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
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 (commonly sold as Phenergan or Lergigan) is a depressant substance of the phenothiazine class. Alongside codeine, it is popularly known as one of the active two ingredients in "lean". It acts as an antihistamine.

Promethazine was developed in the mid-1940s by French chemists. Today, it is available in many countries under many brand names.

Subjective effects include muscle relaxation, nausea suppression, and strong sedation. It also reduces motion sickness and has anticholinergic properties.

Promethazine has been shown to have quality hypnotic effects and is sometimes used for this purpose.

It is highly advised to use harm reduction practices if using this substance.

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 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.

It 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

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, this effect is normally considerably stronger than Diphenhydramine or Doxylamine and it is generally considered to be one of the most sedating antihistamines due to its high anticholinergic, H1 anagonist and weak D2 antagonist activity.
  • Muscle relaxation
    • Physical euphoria - 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.
  • Abnormal heartbeat - This effect is exceptionally rare.
  • Nausea suppression - Promethazine is used to treat motion sickness or nausea.
  • Dry mouth - This is a common side effect of this substance.
  • Difficulty urinating - This side effect is uncommon.

Cognitive effects

• • Anxiety suppression - Usually, promethazine acts as an anti-anxiety agent.
  • Anxiety - Promethazine can occasionaly cause paranoia and Anxiety due to delirium although it is rarer than that of Diphenhydramine, Doxylamine and chlorpheniramine.
  • Euphoria - Usually, promethazine causes minimal euphoria normally only in anxious individuals and can even be dysphoric, however when used at low doses and combined with an opioid such as codeine, oxycodone or hydrocodone, it can effectively potentiate the euphoric effect and allow for a lower opioid dose.
  • Emotion suppression - This effect is mild and occurs due to the mild weak antipsycotic effect, however much weaker than that of chlorpromazine or prochlorperazine.
  • Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others.
  • Sleepiness - Feelings of physical exhaustion and tiredness are a common and pronounced effect of promethazine. The substance is therefore used to treat insomnia and abnormal sleep cycles.
  • 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.

Visual effects

• Distortions

  • Depth perception distortions - This side effect is uncommon.

  Hallucinatory states

  • External hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - The threshold for hallucinations on promethazine is higher than other 1st generation antihistamines like diphenhydramine and doxylamine, occurs mainly heavy doses and can be difficult to reach due to the user likely falling asleep before they can reach delirium, as promethazine is extremely sedating at high doses. It can be comprehensively described through its variations as delirious in believability, controllable or autonomous in controllability and solid in style. The most common themes for these hallucinations include those of both everyday occurrences such as smoking phantom cigarettes, talking to people who are not there, seeing and feeling insects and immersion in sinister or nightmarish experiences.
  • Internal hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - Relative to other hallucinogens, this effect occurs briefly and spontaneously at moderate doses but becomes progressively extended in its occurrence and duration proportional to dosage before eventually becoming all-encompassing. It can be comprehensively described through its variations as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style. Internal hallucinations may occur at lighter dosages than needed to cause external hallucinations and delirium.
  • Peripheral information misinterpretation
  • Shadow people
  • Transformations
  • Unspeakable horrors
  • Object activation

After effects

• • Sleepiness

Experience reports

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

• Experience: 100 mg Promethazine (Oral) - Netflix & Depression

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.

Lethal dosage

The lowest published toxic dose of promethazine in humans (oral) is 3.5 mg/kg. This means that a person weighing 70 kg can show signs of toxicity at 245 mg. The LD50 of promethazine in mice (oral) is 255 mg/kg. If applied to humans, this suggests that 50% of people weighing 70 kg would die after consuming 17.85 grams of promethazine.

Tolerance and addiction potential

Promethazine is not addictive.

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. 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

• Germany: Promethazine is available through a prescription.

• Russia: Promethazine is available through a prescription.

• United States: Promethazine is available through a prescription.

• Canada: Promethazine is available over the counter.
• Japan: Promethazine is available through a prescription.
• Australia: Promethazine is available over the counter.
• United Kingdom: Promethazine is available over the counter.

See also

• Responsible use

External links

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