Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
BACKGROUND: Evidence indicates involvement of the endocannabinoid (eCB) system in both the pathophysiology of schizophrenia and working memory (WM) function. Additionally, schizophrenia patients exhibit relatively strong WM deficits. These findings suggest the possibility that the eCB system is also involved in WM deficits in schizophrenia. In the present study, we examined if perturbation of the eCB system can induce abnormal WM activity in healthy subjects. METHODS: A pharmacological functional magnetic resonance imaging study was conducted with a placebo-controlled, cross-over design, investigating effects of the eCB agonist Δ9-tetrahydrocannabinol on WM function in 17 healthy volunteers, by means of a parametric Sternberg item-recognition paradigm with five difficulty levels. RESULTS: Performance accuracy was significantly reduced after Δ9-tetrahydrocannabinol. In the placebo condition, brain activity increased linearly with rising WM load. Δ9-Tetrahydrocannabinol administration enhanced activity for low WM loads and reduced the linear relationship between WM load and activity in the WM system as a whole and in left dorsolateral prefrontal cortex, inferior temporal gyrus, inferior parietal gyrus, and cerebellum in particular. CONCLUSIONS: Δ9-Tetrahydrocannabinol enhanced WM activity network-wide for low loads, while reducing the load-dependent response for increasing WM loads. These results indicate that a challenged eCB system can induce both abnormal WM activity and WM performance deficits and provide an argument for the possibility of eCB involvement in WM deficits in schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Cannabinoids affect positive and negative affective experience and emotional perception, possibly by modulating limbic brain reactivity. In this double-blind crossover, placebo-controlled functional magnetic resonance imaging study in humans, an acute oral dose of Δ⁹- tetrahydrocannabinol (THC) attenuated subgenual anterior cingulate cortex (sgACC) reactivity during the induction of negative affect. This observation extends prior findings implicating a cortico-limbic, emotion-related central mechanism underlying cannabinoid function. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
CONTEXT: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing.
OBJECTIVE: To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing.
DESIGN: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli.
SETTING: University center.
PARTICIPANTS: Fifteen healthy men with minimal previous cannabis use.
MAIN OUTCOME MEASURES: Symptom ratings, task performance, and regional brain activation.
RESULTS: During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation.
CONCLUSIONS: Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.
[Correction Notice: An erratum for this article was reported in Vol 36(8) of <i>Neuropsychopharmacology</i> (see record [rid]2011-16848-024[/rid]). In the original article, the third author's name was spelled incorrectly; the correct spelling is Sagnik Bhattacharyya.] 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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Intravenosa (IV) Δ9-tetrahidrocannabinol (THC) induce síntomas psicóticos transitorios en sujetos sanos y en pacientes esquizofrénicos, pero el mecanismo psychotomimetic es desconocido. Una posibilidad es que el THC estimula la liberación de dopamina (DA) en el cuerpo estriado. En este estudio hemos probado si IV THC dio lugar a un aumento en la liberación de DA estriatal en comparación con placebo. También se investigó si la liberación de DA y los síntomas psicóticos positivos estaban relacionados. Once voluntarios varones sanos completaron dos 123I-yodobenzamida ([123I] IBZM) de tomografía por emisión de fotón único (SPET) sesiones y recibieron THC IV (2,5 mg) o placebo en un orden aleatorio con contrapeso, en condiciones de doble ciego. datos analizables se obtuvieron de nueve participantes. La Escala de Síntomas Positivos y Negativos (PANSS) se utilizó para evaluar los efectos psicotomiméticas. los valores del índice de unión del cuerpo estriado se calcularon utilizando la corteza occipital como región de referencia. Tanto los síntomas de PANSS positivos y generales se incrementaron significativamente a los 30 minutos tras IV THC. No hubo diferencias significativas en el índice de unión en el caudado putamen o menores de THC en comparación con las condiciones de placebo. síntomas psicóticos positivos y la liberación de DA no estaban relacionados. THC no condujo a un aumento significativo en la liberación de DA pesar de que la dosis fue suficiente para que los participantes tienen síntomas psicóticos. Estos hallazgos no apoyan un papel central para estriatal DA en la psicosis THC-suscitó.
The main reason for recreational use of cannabis is the ‘high’, the primary psychotropic effect of D⁹-tetrahydrocannabinol (THC). This psychoactive compound of cannabis induces a range of subjective, physical and mental reactions. The effect on heart rate is pronounced and complicates bloodflow-based neuroimaging of psychotropic effects of THC. In this study we investigated the effects of THC on baseline brain perfusion and activity in association with the induction of ‘feeling high’. Twenty-three subjects participated in a pharmacological MRI study, where we applied arterial spin labelling (ASL) to measure perfusion, and resting-state functional MRI to assess blood oxygen level-dependent signal fluctuation as a measure of baseline brain activity. Feeling high was assessed with a visual analogue scale and was compared to the imaging measures. THC increased perfusion in the anterior cingulate cortex, superior frontal cortex, and insula, and reduced perfusion in the post-central and occipital gyrus. Baseline brain activity was altered, indicated by increased amplitude of fluctuations in resting-state functional MRI signal after THC administration in the insula, substantia nigra and cerebellum. Perfusion changes in frontal cortex were negatively correlated with ratings of feeling high, suggesting an interaction between cognitive control and subjective effects of THC. In conclusion, an acute THC challenge altered baseline brain perfusion and activity, especially in frontal brain areas involved in cognitive and emotional processes, and the insula, associated with interoceptive awareness. These changes may represent the THC-induced neurophysiological correlates of feeling high. The alterations in baseline brain perfusion and activity also have relevance for studies on task-related effects of THC on brain function. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
ANTECEDENTES: El consumo de cannabis en la adolescencia temprana puede ser un factor de riesgo para el desarrollo de la esquizofrenia. En los animales, Delta9-tetrahidrocannabinol (THC) aumenta la tasa de dopamina disparo neuronal y la liberación en el cuerpo estriado. Por lo tanto el consumo de cannabis puede aumentar la liberación de dopamina en el cuerpo estriado humano que lleva a la vulnerabilidad a la psicosis.
Objetivos: Investigar si el THC, el principal componente psicoactivo del cannabis, puede producir la liberación de dopamina en el cuerpo estriado humano.
MÉTODOS: Trece voluntarios sanos, con experiencia anterior de cannabis, se sometieron a dos exploraciones [11C] La tomografía por emisión de positrones -raclopride (PET) para medir indirectamente los niveles de dopamina del cuerpo estriado ya sea después de 10 mg de THC o placebo.
RESULTADOS: A pesar de que el THC aumentó notablemente los síntomas de tipo psicótico en el Inventario psicotomimética Unidos (PSI), no hubo un efecto significativo de THC en [11C] -raclopride vinculante.
CONCLUSIÓN: En el estudio más grande de su tipo hasta ahora, hemos demostrado que los consumidores de cannabis recreativas no liberan cantidades significativas de dopamina a partir de una dosis de THC oral equivalente a un cigarrillo de cannabis estándar. Este resultado desafía los modelos actuales de la liberación de dopamina del estriado como el mecanismo de mediación de cannabis como factor de riesgo para la esquizofrenia.
Los efectos del cannabis sobre la salud mental recibe cada vez más atención científica y política. Un aumento de la demanda para el tratamiento de la dependencia del cannabis ha reabastecido la discusión sobre el potencial adictivo del cannabis. Una característica clave de todos los fármacos adictivos es la capacidad de aumentar los niveles de dopamina sináptica en el cuerpo estriado, un mecanismo implicado en sus efectos de recompensa y motivación. Sin embargo, actualmente se desconoce si el cannabis puede estimular la neurotransmisión de dopamina estriatal en los seres humanos. Aquí nos muestran que Delta 9-tetrahidrocannabinol (THC), el principal componente psicoactivo de la marihuana, induce la liberación de dopamina en el cuerpo estriado humano. El uso de la dopamina D (2) / (3) trazador receptor [(11) C] racloprida y positrones La tomografía por emisión de siete sujetos sanos, se demuestra que el THC inhalación reduce [(11) C] D Racloprida unión en el cuerpo estriado ventral y la precommissural putamen dorsal, pero no en otras subregiones del cuerpo estriado. Esto es consistente con un incremento en los niveles de dopamina en estas regiones. Estos resultados sugieren que el THC comparte una propiedad potencialmente adictivos con otras drogas de abuso. Además, implica que el sistema cannabinoide endógeno está implicado en la regulación de la liberación de dopamina estriatal. Esto permite que las nuevas direcciones en la investigación sobre los efectos del THC en los trastornos neuropsiquiátricos, como la esquizofrenia.
Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
