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Background: Motivated behaviors are executed by refined brain circuits. Early-life adversity (ELA) is a risk for human affective disorders involving dysregulated reward behaviors. In mice, ELA causes anhedonia-like behaviors in males and augmented reward motivation in females, indicating sex-dependent disruption of reward circuit operations.

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Patients with schizophrenia have significant challenges in adhering to and complying with oral medicines, resulting in adverse consequences such as symptom worsening and psychotic relapse. This study aimed to develop clove oil-based bilosomes using definitive screening design (DSD) to maximize the anti-schizophrenic action of clozapine and promote its nose-to-brain delivery. The target was to optimize the physicochemical properties of bilosomes and incorporate them into mucoadhesive intranasal in situ gels, searching for augmented ex vivo and in vivo clozapine delivery.

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Background: Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia.

Aims: To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia.

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