Disclosures Research Support: CMSC (PI: Beier) NICHD - PDF document

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 Department of Physical Medicine & Rehabilitation, Johns Hopkins University School of Medicine 1 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 organizations 2

Cannabis Use in MS • >100 years of published reports on potential benefits of 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) 3 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 4

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 5 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 6

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) 7 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 8

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 9 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) 10

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 11 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 12

Results • 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 13 Results • Hazardous cannabis use marginally predicted fatigue Β t p CUDIT-R .20 1.82 .07 CUDIT-R x -.04 -0.29 .78 age • Hazardous cannabis use predicted depressive symptoms Β t p CUDIT-R .32 3.18 .002 CUDIT-R x .05 0.37 .72 age 14

Results • Hazardous cannabis predicted anxiety symptoms Β t p CUDIT-R .24 2.50 . 001 CUDIT-R x -.06 -.54 .59 age • Hazardous cannabis use marginally predicted sleep disturbance. Age was a significant moderator. Β t p CUDIT-R .20 1.84 .07 CUDIT-R x .27 2.11 .04 age 15 Results • Age as a moderator Age Β t p < 34 years .01 .05 .96 34-59 years .29 2.13 .04 > 59 years -.33 -1.36 .20 • Associations between hazardous cannabis use and sleep disturbance were strongest for individuals ages 34-59 16

Results • No significant associations between hazardous cannabis use and cognitive performance on BICAMS • No significant age x cognitive function interactions 17 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% 18

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 19 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 20

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 of 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 on 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. 21