The effects of cannabidiol on behavioural and oxidative stress parameters induced by prolonged haloperidol administration.

OBJECTIVES: We investigated the influence of oral cannabidiol (CBD) on vacuous chewing movements (VCM) and oxidative stress parameters induced by short- and long-term administration of haloperidol in a rat model of tardive dyskinesia (TD). METHODS: Haloperidol was administered either sub-chronically via the intraperitoneal (IP) route or chronically via the intramuscular (IM) route to six experimental groups only or in combination with CBD. VCM and oxidative stress parameters were assessed at different time points after the last dose of medication. RESULTS: Oral CBD (5 mg/kg) attenuated the VCM produced by sub-chronic administration of haloperidol (5 mg/kg) but had minimal effects on the VCM produced by chronic administration of haloperidol (50 mg/kg). In both sub-chronic and chronic haloperidol groups, there were significant changes in brain antioxidant parameters compared with CBD only and the control groups. The sub-chronic haloperidol-only group had lower glutathione activity compared with sub-chronic haloperidol before CBD and the control groups; also, superoxide dismutase, catalase, and 2,2-diphenyl-1-picrylhydrazyl activities were increased in the sub-chronic (IP) haloperidol only group compared with the CBD only and control groups. Nitric oxide activity was increased in sub-chronic haloperidol-only group compared to the other groups; however, the chronic haloperidol group had increased malondialdehyde activity compared to the other groups. CONCLUSIONS: Our findings indicate that CBD ameliorated VCM in the sub-chronic haloperidol group before CBD, but marginally in the chronic haloperidol group before CBD. There was increased antioxidant activity in the sub-chronic group compared to the chronic group.

Effects of cannabidiol on vacuous chewing movements, plasma glucose and oxidative stress indices in rats administered high dose risperidone.

Atypical antipsychotics, despite their rapid dissociation from dopamine receptors and reduced tendency to induce oxidative stress, have been associated with difficult-to-manage movement disorders, including tardive dyskinesia (TD). The study set out to investigate the effects of cannabidiol (CBD), a potent antioxidant, on risperidone-induced behavioural and motor disturbances; namely vacuous chewing movements (VCM), and oxidative stress markers (e.g. superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), malondialdehyde (MDA), Nitric oxide (NO), and DPPH (2,2-diphenyl-1-picrylhydrazyl)). Oral risperidone (10 mg/kg) or oral CBD (5 mg/kg) were administered to six experimental groups. While risperidone alone was administered for 28 days, CBD concomitantly or in sequential order with risperidone, was administered for 28 days; and CBD alone was administered for 21 days. Behavioural, motor, and specific biochemical parameters, which included VCM, muscle tone, fasting blood sugar (FBS), and oxidative stress markers were assessed at different time points after the last dose of medication. Oral CBD (5 mg/kg) significantly reduced risperidone-induced elevated FBS when given after the administration of risperidone. Oral CBD also had effects on VCM when administered before risperidone and similarly, attenuated risperidone-induced increased muscle tone. It was also established that concomitant or sequential administration of CBD and risperidone did not have any adverse effects on cognition or locomotion. Both CBD and risperidone increased the activity of antioxidant enzymes and decreased the activity of pro-oxidant enzymes. This study suggests CBD could mitigate metabolic dysregulation and extrapyramidal side effects associated with risperidone without producing cognitive impairments.

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.

Investigation of the effects of cannabidiol on vacuous chewing movements, locomotion, oxidative stress and blood glucose in rats treated with oral haloperidol.

Objectives: Tardive dyskinesia (TD) unlike acute dystonia may be irreversible. This study investigated the effects of oral cannabidiol (CBD) on haloperidol-induced vacuous chewing movement (VCM) model of TD. Methods: There were six experimental groups with different combinations of oral cannabidiol with 5 mg/kg of haloperidol given orally. Behavioural assays and FBS were measured. VCMs were assessed after the last dose of medication. Blood for oxidative stress assays was collected on the 8th day after the administration of the last dose of medication. Results: This study found that CBD co-administration with haloperidol attenuated the VCMs and increased motor tone produced by haloperidol. CBD alone at 5 mg/kg appears to have anxiolytic properties but may not be as effective as haloperidol which exhibited a greater anxiolytic effect at 5 mg/kg. Treatment with CBD alone at 5 mg/kg also appeared to enhance brain DPPH scavenging activity. Conclusions: We confirmed that CBD can ameliorate motor impairments produced by haloperidol. Our data suggest that CBD can be combined with haloperidol to prevent the emergent of extrapyramidal side effects and long-term movement disorders, such as acute dystonic disorder and TD.