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      Motor Adaptation Impairment in Chronic Cannabis Users Assessed by a Visuomotor Rotation Task

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          Abstract

          Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis impact on the brain are available today. The cerebellum is expected to be one of the brain structures that are highly affected by prolonged exposure to cannabis, due to its high density in endocannabinoid receptors. We aim to use a motor adaptation paradigm to indirectly assess cerebellar function in chronic cannabis users (CCUs). Methods—We used a visuomotor rotation (VMR) task that probes a putatively-cerebellar implicit motor adaptation process together with the learning and execution of an explicit aiming rule. We conducted a case-control study, recruiting 18 CCUs and 18 age-matched healthy controls. Our main measure was the angular aiming error. Results—Our results show that CCUs have impaired implicit motor adaptation, as they showed a smaller rate of adaptation compared with healthy controls (drift rate: 19.3 +/− 6.8° vs. 27.4 +/− 11.6°; t(26) = −2.1, p = 0.048, Cohen’s d = −0.8, 95% CI = (−1.7, −0.15)). Conclusions—We suggest that a visuomotor rotation task might be the first step towards developing a useful tool for the detection of alterations in implicit learning among cannabis users.

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          Most cited references31

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          Structure of a cannabinoid receptor and functional expression of the cloned cDNA.

          Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.
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            Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish

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              Endocannabinoid-mediated control of synaptic transmission.

              The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB(1) receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                18 July 2019
                July 2019
                : 8
                : 7
                : 1049
                Affiliations
                [1 ]SPECS Lab, Universitat Pompeu Fabra, 08002 Barcelona, Spain
                [2 ]GRAC, Grup de Recerca en Addiccions Clínic, Villarroel, 170 08036 Barcelona, Spain
                [3 ]IDIBAPS, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Villarroel, 170 08036 Barcelona, Spain
                [4 ]IBEC, Institute for Biomedical Engineering of Catalonia, Universitat Politècnica de Catalunya, 08028 Barcelona, Spain
                [5 ]ICREA, Institució Catalana de Recerca i Estudis Avançats, Passeig Lluís Companys, 08010 Barcelona, Spain
                Author notes
                [* ]Correspondence: MIQUEL@ 123456clinic.cat ; Tel.: +34-93-227-17-19; Fax: +34-93-227-54-54
                [†]

                These authors contributed equally as the first authorship.

                [‡]

                These authors contributed equally as the last authorship.

                Author information
                https://orcid.org/0000-0003-4569-9639
                https://orcid.org/0000-0002-7130-981X
                https://orcid.org/0000-0003-3643-9544
                Article
                jcm-08-01049
                10.3390/jcm8071049
                6678817
                31323815
                95364134-342d-4668-82f1-e123f29dbcb0
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2019
                : 16 July 2019
                Categories
                Article

                cerebellum,cannabis,implicit motor learning,motor adaptation,visuomotor rotation

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