Exploratory survey study on adjunctive use of medical cannabis for Gaucher disease

Abstract

Aims: Using an investigator-designed survey tool to confirm that adult patients with type 1 Gaucher disease (GD1) often self-prescribe cannabis products to try to alleviate symptoms such as lingering fatigue, chronic bone and joint pain, loss of energy, anxiety, and depression that persist despite enzyme replacement therapy (ERT) or substrate restriction therapy (SRT). Additionally, to explore whether patient reports of symptom relief and adverse side effects relate to frequency and duration of cannabis use.

Methods: We conducted an anonymous, cross-sectional questionnaire study to elicit GD1 patient-reported experiences with cannabis used to alleviate symptoms they attributed to their underlying disease. Eligible participants included individuals with GD1 aged ≥ 18 years, regardless of sex, gender, country of residence, ethnicity, state of health or GD1 treatment status. The questions included basic socio-demography (n = 9), GD diagnosis and pre-treatment signs and symptoms (n = 16), GD treatment information (n = 9), current GD symptoms (n = 12), concurrent manifestations of Parkinson’s disease (n = 6), details of cannabis use (n = 24), perceived effect of cannabis on symptoms (n = 13), and interest in participating in future studies (n = 2).

Results: 159 GD1 adults (81.5% US) responded to advertisements on patient online sites. The most frequent pre-treatment symptoms were fatigue (83.8%), bone or joint pain (79.7%), and bleeding problems (73.0%). Hemostasis substantially improved, but pain, achiness, fatigue, and anxiety often persisted. Sixty-two respondents (39%) reported very heterogeneous cannabis use. There was a positive association between the severity of persistent symptoms and the likelihood of cannabis use. Cannabis users reported improvements in muscle pain (84.3%), bone pain (82.4%), joint pain (82.4%), anxiety (70.6%), and general achiness (66.7%). However, moderate and extreme bone manifestations, fatigue, breathing problems, memory loss, and episodic dyscoordination were more prevalent among frequent users of inhaled cannabis than among non-users.

Conclusion: Our results justify further investigations to determine the efficacy and safety of cannabis specifically for GD1 patients. Although randomized controlled trials would be optimal, well-designed observational GD registry studies may be a more practical approach. Although some patients may be reluctant to talk openly with their doctors about cannabis, they should routinely be queried about such use by primary care physicians and GD specialists who, in turn, must be able to provide informed guidance on safety, dosage, and potential interactions with other medications the patient is using.

Keywords

Gaucher disease / cannabis / marijuana / patient-reported outcomes / efficacy / safety

References

[1] Castillon G,Moride Y.Global incidence and prevalence of gaucher disease: a targeted literature review.J Clin Med2022;12:85 PMCID:PMC9821068

[2] Nalysnyk L,Simeone JC,Weinreb N.Gaucher disease epidemiology and natural history: a comprehensive review of the literature.Hematology2017;22:65-73

[3] Daykin EC,Sidransky E.Diagnosing neuronopathic Gaucher disease: new considerations and challenges in assigning Gaucher phenotypes.Mol Genet Metab2021;132:49-58 PMCID:PMC7884077

[4] Horowitz M,Zimran A,Goker-Alpan O.Lysosomal functions and dysfunctions: molecular and cellular mechanisms underlying Gaucher disease and its association with Parkinson disease.Adv Drug Deliv Rev2022;187:114402

[5] Hughes D,Belmatoug N.Gaucher disease in bone: from pathophysiology to practice.J Bone Miner Res2019;34:996-1013 PMCID:PMC6852006

[6] Rosenbloom BE,Weinreb NJ.Cancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry.Am J Hematol2022;97:1337-47 PMCID:PMC9541044

[7] Roh J,Weinreb NJ.Gaucher disease - more than just a rare lipid storage disease.J Mol Med2022;100:499-518

[8] Weinreb NJ,Lee RE.Causes of death in 184 patients with type 1 Gaucher disease from the United States who were never treated with enzyme replacement therapy.Blood Cells Mol Dis2018;68:211-7

[9] Revel-Vilk S,Mehta A.How we manage Gaucher disease in the era of choices.Br J Haematol2018;182:467-80

[10] Weinreb NJ,Charrow J,Mistry P.International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) investigatorsGaucher disease type 1 patients from the ICGG Gaucher registry sustain initial clinical improvements during twenty years of imiglucerase treatment.Mol Genet Metab2021;132:100-11

[11] Andrade-Campos MM,Cebolla JJ.Identification of risk features for complication in Gaucher's disease patients: a machine learning analysis of the Spanish registry of Gaucher disease.Orphanet J Rare Dis2020;15:256 PMCID:PMC7507684

[12] Goker-Alpan O.Therapeutic approaches to bone pathology in Gaucher disease: past, present and future.Mol Genet Metab2011;104:438-47

[13] Grabowski GA,Kolodny EH.Gaucher disease: basic and translational science needs for more complete therapy and management.Mol Genet Metab2021;132:59-75 PMCID:PMC8809485

[14] Sam R,Daykin E.Current and emerging pharmacotherapy for Gaucher disease in pediatric populations.Expert Opin Pharmacother2021;22:1489-503 PMCID:PMC8373623

[15] Els C,Kunyk D.Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane reviews.Cochrane Database Syst Rev2017;10:CD012509 PMCID:PMC6485910

[16] Noori A,Wang L.Comparative benefits and harms of individual opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised trials.Br J Anaesth2022;129:394-406

[17] Almogi-Hazan O.Cannabis, the endocannabinoid system and immunity-the journey from the bedside to the bench and back.Int J Mol Sci2020;21:4448 PMCID:PMC7352399

[18] Cristino L,Di Marzo V.Cannabinoids and the expanded endocannabinoid system in neurological disorders.Nat Rev Neurol2020;16:9-29

[19] Crocq MA.History of cannabis and the endocannabinoid system. Historia del cannabis y del sistema de endocannabinoides. Histoire du cannabis et du système endocannabinoϊde.Dialogues Clin Neurosci2020;22:223-8 PMCID:PMC7605027

[20] Lowin T,Pongratz G.Joints for joints: cannabinoids in the treatment of rheumatoid arthritis.Curr Opin Rheumatol2019;31:271-8

[21] Weiss L,Reich S.Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.Autoimmunity2006;39:143-51

[22] Gallily R,Hanuš LO.The anti-inflammatory properties of terpenoids from cannabis.Cannabis Cannabinoid Res2018;3:282-90 PMCID:PMC6308289

[23] Atalay S,Skrzydlewska E.Antioxidative and anti-inflammatory properties of cannabidiol.Antioxidants2019;9:21 PMCID:PMC7023045

[24] Schieber M.ROS function in redox signaling and oxidative stress.Curr Biol2014;24:R453-62 PMCID:PMC4055301

[25] Cherukury HM,Garcia N.Cannabidiol attenuates hyperalgesia in a mouse model of sickle cell disease.Blood2023;141:203-8 PMCID:PMC9936305

[26] Mackie K.Cannabinoid receptors as therapeutic targets.Annu Rev Pharmacol Toxicol2006;46:101-22

[27] Xin Y,Pan S.Components of the endocannabinoid system and effects of cannabinoids against bone diseases: a mini-review.Front Pharmacol2021;12:793750 PMCID:PMC8815309

[28] Raphael-Mizrahi B.The cannabinoids effect on bone formation and bone healing.Curr Osteoporos Rep2020;18:433-8

[29] Lu HC.Review of the endocannabinoid system.Biol Psychiatry Cogn Neurosci Neuroimaging2021;6:607-15 PMCID:PMC7855189

[30] Florida Cannabis Information. Is CBD oil legal in Florida? Available from: FloridaStateCannabis.org [Last accessed on 22 Aug 2024]

[31] Rog DJ,Friede T.Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.Neurology2005;65:812-9

[32] Collin C,Mutiboko IK.Sativex Spasticity in MS Study GroupRandomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.Eur J Neurol2007;14:290-6

[33] Ware MA,Shapiro S.Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.CMAJ2010;182:E694-701 PMCID:PMC2950205

[34] Naftali T,Scklerovsky Benjaminov F,Matalon ST.Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: a randomized controlled trial.PLoS One2021;16:e0246871 PMCID:PMC7877751

[35] McGuire P,Cubala WJ.Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial.Am J Psychiatry2018;175:225-31

[36] Longo R,Befus D.Cannabis for chronic pain: a rapid systematic review of randomized control trials.Pain Manag Nurs2021;22:141-9

[37] Fisher E,Fogarty AE.Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials.Pain2021;162:S45-66

[38] Arkell TR,Hayley AC.Assessment of medical cannabis and health-related quality of life.JAMA Netw Open2023;6:e2312522 PMCID:PMC10170337

[39] Abuhasira R,Mechoulam R.Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly.Eur J Intern Med2018;49:44-50

[40] Costa B.On the pharmacological properties of Δ₉-tetrahydrocannabinol (THC).Chem Biodivers2007;4:1664-77

[41] Holden SK,Sillau S,Leehey MA.Higher risk, higher reward? Self-reported effects of real-world cannabis use in parkinson's disease.Mov Disord Clin Pract2022;9:340-50 PMCID:PMC8974868

[42] Chesney E,Green A.Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials.Neuropsychopharmacology2020;45:1799-806 PMCID:PMC7608221

[43] Jones JM. Nearly half of U.S. adults have tried marijuana. Available from: https://news.gallup.com/poll/353645/nearly-half-adults-tried-marijuana.aspx [Last accessed on 22 Aug 2024]

[44] ProCon.org. State-by-state recreational marijuana laws. Available from: https://marijuana.procon.org/legal-recreational-marijuana-states-and-dc/ [Last accessed on 22 Aug 2024]

[45] Lal S,Ryan M.Cannabis use amongst patients with inflammatory bowel disease.Eur J Gastroenterol Hepatol2011;23:891-6

[46] Weiss A.Patterns of cannabis use in patients with inflammatory bowel disease: a population based analysis.Drug Alcohol Depend2015;156:84-9

[47] Buckley MC,Swaminath A.Inflammatory bowel disease and cannabis: a practical approach for clinicians.Adv Ther2021;38:4152-61 PMCID:PMC8279986

[48] Wipfler K,Katz P. Cannabis use among patients in a large US rheumatic disease registry. In: 2019 ACR/ARP annual meeting. Available from: https://acrabstracts.org/abstract/cannabis-use-among-patients-in-a-large-us-rheumatic-disease-registry/ [Last accessed on 22 Aug 2024]

[49] Nielsen SW,Eckhoff L,Herrstedt J.Cannabis use among Danish patients with cancer: a cross-sectional survey of sociodemographic traits, quality of life, and patient experiences.Support Care Cancer2022;30:1181-90

[50] Cousins MM,Devasia T.Cannabis use in patients seen in an academic radiation oncology department.Pract Radiat Oncol2023;13:112-21 PMCID:PMC9996408

[51] Cousins MM,Coughlin LN,Ilgen MA.Prevalence of cannabis use among individuals with a history of cancer in the United States.Cancer2021;127:3437-44

[52] Johal H,Chang Y,Vannabouathong C.Cannabinoids in chronic non-cancer pain: a systematic review and meta-analysis.Clin Med Insights Arthritis Musculoskelet Disord2020;13:1179544120906461 PMCID:PMC7031792

[53] Powell A. Medical school’s Kevin hill talks about fearmongering and rosy myths, safe use and addiction. Available from: https://news.harvard.edu/gazette/story/2020/02/professor-explores-marijuanas-safe-use-and-addiction/ [Last accessed on 22 Aug 2024]

[54] Gelberg L,Koerber J.Cannabis use reported by patients receiving primary care in a large health system.JAMA Netw Open2024;7:e2414809 PMCID:PMC11154156

[55] Elstein D,Deegan P.Development and validation of Gaucher disease type 1 (GD1)-specific patient-reported outcome measures (PROMs) for clinical monitoring and for clinical trials.Orphanet J Rare Dis2022;17:9 PMCID:PMC8734239

[56] Balwani M,Desnick RJ,McGovern MM.Use of complementary and alternative medicine by patients with lysosomal storage diseases.Genet Med2009;11:722-7

[57] Mistry PK,Charrow J.Real-world effectiveness of eliglustat in treatment-naïve and switch patients enrolled in the international collaborative Gaucher group Gaucher registry.Am J Hematol2020;95:1038-46 PMCID:PMC7497238

[58] Zimran A,Bembi B.GOS study groupDemographics and patient characteristics of 1209 patients with Gaucher disease: descriptive analysis from the Gaucher outcome survey (GOS).Am J Hematol2018;93:205-12 PMCID:PMC5814927

[59] Weinreb NJ,Feingold E.Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).Orphanet J Rare Dis2015;10:64 PMCID:PMC4471923

[60] Mistry PK,Andersson HC.Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the international collaborative Gaucher group (ICGG) Gaucher registry.Am J Hematol2017;92:929-39 PMCID:PMC5600096

[61] Most Americans favor legalizing marijuana for medical, recreational use. 2024. Available from: www.pewresearch.org/wp-content/uploads/sites/20/2024/03/PP_2024.3.26_marijuana_REPORT.pdf [Last accessed on 22 Aug 2024]

[62] Luc MH,Thrul J,Moran MB.Content analysis of online product descriptions from cannabis retailers in six US states.Int J Drug Policy2020;75:102593

[63] Walker M,Lightfoot D.The effect of recreational cannabis legalization and commercialization on substance use, mental health, and injury: a systematic review.Public Health2023;221:87-96

[64] Sholler DJ,Spindle TR.Therapeutic efficacy of cannabidiol (CBD): a review of the evidence from clinical trials and human laboratory studies.Curr Addict Rep2020;7:405-12 PMCID:PMC7880228

[65] Joehanes R,Marioni RE.Epigenetic signatures of cigarette smoking.Circ Cardiovasc Genet2016;9:436-47

[66] Sophocleous A,Ferreira NB,Fraser WD.Heavy cannabis use is associated with low bone mineral density and an increased risk of fractures.Am J Med2017;130:214-21

[67] Ihejirika-Lomedico R,Buchalter DB.Non-psychoactive cannabidiol prevents osteoporosis in an animal model and increases cell viability, proliferation, and osteogenic gene expression in human skeletal stem and progenitor cells.Calcif Tissue Int2023;112:716-26

[68] Miodownik H,Olivia Ogu U.Frequent health care utilisation and avascular necrosis are associated with cannabis use in adults with sickle cell disease.Br J Haematol2022;196:e41-4 PMCID:PMC9838730

[69] Urbi B,Hughes I.Effects of cannabis in parkinson's disease: a systematic review and meta-analysis.J Parkinsons Dis2022;12:495-508

[70] Figura M,Sławek J.Cannabis in parkinson’s disease - the patient’s perspective versus clinical trials: a systematic literature review.Neurol Neurochir Pol2022;56:21-7

[71] Varshney K,Ansari S,Panag SS.Cannabinoids in treating parkinson’s disease symptoms: a systematic review of clinical studies.Cannabis Cannabinoid Res2023;8:716-30

[72] Ferreira-Junior NC,Guimarães FS.Biological bases for a possible effect of cannabidiol in Parkinson’s disease.Braz J Psychiatry2020;42:218-24 PMCID:PMC7115443

[73] Fernández-Moncada I,Dalla Tor T,Marsicano G.An enquiry to the role of CB1 receptors in neurodegeneration.Neurobiol Dis2023;184:106235

[74] Stella N.THC and CBD: similarities and differences between siblings.Neuron2023;111:302-27 PMCID:PMC9898277

[75] Huang J,Ruan X.Association between cannabis use with urological cancers: a population-based cohort study and a mendelian randomization study in the UK biobank.Cancer Med2023;12:3468-76 PMCID:PMC9939109

[76] Zhang LR,Greenland S.Cannabis and Respiratory Disease Research Group of New ZealandCannabis smoking and lung cancer risk: pooled analysis in the international lung cancer consortium.Int J Cancer2015;136:894-903 PMCID:PMC4262725