VRT as a Biomarker of Cerebellar Dysfunction in Chronic Cannabis Use

Healthy Clinical Trial

Official title:

A Visuomotor Rotation Task as a Biomarker of Cerebellar Dysfunction in Chronic Cannabis Use

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03662737
• Other study ID #: TRV-CAN
• Status: Completed
• Start date: September 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2023
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 18-50 years old
• Right-handed
• Daily consumption of cannabis for at least 2 years (cannabis group) or diagnosed Alcohol Use Disorder (alcohol group)

Exclusion Criteria:

• Non-corrected visual deficits
• Regular consumption of other drugs except nicotine
• Other Axis I or neurological diagnosis

Related Conditions & MeSH terms

• Alcohol Use Disorder
• Alcoholism
• Cannabis Use
• Cerebellar Diseases
• Healthy
• Marijuana Abuse

Intervention

Diagnostic Test:
• Visuomotor adaptation task
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.

Locations

Country	Name	City	State
Spain	Hospital Clínic	Barcelona	Catalonia

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

Country where clinical trial is conducted

Spain, 

References & Publications (18)

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Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009 Oct 17;374(9698):1383-91. doi: 10.1016/S0140-6736(09)61037-0. — View Citation

Kishimoto Y, Kano M. Endogenous cannabinoid signaling through the CB1 receptor is essential for cerebellum-dependent discrete motor learning. J Neurosci. 2006 Aug 23;26(34):8829-37. doi: 10.1523/JNEUROSCI.1236-06.2006. — View Citation

Lorenzetti V, Solowij N, Fornito A, Lubman DI, Yucel M. The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature. Curr Pharm Des. 2014;20(13):2138-67. doi: 10.2174/13816128113199990435. — View Citation

Lorenzetti V, Solowij N, Yucel M. The Role of Cannabinoids in Neuroanatomic Alterations in Cannabis Users. Biol Psychiatry. 2016 Apr 1;79(7):e17-31. doi: 10.1016/j.biopsych.2015.11.013. Epub 2015 Dec 4. — View Citation

Mazzoni P, Krakauer JW. An implicit plan overrides an explicit strategy during visuomotor adaptation. J Neurosci. 2006 Apr 5;26(14):3642-5. doi: 10.1523/JNEUROSCI.5317-05.2006. — View Citation

Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007 Jul 28;370(9584):319-28. doi: 10.1016/S0140-6736(07)61162-3. — View Citation

Prashad S, Filbey FM. Cognitive motor deficits in cannabis users. Curr Opin Behav Sci. 2017 Feb;13:1-7. doi: 10.1016/j.cobeha.2016.07.001. — View Citation

Silins E, Horwood LJ, Patton GC, Fergusson DM, Olsson CA, Hutchinson DM, Spry E, Toumbourou JW, Degenhardt L, Swift W, Coffey C, Tait RJ, Letcher P, Copeland J, Mattick RP; Cannabis Cohorts Research Consortium. Young adult sequelae of adolescent cannabis use: an integrative analysis. Lancet Psychiatry. 2014 Sep;1(4):286-93. doi: 10.1016/S2215-0366(14)70307-4. Epub 2014 Sep 10. — View Citation

Stella N. Chronic THC intake modifies fundamental cerebellar functions. J Clin Invest. 2013 Aug;123(8):3208-10. doi: 10.1172/JCI70226. — View Citation

Taylor JA, Klemfuss NM, Ivry RB. An explicit strategy prevails when the cerebellum fails to compute movement errors. Cerebellum. 2010 Dec;9(4):580-6. doi: 10.1007/s12311-010-0201-x. — View Citation

Taylor JA, Krakauer JW, Ivry RB. Explicit and implicit contributions to learning in a sensorimotor adaptation task. J Neurosci. 2014 Feb 19;34(8):3023-32. doi: 10.1523/JNEUROSCI.3619-13.2014. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in directional error between baseline and after cessation of cannabis use	Directional error of hand movement trajectories towards the target object on the rotation condition of the visuomotor rotation task.	The visuomotor adaptation task duration will not exceed 20 minutes and subjects are expected to realize it at three different time points: baseline, 1 month, 3 months