by Keyword: endocannabinoid system
Blithikioti C, Miquel L, Paniello B, Nuño L, Gual A, Ballester BR, Fernandez A, Herreros I, Verschure P, Balcells-Olivero M, (2022). Chronic cannabis use affects cerebellum dependent visuomotor adaptation Journal Of Psychiatric Research 156, 8-15
Cannabis is one of the most commonly used substances in the world. However, its effects on human cognition are not yet fully understood. Although the cerebellum has the highest density of cannabinoid receptor type 1 (CB1R) in the human brain, literature on how cannabis use affects cerebellar-dependent learning is sparse. This study examined the effect of chronic cannabis use on sensorimotor adaptation, a cerebellar-mediated task, which has been suggested to depend on endocannabinoid signaling.Chronic cannabis users (n = 27) with no psychiatric comorbidities and healthy, cannabis-naïve controls (n = 25) were evaluated using a visuomotor rotation task. Cannabis users were re-tested after 1 month of abstinence (n = 13) to assess whether initial differences in performance would persist after cessation of use.Cannabis users showed lower adaptation rates compared to controls at the first time point. However, this difference in performance did not persist when participants were retested after one month of abstinence (n = 13). Healthy controls showed attenuated implicit learning in the late phase of the adaptation during re-exposure, which was not present in cannabis users. This explains the lack of between group differences in the second time point and suggests a potential alteration of synaptic plasticity required for cerebellar learning in cannabis users.Overall, our results suggest that chronic cannabis users show alterations in sensorimotor adaptation, likely due to a saturation of the endocannabinoid system after chronic cannabis use.Copyright © 2022 Elsevier Ltd. All rights reserved.
JTD Keywords: Addiction, Cannabis, Cerebellum, Endocannabinoid system, Visuomotor adaptation
Amil, AF, Ballester, BR, Maier, M, Verschure, PFMJ, (2022). Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation Addictive Behaviors 131, 107297 
Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency. © 2022
JTD Keywords: adaptation, addiction, alcohol-abuse, cerebellum, chronic cannabis use, cognition, deficits, endocannabinoid system, error processing, explicit, modulation, motor learning, release, synaptic plasticity, Adaptation, Adaptation, physiological, Alcoholism, Article, Behavioral science, Cannabinoid 1 receptor, Cannabis, Cannabis addiction, Cerebellum, Cerebellum cortex, Cerebellum disease, Chronic cannabis use, Computer model, Down regulation, Endocannabinoid, Endocannabinoid system, Endocannabinoids, Error processing, Hallucinogens, Human, Humans, Motor dysfunction, Motor learning, Nerve cell plasticity, Nonhuman, Physiology, Psychedelic agent, Purkinje-cells, Regulatory mechanism, Sensation, Sensory dysfunction, Sensory error processing impairment, Synaptic transmission, Task performance
Tomas-Roig, J., Piscitelli, F., Gil, V., del Río, J. A., Moore, T. P., Agbemenyah, H., Salinas-Riester, G., Pommerenke, C., Lorenzen, S., Beißbarth, T., Hoyer-Fender, S., Di Marzo, V., Havemann-Reinecke, U., (2016). Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice 
Behavioural Brain Research , 303, 34-43
Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.
JTD Keywords: Psychosocial stress, Cerebellum, Calreticulin, Endocannabinoid system, Behavior, RNA seq.
