This is an unofficial archive of PsychonautWiki as of 2025-08-11T15:14:44Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
'''Pethidine''', known as '''meperidine''' in the United States (sold under the brand name '''Demerol'''), is a synthetic [[opioid]] [[pain relief |analgesic]] used for the treatment of moderate to severe pain. Compared to traditional opioids such as [[morphine]], pethidine was originially thought to be much safer and have less potential for abuse. It was later discovered that pethidine is significantly less safe than morphine and its metabolite norpethidine can be extremely toxic.
'''Pethidine''', known as '''meperidine''' in the United States (sold under the brand name '''Demerol'''), is a synthetic [[opioid]] [[pain relief |analgesic]] used for the treatment of moderate to severe pain. Compared to traditional opioids such as [[morphine]], pethidine was originially thought to be much safer and have less potential for abuse. It was later discovered that pethidine is significantly less safe than morphine and its metabolite norpthidine can be extremely toxic.
==Chemistry==
==Chemistry==
{{chemistry}}
{{chemistry}}
Pethidine is an opioid in the phenylpiperidine class.
Pethidine is a synthetic opioid of the phenylpiperidine class. Pethidine is the prototype of a large family of analgesics including the pethidine 4-phenylpiperidines (piminodine, anileridine and others), the prodines (alphaprodine, MPPP, ''etc.''), bemidones (ketobemidone, etc.) and others more distant, including diphenoxylate and analogues.<ref>{{cite journal | journal=Journal of the American Pharmaceutical Association (Scientific ed.) | title=Morphine & Allied Drugs | volume=46 | issue=11 | pages=704 | date= November 1957 | url=https://linkinghub.elsevier.com/retrieve/pii/S0095955315343857 | issn=00959553 | doi=10.1002/jps.3030461119}}</ref> The most coomon hydrochloride form is a white crystalline substance with a melting point of 186 C to 189 C. It is readily soluble in water and has a neutral reaction and a slightly bitter taste.<ref name=":0">{{Citation | title=(+-)-Pethidine hydrochloride, Drug Information, Uses, Side Effects, Chemistry | url=https://www.pharmacompass.com/chemistry-chemical-name/pethidine-hydrochloride}}</ref>
Pethidine can be produced in a two-step synthesis. The first step is reaction of benzyl cyanide and chlormethine in the presence of sodium amide to form a piperidine ring. The nitrile is then converted to an ester.<ref>Patent Appl. DE 679 281 IG Farben 1937.</ref>
==Pharmacology==
==Pharmacology==
[[Opioid]]s exert their effects by binding to and activating the [[Opioid#Mu_.28.CE.BC.29|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 [[physical euphoria|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. The bioavailability of orally administered pethidine can vary from 50% to around 60%.
[[Opioid]]s exert their effects by binding to and activating the [[Opioid#Mu_.28.CE.BC.29|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 [[physical euphoria|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. The bioavailability of orally administered pethidine can vary from 50% to around 60%.
Compared to traditional opioids, pethidine has a very unique pharmacological profile. In addition to being an opioid, pethidine is also a muscarinic [[acetylcholine]] [[receptor]] [[antagonist]]. Pethidine is also a [[dopamine]] [[reuptake inhibitor]] and [[norepinephrine]] reuptake inhibitor. Pethidine is a κ-opioid agonist and its metabolite norpethidine is also an extremely powerful [[serotonin]] reuptake inhibitor.<ref> Meperidine: A Critical Review | https://www.researchgate.net/publication/11575123_Meperidine_A_Critical_Review</ref>
Compared to traditional opioids, pethidine has a very unique pharmacological profile. In addition to being an opioid, pethidine is also a muscarinic [[acetylcholine]] [[receptor]] [[antagonist]]. Pethidine is also a [[dopamine]] [[reuptake inhibitor]] and [[norepinephrine]] reuptake inhibitor. Pethidine is a κ-opioid agonist and its metabolite norpethidine is also an extremely powerful [[serotonin]] reuptake inhibitor.<ref>{{cite journal | vauthors=((Latta, K. S.)), ((Ginsberg, B.)), ((Barkin, R. L.)) | journal=American Journal of Therapeutics | title=Meperidine: A Critical Review: | volume=9 | issue=1 | pages=53–68 | date= January 2002 | url=http://journals.lww.com/00045391-200201000-00010 | issn=1075-2765 | doi=10.1097/00045391-200201000-00010}}</ref>
==Subjective effects==
==Subjective effects==
{{Preamble/SubjectiveEffects}} Many users note that they find pethidine just as, or more euphoric than [[oxycodone]].<ref> Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid μ Agonists in Healthy Volunteers | http://jpet.aspetjournals.org/content/289/3/1454.long </ref>
{{Preamble/SubjectiveEffects}} Many users note that they find pethidine just as, or more euphoric than [[oxycodone]].<ref>{{cite journal | vauthors=((Walker, D. J.)), ((Zacny, J. P.)) | journal=Journal of Pharmacology and Experimental Therapeutics | title=Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid μ Agonists in Healthy Volunteers | volume=289 | issue=3 | pages=1454–1464 | date=1 June 1999 | url=https://jpet.aspetjournals.org/content/289/3/1454 | issn=0022-3565}}</ref>
===Physical effects===
{{effects/base
|{{effects/physical|
The general sensation of pethidine can be described as one of euphoria, relaxation, anxiety suppression and pain relief.
The general sensation of pethidine can be described as one of euphoria, relaxation, anxiety suppression and pain relief.
*'''[[Effect::Pain relief]]'''
*'''[[Effect::Pain relief]]'''
Line 29:
Line 31:
*'''[[Effect::Difficulty urinating]]'''
*'''[[Effect::Difficulty urinating]]'''
*'''[[Effect::Nausea]]'''
*'''[[Effect::Nausea]]'''
*'''[[Effect::Sedation]]''' ''or'' '''[[Effect::Stimulation]]''' - Some users find pethidine sedating, while others find it stimulating.
*'''[[Effect::Sedation]]''' ''or'' '''[[Effect::Stimulation]]''' - While most users report that they find pethidine to be considerably sedating, others report it to be stimulating.
*'''[[Effect::Pupil constriction]]'''
*'''[[Effect::Pupil constriction]]'''
*'''[[Effect::Decreased libido]]'''
*'''[[Effect::Decreased libido]]'''
Line 36:
Line 38:
*'''[[Effect::Seizures]]''' - High doses of pethidine may cause seizures. This is because of its metabolite norpethidine.
*'''[[Effect::Seizures]]''' - High doses of pethidine may cause seizures. This is because of its metabolite norpethidine.
===Cognitive effects===
}}
|{{effects/cognitive|
*'''[[Effect::Cognitive euphoria]]''' - This particular substance can be considered as very intense in its cognitive euphoria. The sensation itself can be described as powerful and overwhelming feeling of emotional bliss, contentment, and happiness.
*'''[[Effect::Cognitive euphoria]]''' - This particular substance can be considered as very intense in its cognitive euphoria. The sensation itself can be described as powerful and overwhelming feeling of emotional bliss, contentment, and happiness.
*'''[[Effect::Anxiety suppression]]'''
*'''[[Effect::Anxiety suppression]]'''
Line 42:
Line 48:
*'''[[Effect::Dream potentiation]]'''
*'''[[Effect::Dream potentiation]]'''
===Visual effects===
}}
{{effects/visual|
*'''[[Effect::Acuity suppression]]''' - Pethidine is a muscarinic acetylcholine receptor antagonist which may cause blurred vision at high doses.
*'''[[Effect::Acuity suppression]]''' - Pethidine is a muscarinic acetylcholine receptor antagonist which may cause blurred vision at high doses.
}}
}}
===Experience reports===
===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:
There are currently no anecdotal reports which describe the effects of this compound within our [[experience index]]. Additional experience reports can be found here:
Pethidine has a [[Toxicity::high 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 [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[benzodiazepines]]]] and generally has a wider range of substances which it is [[pethidine#Dangerous interactions|dangerous to combine with]] in comparison to other opioids.
Pethidine has a [[Toxicity::high 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 [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[benzodiazepines]]]] and generally has a wider range of substances which it is [[pethidine#Dangerous interactions|dangerous to combine with]] in comparison to other opioids.
One of pethdine's metabolites, norpethidine has little to no opioid action, but is known to cause seizures. Pethidine should not be taken during [[Benzodiazepine#Discontinuation|benzodiazepine withdrawals]] as this can potentially cause [[seizure]]s. In 1984, Libby Zion, a teenager was brought to the emergency room due to a "flu-like" ailment. She was previously prescribed and taking phenelzine, a [[MAOI |monoamine oxidase inhibitor]], which in combination caused fatal serotonin syndrome.<ref> Serotonin Syndrome and the Libby Zion Affair | http://epmonthly.com/article/serotonin-syndrome-and-the-libby-zion-affair/ </ref>
One of pethdine's metabolites, norpethidine has little to no opioid action, but is known to cause seizures. Pethidine should not be taken during [[Benzodiazepine#Discontinuation|benzodiazepine withdrawals]] as this can potentially cause [[seizure]]s. In 1984, Libby Zion, a teenager was brought to the emergency room due to a "flu-like" ailment. She was previously prescribed and taking phenelzine, a [[MAOI |monoamine oxidase inhibitor]], which in combination caused fatal serotonin syndrome.<ref>{{Citation | year=2011 | title=Serotonin Syndrome and the Libby Zion Affair |publisher=Emergency Physicians Monthly | url=https://epmonthly.com/article/serotonin-syndrome-and-the-libby-zion-affair/}}</ref>
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
Line 59:
Line 69:
Tolerance to many of the effects of pethidine [[Time to full tolerance::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 [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Pethidine presents cross-tolerance with [[Cross-tolerance::all other [[opioids]]]], meaning that after the consumption of pethidine all [[opioid]]s will have a reduced effect.
Tolerance to many of the effects of pethidine [[Time to full tolerance::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 [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Pethidine presents cross-tolerance with [[Cross-tolerance::all other [[opioids]]]], meaning that after the consumption of pethidine all [[opioid]]s 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.<ref>Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2</ref> 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.<ref>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</ref>
The risk of fatal opioid overdoses rise sharply after a period of cessation and [[relapse]], largely because of reduced tolerance.<ref>Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2</ref> 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.<ref>{{cite journal | vauthors=((Siegel, S.)), ((Hinson, R. E.)), ((Krank, M. D.)), ((McCully, J.)) | journal=Science | title=Heroin “Overdose” Death: Contribution of Drug-Associated Environmental Cues | volume=216 | issue=4544 | pages=436–437 | date=23 April 1982 | url=https://www.science.org/doi/10.1126/science.7200260 | issn=0036-8075 | doi=10.1126/science.7200260}}</ref>
===Dangerous interactions===
===Dangerous interactions===
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. [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.
{{DangerousInteractions/Intro}}
*'''[[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 [https://www.youtube.com/watch?v=uCDa-AhrjHo recovery position] or have a friend move them into it.
{{DangerousInteractions/Opioids}}
*'''[[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 [https://www.youtube.com/watch?v=uCDa-AhrjHo recovery position] or have a friend move them into it.
*'''[[Stimulants]]''' - It is dangerous to combine pethidine, a [[depressant]], with [[stimulant]]s due to the risk of excessive intoxication. Stimulants decrease the [[sedation|sedative]] effect of pethidine, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of pethidine will be significantly increased, leading to intensified [[disinhibition]] as well as [[pethidine#Subjective effects|other effects]]. If combined, one should strictly limit themselves to only taking a certain amount of pethidine.
*'''[[Psychedelic]]s''' - Pethidine is well known to lower seizure threshold and psychedelics also cause occasional seizures.
====[[Serotonin syndrome]] risk====
====[[Serotonin syndrome]] risk====
Pethidine is known to cause serotonin syndrome at a significantly higher rate than other serotonergic opioids such as [[tramadol]].
Pethidine is known to have a significantly increased chance of causing serotonin syndrome than other serotonergic opioids such as [[tramadol]].{{citation needed}}
{{DangerousInteractions/SerotoninSyndrome}}
{{DangerousInteractions/SerotoninSyndrome}}
==Legal issues==
==Legal status==
{{LegalStub}}
{{LegalStub}}
*'''Germany:''' Pethidine is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.<ref>{{Citation | title=Anlage III BtMG - Einzelnorm | url=http://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html}}</ref>
*'''Russia:''' Pethidine is a Schedule I controlled substance.<ref>{{Citation | title=Постановление Правительства РФ от 01.10.2012 N 1002 (ред. от 09.08.2019) | url=https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=331879&dst=100187&date=03.12.2019}}</ref>
*'''Switzerland''': Pethidine is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Turkey''': Pethidine is a 'red prescription' only substance<ref>KIRMIZI REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/K%C4%B1rm%C4%B1z%C4%B1%20Re%C3%A7eteye%20Tabi%20%C4%B0la%C3%A7lar%2005072019_ebcc7e92-6661-4983-870a-fe8983a9c2b7.pdf</ref> and illegal when sold or possessed without a prescription.{{citation needed}}
*'''United Kingdom:''' Pethidine is a Class A, Schedule 2 drug in the United Kingdom.<ref>{{Citation | title=List of most commonly encountered drugs currently controlled under the misuse of drugs legislation | url=https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation}}</ref>
*'''United States:''' Pethidine is a Schedule II Controlled Substance.<ref>DEA Controlled Substances | https://www.deadiversion.usdoj.gov/schedules/orangebook/e_cs_sched.pdf</ref>
*'''United States:''' Pethidine is a Schedule II Controlled Substance.<ref>DEA Controlled Substances | https://www.deadiversion.usdoj.gov/schedules/orangebook/e_cs_sched.pdf</ref>
*'''United Kingdom:''' Pethidine is a Class A, Schedule 2 drug in the United Kingdom.<ref>UK Controlled Drugs | https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation</ref>
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Pethidine, known as meperidine in the United States (sold under the brand name Demerol), is a synthetic opioidanalgesic used for the treatment of moderate to severe pain. Compared to traditional opioids such as morphine, pethidine was originially thought to be much safer and have less potential for abuse. It was later discovered that pethidine is significantly less safe than morphine and its metabolite norpethidine can be extremely toxic.
Pethidine is a synthetic opioid of the phenylpiperidine class. Pethidine is the prototype of a large family of analgesics including the pethidine 4-phenylpiperidines (piminodine, anileridine and others), the prodines (alphaprodine, MPPP, etc.), bemidones (ketobemidone, etc.) and others more distant, including diphenoxylate and analogues.[2] The most coomon hydrochloride form is a white crystalline substance with a melting point of 186 C to 189 C. It is readily soluble in water and has a neutral reaction and a slightly bitter taste.[3]
Pethidine can be produced in a two-step synthesis. The first step is reaction of benzyl cyanide and chlormethine in the presence of sodium amide to form a piperidine ring. The nitrile is then converted to an ester.[4]
Pharmacology
Opioids exert their effects by binding to and activating the μ-opioidreceptor. 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. The bioavailability of orally administered pethidine can vary from 50% to around 60%.
Compared to traditional opioids, pethidine has a very unique pharmacological profile. In addition to being an opioid, pethidine is also a muscarinic acetylcholinereceptorantagonist. Pethidine is also a dopaminereuptake inhibitor and norepinephrine reuptake inhibitor. Pethidine is a κ-opioid agonist and its metabolite norpethidine is also an extremely powerful serotonin reuptake inhibitor.[5]
Subjective effects
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 PsychonautWikicontributors. 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 ☠. Many users note that they find pethidine just as, or more euphoric than oxycodone.[6]
Physical effects
The general sensation of pethidine can be described as one of euphoria, relaxation, anxiety suppression and pain relief.
Physical euphoria - This particular substance can be considered as very intense in its physical euphoria. The sensation itself can be described as extreme feelings of intense physical comfort, warmth, love and bliss.
Respiratory depression - At low to moderate doses, this effect results in the sensation that the breath is 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.
Seizures - High doses of pethidine may cause seizures. This is because of its metabolite norpethidine.
Cognitive effects
Cognitive euphoria - This particular substance can be considered as very intense in its cognitive euphoria. The sensation itself can be described as powerful and overwhelming feeling of emotional bliss, contentment, and happiness.
Acuity suppression - Pethidine is a muscarinic acetylcholine receptor antagonist which may cause blurred vision at high doses.
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:
Pethidine has a high 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 [[Toxicity::potentially lethal when mixed with depressants like alcohol or benzodiazepines]] and generally has a wider range of substances which it is dangerous to combine with in comparison to other opioids.
One of pethdine's metabolites, norpethidine has little to no opioid action, but is known to cause seizures. Pethidine should not be taken during benzodiazepine withdrawals as this can potentially cause seizures. In 1984, Libby Zion, a teenager was brought to the emergency room due to a "flu-like" ailment. She was previously prescribed and taking phenelzine, a monoamine oxidase inhibitor, which in combination caused fatal serotonin syndrome.[7]
As with other opioids, the chronic use of pethidine can be considered extremely 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 pethidine 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). Pethidine presents cross-tolerance with [[Cross-tolerance::all other opioids]], meaning that after the consumption of pethidine 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.
Pethidine is known to have a significantly increased chance of causing serotonin syndrome than other serotonergic opioids such as tramadol.[citation needed]
Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.
. eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.