A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms
Abstract
OBJECTIVES: To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects. DESIGN: A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods. SETTING: Patients attended as outpatients, but took the CME at home. SUBJECTS: Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1). INTERVENTION: Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events. RESULTS: Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME. CONCLUSIONS: Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.
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Although the five studies found improvements in nausea with cannabis use, other studies found nausea to be an adverse event associated with cannabis use among some participants.
“Although these five studies found improvements in nausea with cannabis use, other studies found nausea to be an adverse event associated with cannabis use among some participants.”
From Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions (2024) · cites this paper as [59]
Seven studies assessed CBM use on appetite in participants experiencing chronic pain, including two RCTs, two cross-sectional studies, two case series, and one pre-post study.
“Seven studies assessed CBM use on appetite in participants experiencing chronic pain, including two RCTs,59,63 two cross-sectional studies,79,88 two case series,91,92 and one pre-post study.70”
From Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions (2024) · cites this paper as [59]
A similarly structured study reported improved pain ratings (visual analogue scale) and spasticity severity following cannabidiol and Δ9-THC in patients with mixed neuropathic pain.
“A similarly structured study reported improved pain ratings (VAS) and spasticity severity following CBD and Δ9-THC in patients with mixed neuropathic pain.159”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [159]
Δ9-THC and Sativex additionally improved muscle spasms and spasticity severity.
“Δ9-THC and Sativex® additionally improved muscle spasms and spasticity severity.159”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [159]
Cites
A scaled version of the General Health Questionnaire
Goldberg, D. P., & Hillier, V. F. (1979) · Psychological Medicine · doi:10.1017/s0033291700021644 · Cited by 5,494 · see citing works
The Barthel ADL Index: A reliability study
Collin, C., Wade, D. T., Davies, S., & Horne, V. (1988) · International Disability Studies · doi:10.3109/09638288809164103 · Cited by 2,740 · see citing works
Self-citationArm function after stroke: measurement and recovery over the first three months.
Heller, A., Wade, D. T., WOOD, V. A., Sunderland, A., Hewer, R. L., & Ward, E. (1987) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.50.6.714 · Cited by 591 · see citing works
Self-citationCannabinoids control spasticity and tremor in a multiple sclerosis model
Baker, D., Pryce, G., Croxford, J., Brown, P., Pertwee, R., Huffman, J. W., & Layward, L. (2000) · Nature · doi:10.1038/35003583 · Cited by 546 · see citing works
Gregson, J. M., Leathley, M. J., Moore, A. P., Sharma, A. K., Smith, T. L., & Watkins, C. L. (1999) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/s0003-9993(99)90053-9 · Cited by 429 · see citing works
Campbell, F. A., Tramèr, M. R., Carroll, D., Reynolds, D. J. M., Moore, R. A., & McQuay, H. J. (2001) · BMJ · doi:10.1136/bmj.323.7303.13 · Cited by 422 · see citing works
Marijuana and medicine: assessing the science base
(1999) · Choice Reviews Online · doi:10.5860/choice.37-2206 · Cited by 410 · see citing works
The perceived effects of smoked cannabis on patients with multiple sclerosis.
Consroe, P., Musty, R., Rein, J. A., Tillery, W., & Pertwee, R. (1997) · European Neurology · doi:10.1159/000112901 · Cited by 329 · see citing works
Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?
McPartland, J. M., & Russo, E. B. (2001) · Journal of Cannabis Therapeutics · doi:10.1300/j175v01n03_08 · Cited by 321 · see citing works
Marihuana, the Forbidden Medicine
Grinspoon, L., & Bakalar, J. B. (1993) · doi:10.1038/scientificamerican1269-17 · Cited by 227 · see citing works
Safety, tolerability, and efficacy of orally administered cannabinoids in MS
Killestein, J., Hoogervorst, E. L. J., Reif, M., Kalkers, N. F., Loenen, A. C. V., Staats, P. G. M., Gorter, R. W., Uitdehaag, B. M. J., & Polman, C. H. (2002) · Neurology · doi:10.1212/wnl.58.9.1404 · Cited by 209 · see citing works
Safety, tolerability, and efficacy of orally administered cannabinoids in MS
Russo, E. B. (2003) · Neurology · doi:10.1212/wnl.60.4.729-a · Cited by 184 · see citing works
Tetrahydrocannabinol for tremor in multiple sclerosis
Clifford, D. B. (1983) · Annals of Neurology · doi:10.1002/ana.410130616 · Cited by 166 · see citing works
Delta-9-THC in the Treatment of Spasticity Associated with Multiple Sclerosis
Ungerleider, J. T., Andyrsiak, T., Fairbanks, L. A., Ellison, G. W., & Myers, L. W. (1988) · Advances in Alcohol & Substance Abuse · doi:10.1300/j251v07n01_04 · Cited by 165 · see citing works
Treatment of Human Spasticity with Δ9‐Tetrahydrocannabinol
Petro, D. J., & Ellenberger, C. (1981) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1981.tb02621.x · Cited by 154 · see citing works
Effect of cannabinoids on spasticity and ataxia in multiple sclerosis
Meinck, H. ‐., Sch�nle, P. W., & Conrad, B. (1989) · Journal of Neurology · doi:10.1007/bf00314410 · Cited by 131 · see citing works
Nabilone in the treatment of multiple sclerosis
Martyn, C. N., Illis, L., & Thom, J. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90485-9 · Cited by 122 · see citing works
The Short Orientation–Memory–Concentration Test: a study of its reliability and validity
Wade, D. T., & Vergis, E. (1999) · Clinical Rehabilitation · doi:10.1191/026921599673848768 · Cited by 113 · see citing works
Self-citationRivermead Mobility Index: a brief review of research to date
Forlander, D. A., & Bohannon, R. W. (1999) · Clinical Rehabilitation · doi:10.1191/026921599675502264 · Cited by 85 · see citing works
Marihuana, the Forbidden Medicine
FINK, M. (1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.7.1091 · Cited by 77 · see citing works
The perceived effects of marijuana on spinal cord injured males
Dunn, M., & Davis, R. (1974) · Spinal Cord · doi:10.1038/sc.1974.28 · Cited by 54 · see citing works
Prospects for New Cannabis-Based Prescription Medicines
Whittle, B. A., Guy, G. W., & Robson, P. (2001) · Journal of Cannabis Therapeutics · doi:10.1300/j175v01n03_12 · Cited by 50 · see citing works
Self-citationThe Medical Value of Marijuana and Related Substances
Joy, J. E., Watson, S. J., & BENSON, J. A. (1999) · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077 · see citing works
The endocannabinoid system and the brain.
Mechoulam, R., & Parker, L. A. (2013) · Annual Review of Psychology · doi:10.1146/annurev-psych-113011-143739 · Cited by 1,090 · see citing works
The endocannabinoid system and its therapeutic exploitation
Marzo, V. D., Bifulco, M., & Petrocellis, L. D. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1495 · Cited by 1,090 · see citing works
Agonistic properties of cannabidiol at 5-HT1a receptors
Russo, E. B., Burnett, A., Hall, B., & Parker, K. K. (2005) · Neurochemical Research · doi:10.1007/s11064-005-6978-1 · Cited by 878 · see citing works
Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis
Rog, D. J., Nurmikko, T. J., Friede, T., & Young, C. A. (2005) · Neurology · doi:10.1212/01.wnl.0000176753.45410.8b · Cited by 679 · see citing works
Wade, D. T., Makela, P., Robson, P., House, H., & Bateman, C. (2004) · Multiple Sclerosis Journal · doi:10.1191/1352458504ms1082oa · Cited by 589 · see citing works
Self-citationCannabinoids in medicine: A review of their therapeutic potential
Ben Amar, M. (2006) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2006.02.001 · Cited by 543 · see citing works
Svendsen, K. B., Jensen, T. S., & Bach, F. W. (2004) · BMJ · doi:10.1136/bmj.38149.566979.ae · Cited by 500 · see citing works
Novotna, A., Mares, J., Ratcliffe, S., Novakova, I., Vachova, M., Zapletalova, O., Gasperini, C., Pozzilli, C., Cefaro, L., Comi, G., et al. (2011) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.03328.x · Cited by 475 · see citing works
Stockings, E., Campbell, G., Hall, W. D., Nielsen, S., Zagic, D., Rahman, R., Murnion, B., Farrell, M., Weier, M., & Degenhardt, L. (2018) · Pain · doi:10.1097/j.pain.0000000000001293 · Cited by 460 · see citing works
Borgelt, L. M., Franson, K. L., Nussbaum, A. M., & Wang, G. S. (2013) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1187 · Cited by 423 · see citing works
Cannabinoids for treatment of chronic non‐cancer pain; a systematic review of randomized trials
Lynch, M. E., & Campbell, F. (2011) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2011.03970.x · Cited by 397 · see citing works
Berman, J. S., Symonds, C., & Birch, R. (2004) · Pain · doi:10.1016/j.pain.2004.09.013 · Cited by 362 · see citing works
Adverse effects of medical cannabinoids: a systematic review
Wang, T., Collet, J.-P., Shapiro, S., & Ware, M. A. (2008) · Canadian Medical Association Journal · doi:10.1503/cmaj.071178 · Cited by 357 · see citing works
Phytocannabinoids as novel therapeutic agents in {CNS} disorders.
Hill, A. J., Williams, C. M., Whalley, B. J., & Stephens, G. J. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.09.002 · Cited by 312 · see citing works
Notcutt, W., Price, M., Miller, R., Newport, S., Phillips, C., Simmons, S., & Sansom, C. (2004) · Anaesthesia · doi:10.1111/j.1365-2044.2004.03674.x · Cited by 305 · see citing works
Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
Rahn, E. J., & Hohmann, A. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.002 · Cited by 305 · see citing works
Nugent, S. M., Morasco, B. J., O'Neil, M. E., Freeman, M., Low, A., Kondo, K., Elven, C., Zakher, B., Motu'apuaka, M., Paynter, R., et al. (2017) · Annals of Internal Medicine · doi:10.7326/m17-0155 · Cited by 301 · see citing works
Manzanares, J., Julian, M., & Carrascosa, A. (2006) · Current Neuropharmacology · doi:10.2174/157015906778019527 · Cited by 287 · see citing works
Collin, C., Ehler, E., Waberzinek, G., Alsindi, Z., Davies, P., Powell, K., Notcutt, W., O'Leary, C., Ratcliffe, S., Nováková, I., et al. (2010) · Neurological Research · doi:10.1179/016164109x12590518685660 · Cited by 283 · see citing works
Efficacy of Dronabinol as an Adjuvant Treatment for Chronic Pain Patients on Opioid Therapy
Narang, S., Gibson, D., Wasan, A. D., Ross, E. L., Michna, E., Nedeljkovic, S. S., & Jamison, R. N. (2008) · The Journal of Pain · doi:10.1016/j.jpain.2007.10.018 · Cited by 257 · see citing works
Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain
Iskedjian, M., Bereza, B., Gordon, A., Piwko, C., & Einarson, T. R. (2007) · Current Medical Research and Opinion · doi:10.1185/030079906x158066 · Cited by 216 · see citing works
Cannabis use in HIV for pain and other medical symptoms
Woolridge, E., Barton, S., Samuel, J., Osorio, J., Dougherty, A., & Holdcroft, A. (2005) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2004.07.011 · Cited by 208 · see citing works
Bilbao, A., & Spanagel, R. (2022) · BMC Medicine · doi:10.1186/s12916-022-02459-1 · Cited by 181 · see citing works
Sholler, D. J., Schoene, L., & Spindle, T. R. (2020) · Current Addiction Reports · doi:10.1007/s40429-020-00326-8 · Cited by 143 · see citing works
Experience with the Synthetic Cannabinoid Nabilone in Chronic Noncancer Pain
Berlach, D. M., Shir, Y., & Ware, M. A. (2006) · Pain Medicine · doi:10.1111/j.1526-4637.2006.00085.x · Cited by 96 · see citing works
An Internet survey of marijuana and hot shower use in adults with cyclic vomiting syndrome (CVS)
Venkatesan, T., Sengupta, J., Lodhi, A., Schroeder, A., Adams, K., Hogan, W. J., Wang, Y., Andrews, C., & Storr, M. (2014) · Experimental Brain Research · doi:10.1007/s00221-014-3967-0 · Cited by 86 · see citing works
Dyson, A., Peacock, M., Chen, A., Courade, J.-P., Yaqoob, M., Groarke, A., Brain, C., Loong, Y., & Fox, A. (2005) · Pain · doi:10.1016/j.pain.2005.03.037 · Cited by 85 · see citing works
Bell, A. D., MacCallum, C., Margolese, S., Walsh, Z., Wright, P., Daeninck, P. J., Mandarino, E., Lacasse, G., Kaur Deol, J., de Freitas, L., et al. (2024) · Cannabis & Cannabinoid Research · doi:10.1089/can.2021.0156 · Cited by 78 · see citing works
“Seven studies assessed CBM use on appetite in participants experiencing chronic pain, including two RCTs, 59,63 two cross-sectional studies, 79,88 two case series, 91,92 and one pre-post study.”
BackgroundInfluentialAre oral cannabinoids safe and effective in refractory neuropathic pain?
Attal, N., Brasseur, L., Guirimand, D., Clermond‐Gnamien, S., Atlami, S., & Bouhassira, D. (2004) · European Journal of Pain · doi:10.1016/s1090-3801(03)00084-3 · Cited by 74 · see citing works
The treatment of spasticity with Δ9-tetrahydrocannabinol in persons with spinal cord injury
Hagenbach, U., Luz, S., Ghafoor, N., Berger, J. M., Grotenhermen, F., Brenneisen, R., & Mäder, M. (2007) · Spinal Cord · doi:10.1038/sj.sc.3101982 · Cited by 70 · see citing works
Aggarwal, S. K. (2013) · The Clinical Journal of Pain · doi:10.1097/ajp.0b013e31824c5e4c · Cited by 62 · see citing works
A Conversion of oral cannabidiol to delta9-tetrahydrocannabinol seems not to occur in humans
Nahler, G., Grotenhermen, F., Zuardi, A. W., & Crippa, J. A. S. (2017) · Cannabis & Cannabinoid Research · doi:10.1089/can.2017.0009 · Cited by 61 · see citing works
de Vries, M., Van Rijckevorsel, D. C. M., Vissers, K. C. P., Wilder‐Smith, O. H. G., & Van Goor, H. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12811 · Cited by 54 · see citing works
Spanagel, R., & Bilbao, A. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108680 · Cited by 43 · see citing works
Quais são e pra que servem os medicamentos à base de Cannabis?
Pamplona, F. A. (2014) · Revista da Biologia · doi:10.7594/revbio.13.01.05 · Cited by 20 · see citing works
“Este uso clínico é amparado por evidências anedóticas dos pacientes (Consroe et al., 1997), dados pré-clínicos (Baker et al., 2000) e estudos prévios de Fase II (Killestein et al., 2002, Wade et al., 2003).”
Background
- Authors
- Wade, D. T., Robson, P., House, H., Makela, P., & Aram, J.
- Affiliations
- Warneford Hospital (GB)
- University of Oxford (GB)
- ORCID
- Wade, Derick T
- Venue
- Clinical Rehabilitation
- Publisher
- SAGE Publications
- Published
- 2003-02
- Volume
- 17
- Issue
- 1
- Pages
- 21-29
- ISSN
- 0269-2155 (ISSN-L)
- 1477-0873
- OpenAlex
- W1997513305
- Cited by
- 441
- References
- 23
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 9 · 2023: 19 · 2022: 28 · 2021: 39 · 2020: 24 · 2019: 20 · 2018: 22 · 2017: 15 · 2016: 11 · 2015: 17 · 2014: 21 · 2013: 9 · 2012: 17
- FWCI
- 19.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Rehabilitation (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- GW Pharmaceuticals
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Neurology › Botulinum Toxin and Related Neurological Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- delta-9-tetrahydrocannabinol, cannabidiol, multiple sclerosis, spinal cord injury, neurofibromatosis, neuropathic pain, spasticity, bladder control, muscle spasm, sublingual spray, adverse effects, hypotension, poisoning, symptom relief
- MeSH terms
- Administration, Oral, Cannabidiol, Cannabis, Double-Blind Method, Humans, Hypotension, Phytotherapy, Muscle Spasticity, Nervous System Diseases, Pain, Placebos, Severity of Illness Index, Spasm, Dronabinol, Urination Disorders, Cross-Over Studies, Analgesics, Non-Narcotic, Plant Preparations
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