Multi-drug abuse may be entirely or partially intentional, or unintentional. The first derives mainly from experimenting and the desire to explore the different effects of different drugs. Multi-drug abuse may also occur through the lack of availability of the desired alternative. Unintentional multi-drug abuse occurs as a result of the adulteration of 'street' sold drugs and the ignorance of the buyer. Marijuana and mescaline have been known to be doctored with animal tranquillizers.
Multi-drug abuse is potentially much more dangerous than single drug abuse, since complications arising from the effects of different drug types render treatment difficult and in many cases impossible. Already complex drugs such as opiates are inherently incompatible with many other substances. Some of the most dangerous combinations of drug types are stimulants (amphetamines, coca) and depressants (barbiturates, tranquillizers, hypnotics), and either of these with alcohol. For example, the body's defence mechanism to vomit toxins, such as excess alcohol, can be inhibited when used in combination with drugs like marijuana. When amphetamines are used, as they often are, to counteract the effects of alcohol or sedatives (or vice versa), dependence on both types of drugs is an added risk. The use of alcohol in combination with other drugs, which may be prescribed medically as well as obtained illicitly, is particularly frequent since alcohol is socially and legally acceptable and is not generally considered as a drug. Drug cocktails, with or without alcohol, can cause disabling, even lethal, effects simply by increasing physiological stress on the body through dehydration, raised temperature, or heightened sensitivity to physical effort, such as vigorous dancing.