Highlights
- •Medical cannabis treatment at low dose was safe and well tolerated in MS.
- •Treatment resulted in a reduction in pain intensity, spasticity and sleep disturbances.
- •Treatment showed no impairment in ambulation, dexterity or processing speed.
- •Medical cannabis can be used as an alternative to treat spasticity and pain in MS.
ABSTACT
Introduction
The use of cannabis as medical therapy to treat chronic pain and spasticity in patients
with multiple sclerosis (MS) is increasing. However, the evidence on safety when initiating
treatment with medical cannabis oils is limited. The aim of this study was to investigate
the safety of sublingual medical cannabis oils in patients with MS.
Methods
In this prospective observational safety study 28 patients with MS were treated with
medical cannabis oils (THC-rich, CBD-rich and THC+CBD combined products) and were
followed during a titration period of four weeks. Patients were evaluated at treatment
start (Visit 1) and after four weeks treatment (Visit 2). At each visit neurological
examination (Expanded Disability Status Scale – EDSS), ambulation (Timed 25-Foot Walk
Test - T25FWT), routine blood tests, plasma cannabinoids, dexterity (9-Hole Peg Test
- 9-HPT) and processing speed (Symbol Digit Modalities Test - SDMT) were tested. Adverse
events (AEs) and tolerability were reported at Visit 2. Secondary, efficacy of medical
cannabis on pain, spasticity and sleep disturbances were measured by numeric rating
scale (NRS-11) each day during the 4-week treatment period.
Results
During treatment with cannabis preparations containing 10-25 mg/mL THC, the most common
AEs were dry mouth, drowsiness, dizziness and nausea of mild to moderate degree. Two
patients experienced pronounced symptoms with excessive dreaming and drowsiness, respectively,
which led to treatment stop during the titration. Three serious adverse events (SAE)
were reported but were not associated with the treatment. Mean doses of THC and CBD
were 4.0 mg and 7.0 mg, respectively, and primarily administered as a once-daily evening
dose. Furthermore, pain decreased from a median NRS score of 7 to 4, (p = 0.01), spasticity decreased from a median NRS score of 6 to 2.5 (p = 0.01) and sleep disturbances decreased from a median NRS score of 7 to 3 (p < 0.001). No impairment in disability, ambulation, dexterity or processing speed
was observed.
Conclusion
Treatment with medical cannabis oils was safe and well tolerated, and resulted in
a reduction in pain intensity, spasticity and sleep disturbances in MS patients. This
suggests that medical cannabis oils can be used safely, especially at relatively low
doses and with slow titration, as an alternative to treat MS-related symptoms when
conventional therapy is inadequate.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Validation of a fully automated robotic setup for preparation of whole blood samples for LC-MS toxicology analysis.J. Anal. Toxicol. 2012; 36: 280-287
- Cannabis sativa: The Plant of the Thousand and One Molecules.Front. Plant Sci. 2016; 7: 1-17
- A Cross-Sectional Study of the Impact of Spasticity on Daily Activities in Multiple Sclerosis.Patient. 2016; 9: 537-546
- The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity.Brain Behav. 2018; 8: 1-11
- Cannabinoids concentration variability in cannabis olive oil galenic preparations.J. Pharm. Pharmacol. 2018; 70: 143-149
Danish Medicines Agency, Guidelines for doctors. Available at: https://www.retsinformation.dk/eli/retsinfo/2018/9000 [DANISH], 2018.
- Prevalence and natural history of pain in adults with multiple sclerosis: Systematic review and meta-analysis.Pain. 2013; 154: 632-642https://doi.org/10.1016/j.pain.2012.12.002
- Lower-risk cannabis use guidelines: A comprehensive update of evidence and recommendations.Am. J. Public Health. 2017; 107: e1-e12
- Illegal cannabis use is common among Danes with multiple sclerosis.Mult. Scler. Relat. Disord. 2019; 33: 5-12https://doi.org/10.1016/j.msard.2019.05.008
- Human cannabinoid pharmacokinetics.Chem. Biodivers. 2007; 4: 1770-1804
- Pharmacokinetics of cannabinoids.Pain Res. Manag. 2005; 10: 15A-22A
- Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.Drug Alcohol Depend. 2012; 125: 313-319https://doi.org/10.1016/j.drugalcdep.2012.03.005
- Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials.J. Clin. Med. Res. 2020; 12: 129-141
- Randomised controlled trials may underestimate drug effects: Balanced placebo trial design.PLoS One. 2014; 9: 1-7
- Cannabis-based medicines for chronic neuropathic pain in adults.(Review) - Cochrane Library. 2018;
- Practical considerations in medical cannabis administration and dosing.Eur. J. Intern. Med. 2018; 49: 12-19
- The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research.The National Academies Press, Washington, DC2017https://doi.org/10.17226/24625
- The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.Curr. Neurol. Neurosci. Rep. 2018; 18: 8
National Treatment Guidelines, Spasticity. Available at: https://neuro.dk/wordpress/nnbv/generelt-om-symptomatisk-ms-behandling/ [DANISH], 2020.
NICE Guidelines - Cannabis-based medicinal products, Available at: https://www.ncbi.nlm.nih.gov/books/NBK552238/#cha.s2.2, 2019.
- The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.Curr. Neurol. Neurosci. Rep. 2018; 18 ([Accessed February 20, 2018]): 8
National Treatment Guidelines, Neuropathic pain. Available at: https://neuro.dk/wordpress/nnbv/behandling-af-neuropatiske-smerter/ [DANISH], 2020.
- Cannabidiol: State of the art and new challenges for therapeutic applications.Pharmacol. Ther. 2017; 175: 133-150
- Oral administration of cannabis and Δ-9-tetrahydrocannabinol (Thc) preparations: A systematic review.Med. 2020; 56: 1-28
- Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis galenical preparation (Bedrocan).Int. J. Pharm. Pract. 2019; 27: 264-270
- Cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies.Sleep Med. Rev. 2020; 53101339https://doi.org/10.1016/j.smrv.2020.101339
- Safety and Efficacy of Medical Cannabis in Fibromyalgia.J. Clin. Med. Artic. 2019; 8: 807
- Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia : An-Open Label.Add-On, Pilot Study. 2016; 51: 15-19
- A phase i study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.Eur. J. Clin. Pharmacol. 2013; 69: 1135-1147
The Danish Ministry of Health - Medical cannabis pilot program, Available at: http://www.sum.dk/Aktuelt/Nyheder/Medicin/2016/Nov [DANISH], 2018.
The Danish Multiple Sclerosis Registry, Annual report 2018-2019, 2020. Available at https://www.sundhed.dk/content/cms/93/4693_sclerosebehandlingsregistret_aarsrapport2018-2019_offentliggjort.pdf.
- Immune control by endocannabinoids - New mechanisms of neuroprotection?.J. Neuroimmunol. 2007; 184: 127-135
- Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.Mult. Scler. 2004; 10: 434-441
Article info
Publication history
Published online: December 21, 2020
Accepted:
December 17,
2020
Received in revised form:
November 30,
2020
Received:
September 15,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
