The over-the-counter anti-emetic dimenhydrinate (DMH) (Gravol or Dramamine) has been reported to be abused for non-medicinal purposes. Street drug users abuse DMH for the acute effects of euphoric sensations and hallucinations, while psychiatric patients abuse DMH for its anxiolytic or anti-cholinergic effects. DMH is an H(1) histamine receptor antagonist, but it interacts either directly or indirectly with other neurotransimitter systems, including those using acetylcholine, serotonin, norepinephrine, dopamine, opioids or adenosine. Animal behavioural studies, such as self-administration, conditioned place preference, drug discrimination, and modulation of operant responding, show that anti-histamines have abuse potential. Further support comes from reports of acute and chronic abuse of DMH by humans. Collectively, results confirm the abuse liability of DMH.