Primary negative symptoms of schizophrenia are usually resistant to monotherapy with antipsychotics. The present study sought to assess the efficacy and tolerability of Palmitoylethanolamide (PEA) adjunctive therapy in treatment of negative symptoms in patients with stable schizophrenia.This 8-week (trial timepoints: baseline, week 4, week 8), double-blind, placebo-controlled clinical trial randomized patients with schizophrenia in a 1:1 ratio to compare the efficacy and safety of 600 mg twice a day of PEA and matched placebo alongside a stable dose of risperidone. Outcome measures were the positive and the negative syndrome scale (PANSS), the extrapyramidal symptom rating scale (ESRS), and the Hamilton depression rating scale (HDRS). The primary outcome was change in the negative subscale score during the trial period between the groups. Safety of interventions were controlled and addressed during the trial.A total of 50 participants completed the trial (25 in each group). Baseline characteristics of the groups were comparable (p>0.05). There was significant effect from time-treatment interaction on negative symptoms (p = 0.012) suggesting greater symptom improvement in the PEA group. In contrast, the longitudinal changes in positive symptoms and depressive symptoms were similar between groups (p values>0.05). Safety assessments showed no significant difference regarding extrapyramidal symptoms, measured by ESRS, and also frequency of other complications between PEA and placebo groups (p values>0.05).Adjunctive therapy with PEA and risperidone alleviates schizophrenia-related primary negative symptoms in a safe manner. 

Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial

Schizophrenia is a psychiatric disorder of neurodevelopmental origin that is thought to result from the combination of genetic and socioenvironmental factors. Several studies have linked the endocannabinoid system with the pathophysiology of schizophrenia. Here, we provide a brief overview of the role of the endocannabinoid system (ECS) in the context of biological processes relevant to schizophrenia, such as neurodevelopment, synaptic plasticity, and brain energy metabolism. We also discuss alterations related to the ECS in schizophrenia and current efforts in both in vivo and in vitro studies that have provided a better understanding of the functioning of this system in the context of the disorder. Finally, we highlighted the modulation of the ECS as a potential for discovering novel therapeutic targets, suggesting new avenues for future research in the field. 

Molecular Findings Guiding the Modulation of the Endocannabinoid System as a Potential Target to Treat Schizophrenia.

Mechanism and treatments of antipsychotic-induced weight gain

Schizophrenia is a complex disorder signified by both positive and negative symptoms that include delusion, apathy, and cognitive dysfunction. Adolescence is the most affected age group. Cannabis consists of two active agents namely cannabidiol and delta-9-tetrahydrocannabinol. The consumption of cannabis has repeatedly been linked to the occurrence of psychosis and subsequently, conversion into schizophrenia. The factors that affect the relationship between cannabis use and schizophrenia are dose, age of onset, gender, genetic predisposition, environmental risk, and comorbid substance use. Many structural and functional alterations occur in the central and peripheral tissues because cannabinoid receptors are stimulated that are found all over the central nervous tissues and in some peripheral tissues. Schizophrenia patients who smoke cannabis have a greater chance of recurrence and extended hospital stays, and exhibit extreme positive manifestations. On the other hand, consumption of cannabis has demonstrated a reduction in negative symptoms and improvement in cognitive performance. It diminishes psychotic symptoms and has lesser adverse effects as compared to other antipsychotic drugs. Current evidence suggests that the consumption of high potency cannabis carries a higher chance of onset and progression of schizophrenia. It is recommended to develop preventive programs to avoid the harmful impact of cannabis use in the community. 

Alexandre Seillier

Papers

The endocannabinoid system as a therapeutic target for schizophrenia: Failures and potentials.