Many brain systems may be involved in the anesthetic, intoxicating, and reinforcing effects of different inhalants. Nearly all abused inhalants (other than nitrites) produce a pleasurable effect by depressing the CNS. Nitrites, in contrast, dilate and relax blood vessels rather than act as anesthetic agents.

Evidence from animal studies suggests that a number of commonly abused volatile solvents and anesthetic gases have neurobehavioral effects and mechanisms of action similar to those produced by CNS depressants, which include alcohol and medications such as sedatives and anesthetics.

A 2007 animal study indicates that toluene, a solvent found in many commonly abused inhalants — including model airplane glue, paint sprays, and paint and nail polish removers — activates the brain's dopamine system. The dopamine system has been shown to play a role in the rewarding effects of nearly all drugs of abuse.