|Summary sheet: Pethidine|
|Common names||Pethidine, Meperidine, Demerol, Dolantin, Dolcontral|
|Systematic name||Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate|
|Routes of Administration|
|Selective serotonin re-uptake inhibitors|
|Serotonin-norepinephrine reuptake inhibitors|
Pethidine, known as meperidine in the United States (sold under the brand name Demerol), is a synthetic opioid 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.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Toxicity and harm potential
- 5 Legal issues
- 6 See also
- 7 External links
- 8 References
Pethidine is an opioid in the phenylpiperidine class.
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 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 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.
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These 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 of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death. Many users note that they find pethidine just as, or more euphoric than oxycodone.
The general sensation of pethidine can be described as one of euphoria, relaxation, anxiety suppression and pain relief.
- 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.
- Cough suppression
- Difficulty urinating
- Sedation or Stimulation - While most users report that they find pethidine to be considerably sedating, others report it to be stimulating.
- Pupil constriction
- Decreased libido
- Appetite suppression
- Orgasm suppression
- Seizures - High doses of pethidine may cause seizures. This is because of its metabolite norpethidine.
- Acuity suppression - Pethidine is a muscarinic acetylcholine receptor antagonist which may cause blurred vision at high doses.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
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 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.
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 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 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. 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 psychoactive substances are reasonably safe to use on their own, they can quickly become harmful and even life-threatening when taken with other substances. The following section lists some known dangerous combinations, but it may not include all of them. Furthermore, a combination that seems to be harmless in low doses can still greatly increase the risk of injury or death when the doses are slightly increased. Independent research 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.
- Depressants (1,4-Butanediol, 2M2B, alcohol, benzodiazepines, barbiturates, GHB/GBL, methaqualone, opioids) - This combination potentiates the muscle relaxation, amnesia, sedation, and respiratory depression caused by one another. At higher doses, it can lead to a sudden, unexpected loss of consciousness along with a dangerous amount of depressed respiration. There is also an increased risk of suffocating on one's vomit while unconscious. If nausea or vomiting occurs before a loss of consciousness, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Stimulants - It can be dangerous to combine depressants with stimulants due to the risk of accidental excessive intoxication. Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.
- Dissociatives - This combination can unpredictably potentiate the amnesia, sedation, motor control loss and delusions that can be caused by each other. It may also result in a sudden loss of consciousness accompanied by a dangerous degree of respiratory depression. If nausea or vomiting occurs before consciousness is lost, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Psychedelics - Pethidine is known to lower seizure threshold and psychedelics also cause occasional seizures.
Serotonin syndrome risk
Pethidine is known to have a significantly increased chance of causing serotonin syndrome than other serotonergic opioids such as tramadol. Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.
- MAOIs such as syrian rue, banisteriopsis caapi, 2C-T-7, αMT, phenelzine, selegiline, and moclobemide
- Serotonin releasers such as MDMA, 4-FA, methamphetamine, methylone and αMT
- Selective serotonin re-uptake inhibitors (SSRIs)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as tramadol and DXM
This legality section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
- United States: Pethidine is a Schedule II Controlled Substance.
- United Kingdom: Pethidine is a Class A, Schedule 2 drug in the United Kingdom.
- Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- Meperidine: A Critical Review | https://www.researchgate.net/publication/11575123_Meperidine_A_Critical_Review
- Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid μ Agonists in Healthy Volunteers | http://jpet.aspetjournals.org/content/289/3/1454.long
- Serotonin Syndrome and the Libby Zion Affair | http://epmonthly.com/article/serotonin-syndrome-and-the-libby-zion-affair/
- 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
- Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210
- DEA Controlled Substances | https://www.deadiversion.usdoj.gov/schedules/orangebook/e_cs_sched.pdf
- 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