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Aim: To investigate a possible association between headache and psychoactive substance use., Methods: 1055 psychoactive substance abusers were consecutively admitted. All patients filled out a detailed headache questionnaire and 1015 patients were included., Results: Twenty seven percent of patients reported having headache. Eighteen percent of patients reported having headache attributed to a substance or its withdrawal and 1.4% had unclassified headache. The most commonly used substances were cannabis (80.5%), alcohol (74.6%), methylamphetamine (18.7%), benzodiazepine (10.4%), volatile solvent (5.8%), cocaine (4.4%), heroin (2.1%), opioids (0.5%), and other substances (1.7%). Fifteen patients reported that onset of headache occurred prior to onset of substance use, while 94.5% had headaches occurred after substance abuse. A higher incidence of headache was found in the benzodiazepine, methylamphetamine, cocaine, heroin, volatile solvent abusers. Seventy-eight percent of headache patients have never sought help from a physician despite the severity and frequency of headache., Conclusions: In our study, the prevalence of headache among all psychoactive substance abusers was 26.9%. Although this is one-group study without any comparison with non-addict population and associational data must be interpreted with caution, the results of this study indicate a possible relationship may exist between headache and substance use since 94.5% of substance users described headaches after the onset of substance use. The younger start and the longer duration of cannabis use caused the higher incidence of headache, but this correlation was not observed in other substance use. Migraine was far more prevalent in the abusers than in previously reported community populations., (Copyright © 2012 Elsevier B.V. All rights reserved.)