Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Δ9-tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis
Open accessAbstract
Purpose The aim of the present study was to evaluate the efficacy of an oral formulation of Δ9-tetrahydrocannabinol (ECP002A) in patients with progressive multiple sclerosis (MS).Methods This accelerated proof-of-concept study consisted of 2 phases: a crossover challenge (dose-finding) phase and a 4-week, parallel, randomized, placebo-controlled treatment phase. Twenty-four patients with progressive MS and moderate spasticity were enrolled. During the treatment phase, biomarkers for efficacy and secondary pharmacodynamic effects were measured at baseline and after 2 and 4 weeks of treatment. Serum samples were collected to determine pharmacokinetic properties and perform population modeling. Safety and tolerability profiles were assessed based on adverse events and safety measurements.Findings Pain was significantly reduced when measured directly after administration of ECP002A in the clinic but not when measured in a daily diary. A similar pattern was observed in subjective muscle spasticity. Other clinical outcomes were not significantly different between active treatment and placebo. Cognitive testing indicated that there was no decline in cognition after 2 or 4 weeks of treatment attributable to ECP002A compared with placebo. Implications This study specifically underlines the added value of thorough investigation of pharmacokinetic and pharmacodynamic associations in the target population. Despite the complex interplay of psychoactive effects and analgesia, the current oral formulation of Δ9-tetrahydrocannabinol may play a role in the treatment of spasticity and pain associated with MS because it was well tolerated and had a stable pharmacokinetic profile.
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Troublesome News, Fake News, Biased or Incomplete News
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- Authors
- van Amerongen, G., Kanhai, K., Baakman, A. C., Heuberger, J., Klaassen, E., Beumer, T. L., Strijers, R. L. M., Killestein, J., van Gerven, J., Cohen, A., & Groeneveld, G. J.
- Affiliations
- Centre for Human Drug Research (NL)
- Echo Pharmaceuticals (Netherlands) (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- ORCID
- Venue
- Clinical Therapeutics
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 40
- Issue
- 9
- Pages
- 1467-1482
- ISSN
- 0149-2918 (ISSN-L)
- OpenAlex
- W2586362005
- Cited by
- 86
- References
- 46
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 14 · 2021: 14 · 2020: 12 · 2019: 7 · 2018: 6 · 2017: 3
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Biogen
- IC Design Education Center
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Botulinum Toxin and Related Neurological Disorders
- Keywords
- delta-9-tetrahydrocannabinol, progressive multiple sclerosis, spasticity, neuropathic pain, pharmacokinetics, pharmacodynamics, cognitive function, analgesia, adverse events
- MeSH terms
- Proof of Concept Study, Administration, Oral, Adult, Aged, Cognition, Female, Humans, Male, Middle Aged, Muscle Spasticity, Neuralgia, Pain Measurement, Dronabinol, Cross-Over Studies, Multiple Sclerosis, Chronic Progressive
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