

This compound was initially developed by a team at Upjohn in the 1970s.[3] Upjohn created over a dozen patents on related compounds[4][5][6][7][8][9][10][11] until they discovered that U-47700 was the most active.[12] This was done by looking for the key functional groups which gave the greatest activity.[13]

Very little is known about the toxicity of U-47700 and it has very little history of human usage. It is currently available as a gray-area research chemical distributed by online vendors. Many reports suggest that it possesses unique physical properties relative to most opioids such as an unusual amount of causticity (ability to destroy living tissue) that may make it significantly more harmful to expose to the body, particularly when it is injected. It is strongly advised to use harm reduction practices if choosing to use this substance.

Chemistry

U-47700 is an atypical opioid of the benzamide class. It features core phenyl ring with two chlorine atoms at carbons R 3 and R 4 . This ring is connected to an amine group through a carboxyl group (C=O). The terminal nitrogen atom of the amide group is bonded to a methyl carbon and substituted cyclohexane ring. The cyclohexane ring is further substituted at R 2 with a dimethylamino group, thus forming the structure of U-47700.

Pharmacology

U-47700 is selective for the µ-opioid receptor, with various sources claiming 7.5x the potency of morphine.[14][15]

Opioids exert their effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found in the body and also work with 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.

U-47700 may also be an agonist for the kappa-opioid receptor system. As a result of this, it has become the lead compound of selective kappa-opioid receptor ligands such as U-50488 and U-69,593, which share very similar structures.[16] Its structure led to other chemists experimenting with it to see if rigid analogs would retain activity.[17] Although not used medically, the selective kappa ligands are used in research.[18]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature which relies on collected anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.

Experience reports

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

Additional experience reports can be found here:

Toxicity and harm potential

U-47700 has a high toxicity relative to its dose due to its extreme potency. 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 worth noting that U-47700 crystals are particularly corrosive and somewhat caustic to mucous membranes. Careless use may deteriorate the chosen routes of administration so it is important to practice routine maintenance such as soaking the sinus cavity with water prior to and following insufflation. Even if following a regular saline wash of the nasal cavity, multiday use of this substance can create bleeding sores and scabs in the septum and nasal lining. These scabs may persist for days even after all use is ceased. It is unwise to vaporize the substance as it can damage the lungs. Sublingual administration is likely to damage the skin in the mouth.

Combined consumption of U-47700 and fentanyl caused one fatality in Belgium.[20] At least 17 opioid overdoses and several deaths in the USA have also been connected with the use of U-47700.[21]

It is strongly recommended that one use harm reduction practices, and take extreme caution when using this substance.

Tolerance and addiction potential

As with other opioids, the chronic use of U-47700 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 U-47700 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). U-47700 presents cross-tolerance with all other opioids, meaning that after the consumption of U-47700 all opioids will have a reduced effect.

U-47700 withdrawal symptoms can be especially painful and emerge after 2-4 hours after the last dose administration. It is highly advisable not to become physically dependent on this substance, as physical dependence can develop in a short period.

The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance.[22] 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.[23]

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed 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

- 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 Amphetamines - 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.

- 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.

- 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. Cocaine - 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 patient and cause respiratory arrest.

- 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 patient and cause respiratory arrest. 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.

- 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

- 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.

- 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.

- 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.

- 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.

- 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.

- 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

- 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[24]. 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[24]. 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.

Legal status

Austria : U-47700 is illegal to possess, produce and sell under the SMG (Suchtmittelgesetz Österreich) as of June 26, 2019. [25]

: U-47700 is illegal to possess, produce and sell under the SMG (Suchtmittelgesetz Österreich) as of June 26, 2019. Brazil: Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344. [26]

Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344. Finland: U-47700 is an Annex 1 drug in Finland, making its sale, production, and importation illegal. [27]

U-47700 is an Annex 1 drug in Finland, making its sale, production, and importation illegal. Germany: U-47700 is controlled under BtMG Anlage II, making it illegal to manufacture, import, possess, sell, or transfer it without a license. [28]

U-47700 is controlled under BtMG Anlage II, making it illegal to manufacture, import, possess, sell, or transfer it without a license. Russia: U-47700 is a Schedule I controlled substance. [29]

U-47700 is a Schedule I controlled substance. Sweden: Following its sale as a designer drug, U-47700 was made illegal in Sweden on 26 January 2016. [30]

Following its sale as a designer drug, U-47700 was made illegal in Sweden on 26 January 2016. Switzerland: U-47700 is a controlled substance specifically named under Verzeichnis D. [31]

U-47700 is a controlled substance specifically named under Verzeichnis D. United Kingdom: U-47700 is a class A drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. [32]

U-47700 is a class A drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. United States: While U-47700 is not scheduled on a federal level, the State of Ohio recently made U-47700 a Schedule I drug. This is not a federal or nationwide action and can only be enforced in the state of Ohio.[33] On September 7th, 2016, the DEA Office of Diversion Control announced that they intend to schedule U-47700 as a Schedule temporarily I drug.[34]

See also

References



