Although the effects of cannabis on perception are well documented, little is known about their neural basis or how these may contribute to the formation of psychotic symptoms. We used functional magnetic resonance imaging (fMRI) to assess the effects of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during visual and auditory processing in healthy volunteers. In total, 14 healthy volunteers were scanned on three occasions. Identical 10 mg THC, 600 mg CBD, and placebo capsules were allocated in a balanced double-blinded pseudo-randomized crossover design. Plasma levels of each substance, physiological parameters, and measures of psychopathology were taken at baseline and at regular intervals following ingestion of substances. Volunteers listened passively to words read and viewed a radial visual checkerboard in alternating blocks during fMRI scanning. Administration of THC was associated with increases in anxiety, intoxication, and positive psychotic symptoms, whereas CBD had no significant symptomatic effects. THC decreased activation relative to placebo in bilateral temporal cortices during auditory processing, and increased and decreased activation in different visual areas during visual processing. CBD was associated with activation in right temporal cortex during auditory processing, and when contrasted, THC and CBD had opposite effects in the right posterior superior temporal gyrus, the right-sided homolog to Wernicke's area. Moreover, the attenuation of activation in this area (maximum 61, -15, -2) by THC during auditory processing was correlated with its acute effect on psychotic symptoms. Single doses of THC and CBD differently modulate brain function in areas that process auditory and visual stimuli and relate to induced psychotic symptoms.
BACKGROUND: Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia, dissociative states, and other psychiatric conditions. Cannabidiol (CBD), a cannabinoid-1/2 (CB1/2) receptor weak partial agonist or antagonist, may play a role in the treatment of schizophrenia.
OBJECTIVE: This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist, ketamine, in healthy human subjects.
METHODS: Ten male healthy volunteers were evaluated twice in a randomized order. In both sessions they received ketamine (bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25mg/kg over 30 min) preceded by either CBD (600 mg) or placebo. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS) and the CADSS (Clinician Administered Dissociative States Scale) at regular intervals from 30 min before to 90 min after ketamine administration.
RESULTS: CBD significantly augmented the activating effects of ketamine, as measured by the activation subscales of the BPRS. However, CBD also showed a non-significant trend to reduce ketamine-induced depersonalization, as measured by the CADSS.
CONCLUSION: These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment.
Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.
Trastorno de Ansiedad Social Generalizada (SAD) es una de las condiciones de ansiedad más comunes con deterioro en la vida social. El cannabidiol (CBD), uno de los principales compuesto no psicotomimética de la planta cannabis sativa, ha mostrado efectos ansiolíticos, tanto en humanos como en animales. Este estudio preliminar tuvo como objetivo comparar los efectos de una prueba de simulación de hablar en público (SPST) el control de salud (HC) de los pacientes y los pacientes SAD sin tratamiento previo que recibieron una dosis única de CDB o placebo. Un total de 24 pacientes no tratados con SAD fueron asignados para recibir ya sea CDB (600 mg; n = 12) o placebo (placebo, n = 12) en un estudio doble ciego aleatorizado de diseño 1 hora y media antes de la prueba. El mismo número de HC (n = 12) realiza el SPST sin recibir ninguna medicación. Cada voluntario sólo participó en una sesión experimental en un procedimiento de doble ciego. Calificaciones subjetivas sobre la analógica Mood Escala Visual (VAMS) y Negativo escala auto-declaración (SSPS-N) y medidas fisiológicas (presión arterial, frecuencia cardiaca y conductancia de la piel) se midieron en seis puntos diferentes de tiempo durante el SPST. Los resultados fueron sometidos a un análisis de medidas repetidas de la varianza. El pretratamiento con CDB redujo significativamente la ansiedad, deterioro cognitivo y la incomodidad en su desempeño habla y disminuyó significativamente alerta en su discurso anticipatorio. El grupo placebo presentó mayor ansiedad, deterioro cognitivo, incomodidad, y los niveles de alerta cuando se compara con el grupo control tal como se evaluó con el VAMS. Las puntuaciones SSPS-N evidenciaron aumentos significativos durante la prueba de grupo de placebo que fue casi abolida en el grupo CDB. No se observaron diferencias significativas entre el CDB y HC en las puntuaciones SSPS-N o en el deterioro cognitivo, la incomodidad, y los factores de alerta de VAMS. El aumento de la inducida por el SPST en sujetos con ansiedad SAD se redujo con el uso de CDB, lo que resulta en una respuesta similar a la HC.
Este estudio comparó la eficacia de un tetrahidrocannabinol: cannabidiol (THC: CBD) extraer, un analgésico no opioide modulador del sistema endocannabinoide, y un extracto de THC, con el placebo, en el alivio del dolor en pacientes con cáncer avanzado. En total, 177 pacientes con dolor por cáncer, que experimentaron analgesia inadecuada a pesar de dosificación crónica con opiáceos, entraron en un período de dos semanas, multicéntrico, doble ciego,,, ensayo de grupos paralelos y controlado con placebo aleatorio. Los pacientes fueron asignados al azar a THC: extracto de la CDB (n = 60), extracto de THC (n = 58) o placebo (n = 59). El análisis primario de cambio desde el inicio del dolor medio numérico Rating Scale (NRS) marcador era estadísticamente significativa a favor de THC: CBD en comparación con el placebo (mejora de -1,37 vs -0,69), mientras que el grupo THC mostró un cambio no significativo (- 1,01 vs. -0,69). El doble de los pacientes que tomaron THC: CBD mostraron una reducción de más del 30% del dolor basal puntuación NRS en comparación con el placebo (23 [43%] frente a 12 [21%]). El odds ratio asociado fue estadísticamente significativa, mientras que el número de respondedores grupo THC fue similar a placebo (12 [23%] frente a 12 [21%]) y no alcanzó significación estadística. No había ningún cambio desde el inicio de la dosis media de la medicación opioide fondo o el número de dosis de la medicación avance a través de los grupos de tratamiento significa. No se encontraron diferencias significativas entre los grupos en las puntuaciones de calidad o náuseas sueño NRS o la evaluación de control del dolor. Sin embargo, los resultados de la Organización Europea para la Investigación y Tratamiento del Cáncer de Calidad de Vida del Cáncer Cuestionario mostró un empeoramiento de las náuseas y vómitos con THC: CBD en comparación con placebo (p = 0,02), mientras que el THC no tenía ninguna diferencia (P = 1,0). La mayoría de los acontecimientos adversos relacionados con el fármaco fueron leves / moderados en gravedad. Este estudio demuestra que el THC: extracto CDB es eficaz para el alivio del dolor en pacientes con dolor por cáncer avanzado no totalmente relevado por opioides fuertes.
Objective: The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. Method: The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300mg or cannabidiol 600mg or placebo. Results: The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300mg performing better than those who received cannabidiol 600mg. Conclusion: The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.
Revista»The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
Although the effects of cannabis on perception are well documented, little is known about their neural basis or how these may contribute to the formation of psychotic symptoms. We used functional magnetic resonance imaging (fMRI) to assess the effects of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during visual and auditory processing in healthy volunteers. In total, 14 healthy volunteers were scanned on three occasions. Identical 10 mg THC, 600 mg CBD, and placebo capsules were allocated in a balanced double-blinded pseudo-randomized crossover design. Plasma levels of each substance, physiological parameters, and measures of psychopathology were taken at baseline and at regular intervals following ingestion of substances. Volunteers listened passively to words read and viewed a radial visual checkerboard in alternating blocks during fMRI scanning. Administration of THC was associated with increases in anxiety, intoxication, and positive psychotic symptoms, whereas CBD had no significant symptomatic effects. THC decreased activation relative to placebo in bilateral temporal cortices during auditory processing, and increased and decreased activation in different visual areas during visual processing. CBD was associated with activation in right temporal cortex during auditory processing, and when contrasted, THC and CBD had opposite effects in the right posterior superior temporal gyrus, the right-sided homolog to Wernicke's area. Moreover, the attenuation of activation in this area (maximum 61, -15, -2) by THC during auditory processing was correlated with its acute effect on psychotic symptoms. Single doses of THC and CBD differently modulate brain function in areas that process auditory and visual stimuli and relate to induced psychotic symptoms.
