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'''Promethazine''' (commonly sold as '''Phenergan''' or '''Lergigan,''' and popularly known as one of the two active ingredients in "lean") is a first-generation [[psychoactive class::antihistamine]] of the [[chemical class::phenothiazine]] chemical class that produces [[muscle relaxation|muscle relaxing]], [[nausea suppression|nausea relieving]] and strong [[sedation|sedative]] effects when [[administered]]. It also reduces motion sickness and has anticholinergic properties.
'''Promethazine''' (commonly sold as '''Phenergan''' or '''Lergigan''') is a [[psychoactive class::depressant]] substance of the [[chemical class::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 when a team of scientists from Rhône-Poulenc laboratories was able to synthesize it from phenothiazine and a diamine side chain of diphenhydramine.<ref>Li, Jie Jack (2006). Laughing Gas, Viagra, and Lipitor: The Human Stories behind the Drugs We Use. United Kingdom: Oxford University Press. p. 146. ISBN 9780199885282. Retrieved July 9, 2016.</ref> It was previously used as an antipsychotic,<ref>https://web.archive.org/web/20110718172715/http://www.cja-jca.org/cgi/reprint/6/4/375.pdf. Archived from the original (PDF) on July 18, 2011. Retrieved October 30, 2008</ref> although it is generally not administered for this purpose now. It has approximately 1/10 of the antipsychotic strength of chlorpromazine.
Promethazine was developed in the mid-1940s by French chemists.<ref name="Li2006">{{cite book | vauthors=((Li, J. J.)) | date= 2006 | title=Laughing gas, Viagra, and Lipitor: the human stories behind the drugs we use | publisher=Oxford University Press | isbn=9780195300994}}</ref> Today, it is available in many countries under many brand names.
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.<ref>Adam K & Oswald, I. (1986). The hypnotic effects of an antihistamine: promethazine. British journal of clinical pharmacology, 22(6), 715-717.</ref>
[[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.<ref>{{cite journal | vauthors=((Adam, K.)), ((Oswald, I.)) | journal=British Journal of Clinical Pharmacology | title=The hypnotic effects of an antihistamine: promethazine. | volume=22 | issue=6 | pages=715–717 | date= December 1986 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.1986.tb02962.x | issn=03065251 | doi=10.1111/j.1365-2125.1986.tb02962.x}}</ref>
It is highly advised to use harm reduction practices if using this substance.
==History and culture==
==History and culture==
{{historyStub}}
{{historyStub}}
Promethazine became popular among the Houston rap and hip-hop scene in around 1990<ref>(2005) Tamara Palmer. Country Fried Soul: Adventures in Dirty South Hip-Hop</ref>, 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.
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.<ref name="Li2006" /> 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<ref>{{cite book | vauthors=((Palmer, T.)) | date= 2005 | title=Country fried soul: adventures in dirty south hip hop | publisher=Backbeat | isbn=9780879308575}}</ref>, 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==
==Chemistry==
{{chemistry}}
{{chemistry}}
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|{{effects/physical|
|{{effects/physical|
*'''[[Effect::Sedation]]''' - Promethazine causes pronounced sedation and a general feeling of slowness, usually with the feeling of not wanting to move.
*'''[[Effect::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.
*'''[[Effect::Physical euphoria]]'''
*'''[[Effect::Muscle relaxation]]'''
**'''[[Effect::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. {{citation needed}}
**'''[[Effect::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. {{citation needed}}
*'''[[Effect::Increased heart rate]]''' and '''[[Effect::Increased blood pressure]]'''<ref>Tsay, M. E., Procopio, G., Anderson, B. D., & Klein-Schwartz, W. (2015). Abuse and intentional misuse of promethazine reported to US poison centers: 2002 to 2012. Journal of addiction medicine, 9(3), 233-237. | PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed/25822213</ref> - Anticholinergic activity at muscarinic acetylcholine receptors causes these effects.
*'''[[Effect::Increased heart rate]]''' and '''[[Effect::increased blood pressure]]'''<ref name="Tsay2015">{{cite journal | vauthors=((Tsay, M. E.)), ((Procopio, G.)), ((Anderson, B. D.)), ((Klein-Schwartz, W.)) | journal=Journal of Addiction Medicine | title=Abuse and Intentional Misuse of Promethazine Reported to US Poison Centers: 2002 to 2012 | volume=9 | issue=3 | pages=233–237 | date= June 2015 | issn=1935-3227 | doi=10.1097/ADM.0000000000000124}}</ref> - Anticholinergic activity at muscarinic acetylcholine receptors causes these effects.
*'''[[Effect::Nausea suppression]]'''
*'''[[Effect::Abnormal heartbeat]]''' - This effect is exceptionally rare.
*'''[[Effect::Dry mouth]]'''
*'''[[Effect::Nausea suppression]]''' - Promethazine is used to treat motion sickness or nausea.
*'''[[Effect::Dry mouth]]''' - This is a common side effect of this substance.
*'''[[Effect::Difficulty urinating]]''' - This side effect is uncommon.
}}
}}
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*'''[[Effect::Anxiety suppression]]''' - Usually, promethazine acts as an [[anxiolytic|anti-anxiety]] agent.
*'''[[Effect::Anxiety suppression]]''' - Usually, promethazine acts as an [[anxiolytic|anti-anxiety]] agent.
*'''[[Effect::Addiction suppression]]'''
*'''[[Effect::Anxiety]]''' - Promethazine can occasionaly cause paranoia and Anxiety due to delirium although it is rarer than that of Diphenhydramine, Doxylamine and chlorpheniramine.
*'''[[Effect::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.
*'''[[Effect::Emotion suppression]]''' - This effect is mild and occurs due to the mild weak antipsycotic effect, however much weaker than that of chlorpromazine or prochlorperazine.{{citation needed}}
*'''[[Effect::Delusions|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.
*'''[[Effect::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.
*'''[[Effect::Delirium]]''' and '''[[Effect::Confusion|confusion]]'''<ref name="Tsay2015"/> - 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.
}}
{{effects/visual|
====Distortions====
*'''[[Effect::Depth perception distortions]]''' - This side effect is uncommon.
====Hallucinatory states====
*'''[[Effect::External hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::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 [[Visual_effects:_Internal_hallucinations#Variations|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.
*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::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 [[Visual_effects:_Internal_hallucinations#Variations|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]].
*'''[[Effect::Peripheral information misinterpretation]]'''
*'''[[Effect::Shadow people]]'''
*'''[[Effect::Transformations]]'''
*'''[[Effect::Unspeakable horrors]]'''
*'''[[Effect::Object activation]]'''
*'''[[Effect::Anxiety]]''' - Anxiety may occur as a result of delirium.{{citation needed}}
}}
{{effects/aftereffects|
*'''[[Effect::Sleepiness]]'''
*'''[[Effect::Sleepiness]]'''
*'''[[Effect::Delirium]]''' and '''[[Effect::Confusion|confusion]]'''<ref>Tsay, M. E., Procopio, G., Anderson, B. D., & Klein-Schwartz, W. (2015). Abuse and intentional misuse of promethazine reported to US poison centers: 2002 to 2012. Journal of addiction medicine, 9(3), 233-237. | PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed/25822213</ref> - 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.
}}
}}
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===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:
Anecdotal reports which describe the effects of this compound within our [[experience index]] include:
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
===Lethal dosage===
===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. <ref>https://www.caymanchem.com/msdss/16478m.pdf</ref>
===Tolerance and addiction potential===
===Tolerance and addiction potential===
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==Legal status==
==Legal status==
{{LegalStub}}
*'''Germany''': Promethazine is available through a prescription.{{citation needed}}
*'''Russia''': Promethazine is available through a prescription.{{citation needed}}
*'''Russia''': Promethazine is available through a prescription.{{citation needed}}
*'''United States''': Promethazine is available through a prescription.<ref>FDA. Promethazine Monograph. https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/07935s030lbl.pdf</ref>
*'''Canada''': Promethazine is available over the counter.{{citation needed}}
*'''Japan''': Promethazine is available through a prescription.{{citation needed}}
*'''Australia''': Promethazine is available over the counter.{{citation needed}}
*'''United Kingdom''': Promethazine is available over the counter.{{citation needed}}
It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.
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.
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.
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.[2] Today, it is available in many countries under many brand names.
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.[2] 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[4], 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.
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. [citation needed]
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 ☠.
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.
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. [citation needed]
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.[citation needed]
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[5] - 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.
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.
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.
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. [6]
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.
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. [citation needed]
Anticholinergics - Promethazine with anticholinergics (or antimuscarinics) can cause increased blocking of acetylcholine, being potentially dangerous with cardiovascular effects as well as delirium. [citation needed]
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.[citation needed]
Russia: Promethazine is available through a prescription.[citation needed]
United States: Promethazine is available through a prescription.[7]
Canada: Promethazine is available over the counter.[citation needed]
Japan: Promethazine is available through a prescription.[citation needed]
Australia: Promethazine is available over the counter.[citation needed]
United Kingdom: Promethazine is available over the counter.[citation needed]
↑Palmer, T. (2005). Country fried soul: adventures in dirty south hip hop. Backbeat. ISBN9780879308575.
↑ 5.05.1Tsay, M. E., Procopio, G., Anderson, B. D., Klein-Schwartz, W. (June 2015). "Abuse and Intentional Misuse of Promethazine Reported to US Poison Centers: 2002 to 2012". Journal of Addiction Medicine. 9 (3): 233–237. doi:10.1097/ADM.0000000000000124. ISSN1935-3227.
