Skip to main content
SpringerLink
Log in

Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis

  • Chapter
Endocannabinoids

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 231))

Abstract

There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS). These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms. This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 379.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

2-AG:

2-Arachidonoyl glycerol

AEA:

Anandamide

ALS:

Amyotrophic lateral sclerosis

EDSS:

Expanded disability status scale

EPSC:

Excitatory post-synaptic current

FAAH:

Fatty acid amide hydrolase

FTD:

Fronto-temporal dementia

GABA:

Gamma aminobutyric acid

MAG lipase:

Monoacylglycerol lipase

MS:

Multiple sclerosis

OEA:

Oleoylethanolamide

PEA:

Palmitoylethanolamide

SOD-1:

Superoxide dismutase 1

THC:

Δ9-tetrahydrocannabinol

References

  • Amato MP, Ponziani G (2000) A prospective study on the prognosis of multiple sclerosis. Neurol Sci 21:S831–S838. doi:10.1007/s100720070021

    Article  CAS  PubMed  Google Scholar 

  • Amtmann D, Weydt P, Johnson KL, Jensen MP, Carter GT (2004) Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care 21:95–104. doi:10.1177/104990910402100206

    Article  PubMed  Google Scholar 

  • Andersson PB, Waubant E, Gee L, Goodkin DE (1999) Multiple sclerosis that is progressive from the time of onset: clinical characteristics and progression of disability. Arch Neurol 56:1138–1142. doi:10.1001/archneur.56.9.1138

    Article  CAS  PubMed  Google Scholar 

  • Ascherio A, Munger KL (2010) Epstein-Barr virus infection and multiple sclerosis: a review. J Neuroimmune Pharmacol 5:271–277. doi:10.1007/s11481-010-9201-3

    Article  PubMed  Google Scholar 

  • Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Huffman JW, Layward L (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 404:84–87. doi:10.1038/35003583

    Article  CAS  PubMed  Google Scholar 

  • Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo V (2001) Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15:300–302. doi:10.1096/fj.00-0399fje

    CAS  PubMed  Google Scholar 

  • Barnett MH, Prineas JW (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55:458–468. doi:10.1002/ana.20016

    Article  PubMed  Google Scholar 

  • Benito C, Romero JP, Tolón RM, Clemente D, Docagne F, Hillard CJ, Guaza C, Romero J (2007) Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J Neurosci 27:2396–2402. doi:10.1523/JNEUROSCI.4814-06.2007

    Article  CAS  PubMed  Google Scholar 

  • Bernal-Chico A, Canedo M, Manterola A, Victoria Sánchez-Gómez M, Pérez-Samartín A, Rodríguez-Puertas R, Matute C, Mato S (2015) Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and prevents demyelination in vivo. Glia 63:163–176. doi:10.1002/glia.22742

    Article  PubMed  Google Scholar 

  • Berrendero F, Sánchez A, Cabranes A, Puerta C, Ramos JA, García-Merino A, Fernández-Ruiz J (2001) Changes in cannabinoid CB(1) receptors in striatal and cortical regions of rats with experimental allergic encephalomyelitis, an animal model of multiple sclerosis. Synapse 41:195–202. doi:10.1002/syn.1075

    Article  CAS  PubMed  Google Scholar 

  • Bilsland LG, Dick JR, Pryce G, Petrosino S, Di Marzo V, Baker D, Greensmith L (2006) Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. FASEB J 20:1003–1005. doi:10.1096/fj.05-4743fje

    Article  CAS  PubMed  Google Scholar 

  • Bilsland LG, Nirmalananthan N, Yip J, Greensmith L, Duchen MR (2008) Expression of mutant SOD1 in astrocytes induces functional deficits in motoneuron mitochondria. J Neurochem 107:1271–1283. doi:10.1111/j.1471-4159.2008.05699.x

    Article  CAS  PubMed  Google Scholar 

  • Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901. doi:10.1002/1531-8249(200012)48:6<893::AID-ANA10>3.0.CO;2-B

  • Bjartmar C, Wujek JR, Trapp BD (2003) Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 206:165–171. doi:10.1016/S0022-510X(02)00069-2

    Article  CAS  PubMed  Google Scholar 

  • Cabranes A, Venderova K, de Lago E, Fezza F, Sánchez A, Mestre L, Valenti M, García-Merino A, Ramos JA, Di Marzo V, Fernández-Ruiz J (2005) Decreased endocannabinoid levels in the brain and beneficial effects of agents activating cannabinoid and/or vanilloid receptors in a rat model of multiple sclerosis. Neurobiol Dis 20:207–217. doi:10.1016/j.nbd.2005.03.002

    Article  CAS  PubMed  Google Scholar 

  • Carter GT, Abood ME, Aggarwal SK, Weiss MD (2010) Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. Am J Hosp Palliat Care 27:347–356. doi:10.1177/104990910402100206

    Article  PubMed  Google Scholar 

  • Centonze D, Bari M, Rossi S, Prosperetti C, Furlan R, Fezza F, De Chiara V, Battistini L, Bernardi G, Bernardini S, Martino G, Maccarrone M (2007) The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Brain 130:2543–2553. doi:10.1093/brain/awm160

    Article  PubMed  Google Scholar 

  • Chang A, Smith MC, Yin X, Fox RJ, Staugaitis SM, Trapp BD (2008) Neurogenesis in the chronic lesions of multiple sclerosis. Brain 131:2366–2375. doi:10.1093/brain/awn157

    Article  PubMed Central  PubMed  Google Scholar 

  • Cheah BC, Vucic S, Krishnan AV, Kiernan MC (2010) Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr Med Chem 17:1942–1949. doi:10.2174/ 092986710791163939

  • Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231. doi:10.1016/S0140-6736(02)08220-X

    Article  PubMed  Google Scholar 

  • Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517. doi:10.1016/S0140-6736(08)61620-7

    Article  CAS  PubMed  Google Scholar 

  • Confavreux C, Vukusic S (2006) Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin Neurol Neurosurg 108:327–332. doi:10.1016/j.clineuro.2005.11.018

    Article  PubMed  Google Scholar 

  • Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438. doi:10.1056/NEJM200011163432001

    Article  CAS  PubMed  Google Scholar 

  • Croxford JL, Pryce G, Jackson SJ, Ledent C, Giovannoni G, Pertwee RG, Yamamura T, Baker D (2008) Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J Neuroimmunol 193:120–129. doi:10.1016/j.jneuroim.2007.10.024

    Article  CAS  PubMed  Google Scholar 

  • De Jesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256. doi:10.1016/j.neuron.2011.09.011

    Article  Google Scholar 

  • de Lago E, Ligresti A, Ortar G, Morera E, Cabranes A, Pryce G, Bifulco M, Baker D, Fernandez-Ruiz J, Di Marzo V (2004) In vivo pharmacological actions of two novel inhibitors of anandamide cellular uptake. Eur J Pharmacol 484:249–257. doi:10.1016/j.ejphar.2003.11.027

    Article  PubMed  Google Scholar 

  • de Lago E, Fernández-Ruiz J, Ortega-Gutiérrez S, Cabranes A, Pryce G, Baker D, López-Rodríguez M, Ramos JA (2006) UCM707, an inhibitor of the anandamide uptake, behaves as a symptom control agent in models of Huntington’s disease and multiple sclerosis, but fails to delay/arrest the progression of different motor-related disorders. Eur Neuropsychopharmacol 16:7–18. doi:10.1016/j.euroneuro.2005.06.001

    Article  PubMed  Google Scholar 

  • Di Filippo M, Pini LA, Pelliccioli GP, Calabresi P, Sarchielli P (2008) Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis. J Neurol Neurosurg Psychiatry 79:1224–1229. doi:10.1136/jnnp.2007.139071

    Article  PubMed  Google Scholar 

  • Ebers GC, Sadovnick AD (1993) The geographic distribution of multiple sclerosis: a review. Neuroepidemiology 12:1–5. doi:10.1159/000110293

    Article  CAS  PubMed  Google Scholar 

  • Flachenecker P, Henze T, Zettl UK (2014) Nabiximols (THC/CBD oromucosal spray, Sativex®) in clinical practice–results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity. Eur Neurol 71:271–279. doi:10.1159/000357427

    Article  CAS  PubMed  Google Scholar 

  • Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV (2010) An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One 5, e12496. doi:10.1371/journal.pone.0012496

    Article  PubMed Central  PubMed  Google Scholar 

  • Hernández-Torres G, Cipriano M, Hedén E, Björklund E, Canales A, Zian D, Feliú A, Mecha M, Guaza C, Fowler CJ, Ortega-Gutiérrez S, López-Rodríguez ML (2014) A reversible and selective inhibitor of monoacylglycerol lipase ameliorates multiple sclerosis. Angew Chem Int Ed Engl 53(50):13765–13770. doi:10.1002/anie.201407807

    Article  PubMed  Google Scholar 

  • Jackson SJ, Pryce G, Diemel LT, Cuzner ML, Baker D (2005) Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and caspase 3 activation. Neuroscience 134:261–268. doi:10.1016/j.neuroscience.2005.02.045

    Article  CAS  PubMed  Google Scholar 

  • Jean-Gilles L, Feng S, Tench CR, Chapman V, Kendall DA, Barrett DA, Constantinescu CS (2009) Plasma endocannabinoid levels in multiple sclerosis. J Neurol Sci 287:212–215. doi:10.1016/j.jns.2009.07.021

    Article  CAS  PubMed  Google Scholar 

  • Jones JL, Coles AJ (2010) New treatment strategies in multiple sclerosis. Exp Neurol 225:34–39. doi:10.1016/j.expneurol.2010.06.003

    Article  PubMed  Google Scholar 

  • Kong W, Li H, Tuma RF, Ganea D (2014) Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS. Cell Immunol 287:1–17. doi:10.1016/j.cellimm.2013.11.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kurtzke JF (1993) Epidemiologic evidence for multiple sclerosis as an infection. Clin Microbiol Rev 6:382–427

    PubMed Central  CAS  PubMed  Google Scholar 

  • Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G (2010) Evidence for a two-stage disability progression in multiple sclerosis. Brain 133:1900–1913. doi:10.1093/brain/awq076

    Article  PubMed Central  PubMed  Google Scholar 

  • Logroscino G, Traynor BJ, Hardiman O, Chiò A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E, EURALS (2010) Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81:385–390. doi:10.1136/jnnp.2009.183525

    Article  PubMed Central  PubMed  Google Scholar 

  • Lorente Fernández L, Monte Boquet E, Pérez-Miralles F, Gil Gómez I, Escutia Roig M, Boscá Blasco I, Poveda Andrés JL, Casanova-Estruch B (2014) Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. Neurologia 29:257–260. doi:10.1016/j.nrl.2013.06.014

    Article  PubMed  Google Scholar 

  • Lourbopoulos A, Grigoriadis N, Lagoudaki R, Touloumi O, Polyzoidou E, Mavromatis I, Tascos N, Breuer A, Ovadia H, Karussis D, Shohami E, Mechoulam R, Simeonidou C (2011) Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis. Brain Res 1390:126–141. doi:10.1016/j.brainres.2011.03.020

    Article  CAS  PubMed  Google Scholar 

  • Malik B, Nirmalananthan N, Gray AL, La Spada AR, Hanna MG, Greensmith L (2013) Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy. Brain 136:926–943. doi:10.1093/brain/aws343

    Article  PubMed Central  PubMed  Google Scholar 

  • Maresz K, Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, Ledent C, Cheng X, Carrier EJ, Mann MK, Giovannoni G, Pertwee RG, Yamamura T, Buckley NE, Hillard CJ, Lutz B, Baker D, Dittel BN (2007) Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat Med 13:492–497. doi:10.1038/nm1561

    Article  CAS  PubMed  Google Scholar 

  • Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutiérrez SO, van der Stelt M, López-Rodriguez ML, Casanova E, Schütz G, Zieglgänsberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88. doi:10.1126/science.1088208

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto SI, Goto S, Kusaka H, Imai T, Hashizume Y, Okazaki H, Hirano A (1993) Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: a comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and Werdnig-Hoffmann disease. J Neurol Sci 115:208–213. doi:10.1016/0022-510X(93)90226-O

    Article  CAS  PubMed  Google Scholar 

  • Miller DH, Leary SM (2007) Primary-progressive multiple sclerosis. Lancet Neurol 6:903–912. doi:10.1016/S1474-4422(07)70243-0

    Article  PubMed  Google Scholar 

  • Moreno-Martet M, Espejo-Porras F, Fernández-Ruiz J, de Lago E (2014) Changes in endocannabinoid receptors and enzymes in the spinal cord of SOD1(G93A) transgenic mice and evaluation of a Sativex(®)-like combination of phytocannabinoids: interest for future therapies in amyotrophic lateral sclerosis. CNS Neurosci Ther 20:809–815. doi:10.1111/cns.12262

    Article  CAS  PubMed  Google Scholar 

  • Musella A, Sepman H, Mandolesi G, Gentile A, Fresegna D, Haji N, Conrad A, Lutz B, Maccarrone M, Centonze D (2014) Pre- and postsynaptic type-1 cannabinoid receptors control the alterations of glutamate transmission in experimental autoimmune encephalomyelitis. Neuropharmacology 79:567–572. doi:10.1016/j.neuropharm.2014.01.007

    Article  CAS  PubMed  Google Scholar 

  • Parratt JD, Prineas JW (2010) Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes. Mult Scler 16:1156–1172. doi:10.1177/1352458510382324

    Article  PubMed  Google Scholar 

  • Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW, Investigators AFFIRM (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910. doi:10.1056/NEJMoa044397

    Article  CAS  PubMed  Google Scholar 

  • Prat E, Tomaru U, Sabater L, Park DM, Granger R, Kruse N, Ohayon JM, Bettinotti MP, Martin R (2005) HLA-DRB5*0101 and -DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype. J Neuroimmunol 167:108–119. doi:10.1016/j.jneuroim.2005.04.027

    Article  CAS  PubMed  Google Scholar 

  • Pryce G, Baker D (2007) Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors. Br J Pharmacol 150:519–525. doi:10.1038/sj.bjp.0707003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pryce G, Ahmed Z, Hankey DJ, Jackson SJ, Croxford JL, Pocock JM, Ledent C, Petzold A, Thompson AJ, Giovannoni G, Cuzner ML, Baker D (2003) Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126:2191–2202. doi:10.1093/brain/awg224

    Article  PubMed  Google Scholar 

  • Pryce G, Cabranes A, Fernández-Ruiz J, Bisogno T, Di Marzo V, Long JZ, Cravatt BF, Giovannoni G, Baker D (2013) Control of experimental spasticity by targeting the degradation of endocannabinoids using selective fatty acid amide hydrolase inhibitors. Mult Scler 19:1896–1904. doi:10.1177/1352458513485982

    Article  CAS  PubMed  Google Scholar 

  • Ramagopalan SV, Maugeri NJ, Handunnetthi L, Lincoln MR, Orton SM, Dyment DA, Deluca GC, Herrera BM, Chao MJ, Sadovnick AD, Ebers GC, Knight JC (2009) Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 5:e1000369. doi:10.1371/journal.pgen.1000369

    Article  PubMed Central  PubMed  Google Scholar 

  • Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton SM, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC (2010) A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res 2:1352–1360. doi:10.1101/gr.107920.110

    Article  Google Scholar 

  • Rao SD, Weiss JH (2004) Excitotoxic and oxidative cross-talk between motor neurons and glia in ALS pathogenesis. Trends Neurosci 27:17–23. doi:10.1016/j.tins.2003.11.001

    Article  CAS  PubMed  Google Scholar 

  • Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chiò A, Restagno G, Borghero G, Sabatelli M, ITALSGEN Consortium, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268. doi:10.1016/j.neuron.2011.09.010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, Van den Bergh R, Hung W, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak-Vance MA, Haines J, Rouleau GA, Gusella JS, Horvitz HR, Robert H, Brown RH Jr (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62. doi:10.1038/362059a0

    Article  CAS  PubMed  Google Scholar 

  • Rossi S, De Chiara V, Musella A, Cozzolino M, Bernardi G, Maccarrone M, Mercuri NB, Carrì MT, Centonze D (2010) Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis. Amyotroph Lateral Scler 11:83–90. doi:10.3109/17482960902977954

    Article  CAS  PubMed  Google Scholar 

  • Rossi S, Furlan R, De Chiara V, Muzio L, Musella A, Motta C, Studer V, Cavasinni F, Bernardi G, Martino G, Cravatt BF, Lutz B, Maccarrone M, Centonze D (2011) Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis. Brain Behav Immun 25:1242–1248. doi:10.1016/j.bbi.2011.03.017

    Article  CAS  PubMed  Google Scholar 

  • Runmarker B, Andersen O (1993) Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 116:117–134. doi:10.1093/brain/116.1.117

    Article  PubMed  Google Scholar 

  • Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D’alfonso S, Blackburn H, Martinelli BF, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, D’hooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppä V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Rückert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sørensen PS, Søndergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvänen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P, Compston A (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476:214–219. doi:10.1038/nature10251

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Serpell MG, Notcutt W, Collin C (2013) Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol 260:285–295. doi:10.1007/s00415-012-6634-z

    Article  PubMed  Google Scholar 

  • Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL (2007) The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J Neurochem 101:87–98. doi:10.1111/j.1471-4159.2006.04346.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sisay S, Pryce G, Jackson SJ, Tanner C, Ross RA, Michael GJ, Selwood DL, Giovannoni G, Baker D (2013) Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis. PLoS One 8(10):e76907. doi:10.1371/journal.pone.0076907

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Smith T, Groom A, Zhu B, Turski L (2000) Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med 6:62–66. doi:10.1038/71548

    Article  CAS  PubMed  Google Scholar 

  • Stover JF, Pleines UE, Morganti-Kossmann MC, Kossmann T, Lowitzsch K, Kempski OS (1997) Neurotransmitters in cerebrospinal fluid reflect pathological activity. Eur J Clin Invest 27:1038–1043. doi:10.1046/j.1365-2362.1997.2250774.x

    Article  CAS  PubMed  Google Scholar 

  • Ström AL, Shi P, Zhang F, Gal J, Kilty R, Hayward LJ, Zhu H (2008) Interaction of amyotrophic lateral sclerosis (ALS)-related mutant copper-zinc superoxide dismutase with the dynein-dynactin complex contributes to inclusion formation. J Biol Chem 283:22795–22805. doi:10.1074/jbc.M800276200

    Article  PubMed Central  PubMed  Google Scholar 

  • Tu PH, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Natl Acad Sci U S A 93:3155–3160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Visser EM, Wilde K, Wilson JF, Yong KK, Counsell CE (2012) A new prevalence study of multiple sclerosis in Orkney, Shetland and Aberdeen city. J Neurol Neurosurg Psychiatry 83:719–724. doi:10.1136/jnnp-2011-301546

    Article  PubMed  Google Scholar 

  • Weber M, Goldman B, Truniger S (2010) Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J Neurol Neurosurg Psychiatry 81:1135–1140. doi:10.1136/jnnp.2009.200642

    Article  CAS  PubMed  Google Scholar 

  • Webb M, Luo L, Ma JY, Tham CS (2008) Genetic deletion of fatty acid amide hydrolase results in improved long-term outcome in chronic autoimmune encephalitis. Neurosci Lett 439:106–110. doi:10.1016/j.neulet.2008.04.090

    Article  CAS  PubMed  Google Scholar 

  • Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC (1989) The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain 112:133–146. doi:10.1093/brain/112.1.133

    Article  PubMed  Google Scholar 

  • Wijesekera LC, Leigh PN (2009) Amyotrophic lateral sclerosis. Orphanet J Rare Dis 4:3. doi:10.1186/1750-1172-4-3

    Article  PubMed Central  PubMed  Google Scholar 

  • Willer CJ, Dyment DA, Sadovnick AD, Rothwell PM, Murray TJ, Ebers GC, Canadian Collaborative Study Group (2005) Timing of birth and risk of multiple sclerosis: population based study. BMJ 330:120–123. doi:10.1136/bmj.38301.686030.63

    Article  PubMed Central  PubMed  Google Scholar 

  • Wilson RI, Nicoll RA (2002) Endocannabinoid signalling in the brain. Science 296:678–682. doi:10.1126/science.1063545

    Article  CAS  PubMed  Google Scholar 

  • Witting A, Weydt P, Hong S, Kliot M, Moller T, Stella N (2004) Endocannabinoids accumulate in spinal cord of SOD1 G93A transgenic mice. J Neurochem 89:1555–1557. doi:10.1111/j.1471-4159.2004.02544.x

    Article  CAS  PubMed  Google Scholar 

  • Witting A, Chen L, Cudaback E, Straiker A, Walter L, Rickman B, Möller T, Brosnan C, Stella N (2006) Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. Proc Natl Acad Sci U S A 103:6362–6367. doi:10.1073/pnas.0510418103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ (2005) Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry 76:1664–1669. doi:10.1136/jnnp.2005.070136

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG, MUSEC Research Group (2012) Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry 83:1125–1132. doi:10.1136/jnnp-2012-302468

    Article  PubMed  Google Scholar 

  • Zajicek J, Ball S, Wright D, Vickery J, Nunn A, Miller D, Gomez Cano M, McManus D, Mallik S, Hobart J, CUPID investigator group (2013) Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial. Lancet Neurol 12:857–865. doi:10.1016/S1474-4422(13)70159-5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao P, Ignacio S, Beattie EC, Abood ME (2008) Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity. Eur J Neurosci 27:572–579. doi:10.1111/j.1460-9568.2008.06041.x

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhao P, Leonoudakis D, Abood ME, Beattie EC (2010) Cannabinoid receptor activation reduces TNFalpha-induced surface localization of AMPAR-type glutamate receptors and excitotoxicity. Neuropharmacology 58:551–558. doi:10.1016/j.neuropharm.2009.07.035

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroimmunology, Neuroscience and Trauma Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK

    Gareth Pryce & David Baker

Authors
  1. Gareth Pryce
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gareth Pryce .

Editor information

Editors and Affiliations

  1. Professor of Neuropharmacology, University of Aberdeen Institute of Medical Sciences, Aberdeen, United Kingdom

    Roger G. Pertwee

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Pryce, G., Baker, D. (2015). Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis. In: Pertwee, R. (eds) Endocannabinoids. Handbook of Experimental Pharmacology, vol 231. Springer, Cham. https://doi.org/10.1007/978-3-319-20825-1_7

Download citation

Publish with us

Policies and ethics

Search

Navigation