VRT as a Biomarker of Cerebellar Dysfunction in Chronic Cannabis Use

NCT03662737 | Completed

• 1 other identifier: TRV-CAN
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cannabis Use; Alcohol Use Disorder; Healthy

Keywords

Visuomotor task

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Group 1 -Chronic cannabis use

Individuals between 18 and 50 years old who have been using at least 2 joints per day for at least 3 years. They should have used cannabis during the last 24h but not during the 3h prior to participation to the study and they should test positive for cannabis in their urine. Individuals with another substance use or severe mental disorder will be excluded (except tobacco use)

Diagnostic Test: Visuomotor adaptation task

Group 2 - Alcohol dependence

Individuals between 18 and 50 years old diagnosed with alcohol use disorder according to DSM-V criteria and have been consuming alcohol for at least 3 years. Individuals who are diagnosed with another substance use or severe mental disorder will be excluded (except tobacco use).

Diagnostic Test: Visuomotor adaptation task

Control Group

Individuals matched in gender and age with the experimental groups and with no diagnosis of substance use or severe mental disorder (except tobacco use)

Diagnostic Test: Visuomotor adaptation task

Interventions

Visuomotor adaptation task DIAGNOSTIC_TEST

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.

Control Group; Group 1 -Chronic cannabis use; Group 2 - Alcohol dependence

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead

Study Sites (1)

Hospital Clínic

Barcelona, Catalonia, 08036, Spain

Location

Related Publications (18)

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  PMID: 19837255 BACKGROUND

• 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.

  PMID: 17662880 BACKGROUND

• 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.

  PMID: 26360862 BACKGROUND

• Batalla A, Bhattacharyya S, Yucel M, Fusar-Poli P, Crippa JA, Nogue S, Torrens M, Pujol J, Farre M, Martin-Santos R. Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings. PLoS One. 2013;8(2):e55821. doi: 10.1371/journal.pone.0055821. Epub 2013 Feb 4.

  PMID: 23390554 BACKGROUND

• 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.

  PMID: 26858212 BACKGROUND

• 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.

  PMID: 23829361 BACKGROUND

• Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med. 2011 Mar;5(1):1-8. doi: 10.1097/ADM.0b013e31820c23fa.

  PMID: 21321675 BACKGROUND

• Bossong MG, Jager G, Bhattacharyya S, Allen P. Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies. Curr Pharm Des. 2014;20(13):2114-25. doi: 10.2174/13816128113199990436.

  PMID: 23829369 BACKGROUND

• Broyd SJ, van Hell HH, Beale C, Yucel M, Solowij N. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. Biol Psychiatry. 2016 Apr 1;79(7):557-67. doi: 10.1016/j.biopsych.2015.12.002. Epub 2015 Dec 8.

  PMID: 26858214 BACKGROUND

• Burns HD, Van Laere K, Sanabria-Bohorquez S, Hamill TG, Bormans G, Eng WS, Gibson R, Ryan C, Connolly B, Patel S, Krause S, Vanko A, Van Hecken A, Dupont P, De Lepeleire I, Rothenberg P, Stoch SA, Cote J, Hagmann WK, Jewell JP, Lin LS, Liu P, Goulet MT, Gottesdiener K, Wagner JA, de Hoon J, Mortelmans L, Fong TM, Hargreaves RJ. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9800-5. doi: 10.1073/pnas.0703472104. Epub 2007 May 29.

  PMID: 17535893 BACKGROUND

• 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.

  PMID: 16928872 BACKGROUND

• 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.

  PMID: 16597717 BACKGROUND

• 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.

  PMID: 20697860 BACKGROUND

• Thames AD, Arbid N, Sayegh P. Cannabis use and neurocognitive functioning in a non-clinical sample of users. Addict Behav. 2014 May;39(5):994-9. doi: 10.1016/j.addbeh.2014.01.019. Epub 2014 Feb 6.

  PMID: 24556155 BACKGROUND

• 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.

  PMID: 24553942 BACKGROUND

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

  PMID: 23863631 BACKGROUND

• 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.

  PMID: 27482533 BACKGROUND

• Bastian AJ. Moving, sensing and learning with cerebellar damage. Curr Opin Neurobiol. 2011 Aug;21(4):596-601. doi: 10.1016/j.conb.2011.06.007. Epub 2011 Jul 5.

  PMID: 21733673 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Antoni Gual, MD,PhD

  Hospital clinic Bracelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Head of Addiction Unit

Study Record Dates

• First Submitted: September 3, 2018
• First Posted: September 7, 2018
• Study Start: September 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)