Lean (drug)

Recreational drug beverage

This article is about the opioid cough syrup drink. For dextromethorphan cough syrup drinks also called lean, see Recreational use of dextromethorphan. "Purple Drank" redirects here. For the album by Indo G, see Purple Drank (album).

Lean

Type| Polysubstance drink
Region of origin| Southern United States
Introduced| 1960s
Colour| Purple, red, green, or yellow; varies based on cough syrup brand and soda mixer
Ingredients| Opioid cough syrup, soft drink
Related products| Dextromethorphan syrup

Lean or purple drank (known by numerous local and street names) is a polysubstance drink used as a recreational drug. It is prepared by mixing prescription-grade cough or cold syrup containing an opioid drug and an anti-histamine drug with a soft drink and sometimes hard candy. The beverage originated in Houston as early as the 1960s and is popular in hip hop culture, especially within the Southern United States.[1] Codeine/promethazine syrup is usually used to make lean, but other syrups are also used.

Users of lean are at risk of addiction, and serious complications include respiratory depression, respiratory arrest, and cardiac arrest. Lean is especially dangerous when consumed with alcohol.

## Names

[edit]

The term lean refers to the tendency for users to have difficulty standing up straight while under the influence of the drug.[2] "Purple drank" references its typically purple hue, as the cough syrups employed are often purple in color, and an African-American Vernacular English term for an alcoholic beverage or intoxicating drink. Other names include "syrup/sizzurp", "jelly", "Tussin/Tuss'", "barre", "Wock'", "Act'", "Texas tea", "mud", "dirty Sprite", and "tsikuni".[3][4][5][6][7][8][9] In areas where lean had not yet been introduced, codeine-based cough syrup mixed with pills was called "juice and beans".[10] Lean is also sometimes referred to by its color in slang, usually purple (or "purp'"), but can also be red, green, or yellow based on the ingredients used.[citation needed]

## Preparation

[edit]

Not to be confused with lean manufacturing.

Ingredients for creating lean, including codeine-promethazine cough syrup, Jolly Rancher candies, and Sprite. Note the label on the bottled syrup, printed with instructions on how to prepare the lean. Some of the syrup has been decanted into a plastic container. A spoonful of promethazine/​codeine syrup showing the characteristic purple color

Typically, the base for lean is a strong prescription cold medicine, specifically cough syrup that contains both promethazine and codeine. Other preparations use codeine/guaifenasin, hydrocodone/chlorphenamine, hydrocodone/APAP, and hydrocodone/homatropine. Over-the-counter cold medicines that contain dextromethorphan (often paired with guaifenasin or acetaminophen) as the active ingredient have also been used, as they do not require acquiring a prescription.[11][12]

To create a drinkable mixture, the cough syrup is combined with soft drinks, especially fruit-flavored drinks such as Sprite, Mountain Dew, or Fanta, and is typically served in two foam cups.[13][14] A hard candy, usually a Jolly Rancher, may be added to give the mixture a sweeter flavor.[1] Masking the undesired taste may impair judgment of the potency, which is a factor in overdosing.[citation needed]

## Effects

[edit]

The physiological effects of lean on the user are to produce mild "euphoric side effects", which are accompanied by "motor-skill impairment, lethargy, drowsiness, and a dissociative feeling from all other parts of the body."[14] It has been suggested that the super-sweet combination of soda, cough syrup, and Jolly Ranchers provides a pleasing flavor and mouthfeel that lingers on the user's tongue for an extended duration. This phenomenon is often appealing to first-time users.[15] Lean is often used in combination with alcohol and/or other drugs.[14]

### Hazards

[edit]

When taken in prescribed quantities, codeine-promethazine is quite safe,[16] but dangers arise in higher doses since promethazine is a depressant of the central nervous system (CNS), and codeine is a respiratory depressant. When codeine is taken in very large amounts, it can cause one to stop breathing.[16] Using alcohol and other drugs alongside lean increases the chance of respiratory depression.[16] It seems that the concoction does not cause seizures itself, but increases their likelihood in those susceptible to them.[16] The drink includes a massive amount of the opiate codeine, and it has been suggested that promethazine may heighten the euphoric effects of codeine.[16]

The addictive nature of the drink means that trying to discontinue regular usage can bring about symptoms of withdrawal.[16] In a 2008 interview with MTV News, Lil Wayne described the withdrawal as feeling "like death in your stomach when you stop. Everybody wants me to stop all this and all that. It ain't that easy."[17]

Respiratory depression is a potentially serious or fatal adverse drug reaction associated with the use of codeine, but mainly the danger lies in the much more potent and CNS-depressing phenothiazine-related antihistamine promethazine. This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose: respiratory or cardiac arrest. As with most CNS depressants, mixing with alcohol greatly increases the risk of respiratory failure and other complications.[18]

## History

[edit]

Lean is thought to have developed in Houston around the 1960s, when blues musicians would take Robitussin and cut it with beer. Later, when wine coolers came onto the market, they substituted for beer.[15] These blues musicians lived in Houston's Fifth Ward, Third Ward, and South Park neighborhoods and the practice was taken up by the generation of rappers growing up in the same parts of the city.[15] In the 1980s and 1990s the formula changed to using codeine promethazine cough syrup, somewhat like the glutethimide and codeine combination that was popular from the 1970s up to the early 1990s.[15] Codeine-based cough syrups were also turned to as an alternative to pentazocine/tripelennamine ("T's and blues") after the pharmaceutical industry added naloxone to its constituent drugs, effectively blocking their potential for abuse.[10]

Lean remained a local phenomenon in Houston until the 1990s, when the American rapper DJ Screw released several tunes mentioning the drink in his mixtapes, which were extremely popular in the Houston area.[15] DJ Screw's music was particularly appropriate for Houston's climate. Due to the heat and expanse of the Houston area residents spent long drives in their cars, "the music that most appropriately complements that has always been the music of DJ Screw, it's slowed down—and when I say slowed down I mean he would record sessions in his apartment with rappers freestyling over beats and he would make these big mixtapes and then he would actually slow them down even further on his cassette recorder."[15] DJ Screw's invoking lean in his lyrics and his use of slow tempos had caused his style to be characterized "[a]s if the song itself has taken too much codeine promethazine".[15] Rappers far beyond Houston would come to adopt aspects of DJ Screw's unique style, but not before he died of a codeine overdose in 2000.[19]

### Popularization

[edit]

In 2019, rapper Future publicly spoke about quitting lean after learning about how his music influenced teenagers to try the drug.[20]

Houston producer DJ Screw popularized the concoction, which is widely attributed as a source of inspiration for the chopped-and-screwed style of hip hop music.[21][22] The promethazine and codeine concoction first gained popularity in the underground hip hop scene in Houston,[22] where musician Big Hawk said it was consumed as early as the 1960s and 1970s, becoming more widely used in the early 1990s.[23] Because of usage by rap artists in Houston, it became more popular in the 1990s.[24] Its use later spread to other States in the South.[21] In June 2000, Three 6 Mafia's single "Sippin' on Some Syrup", featuring UGK, brought the term purple drank to a nationwide audience.[25]

In 2004, the University of Texas at Austin found that 8.3% of secondary school students in Texas had taken codeine syrup to get high.[21] The Drug Enforcement Administration reports busts involving syrup across the Southern United States, particularly in Texas and Florida.[21] As of 2011, the price of lean in Houston was twice the price it is in Los Angeles.[24]

In a 2019 interview, American rapper Future spoke about quitting lean and stated that he was afraid that his fans would believe his music has changed if he had publicly admitted to quitting earlier.[20] Future expressed disappointment after American rapper Juice Wrld told him that he was influenced by his music to try lean when he was young. Future stated "It's like, 'Oh shit.' How many other sixth-graders did I influence to drink lean?"[20] The two artists had released a collaborative mixtape titled Wrld on Drugs in October 2018.[20] Lil Nas X's hit song "Old Town Road" includes the line "Lean all in my bladder", though Lil Nas X has stated he does not endorse the drug.[26]

### Notable incidents of use

[edit]

DJ Screw, who popularized the codeine-based drink, died of a codeine–promethazine, Valium, and PCP overdose on November 16, 2000, several months after the video of Three 6 Mafia's single debuted.[27]

Big Moe, a DJ Screw protégé whose albums City of Syrup and Purple World were based on the drink and who has been described as having "rapped obsessively about the drug",[28] died at age 33 on October 14, 2007, after suffering a heart attack one week earlier that left him in a coma.[29] There was speculation that lean may have contributed to his death.[30][31]

Pimp C, a widely influential rapper from Port Arthur, Texas and member of the rap duo UGK, was found dead on December 4, 2007, at the Mondrian Hotel in West Hollywood, California. The Los Angeles County Coroner's Office reported that the rapper's death was "due to promethazine-codeine effects and other unestablished factors." Ed Winter, assistant chief of the Coroner's Office, said the levels of the medication were elevated, but not enough to deem the death an overdose. However, Pimp C had a history of sleep apnea, a condition that causes one to stop breathing for short periods during sleep. A spokesman for the coroner's office said that the combination of sleep apnea and cough medication probably suppressed Pimp C's breathing long enough to bring on his death.[32][28]

Fredo Santana, an American rapper who frequently made references to the drink in his music, died of a seizure on January 19, 2018. According to TMZ, he had been suffering from liver and kidney problems, which were believed to be the result of his addiction.[33]

In September 2006, Terrence Kiel, a San Diego Chargers player, was arrested during practice for the possession with intent to sell prescription cough syrup for use in making the drink.[21] Kiel was caught trying to ship a case of syrup to a friend via FedEx. Kiel was charged with two felony counts of transporting a controlled substance and three counts of possession for sale of a controlled substance.[34]

On July 8, 2008, Johnny Jolly, a Green Bay Packers player, was pulled over in his car by the police for playing excessively loud music in a nightclub parking lot. The officers found a Dr Pepper bottle in a holder next to two Styrofoam cups containing soda and ice.[35] The case was dismissed,[36] but charges were refiled in December 2009 after the Houston Police Department acquired new equipment that allowed the police to test the evidence again. Jolly faced a possible maximum sentence of up to 20 years in jail, but as a first time offender he would be eligible for probation.[37]

On July 5, 2010, former Oakland Raiders quarterback JaMarcus Russell was arrested at his home in Mobile, Alabama, for possession of codeine syrup without a prescription. He was arrested as part of an undercover narcotics investigation. Russell was booked into city jail and released soon afterwards after making his bail.[38]

On June 11, 2013, just days after being robbed at gunpoint in San Francisco, rapper 2 Chainz was arrested at Los Angeles International Airport on charges of possessing promethazine and codeine (the primary ingredients of lean) along with marijuana.[39]

Mac Miller, who died of a drug overdose not involving lean, spoke openly of his addiction to lean.[40]

On April 7, 2015, Swedish rapper Yung Lean, while living in Miami Beach, Florida, and recording his second studio album Warlord, was hospitalized at Mount Sinai Medical Center due to an overdose stemming from an addiction to Xanax, cocaine, and lean.[41]

## Commercial products

[edit]

Several legal commercial products loosely based on the concept of "purple drank" are marketed in the United States. In June 2008, Innovative Beverage Group, a Houston, Texas-based company, released a beverage called "Drank". The commercial product contains no codeine or promethazine, but claims to "Slow Your Roll" with a combination of herbal ingredients such as valerian root and rose hips as well as the hormone melatonin.[42][43] Similar "anti-energy" or relaxation drinks on the commercial market use the names "Purple Stuff", "Sippin Syrup", and "Lean".[44][45][46]

These commercial products have been criticized for their potential to serve as gateways to the dangerous illegal concoction.[45][46][47] The marketing push has been described as akin to the making of candy cigarettes.[47]

## See also

[edit]

* Ayahuasca
* Benadryl challenge
* Coca wine
* Recreational use of dextromethorphan

## References

[edit]

1. ^ a b Palmer, Tamara (2005). Country Fried Soul: Adventures in Dirty South Hip-hop. Outline Press Limited. p. 188.
2. ^ Richard Klemme, USE OF PROMETHAZINE WITH CODEINE SYRUP: COUGH/COLD EPIDEMIC OR SIGNIFICANT ABUSE? Archived May 16, 2008, at the Wayback Machine, Texas State Board of Pharmacy Newsletter, Volume XXV, Number 2, Spring 2001. The name "lean" refers to "users’ propensity of having difficulty in standing up straight."
3. ^ Bryan Robinson, Cough Syrup Abuse in Texas Takes Center Stage Archived March 29, 2022, at the Wayback Machine, ABC News, August 17, 2005
4. ^ "What is Lean (Purple Drank), How It's Made, Side Effects and Dangers". Archived from the original on January 23, 2021. Retrieved June 4, 2020.
5. ^ Shaheem Reid, Lil Wayne On Syrup: 'Everybody Wants Me To Stop ... It Ain't That Easy' Archived December 22, 2010, at the Wayback Machine, MTV.com, February 28, 2008
6. ^ ""Dirty Sprite" gains popularity among teens | News - Home". Archived from the original on October 26, 2015. Retrieved October 19, 2015.
7. ^ PA, The Ranch (November 4, 2019). "Sipping On Some Nonsense: What Is Lean?". The Ranch PA. Archived from the original on March 20, 2022. Retrieved February 25, 2022.
8. ^ Skelton, Eric (October 6, 2022). "Lil Yachty Took the WoOoOOoOoock to Poland". Complex. Retrieved October 12, 2022.
9. ^ Marso, Andy. "Pharmacy board recommends tracking 'sizzurp' ingredient". The Topeka Capital-Journal. Retrieved February 1, 2024.
10. ^ a b Spencer, Jim (September 19, 1984). "Abuse of 'juice': The burgeoning ills of cough syrup". Chicago Tribune.
11. ^ "Dextromethorphan (Oral Route) Description and Brand Names - Mayo Clinic". www.mayoclinic.org. Archived from the original on March 29, 2022. Retrieved August 19, 2019.
12. ^ Painter, Kim. "Sizzurp: What you need to know about cough syrup high". USA TODAY. Archived from the original on March 29, 2022. Retrieved August 19, 2019.
13. ^ "T.I. Arrest -- Sippin' on Sizzurp?". TMZ. September 2, 2010. Archived from the original on April 5, 2022. Retrieved August 19, 2019.
14. ^ a b c Leon, Melissa (March 17, 2013). "Lil Wayne Hospitalization: What the Hell Is Sizzurp?". The Daily Beast. Archived from the original on May 4, 2017. Retrieved January 20, 2014.
15. ^ a b c d e f g Eakin, Marah (March 26, 2013). "Learn all about the long, lean history of "sizzurp" with this 7-minute audio primer". A.V. Club. Archived from the original on August 17, 2017. Retrieved January 20, 2014.
16. ^ a b c d e f Khan, Amina (March 18, 2013). "Doctor explains sizzurp's powerful high -- and deadly side effects". Archived from the original on February 21, 2014. Retrieved January 20, 2014.
17. ^ Reid, Shaheem (February 28, 2008). "LIL WAYNE ON SYRUP: 'EVERYBODY WANTS ME TO STOP ... IT AIN'T THAT EASY'". MTV. Archived from the original on April 12, 2022. Retrieved November 13, 2020.
18. ^ "Alcohol Interactions with Other Drugs". Alcohol and Other Drugs Program Public Health Division, Health Department of Western Australia. 1999. Archived from the original on January 18, 2016. Retrieved June 4, 2013.
19. ^ Strauss, Neil (November 23, 2000). "THE POP LIFE; Rap Is Slower Around Houston". The New York Times. Retrieved April 13, 2017.
20. ^ a b c d Holmes, Charles (January 17, 2019). "Future Changed Rap for a Generation. He Doesn't Know How to Feel About It". Rolling Stone. Archived from the original on May 24, 2019. Retrieved January 28, 2020.
21. ^ a b c d e Leinwand, Donna (October 18, 2006). "DEA warns of soft drink-cough syrup mix". USA Today. Archived from the original on November 28, 2006. Retrieved October 23, 2006.
22. ^ a b Corcoran, Michael Joseph (2005). "The Geto Boys and DJ Screw: Where the Dirty South Began". All Over the Map: True Heroes of Texas Music (1st ed.). Austin: University of Texas Press. pp. 23–26\. ISBN 978-0-292-70976-8.
23. ^ Joseph Patel, Chopped & Screwed: A History Archived March 11, 2007, at the Wayback Machine, page 2, MTV.com. Accessed January 7, 2010.
24. ^ a b Schiller, Dane. "Purple Drank scheme allegedly made millions for smuggling ring Archived April 12, 2022, at the Wayback Machine." Houston Chronicle. Wednesday October 19, 2011. Retrieved on October 23, 2011.
25. ^ Walker, Yolanda (October 20, 2006). "Drug-laced cough syrup tempts Texas teens". WFAA. Archived from the original on January 25, 2007. Retrieved October 28, 2006.
26. ^ Mauro, Haleigh (January 24, 2020). "The Real Meaning of the "Old Town Road" Lyrics". Cosmopolitan. Archived from the original on April 12, 2022. Retrieved January 28, 2020.
27. ^ Demby, Eric (January 11, 2001). "Codeine Overdose Killed DJ Screw, Medical Examiner Says". MTV.com. Archived from the original on December 20, 2008. Retrieved October 28, 2006.
28. ^ a b Kristie Rieken, Cough syrup found in Pimp C's hotel had no label Archived June 12, 2011, at the Wayback Machine, Associated Press, February 5, 2008
29. ^ DJs – Rapper Big Moe Dies Archived April 8, 2009, at the Wayback Machine, contactmusic.com, October 15, 2007
30. ^ Leslie Casimir, Rapper's death leads teens to re-evaluate lifestyle; Fans and friends wonder whether drug was a factor in his heart attack Archived May 6, 2010, at the Wayback Machine, Houston Chronicle, October 20, 2007
31. ^ Houston rappers remember Big Moe Archived August 5, 2011, at the Wayback Machine, by Eyder Peralta, Houston Chronicle, October 16, 2007
32. ^ "Cough syrup cited in rapper Pimp C's death". Los Angeles Times. February 5, 2008. Archived from the original on February 12, 2008. Retrieved March 15, 2008.
33. ^ "Rapper Fredo Santana Dead from Fatal Seizure". TMZ.com. January 20, 2018. Archived from the original on January 21, 2018. Retrieved January 20, 2018.
34. ^ Chargers safety Kiel arrested on drug charges Archived July 19, 2009, at the Wayback Machine, USA Today, September 28, 2006
35. ^ "Purple Drank and the NFL: Johnny Jolly Isn't the Only One Getting Caught". Bleacher Report. Archived from the original on March 4, 2022. Retrieved March 3, 2022.
36. ^ Case against Jolly dismissed Archived August 12, 2022, at the Wayback Machine, "Milwaukee Journal Sentinel", July 16, 2009
37. ^ "540 ESPN Milwaukee". Espnmilwaukee.com. Archived from the original on December 20, 2009. Retrieved January 4, 2010.
38. ^ 2010-07-05 Archived July 8, 2010, at the Wayback Machine
39. ^ "2013-11-06". News.radio.com. June 11, 2013. Archived from the original on March 10, 2018. Retrieved April 10, 2014.
40. ^ Streit, Kate (September 14, 2018). "Here's What You Need To Know About Lean—The Cough Syrup Drink That Mac Miller Spoke About Before His Death". Simplemost. Archived from the original on January 23, 2022. Retrieved July 30, 2019.
41. ^ "Yung Lean's Second Chance". The FADER. Archived from the original on June 15, 2020. Retrieved February 9, 2022.
42. ^ "'Slow Your Roll' With DRANK From Innovative Beverage Group – the World's First Extreme Lifestyle Relaxation Beverage". Yahoo. June 10, 2008. Archived from the original on December 2, 2008. Retrieved September 16, 2008.
43. ^ Adventures in Press Releases: The Anti-Energy Drink Archived April 4, 2009, at the Wayback Machine By Sarah DiGregorio in Edible News, June 4, 2008
44. ^ 'Sippin Syrup' being sold in stores creates controversy Archived February 25, 2012, at the Wayback Machine, theGrio website, September 25, 2009. Retrieved November 27, 2009.
45. ^ a b Jemimah Noonoo, Anti-Energy Drink Fuels Concerns Over Marketing Archived July 6, 2010, at the Wayback Machine, Houston Chronicle, November 28, 2008; retrieved from commercialalert.org website on November 27, 2009
46. ^ a b Boyce Watkins, Company Makes Money from Deadly Urban Trend: "Sipping Syrup" Archived November 2, 2020, at the Wayback Machine, AOL Black Voices, September 29, 2009
47. ^ a b Kim Horner, Anti-energy drink hard for some mental health experts to swallow Archived November 18, 2010, at the Wayback Machine, Dallas Morning News, February 18, 2010

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* Aceclidine
* Acetylcholine
* AF30
* AF150(S)
* AF267B
* Alvameline
* AQRA-741
* Arecoline
* Bethanechol
* Butyrylcholine
* Carbachol
* CDD-0034
* CDD-0078
* CDD-0097
* CDD-0098
* CDD-0102
* Cevimeline
* Choline
* cis-Dioxolane
* Desmethylclozapine (norclozapine)
* Ethoxysebacylcholine
* Itameline
* LY-593,039
* L-689,660
* LY-2,033,298
* McNA343
* Methacholine
* Milameline
* Muscarine
* NGX-267
* Ocvimeline
* Oxotremorine
* PD-151,832
* Pilocarpine
* RS86
* Sabcomeline
* SDZ 210-086
* Sebacylcholine
* Suberyldicholine
* Talsaclidine
* Tazomeline
* Thiopilocarpine
* Vedaclidine
* VU-0029767
* VU-0090157
* VU-0152099
* VU-0152100
* VU-0238429
* WAY-132,983
* Xanomeline
* YM-796

|

Antagonists|

* 3-Quinuclidinyl benzilate
* 4-DAMP
* Aclidinium bromide (+formoterol)
* Abediterol
* AF-DX 250
* AF-DX 384
* Ambutonium bromide
* Anisodamine
* Anisodine
* Antihistamines (first-generation) (e.g., brompheniramine, buclizine, captodiame, chlorphenamine (chlorpheniramine), cinnarizine, clemastine, cyproheptadine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, meclizine, mequitazine, perlapine, phenindamine, pheniramine, phenyltoloxamine, promethazine, propiomazine, triprolidine)
* AQ-RA 741
* Atropine
* Atropine methonitrate
* Atypical antipsychotics (e.g., clozapine, fluperlapine, olanzapine (+fluoxetine), rilapine, quetiapine, tenilapine, zotepine)
* Benactyzine
* Benzatropine (benztropine)
* Benzilone
* Benzilylcholine mustard
* Benzydamine
* Bevonium
* BIBN 99
* Biperiden
* Bornaprine
* Camylofin
* CAR-226,086
* CAR-301,060
* CAR-302,196
* CAR-302,282
* CAR-302,368
* CAR-302,537
* CAR-302,668
* Caramiphen
* Cimetropium bromide
* Clidinium bromide
* Cloperastine
* CS-27349
* Cyclobenzaprine
* Cyclopentolate
* Darifenacin
* DAU-5884
* Desfesoterodine
* Dexetimide
* DIBD
* Dicycloverine (dicyclomine)
* Dihexyverine
* Difemerine
* Diphemanil metilsulfate
* Ditran
* Drofenine
* EA-3167
* EA-3443
* EA-3580
* EA-3834
* Emepronium bromide
* Etanautine
* Etybenzatropine (ethybenztropine)
* Fenpiverinium
* Fentonium bromide
* Fesoterodine
* Flavoxate
* Glycopyrronium bromide (+beclometasone/formoterol, +indacaterol, +neostigmine)
* Hexahydrodifenidol
* Hexahydrosiladifenidol
* Hexbutinol
* Hexocyclium
* Himbacine
* HL-031,120
* Homatropine
* Imidafenacin
* Ipratropium bromide (+salbutamol)
* Isopropamide
* J-104,129
* Hyoscyamine
* Mamba toxin 3
* Mamba toxin 7
* Mazaticol
* Mebeverine
* Meladrazine
* Mepenzolate
* Methantheline
* Methoctramine
* Methylatropine
* Methylhomatropine
* Methylscopolamine
* Metixene
* Muscarinic toxin 7
* N-Ethyl-3-piperidyl benzilate
* N-Methyl-3-piperidyl benzilate
* Nefopam
* Octatropine methylbromide (anisotropine methylbromide)
* Orphenadrine
* Otenzepad (AF-DX 116)
* Otilonium bromide
* Oxapium iodide
* Oxitropium bromide
* Oxybutynin
* Oxyphencyclimine
* Oxyphenonium bromide
* PBID
* PD-102,807
* PD-0298029
* Penthienate
* Pethidine
* pFHHSiD
* Phenglutarimide
* Phenyltoloxamine
* Pipenzolate bromide
* Piperidolate
* Pirenzepine
* Piroheptine
* Pizotifen
* Poldine
* Pridinol
* Prifinium bromide
* Procyclidine
* Profenamine (ethopropazine)
* Propantheline bromide
* Propiverine
* Quinidine
* 3-Quinuclidinyl thiochromane-4-carboxylate
* Revefenacin
* Rociverine
* RU-47,213
* SCH-57,790
* SCH-72,788
* SCH-217,443
* Scopolamine (hyoscine)
* Scopolamine butylbromide (hyoscine butylbromide)
* Silahexacyclium
* Sofpironium bromide
* Solifenacin
* SSRIsTooltip Selective serotonin reuptake inhibitors (e.g., femoxetine, paroxetine)
* Telenzepine
* Terodiline
* Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine)
* Tiemonium iodide
* Timepidium bromide
* Tiotropium bromide
* Tiquizium bromide
* Tofenacin
* Tolterodine
* Tricyclic antidepressants (e.g., amitriptyline (+perphenazine), amitriptylinoxide, butriptyline, cidoxepin, clomipramine, desipramine, desmethyldesipramine, dibenzepin, dosulepin (dothiepin), doxepin, imipramine, lofepramine, nitroxazepine, northiaden (desmethyldosulepin), nortriptyline, protriptyline, quinupramine, trimipramine)
* Tridihexethyl
* Trihexyphenidyl
* Trimebutine
* Tripitamine (tripitramine)
* Tropacine
* Tropatepine
* Tropicamide
* Tropine benzilate
* Trospium chloride
* Typical antipsychotics (e.g., chlorpromazine, chlorprothixene, cyamemazine (cyamepromazine), loxapine, mesoridazine, thioridazine)
* Umeclidinium bromide (+vilanterol)
* WIN-2299
* Xanomeline
* Zamifenacin

Precursors
(and prodrugs)|

* Acetyl-coA
* Adafenoxate
* Choline (lecithin)
* Citicoline
* Cyprodenate
* Dimethylethanolamine
* Glycerophosphocholine
* Meclofenoxate (centrophenoxine)
* Phosphatidylcholine
* Phosphatidylethanolamine
* Phosphorylcholine
* Pirisudanol

See also
Receptor/signaling modulators
Nicotinic acetylcholine receptor modulators
Acetylcholine metabolism/transport modulators

* v
* t
* e

Nicotinic acetylcholine receptor modulators

nAChRsTooltip Nicotinic acetylcholine receptors|

| Agonists
(and PAMsTooltip positive allosteric modulators)|

* 5-HIAA
* 6-Chloronicotine
* A-84,543
* A-366,833
* A-582,941
* A-867,744
* ABT-202
* ABT-418
* ABT-560
* ABT-894
* Acetylcholine
* Altinicline
* Anabasine
* Anatabine
* Anatoxin-a
* AR-R17779
* Bephenium hydroxynaphthoate
* Butinoline
* Butyrylcholine
* Carbachol
* Choline
* Choline m-bromophenyl ether
* Cotinine
* Cytisine
* Decamethonium
* Desformylflustrabromine
* Dianicline
* Dimethylphenylpiperazinium
* Epibatidine
* Epiboxidine
* Ethanol (alcohol)
* Ethoxysebacylcholine
* EVP-4473
* EVP-6124
* Galantamine
* GTS-21
* Ispronicline
* Ivermectin
* JNJ-39393406
* Levamisole
* Lobeline
* MEM-63,908 (RG-3487)
* Morantel
* Nicotine (tobacco)
* NS-1738
* PHA-543,613
* PHA-709,829
* PNU-120,596
* PNU-282,987
* Pozanicline
* Pyrantel
* Rivanicline
* RJR-2429
* Sazetidine A
* SB-206553
* Sebacylcholine
* SIB-1508Y
* SIB-1553A
* SSR-180,711
* Suberyldicholine
* Suxamethonium (succinylcholine)
* Suxethonium (succinyldicholine)
* TC-1698
* TC-1734
* TC-1827
* TC-2216
* TC-5214
* TC-5619
* TC-6683
* Tebanicline
* Tribendimidine
* Tropisetron
* UB-165
* Varenicline
* WAY-317,538
* XY-4083

|

Antagonists
(and NAMsTooltip negative allosteric modulators)|

* 18-MAC
* 18-MC
* α-Neurotoxins (e.g., α-bungarotoxin, α-cobratoxin, α-conotoxin, many others)
* ABT-126
* Alcuronium
* Allopregnanolone
* Amantadine
* Anatruxonium
* AQW051
* Atracurium
* Barbiturates (e.g., pentobarbital, sodium thiopental)
* BNC-210
* Bungarotoxins (e.g., α-bungarotoxin, κ-bungarotoxin)
* Bupropion
* BW284C51
* BW-A444
* Candocuronium iodide (chandonium iodide)
* Chlorisondamine
* Cisatracurium
* Coclaurine
* Coronaridine
* Curare
* Cyclopropane
* Dacuronium bromide
* Decamethonium
* Dehydronorketamine
* Desflurane
* Dextromethorphan
* Dextropropoxyphene
* Dextrorphan
* Diadonium
* DHβE
* Dihydrochandonium
* Dimethyltubocurarine (metocurine)
* Dioscorine
* Dipyrandium
* Dizocilpine (MK-801)
* Doxacurium
* Encenicline
* Enflurane
* Erythravine
* Esketamine
* Fazadinium
* Gallamine
* Gantacurium chloride
* Halothane
* Hexafluronium
* Hexamethonium (benzohexonium)
* Hydroxybupropion
* Hydroxynorketamine
* Ibogaine
* Isoflurane
* Ketamine
* Kynurenic acid
* Laudanosine
* Laudexium (laudolissin)
* Levacetylmethadol
* Levomethadone
* Malouetine
* ME-18-MC
* Mecamylamine
* Memantine
* Methadone
* Methorphan (racemethorphan)
* Methyllycaconitine
* Metocurine
* Mivacurium
* Morphanol (racemorphan)
* Neramexane
* Nitrous oxide
* Norketamine
* Pancuronium bromide
* Pempidine
* Pentamine
* Pentolinium
* Phencyclidine
* Pipecuronium bromide
* Progesterone
* Promegestone
* Radafaxine
* Rapacuronium bromide
* Reboxetine
* Rocuronium bromide
* Sevoflurane
* Stercuronium iodide
* Surugatoxin
* Thiocolchicoside
* Threohydrobupropion
* Toxiferine
* Tramadol
* Trimetaphan camsilate (trimethaphan camsylate)
* Tropeinium
* Tubocurarine
* Vanoxerine
* Vecuronium bromide
* Xenon

Precursors
(and prodrugs)|

* Acetyl-coA
* Adafenoxate
* Choline (lecithin)
* Citicoline
* Cyprodenate
* Dimethylethanolamine
* Glycerophosphocholine
* Meclofenoxate (centrophenoxine)
* Phosphatidylcholine
* Phosphatidylethanolamine
* Phosphorylcholine
* Pirisudanol

See also
Receptor/signaling modulators
Muscarinic acetylcholine receptor modulators
Acetylcholine metabolism/transport modulators

* v
* t
* e

Opioid receptor modulators

μ-opioid
(MOR)|

| Agonists
(abridged;
full list)|

* 3-HO-PCP
* 7-Acetoxymitragynine
* 7-Hydroxymitragynine
* ψ-Akuammigine
* α-Chlornaltrexamine
* α-Narcotine
* Acetyldihydrocodeine
* Acetylfentanyl
* Acrylfentanyl
* Adrenorphin (metorphamide)
* AH-7921
* Akuammicine
* Akuammidine
* Alfentanil
* Anileridine
* Apparicine
* β-Endorphin
* BAM-12P
* BAM-18P
* BAM-22P
* Benzhydrocodone
* Benzylmorphine
* Bezitramide
* Biphalin
* BU08070
* Buprenorphine
* Butorphan
* Butorphanol
* Butyrfentanyl
* BW373U86
* Carfentanil
* Casokefamide
* Cebranopadol
* Chloroxymorphamine
* Codeine
* DADLE
* DAMGO (DAGO)
* Dermorphin
* Desmetramadol (desmethyltramadol)
* Desomorphine
* Deumitragynine
* Dextromoramide
* Dextropropoxyphene (propoxyphene)
* Dezocine
* Dimenoxadol
* Dimethylaminopivalophenone
* Eluxadoline
* Diamorphine (heroin)
* Dihydrocodeine
* Dihydroetorphine
* Dihydromorphine
* Dinalbuphine sebacate
* Diphenoxylate
* Dipipanone
* Dynorphin A
* Embutramide
* Endomorphin-1
* Endomorphin-2
* Eseroline
* Ethylmorphine
* Etorphine
* Fentanyl
* Fluorophen
* Frakefamide
* Furanylfentanyl
* Hemorphin-4
* Herkinorin
* Hodgkinsine
* Hydrocodone
* Hydromorphinol
* Hydromorphone
* IBNtxA
* Ketamine
* Ketobemidone
* Kratom
* Laudanosine
* Lefetamine
* Leu-enkephalin
* Levacetylmethadol
* Levomethorphan
* Levorphanol
* Lexanopadol
* Loperamide
* Loxicodegol
* LS-115509
* Matrine
* Meptazinol
* Met-enkephalin (metenkefalin)
* Methadone
* Metkefamide
* Metopon
* Mitragynine
* Mitragynine pseudoindoxyl
* Morphiceptin
* Morphine
* Nalbuphine
* Naloxone benzoylhydrazone (NalBzOH)
* Nalmexone
* Naltalimide
* Neopine
* NFEPP
* Nicocodeine
* Nicodicodine
* Nicomorphine
* Norketamine
* Nufenoxole
* Octreotide
* Oliceridine
* Oxycodegol
* Oxymorphone-3-methoxynaltrexonazine (OM-3-MNZ)
* Oripavine
* Oxycodone
* Oxymorphazone
* Oxymorphonazine
* Oxymorphone
* Oxymorphone phenylhydrazone
* OxyPNPH
* Papaver somniferum (opium)
* Pentazocine
* Pericine
* Pethidine (meperidine)
* Phenazocine
* Phencyclidine
* Piminodine
* Piritramide
* PL-017
* Prodine
* Propiram
* PZM21
* Racemethorphan
* Racemorphan
* Remifentanil
* Salsolinol
* SC-17599
* Sinomenine
* Sufentanil
* Tapentadol
* Tetrahydropapaveroline
* TH-030418
* Thebaine
* Thienorphine
* Tianeptine
* Tilidine
* Tramadol
* Trimebutine
* TRIMU 5
* TRV734
* Tubotaiwine
* U-47700
* Valorphin
* Viminol
* Xorphanol

|

Antagonists|

* (3S,4S)-Picenadol
* 2-(S)-N,N-(R)-Viminol
* 3CS-nalmefene
* 4-Caffeoyl-1,5-quinide
* 4′-Hydroxyflavanone
* 4',7-Dihydroxyflavone
* 6β-Naltrexol
* 6β-Naltrexol-d4
* 18-MC
* α-Gliadin
* β-Chlornaltrexamine
* β-Funaltrexamine
* Akuammine
* Alvimopan
* AM-251
* Apigenin
* AT-076
* Axelopran
* Bevenopran
* Catechin
* Catechin gallate
* Clocinnamox
* CTAP
* CTOP
* Cyclofoxy
* Cyprodime
* Diacetylnalorphine
* Diprenorphine
* ECG
* EGC
* Epicatechin
* Eptazocine
* Gemazocine
* Ginsenoside R
* Hyperoside
* Ibogaine
* JDTic
* Levallorphan
* Lobeline
* LY-255582
* LY-2196044
* Methocinnamox
* Methylnaltrexone
* Methylsamidorphan chloride
* Naldemedine
* Nalmefene
* Nalodeine (N-allylnorcodeine)
* Nalorphine
* Nalorphine dinicotinate
* Naloxazone
* Naloxegol
* Naloxol
* Naloxonazine
* Naloxone
* Naltrexazone
* Naltrexonazine
* Naltrexone
* Naltrindole
* Naringenin
* Noribogaine
* Oxilorphan
* Pawhuskin A
* Rimonabant
* Quadazocine
* Samidorphan
* Taxifolin

δ-opioid
(DOR)|

| Agonists|

* 3CS-nalmefene
* 6'-GNTI
* 7-SIOM
* ADL-5747 (PF-04856881)
* ADL-5859
* Alazocine (SKF-10047)
* Amoxapine
* AR-M100390 (ARM390)
* AZD2327
* β-Endorphin
* BAM-18P
* Biphalin
* BU-48
* Butorphan
* Butorphanol
* BW373U86
* Casokefamide
* Cebranopadol
* Codeine
* Cyclazocine
* DADLE
* Deltorphin A
* Deltorphin I
* Deltorphin II
* Desmethylclozapine
* Desmetramadol (desmethyltramadol)
* Dezocine
* Diamorphine (heroin)
* Dihydroetorphine
* Dihydromorphine
* DPDPE
* DPI-221
* DPI-3290
* DSLET
* Ethylketazocine
* Etorphine
* Fentanyl
* FIT
* Fluorophen
* Hemorphin-4
* Hydrocodone
* Hydromorphone
* Ibogaine
* Isomethadone
* JNJ-20788560
* KNT-127
* Kratom
* Laudanosine
* Leu-enkephalin
* Levomethorphan
* Levorphanol
* Lexanopadol
* Lofentanil
* Met-enkephalin (metenkefalin)
* Metazocine
* Metkefamide
* Mitragynine
* Mitragynine pseudoindoxyl
* Morphine
* N-Phenethyl-14-ethoxymetopon
* Norbuprenorphine
* NalBzOH
* Oripavine
* Oxycodone
* Oxymorphone
* Pethidine (meperidine)
* Proglumide
* Racemethorphan
* Racemorphan
* RWJ-394674
* Samidorphan
* SB-235863
* SNC-80
* SNC-162
* TAN-67 (SB-205,607)
* TH-030418
* Thebaine
* Thiobromadol (C-8813)
* Tonazocine
* Tramadol
* TRV250
* Xorphanol
* Zenazocine

|

Antagonists|

* 4',7-Dihydroxyflavone
* 5'-NTII
* 6β-Naltrexol
* 6β-Naltrexol-d4
* α-Santolol
* β-Chlornaltrexamine
* Apigenin
* AT-076
* Axelopran
* Bevenopran
* BNTX
* Catechin
* Catechin gallate
* Clocinnamox
* Diacetylnalorphine
* Diprenorphine
* ECG
* EGC
* Eluxadoline
* Epicatechin
* ICI-154129
* ICI-174864
* LY-255582
* LY-2196044
* Methylnaltrexone
* Methylnaltrindole
* N-Benzylnaltrindole
* Nalmefene
* Nalorphine
* Naltrexone
* Naltriben
* Naltrindole
* Naloxone
* Naringenin
* Noribogaine
* Pawhuskin A
* Quadazocine
* SDM25N
* SoRI-9409
* Taxifolin
* Thienorphine

κ-opioid
(KOR)|

| Agonists|

* 3CS-nalmefene
* 6'-GNTI
* 8-CAC
* 18-MC
* 14-Methoxymetopon
* β-Chlornaltrexamine
* β-Funaltrexamine
* Adrenorphin (metorphamide)
* Akuammicine
* Alazocine (SKF-10047)
* Allomatrine
* Apadoline
* Asimadoline
* BAM-12P
* BAM-18P
* BAM-22P
* Big dynorphin
* Bremazocine
* BRL-52537
* Butorphan
* Butorphanol
* BW373U86
* Cebranopadol
* Ciprefadol
* CR665
* Cyclazocine
* Cyclorphan
* Cyprenorphine
* Desmetramadol (desmethyltramadol)
* Diamorphine (heroin)
* Diacetylnalorphine
* Difelikefalin
* Dihydroetorphine
* Dihydromorphine
* Dinalbuphine sebacate
* Diprenorphine
* Dynorphin A
* Dynorphin B (rimorphin)
* Eluxadoline
* Enadoline
* Eptazocine
* Erinacine E
* Ethylketazocine
* Etorphine
* Fedotozine
* Fentanyl
* Gemazocine
* GR-89696
* GR-103545
* Hemorphin-4
* Herkinorin
* HS665
* Hydromorphone
* HZ-2
* Ibogaine
* ICI-199,441
* ICI-204,448
* Ketamine
* Ketazocine
* Laudanosine
* Leumorphin (dynorphin B-29)
* Levallorphan
* Levomethorphan
* Levorphanol
* Lexanopadol
* Lofentanil
* LPK-26
* Lufuradom
* Matrine
* MB-1C-OH
* Menthol
* Metazocine
* Metkefamide
* Mianserin
* Mirtazapine
* Morphine
* Moxazocine
* MR-2034
* N-MPPP
* Nalbuphine
* NalBzOH
* Nalfurafine
* Nalmefene
* Nalodeine (N-allylnorcodeine)
* Nalorphine
* Naltriben
* Niravoline
* Norbuprenorphine
* Norbuprenorphine-3-glucuronide
* Noribogaine
* Norketamine
* Oripavine
* Oxilorphan
* Oxycodone
* Pentazocine
* Pethidine (meperidine)
* Phenazocine
* Proxorphan
* Racemethorphan
* Racemorphan
* RB-64
* Salvinorin A (salvia)
* Salvinorin B ethoxymethyl ether
* Salvinorin B methoxymethyl ether
* Samidorphan
* Spiradoline (U-62066)
* TH-030418
* Thienorphine
* Tifluadom
* Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline)
* U-50488
* U-54494A
* U-69593
* Xorphanol

|

Antagonists|

* 4′-Hydroxyflavanone
* 4',7-Dihydroxyflavone
* 5'-GNTI
* 6'-GNTI
* 6β-Naltrexol
* 6β-Naltrexol-d4
* β-Chlornaltrexamine
* Buprenorphine/samidorphan
* Amentoflavone
* ANTI
* Apigenin
* Arodyne
* AT-076
* Aticaprant
* Axelopran
* AZ-MTAB
* Binaltorphimine
* BU09059
* Buprenorphine
* Catechin
* Catechin gallate
* CERC-501 (LY-2456302)
* Clocinnamox
* CVL-354
* Cyclofoxy
* Dezocine
* DIPPA
* EGC
* ECG
* Epicatechin
* Hyperoside
* JDTic
* LY-255582
* LY-2196044
* LY-2444296
* LY-2459989
* LY-2795050
* MeJDTic
* Methylnaltrexone
* ML190
* ML350
* MR-2266
* N-Fluoropropyl-JDTic
* Naloxone
* Naltrexone
* Naltrindole
* Naringenin
* Navacaprant
* Norbinaltorphimine
* Noribogaine
* Pawhuskin A
* PF-4455242
* RB-64
* Quadazocine
* Taxifolin
* UPHIT
* Zyklophin

Nociceptin
(NOP)|

| Agonists|

* (Arg14,Lys15)Nociceptin
* ((pF)Phe4)Nociceptin(1-13)NH2
* (Phe1Ψ(CH2-NH)Gly2)Nociceptin(1-13)NH2
* Ac-RYYRWK-NH2
* Ac-RYYRIK-NH2
* BU08070
* Buprenorphine
* Cebranopadol
* Dihydroetorphine
* Etorphine
* JNJ-19385899
* Levomethorphan
* Levorphanol
* Lexanopadol
* MCOPPB
* MT-7716
* NNC 63-0532
* Nociceptin (orphanin FQ)
* Nociceptin (1-11)
* Nociceptin (1-13)NH2
* Norbuprenorphine
* Racemethorphan
* Racemorphan
* Ro64-6198
* Ro65-6570
* SCH-221510
* SCH-486757
* SR-8993
* SR-16435
* Sunobinop (S-117957)
* TH-030418

|

Antagonists|

* (Nphe1)Nociceptin(1-13)NH2
* AT-076
* BAN-ORL-24
* BTRX-246040 (LY-2940094)
* J-113397
* JTC-801
* NalBzOH
* Nociceptin (1-7)
* Nocistatin
* SB-612111
* SR-16430
* Thienorphine
* Trap-101
* UFP-101

Others|

* Enkephalinase inhibitors: Amastatin
* BL-2401
* Candoxatril
* D-Phenylalanine
* Dexecadotril (retorphan)
* Ecadotril (sinorphan)
* Kelatorphan
* Racecadotril (acetorphan)
* RB-101
* RB-120
* RB-3007
* Opiorphan
* Selank
* Semax
* Spinorphin
* Thiorphan
* Tynorphin
* Ubenimex (bestatin)

* Propeptides: β-Lipotropin (proendorphin)
* Prodynorphin
* Proenkephalin
* Pronociceptin
* Proopiomelanocortin (POMC)

* Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)

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*[mAChRs]: Muscarinic acetylcholine receptors
*[SSRIs]: Selective serotonin reuptake inhibitors
*[nAChRs]: Nicotinic acetylcholine receptors
*[PAMs]: positive allosteric modulators
*[NAMs]: negative allosteric modulators