Promethazine

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Death may occur when promethazine is combined with other depressants, such as opioids, benzodiazepines, barbiturates, thienodiazepines or other GABAergic substances like alcohol.

Additionally, promethazine is an anticholinergic, and at high doses it may cause delirium and extremely unpleasant if not dangerous experiences. Please be extremely careful when trying this pharmaceutical and use responsible use practices such as always having a tripsitter when using promethazine, especially at high doses.

Summary sheet: Promethazine

Promethazine (commonly sold as Phenergan or Lergigan, and popularly known as one of the two active ingredients in "lean") is a first-generation antihistamine of the phenothiazine chemical class that produces muscle relaxing, nausea relieving and strong sedative effects when administered. It also reduces motion sickness and has anticholinergic properties.

Promethazine
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Chemical Nomenclature
Common names	Phenergan, Lergigan
Substitutive name	Promethazine
Systematic name	N,N,α-trimethyl-10H-phenothiazine-10-ethanamine
Class Membership
Psychoactive class	Deliriant / Depressant
Chemical class	Phenothiazine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Threshold 5 - 12.5 mg Light 12.5 - 25 mg Common 25 - 50 mg Strong 50 - 100 mg Heavy 100 mg + Duration Total 4 - 6 hours Onset 30 - 60 minutes Come up 20 - 60 minutes Peak 1 - 2 hours Offset 3 - 5 hours After effects 12 hours 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.
Interactions

Promethazine was developed in the mid-1940s when a team of scientists from Rhône-Poulenc laboratories was able to synthesize it from phenothiazine and a diamine side chain of diphenhydramine. It was previously used as an antipsychotic, although it is generally not administered for this purpose now. It has approximately 1/10 of the antipsychotic strength of chlorpromazine.

Today, promethazine is available in many countries under many brand names. Promethazine has been shown to have quality hypnotic effects and is sometimes used for this purpose.

History and culture

This History and culture section is a stub. As a result, it may contain incomplete or wrong information. You can help by expanding it.

Promethazine became popular among the Houston rap and hip-hop scene in around 1990, and the trend resurfaced in around 2015 to 2016. Often, it was combined with the opiate drug codeine in a preparation called "lean." Lean usually consists of ice, Sprite or a citrus soda, the promethazine/codeine cough syrup, and occasionally jolly ranchers for enhanced flavor.

Chemistry

This chemistry section is incomplete. You can help by adding to it.

Promethazine is a phenothiazine-based compound.

Pharmacology

This pharmacology section is incomplete. You can help by adding to it.

Promethazine is a direct antagonist of histamine H1 receptors, whereas diphenhydramine is an inverse agonist. It is also an antagonist of muscarinic acetylcholine receptors, which is likely the cause of sedation and delirium that occurs with higher doses. It blocks dopaminergic D2 receptors, but weakly.

Subjective effects

This subjective effects section is a stub. As such, it is still in progress and may contain incomplete or wrong information. You can help by expanding or correcting it.

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 ☠.

Physical effects

• • Sedation - Promethazine causes pronounced sedation and a general feeling of slowness, usually with the feeling of not wanting to move.
  • Physical euphoria
    • Muscle relaxation - This can lead to a very pleasant feeling of the entire body relaxing, feeling like warm gel. It is similar to but distinct from an opioid's physical euphoria.
  • Increased heart rate and Increased blood pressure - Anticholinergic activity at muscarinic acetylcholine receptors causes these effects.
  • Nausea suppression

Cognitive effects

• • Anxiety suppression - Usually, promethazine acts as an anti-anxiety agent.
  • Addiction suppression
  • Anxiety - Anxiety may occur as a result of delirium.
  • Sleepiness
  • Delirium and confusion - In low to moderate doses, promethazine presents a harmless sense of being confused or delirious. In high doses and overdose, it can become (but rarely does) so severe that the patient or user experiences excited delirium, a state of severe agitation and confusion.

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: Promethazine

Toxicity and harm potential

This toxicity and harm potential section is a stub. As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. Note: Always conduct independent research and use harm reduction practices if using this substance.

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

Tolerance and addiction potential

Promethazine is not addicting.

Dangerous interactions

This dangerous interactions section is a stub. As such, it may contain incomplete or invalid information. You can help by expanding upon or correcting it.

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. 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. 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.

Promethazine, because of its extensive pharmacology, has many interactions. According to the interactions checker on Drugs.com, promethazine is known to interact with over 1000 other prescription and OTC drugs.

• Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - 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 try to fall asleep in the recovery position or have a friend move them into it.
• Anti-dopaminergics - Because promethazine also blocks dopamine receptors, other drugs and substances that do this will increase the chances of developing acute or tardive dyskinesia, neuroleptic malignant syndrome, or parkinsonism.
• Anticholinergics - Promethazine with anticholinergics (or antimuscarinics) can cause increased blocking of acetylcholine, being potentially dangerous with cardiovascular effects as well as delirium.
• Stimulants - Due to promethazine's excitatory cardiac effect, combining it with stimulants poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack as well as other cardiovascular events.

Legal status

This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it.

• Russia: Promethazine is available through a prescription.

See also

• Responsible use

External links

• Promethazine (Wikipedia)
• Promethazine (Erowid Vault)
• Promethazine (TiHKAL / Isomer Design)