BackgroundTo date, the burden and impact of substance use among epileptic patients were studied in a small number of studies and showed inconsistent findings, which may be attributed to the variation in age, test batteries, epilepsy subtypes, and substance use characteristics across research. The aim of the study was to determine the burden and impact of substance abuse among a sample of epileptic patients attending Alexandria University outpatient clinics. This study was conducted on 200 epileptic patients (100 male and 100 female patients). The diagnosis of epilepsy in those patients was confirmed by expert neurologists. Using the international league against epilepsy 2017 classification, they underwent a complete physical examination. EEG was done for all patients. Every patient was assessed using a semi-structured interview and a self-designed questionnaire to collect data concerning history of epilepsy, seizure type, EEG findings, as well as questions derived from the Addiction Severity Index (ASI). The Timeline between epilepsy and substance abuse, as well as the Effect of substance intake on epileptic seizures, were assessed.ResultsA total of 27 epileptic patients had a history of substance abuse; hence, the percentage of substance use among epileptic patients was 13.5%. Mean age in the male age group was (29.74 ± 11.52) years and (27.34 ± 9.35) years in females; mean seizure frequency per month was higher among males than females and this was statistically significant (P = 0.037*). More male (24%) than females (3%) had history of substance use and this was statistically significant (P < 0.001*). Regarding the Effect of substance intake on epileptic seizures, the male group (91.7%) had Seizure worsening, while in the female group, all three patients (100%) had seizures worsening with substance use. The mean Frequency of seizures was 4.48 ± 5.08 attacks per month for substance users and 2.49 ± 3.84 attacks per month for non-users; this was statistically significant. (t = 2.392) (P = 0.018*). Non-substance use patients had better compliance to treatment (79%) in comparison to 44.4%) of Substance use patients and this was statistically significant (P < 0.001*).ConclusionDrug abuse can have a negative impact on epilepsy in both sexes regarding seizure severity frequency, and even compliance with medication.