Polysubstance use

Some common combinations that are used recreationally include

• Dimenhydrinate (8-chlorotheophylline/diphenhydramine) – used to treat motion sickness and nausea
• Adderall (dextroamphetamine sulfate/amphetamine sulfate/dextroamphetamine saccharate/amphetamine aspartate monohydrate) – treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.

Ayahuasca

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

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.

Pre-workout

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.^[4][5] 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.^[6]

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.

Common combinations of drug classes

• Alcohol combined with cannabis – known as cross-fading; may easily cause spins in people who are drunk and use potent cannabis.
• Caffeinated alcoholic drinks
• Nicotini: Alcohol combined with nicotine.

Dangerous combinations of drug classes

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:
  • Benzodiazepines can cause death when mixed with other CNS depressants such as opioids, alcohol, or barbiturates.^[7][8][9]
  • GHB combined with alcohol can lead to a long-lasting coma-like state (‘G-sleep’) or even death, because it is hard to dose GHB.
• Depressants combined with stimulants. For example:
  • Alcohol and cocaine (for example coca wine) increase cardiovascular toxicity;^[10] 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.^[11]

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.^[11]

The phenomenon is the subject of established academic literature.^[12]

A study among treatment admissions found that it is more common for younger people to report polysubstance use.^[13]

• Martin, Christopher S.; Chung, Tammy; Langenbucher, James W. (2017). "Part 1: Defining and Characterizing the Nature and Extent of Substance Use Disorders – Historical and Cultural Perspectives on Substance Use and Substance Use Disorders". In Sher, Kenneth J. (ed.). The Oxford Handbook of Substance Use and Substance Use Disorders: Volume 1. Oxford Library of Psychology. Oxford and New York: Oxford University Press. pp. 27–59. doi:10.1093/oxfordhb/9780199381678.013.001. ISBN 9780199381678. LCCN 2016020729.
• 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.
• Hernández-Serrano, Olga; Gras, Maria E.; Font-Mayolas, Sílvia; Sullman, Mark J. M. (2016). "Part VI: Dual and Polydrug Abuse – Chapter 83: Types of Polydrug Usage". In Preedy, Victor R. (ed.). Neuropathology of Drug Addictions and Substance Misuse, Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Cambridge, Massachusetts: Academic Press, imprint of Elsevier. pp. 839–849. doi:10.1016/B978-0-12-800634-4.00083-4. ISBN 978-0-12-800634-4.

• "The Science of Drug Use: A Resource for the Justice Sector". www.drugabuse.gov. North Bethesda, Maryland: National Institute on Drug Abuse. 26 May 2020. Retrieved 23 December 2021.
• School-Based Drug Abuse Prevention: Promising and Successful Programs (PDF). Ottawa, Ontario: Public Safety Canada. 31 January 2018. ISBN 978-1-100-12181-9. Archived (PDF) from the original on 19 May 2021. Retrieved 23 December 2021. {{cite book}}: |website= ignored (help)
• Sacco LN, Finklea K (3 May 2016). "Synthetic Drugs: Overview and Issues for Congress" (PDF). Washington, D.C.: Congressional Research Service. Archived (PDF) from the original on 8 December 2021. Retrieved 23 December 2021.