Effects of cannabidiol on weight and fasting blood sugar with chronic and subchronic haloperidol administration

OBJECTIVES: The duration of administration (e.g., subchronic or chronic) of haloperidol may influence its adverse effects. We studied the effects of duration of administration of haloperidol on body weight and fasting blood sugar (FBS). In addition, we examined whether orally administered cannabidiol (CBD) had any putative mitigating influence on haloperidol-induced body weight changes and FBS elevation. METHODS: Haloperidol (5 mg/kg/day) was administered for 21 days (subchronic administration), via the intraperitoneal (IP) route, or monthly (50 mg/kg monthly) for 3 months (chronic administration), via the intramuscular (IM) route, either alone or before CBD (5 mg/kg/day). Oral CBD (5 mg/kg/day) alone and distilled water alone were administered for 21 days. Weight and FBS were measured before administration of pharmacological agents (distilled water in the control group) and post-administration. RESULTS: Group differences in average weight across time were significant. Pairwise comparisons showed that mean weight of the subchronic (IP) haloperidol alone group (Group A) and the chronic (IM) haloperidol before CBD group (Group F) increased significantly over time. Post medications, there was a significant increase in mean FBS in the subchronic (IP) haloperidol group compared to the subchronic (IP) haloperidol before CBD group. There was also a significant reduction in mean FBS from the baseline for the control group only. CONCLUSION: We demonstrated that the duration of administration of haloperidol influenced weight and FBS in rats, suggesting that metabolic side effects, may be influenced by duration of administration. CBD ameliorated the increase in weight and FBS observed in the subchronic (IP) haloperidol groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44192-022-00021-2.