Publications

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

Aims: Cognitive impairment in patients with alcohol use disorder (AUD) is highly prevalent, and it negatively impacts treatment outcome. However, this condition is neither systematically assessed nor treated. Thus, we aimed to explore the usability of a virtual reality-based protocol ('Rehabilitation Gaming System', RGS) for patients with AUD. Methods: Twenty AUD patients (50% also cognitive impairment) underwent a single session of the RGS protocol (four cognitive training tasks, 10 minutes each). System Usability Scale (SUS) and Post-Study System Usability Questionnaire (PSSUQ) were applied to assess the RGS usability and patients' satisfaction with it. Also, the Perceived Competence Scale was administered to assess the patients' feelings of competence when using the training protocol. Comparisons of the responses to these questionnaires were performed between AUD patients with cognitive impairment and those without cognitive impairment. Results: RGS usability was very positively rated (median SUS score = 80, Interquartile Range, IQR = 68.13-86-88). No significant differences were found in the median SUS scores for any of the sociodemographic or clinical variables, excepting for gender (women median score = 85; IQR = 80-94.38 vs. men median score = 71.25; IQR = 61.25-89.25; P-value = 0.035). The quality of the information provided by the RGS training scenarios and the usability were positively rated (PSSUQ), and patients experienced high feelings of competence. Conclusions: The RGS has been found to be usable in the short term and patients with AUD stated to be satisfied with it. Future larger, randomized trials are needed to explore the effectiveness of this tool to help overcome the cognitive deficits in AUD patients. Short Summary: Although cognitive impairments are highly prevalent in alcohol use disorder (AUD), no long-term gold standard intervention has yet been identified. The Rehabilitation Gaming System (virtual reality-based cognitive training protocol) has shown short-term high usability in AUD. Its effectiveness in providing engaging, long-term cognitive rehabilitation in AUD should be further assessed.

JTD Keywords: Addiction, Brain-damage, Deficits, Impact, Neurocognitive impairment, Therapy

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

© 2020 The Author(s) The dominant biomedical perspective on addictions has been that they are chronic brain diseases. While we acknowledge that the brains of people with addictions differ from those without, we argue that the “broken brain” model of addiction has important limitations. We propose that a systems-level perspective more effectively captures the integrated architecture of the embodied and situated human mind and brain in relation to the development of addictions. This more dynamic conceptualization places addiction in the broader context of the addicted brain that drives behavior, where the addicted brain is the substrate of the addicted mind, that in turn is situated in a physical and socio-cultural environment. From this perspective, neurorehabilitation should shift from a “broken-brain” to a systems theoretical framework, which includes high-level concepts related to the physical and social environment, motivation, self-image, and the meaning of alternative activities, which in turn will dynamically influence subsequent brain adaptations. We call this integrated approach system-oriented neurorehabilitation. We illustrate our proposal by showing the link between addiction and the architecture of the embodied brain, including a systems-level perspective on classical conditioning, which has been successfully translated into neurorehabilitation. Central to this example is the notion that the human brain makes predictions on future states as well as expected (or counterfactual) errors, in the context of its goals. We advocate system-oriented neurorehabilitation of addiction where the patients' goals are central in targeted, personalized assessment and intervention.

JTD Keywords: addiction, brain disease model, neurorehabilitation, Addiction, Brain disease model, Neurorehabilitation, Systems approach