Polysubstance use

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Polysubstance use
Caffeinated alcoholic beverages, such as these caffè corretto cocktails based on espresso and liquor are widespread and legal.
ComplicationsCombined drug intoxication, drug overdose[1]
Ayahuasca being prepared in the Napo region of Ecuador
Close-up photo of a metal spoon filled with a viscous, clear purple fluid
A spoonful of promethazine/​codeine cough syrup showing the characteristic purple color that gave rise to the name purple drink.

Polysubstance use or poly drug use refers to the use of combined psychoactive substances. Polysubstance use may be used for entheogenic, recreational, or off-label indications, with both legal and illegal substances. In many cases one drug is used as a base or primary drug, with additional drugs to leaven or compensate for the side effects, or tolerance, of the primary drug and make the experience more enjoyable with drug synergy effects, or to supplement for primary drug when supply is low.[2]

Common combinations[edit]

The most common psychoactive substances are alcohol, caffeine, cannabis, and nicotine (tobacco, and nicotine replacement therapy). Some other common polysubstance combinations are:

Combination drugs[edit]

Some common combinations that are used recreationally include

Drug synergy[edit]


Some substances, such as the powerful psychedelic drug DMT, are not psychoactive when ingested alone. Ayahuasca, or pharmahuasca, notably consists of DMT combined with MAOIs that interfere with the action of the MAO enzyme and stop the breakdown in the stomach of chemical compounds, which make the DMT psychoactive. The MAOIs are also psychoactive and thus produce a polysubstance effect with the DMT. However, the MAOIs may cause combined drug intoxication with the majority of all psychoactive substances and are therefore usually only combined with DMT.


TOMSO is a lesser-known psychedelic drug and a substituted amphetamine. TOMSO is inactive on its own; it is activated with the consumption of alcohol.

Proprietary blends[edit]


Some ingredients such as caffeine, creatine and β-alanine are found in nearly all pre-workout blends, but each branded product is a "proprietary blend" with an average of 18 different ingredients, the exact composition and proportions of which can vary widely between different products.[3][4] Additionally legal psychoactive substances occasionally used in these proprietary blends that are typically legal include 5-HTP, tyrosine, and yohimbine. Although these products are not banned, the Food and Drug Administration (FDA) warns consumers to be cautious when consuming pre-workout.[5]

Combined drug intoxication[edit]

Tranquillizers, sleeping pills, opiates and alcohol. Opioid-related deaths often involve alcohol.

Combined drug intoxication use often carries with it more risk than use of a single drug, due to an increase in side effects, and drug synergy. The potentiating effect of one drug on another is sometimes considerable and here the licit drugs and medicines – such as alcohol, nicotine and antidepressants – have to be considered in conjunction with the controlled psychoactive substances. The risk level will depend on the dosage level of both substances. If the drugs taken are illegal, they have a chance of being mixed (also known as "cutting") with other substances which dealers are reported to do to increase the perceived quantity when selling to others to increase their returns. This is particularly common with powdered drugs such as cocaine or MDMA which can be mixed with relative ease by adding another white powdery substance to the drug. This cumulative effect can lead to further unintended harm to health dependent on what is being covertly added.

Dangerous combinations of drug classes[edit]

Concerns exist about a number of pharmacological pairings, especially:

  • Antidepressants
    • MAOIs combined with most drug classes, especially stimulants.
    • SSRIs combined with MAOIs, or opioids.
  • Depressants combined with depressant. For example:
  • Depressants combined with stimulants. For example:
    • Alcohol and cocaine increase cardiovascular toxicity;[9] alcohol or depressant drugs, when taken with opioids, lead to an increased risk of overdose
    • Opioids or cocaine taken with ecstasy or amphetamines also result in additional acute toxicity.[10]


Within the general concept of multiple drug use, several specific meanings of the term must be considered. At one extreme is planned use, where the effects of more than one drug are taken for a desired effect. Another type is when other drugs are used to counteract the negative side effects of a different drug (e.g. depressants are used to counteract anxiety and restlessness from taking stimulants). On the other hand, the use of several substances in an intensive and chaotic way, simultaneously or consecutively, in many cases each drug substituting for another according to availability.[10]


The phenomenon is the subject of established academic literature.[11]

A study among treatment admissions found that it is more common for younger people to report polysubstance use.[12]

See also[edit]


  1. ^ a b Anthony, James; Barondess, David A.; Radovanovic, Mirjana; Lopez-Quintero, Catalina (2017). "Part 1: Psychiatric Comorbidity – Polydrug Use: Research Topics and Issues". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 2. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381708.013.006. ISBN 9780199381708. LCCN 2016020729.
  2. ^ "Polydrug use | www.emcdda.europa.eu". www.emcdda.europa.eu.
  3. ^ Harty PS, Zabriskie HA, Erickson JL, Molling PE, Kerksick CM, Jagim AR (August 2018). "Multi-ingredient pre-workout supplements, safety implications, and performance outcomes: a brief review". Journal of the International Society of Sports Nutrition. 15 (1): 41. doi:10.1186/s12970-018-0247-6. PMC 6083567. PMID 30089501.
  4. ^ Jagim AR, Harty PS, Camic CL (January 2019). "Common Ingredient Profiles of Multi-Ingredient Pre-Workout Supplements". Nutrients. 11 (2): 254. doi:10.3390/nu11020254. PMC 6413194. PMID 30678328.
  5. ^ Office of the Commissioner (2019-02-09). "FDA 101: Dietary Supplements". FDA.
  6. ^ Serfaty M, Masterton G (1993). "Fatal poisonings attributed to benzodiazepines in Britain during the 1980s". Br J Psychiatry. 163 (3): 386–93. doi:10.1192/bjp.163.3.386. PMID 8104653. S2CID 46001278.
  7. ^ Buckley NA, Dawson AH, Whyte IM, O'Connell DL (1995). "[Relative toxicity of benzodiazepines in overdose.]". BMJ. 310 (6974): 219–21. doi:10.1136/bmj.310.6974.219. PMC 2548618. PMID 7866122.
  8. ^ Drummer OH; Ranson DL (December 1996). "Sudden death and benzodiazepines". Am J Forensic Med Pathol. 17 (4): 336–42. doi:10.1097/00000433-199612000-00012. PMID 8947361.
  9. ^ Pergolizzi, Joseph; Breve, Frank; Magnusson, Peter; LeQuang, Jo Ann K.; Varrassi, Giustino (2022-02-22). "Cocaethylene: When Cocaine and Alcohol Are Taken Together". Cureus. 14 (2): e22498. doi:10.7759/cureus.22498. ISSN 2168-8184. PMC 8956485. PMID 35345678.
  10. ^ a b "EMCDDA Annual Report 2006 ch. 8".
  11. ^ Scholey AB, Parrott AC, Buchanan T, Heffernan TM, Ling J, Rodgers J (June 2004). "Increased intensity of Ecstasy and polydrug usage in the more experienced recreational Ecstasy/MDMA users: a WWW study" (PDF). Addict Behav. 29 (4): 743–52. doi:10.1016/j.addbeh.2004.02.022. PMID 15135556.
  12. ^ "Polydrug Use Among Treatment Admissions: 1998." OAS Home: Alcohol, Tobacco & Drug Abuse and Mental Health Data from SAMHSA, Office of Applied Studies. Web. 29 Sept. 2011. [1]


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