VRT as a Biomarker of Cerebellar Dysfunction in Chronic Cannabis Use
Condition: Cannabis Use; Alcohol Use Disorder; Healthy
MeSH terms: Cerebellar Diseases; Marijuana Abuse; Alcoholism
Study type: Observational

Summary: 
      Chronic cannabis consumption has been associated with poor psychosocial functioning that
      could be associated to cerebellar dysfunction. The cerebellum has a relevant role in
      adaptation processes and has a high density of cannabinoid 1 receptor (CB1R). Implicit motor
      learning is a cerebellum dependent function that can be measured with a visuomotor rotation
      task (VRT).

      The project aims to identify a sensitive and specific biomarker of cerebellum dysfunction in
      chronic cannabis users. The investigators would like to demonstrate that the visuomotor
      rotation paradigm is valid to measure and quantify such a dysfunction.

      A longitudinal prospective study with a 3 month follow-up is proposed. 3 groups will be
      included: 1) chronic cannabis users; 2) individuals with an alcohol use disorder; and 3)
      healthy controls. All groups will be matched by sex and age. Forty individuals will be
      included in each group. Individuals will be assessed at baseline, at first month and at
      3-months of follow-up. Sociodemographic and clinical data will be recorded. Information on
      cannabis consumption will be registered using an App.

      Participants will do the visuomotor rotation task and answer three questionnaires: the
      Intrinsic Motivation Inventory, the Scale for the assessment and rating of ataxia (SARA) and
      the Harris tests for lateral dominance.

      The biomarker developed by this project will facilitate the detection of cerebellar
      alterations in chronic cannabis users, and will permit to quantify and monitor such
      alteration over time. The team's intention is to patent the proposed model and disseminate it
      in order to use it in clinical practice at both primary and specialized health centres.
    

Detailed description: 
      The subjects have to realize movements towards a target, at a digitizing tablet, holding a
      digitizing pencil. Visual feedback is projected on a screen surface in front of the subject,
      which hides the sight of actual movements from the latter. In the experimental condition of
      rotation, the experimenter introduces a rotation of 45 grades between the movement realized
      by the subject and the visual feedback that is provided on the screen. Then, the subject is
      provided with a strategy in order to overcome this perturbation: that is, to make the
      movement aiming 45 grades to the opposite direction from the introduced rotation. This
      explicit strategy leads to immediate correction of the error, but as the time passes subjects
      tend to commit more and more errors due to implicit motor adaptation. This happens because
      the motor control system tends to correct the perceived perturbation between the anticipated
      and the actual location of the hand in an automatic and unconscious way. The conflict between
      the implicit and explicit strategies has the surprising consequence of a persistent and
      accumulative deterioration of performance that can only be resolved when the participants
      abandon the explicit strategy. Subjects with cerebellar damage show deficits in implicit
      motor learning and for this reason they do not show this progressive deterioration of
      performance. Given that chronic cannabis abuse can lead to cerebellar damage, the
      investigators hypothesize that subjects from the experimental group 1 (cannabis use) will
      have a significant smaller directional error on the rotation condition than controls. A
      second hypothesis is that this effect will be cannabis-specific, due to the high CB1R
      concentration on the cerebellum, so the alcohol dependence group is expected to perform
      similarly to control group
    

Intervention name(s): Visuomotor adaptation task
Intervention type(s): Diagnostic Test
Intervention description(s): We will measure performance of the subjects of each group on the visuomotor adaptation task, especially in the rotation condition, in which a perturbation will be induced between the anticipated location of the hand and the provided visual feedback, and in the washout condition, in which the rotation will be removed. We expect that subjects with cannabis use disorder will not show the expected implicit motor adaptation to the perturbation and consequently no deterioration of performance on the task, due to cannabis-induced cerebellar damage. In other words, we want to show that this visuomotor task is a cheap and quick biomarker of cerebellar dysfunction in chronic cannabis users.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The experimental group 1 (cannabis use) will consist of the patients of the Addiction Unit
        of Hospital Clinic that are seeking or already are in treatment for cannabis use or
        participants that fulfil the eligibility criteria and contact the responsible for this
        study investigators , after the diffusion of the study. The experimental group 2 (alcohol
        use) will consist of patients of the Addiction Unit of Hospital Clinic that are in
        treatment for alcohol dependency. The control subjects will be recruited through the public
        diffusion of the study.
      
Biospecimen description: 
      Urine
    
Keywords: Visuomotor task