ABSTRACT: The lack of consensus on the issue of whether the consumption of cannabis favors neurocognition among schizophrenia-diagnosed patients or not, plus methodological problems found in available evidence and the limitations of studies focused on diagnosis and treatment for positive symptoms are sufficient reason for designing new research proposals based on recent brain connectivity models. The objective of this paper is to review available literature databases, selected for neurocognition in cannabis-using schizophrenia patients and to analyze contributions made by functional connectivity studies. Cognitive impairment among schizophrenia patients is found even before the appearance of the first psychotic symptoms. Measuring cognitive function in these patients, techniques such as fMRI and EEG have found brain impairment. Furthermore, regarding schizophrenia-diagnosed patients who use cannabis, some studies have shown less deterioration among cognitive domains, which may apparently be related with one of its components (CBD). Measuring brain connectivity can be useful for clarifying neurophysiological mechanisms of cognition in marihuana-using schizophrenia patients. Cognitive decline is generalized in schizophrenia patients and is considered fundamental for disease physiopathology.
Background: Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Methods: Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis. Results: One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders. Conclusion: Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD’s therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.
El cannabidiol (CBD), un componente importante fitocannabinoide de cannabis, está atrayendo cada vez más atención en medicina por su ansiolíticos, antipsicóticos, antieméticos y propiedades anti-inflamatorias. Sin embargo, hasta este momento, una revisión exhaustiva de la literatura de los efectos del CDB en los seres humanos es insuficiente. El objetivo de la presente revisión sistemática es examinar los estudios aleatorizados y cruzados que administraron CDB con los controles sanos y pacientes clínicos. Una búsqueda sistemática se realizó en las bases de datos electrónicas PubMed y EMBASE usando la palabra clave "cannabidiol". Se incluyeron en monoterapia y combinación de estudios (por ejemplo, el CDB + Δ9-THC). Un total de 34 estudios se identificaron: 16 de ellos eran estudios experimentales, realizado en individuos sanos, y 18 se realizaron en poblaciones clínicas, incluyendo la esclerosis múltiple (seis estudios), la esquizofrenia y la manía bipolar (cuatro estudios), el trastorno de ansiedad social (dos estudios), neuropático y dolor por cáncer (dos estudios), anorexia cáncer (un estudio), la enfermedad de Huntington (un estudio), el insomnio (un estudio), y la epilepsia (un estudio). Los estudios experimentales indican que se requiere una alta dosis de inhalación / intravenosa CDB para inhibir los efectos de una dosis más baja de Δ9-THC. Por otra parte, algunos estudios experimentales y clínicos sugieren que la vía oral / vía bucal CDB puede prolongar y / o intensificar Δ9-THC-inducida efectos, mientras que otros sugieren que puede inhibir los efectos inducidos por el Δ9-THC. Por último, los ensayos clínicos preliminares sugieren que altas dosis oral de CDB (150-600 mg / d) puede ejercer un efecto terapéutico para el trastorno de ansiedad social, el insomnio y la epilepsia, sino que también puede causar sedación mental. Se discuten farmacocinéticos y farmacodinámicos posibles explicaciones para estos resultados.
The lack of consensus on the issue of whether the consumption of cannabis favors neurocognition among schizophrenia-diagnosed patients or not, plus methodological problems found in available evidence and the limitations of studies focused on diagnosis and treatment for positive symptoms are sufficient reason for designing new research proposals based on recent brain connectivity models. The objective of this paper is to review available literature databases, selected for neurocognition in cannabis-using schizophrenia patients and to analyze contributions made by functional connectivity studies. Cognitive impairment among schizophrenia patients is found even before the appearance of the first psychotic symptoms. Measuring cognitive function in these patients, techniques such as fMRI and EEG have found brain impairment. Furthermore, regarding schizophrenia-diagnosed patients who use cannabis, some studies have shown less deterioration among cognitive domains, which may apparently be related with one of its components (CBD). Measuring brain connectivity can be useful for clarifying neurophysiological mechanisms of cognition in marihuana-using schizophrenia patients. Cognitive decline is generalized in schizophrenia patients and is considered fundamental for disease physiopathology.
