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Neurobehavioral Correlates of Hazardous Cannabis Use in Multiple Sclerosis Annual Meeting of the Consortium of MS Centers May 31 st , 2019 Abbey J. Hughes, PhD, Aeysha Brown, MA, Krina Patel, BS, Trisha Chaffee, MS, & Meghan Beier, PhD

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Neurobehavioral Correlates of Hazardous Cannabis Use in Multiple Sclerosis

Annual Meeting of the Consortium of MS Centers May 31st, 2019

Abbey J. Hughes, PhD, Aeysha Brown, MA, Krina Patel, BS, Trisha Chaffee, MS, & Meghan Beier, PhD Department of Physical Medicine & Rehabilitation, Johns Hopkins University School of Medicine

Disclosures

  • Research Support:

– CMSC (PI: Beier) – NICHD 1K23HD086154 (PI: Hughes) – NMSS R-1702-27078 (PI: Beier)

  • Consultant:

– Can Do MS (Hughes, Beier)

  • The present research represents no conflicts of

interest with any of our funding sources or consulting

  • rganizations

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Cannabis Use in MS

  • >100 years of published reports on potential benefits
  • f cannabis for chronic medical conditions (Clark et al.,

2004)

– Variability in study quality and design – Variability in measurement, dosing, administration

  • MS symptoms/outcomes of interest
  • Spasticity
  • Sleep
  • Disease progression
  • Pain
  • Mood
  • Bladder/bowel function
  • Mobility
  • Disability
  • Tremor/ataxia
  • QOL
  • Cognition
  • Adverse effects (AEs)

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Cannabis Use in MS

  • Survey Studies

– 2004: 31% “used ever”; 14% “current use” (Clark et al.,

2004)

– 2017: 26% “used ever”; 16% current use (NARCOMS;

Cofield et al., 2017)

– 88% reported perceived benefits – AEs: drowsiness (71%), dry mouth (41%), paranoia (9%), anxiety (9%), palpitations (9%) – Limitations: self-report, wide range of dosing/modality

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Cannabis Use in MS

  • Patient interview study (Ghaffar & Feinstein, 2008)

– 7% (n = 140) were frequent users (≥ 1 month, SCID-IV) – Neuropsychological Battery for MS: SRT, 7/24, PASAT, COWAT, SDMT – Cannabis users exhibited slower SDMT performance, more likely to have psychiatric diagnosis

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Cannabis Use in MS

  • Group comparison studies

– Medical and non-medicinal cannabis use (Honarmand et al., 2011)

  • 32% medical, 56% medical and non-medical use
  • MACFIMS
  • Users exhibited poorer processing speed/working

memory (SDMT and PASAT), visuospatial processing (JLO), and reasoning/problem solving (DKEFS)

– MRI correlates (Pavisian et al., 2014)

– Increased activation during working memory task in parietal and anterior cingulate regions for users

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Systematic Reviews and Guidelines

  • Two systematic reviews (Koppel et al., 2014; Nielsen et

al, 2018)

– Included CAMS and MUSEC (Zajicek et al., 2003, 2012)

  • Development of AAN Guidelines

– nabixomol oral spray, oral cannabis extract, and synthetic THC probably effective for pain and spasticity – Insufficient evidence for:

  • other symptoms (e.g., tremor)
  • reducing progression
  • long-term safety/AEs (e.g., mental health, cognition)

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Objective

  • To examine correlations between hazardous

cannabis use and neurobehavioral symptoms: fatigue, depressive symptoms, anxiety symptoms, poor sleep, and cognitive function

  • To explore age as a potential moderator of

associations between cannabis use and neurobehavioral symptoms

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Participants

  • N = 100
  • Recruited from a university-affiliated MS center

– Gender: 76% female – Race: 83% white – Age: mean 46.2 years (19-72) – Education: mean 15.5 years (10-22) – MS Type: 77% RRMS

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Measures

  • Measures

– Cannabis Use Disorder Identification Test – Revised (CUDIT-R)

  • 8 items, total score ≥ 8 coded as hazardous use

– Frequency – Duration of effects – Dysfunction: can’t stop, impaired daily activities, lost time, memory/concentration issues, physically hazardous use – Attempts to cut down (and how recent)

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Measures

  • Measures

– Fatigue: FSS total – Depression: PHQ-8 total – Anxiety: GAD-7 total – Sleep disturbance: PHQ item 3 (dichotomized) – Cognition: BICAMS

  • CVLT-II: verbal learning trials
  • BVMT-R: visuospatial learning trials
  • SDMT: total score

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Analyses

  • Zero-order correlations to determine potential

covariates

– Covariates: age, gender, years of education, type of MS – Outcomes: neurobehavioral symptoms (FSS, PHQ-8, GAD- 7, sleep item, BICAMS)

  • Multiple linear regression

– Step 1: covariates – Step 2: CUDIT-R – Step 3: Age x CUDIT-R interaction – Outcomes: neurobehavioral symptoms

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Results

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  • Descriptives

– FSS: 38 (9-63) – PHQ-8: 6.9 (0-23) – GAD-7: 4.8 (0-21) – PHQ sleep item: 38% – CUDIT-R: 2.26 (0-18)

  • 31% reported using at least monthly
  • 12% met criteria for hazardous use

Results

  • Hazardous cannabis use marginally predicted fatigue
  • Hazardous cannabis use predicted depressive symptoms

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Β t p CUDIT-R .20 1.82 .07 CUDIT-R x age

  • .04
  • 0.29

.78 Β t p CUDIT-R .32 3.18 .002 CUDIT-R x age .05 0.37 .72

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Results

  • Hazardous cannabis predicted anxiety symptoms
  • Hazardous cannabis use marginally predicted sleep
  • disturbance. Age was a significant moderator.

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Β t p CUDIT-R .24 2.50 . 001 CUDIT-R x age

  • .06
  • .54

.59 Β t p CUDIT-R .20 1.84 .07 CUDIT-R x age .27 2.11 .04

Results

  • Age as a moderator
  • Associations between hazardous cannabis use and

sleep disturbance were strongest for individuals ages 34-59

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Age Β t p < 34 years .01 .05 .96 34-59 years .29 2.13 .04 > 59 years

  • .33
  • 1.36

.20

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Results

  • No significant associations between hazardous

cannabis use and cognitive performance on BICAMS

  • No significant age x cognitive function interactions

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Conclusions

  • Limitations

– Cross-sectional data – Sleep assessment limited to single-item self-report – Highly-resourced sample – Possible role of DMT

  • Cannabis use is common in MS (~15-30%)

– Hazardous use ~12%

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Conclusions

  • Screening for hazardous cannabis use is an

important aspect of clinical care, and can be done with brief measures like the CUDIT-R

  • Although the CUDIT-R might not predict objective

cognitive function, it is relevant for assessing important psychosocial aspects of MS symptom management

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Acknowledgements

  • Johns Hopkins MS Rehabilitation Research

Laboratory

– Co-PI: Meghan Beier, PhD – NMSS Fellow: Jagriti “Jackie” Bhattarai, PhD – Lab Manager: Trisha Chaffee, MS – Trainees: Aeysha Brown, MA; Krina Patel, BS

  • Johns Hopkins Precision Medicine Center of

Excellence for MS

  • Consortium of MS Centers Pilot Grant

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References

  • Clark, A.J., Ware, M.A., Yazer, E., Murray, T.J. and Lynch, M.E., 2004. Patterns of cannabis use among patients w ith

multiple sclerosis. Neurology, 62(11), pp.2098-2100.

  • Cofield, S.S., Salter, A., Tyry, T., Crow e, C., Cutter, G.R., Fox, R.J. and Marrie, R.A., 2017. Perspectives on

marijuana use and effectiveness: A survey of NARCOMS participants. Neurology: Clinical Practice, 7(4), pp.333-343.

  • Ghaffar, O. and Feinstein, A., 2008. Multiple sclerosis and cannabis: a cognitive and psychiatric
  • study. Neurology, 71(3), pp.164-169.
  • Honarmand, K., Tierney, M.C., O'Connor, P. and Feinstein, A., 2011. Effects of cannabis on cognitive function in

patients w ith multiple sclerosis. Neurology, 76(13), pp.1153-1160.Koppel, B.S., Brust, J.C., Fife, T., Bronstein, J., Youssof, S., Gronseth, G. and Gloss, D., 2014. Systematic review : efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of

  • Neurology. Neurology, 82(17), pp.1556-1563.
  • Nielsen, S., Germanos, R., Weier, M., Pollard, J., Degenhardt, L., Hall, W., Buckley, N. and Farrell, M., 2018. The use
  • f cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systematic review of review s. Current

neurology and neuroscience reports, 18(2), p.8.

  • Pavisian, B., MacIntosh, B.J., Szilagyi, G., Staines, R.W., O'Connor, P. and Feinstein, A., 2014. Effects of cannabis
  • n cognition in patients w ith MS: a psychometric and MRI study. Neurology, 82(21), pp.1879-1887.
  • Ware, M.A., Wang, T., Shapiro, S., Collet, J.P., Boulanger, A., Esdaile, J.M., Gordon, A., Lynch, M., Moulin, D.E. and

O'Connell, C., 2015. Cannabis for the management of pain: assessment of safety study (COMPASS). The Journal of Pain, 16(12), pp.1233-1242.

  • Zajicek, J., Fox, P., Sanders, H., Wright, D., Vickery, J., Nunn, A., Thompson, A. and UK MS research group, 2003.

Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. The Lancet, 362(9395), pp.1517-1526.

  • Zajicek, J.P., Hobart, J.C., Slade, A., Barnes, D., Mattison, P.G. and MUSEC Research Group, 2012. Multiple

sclerosis and extract of cannabis: results of the MUSEC trial. Journal of Neurology, Neurosurgery & Psychiatry, 83(11), pp.1125-1132.

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