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Polydrug use refers to the use of two or more psychoactive drugs in combination to achieve a particular effect. Often called "cross fading", it is usual among problem drug users who have a multi-drug dependence. In many cases one drug is used as a base-primary - or preferred drug, with additional drugs to leaven or compensate for the side effects of the primary drug and make the experience more enjoyable with drug synergy effects, or to supplement for primary drug when supply is low.

Poly drug 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. Concerns exist about a number of pharmacological pairings: alcohol and cocaine increase cardiovascular toxicity; alcohol or depressant drugs, when taken with opioids, lead to an increased risk of overdose; and opioids or cocaine taken with ecstasy or amphetamines also result in additional acute toxicity.[1] The risk for aggression and violent outbursts increase when some benzodiazepines, for example Flunitrazepam, are combined with alcohol. Combining cannabis and cocaine (as in the case of snow cones) has a strong effect on the heart as both drugs have effects on heart rate.

Within the general concept of multiple drug use, several specific meanings of the term must be considered. At one extreme is planned use. 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.[1]

The phenomenon is the subject of established academic literature (e.g., Scholey AB, Parrott AC, Buchanan T, Heffernan TM, Ling J, Rodgers J (2004). "Increased intensity of Ecstasy and polydrug use in the more experienced Ecstasy/MDMA users: a WWW study." Addictive Behaviors, 29, 743-752).

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