Nabiximols (USAN,[1] trade name Sativex) is a specific Cannabis extract that was approved in 2010 as a botanical drug in the United Kingdom. Nabiximols is sold as a mouth spray intended to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms of multiple sclerosis; it was developed by the UK company GW Pharmaceuticals.[2][3] In 2019, it was proposed that following application of the spray, nabiximols is washed away from the oral mucosa by the saliva flow and ingested into the stomach, with subsequent absorption from the gastro-intestinal tract.[4][5] Nabiximols is a combination drug standardized in composition, formulation, and dose. Its principal active components are the cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). Each spray delivers a dose of 2.7 mg THC and 2.5 mg CBD.
Nabiximols
Chemical structures of tetrahydrocannabinol (top) and cannabidiol (bottom)
In 2003, GW Pharmaceuticals partnered with Bayer to market the drug under the brand name Sativex. In 2011, GW licensed the rights to commercialise nabiximols to Novartis for Asia (excluding China and Japan), Africa and the Middle East (excluding Israel).[6]
In June 2010, the Medicines and Healthcare products Regulatory Agency of the United Kingdom licensed nabiximols as a prescription-only medicine for the treatment of spasticity due to multiple sclerosis. This regulatory authorization represents the world's first full regulatory approval for the medicine. The spray is being marketed in the UK by Bayer Schering Pharma. Many people with MS cannot receive nabiximols due to local National Health Service (NHS) resistance to its funding;[7][8] but, in August 2014, the NHS in Wales agreed to fund Sativex for people with multiple sclerosis.[9]
Nabiximols was also approved in Spain for MS spasticity in the second half of 2010, and was launched in that country in March 2011. It was approved in the Czech Republic in April 2011, in Germany in May 2011, in Denmark in June 2011, and in Sweden in January 2012 to people with MS who have not responded adequately to other medication for spasticity.[10] It has also been recommended for approval in Italy and Austria with formal approvals expected in these countries during 2011. In Spain and other European markets (excluding the UK), nabiximols will be marketed by Almirall.
In Canada, nabiximols has been approved by Health Canada for the treatment of MS spasticity. It has also received a licence with conditions (NOC/c) for two additional uses: as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis,[11] and also for pain due to cancer.[12][13]
Nabiximols is available in a number of countries as an unlicensed medicine, which enables doctors to prescribe the product to people who they consider may benefit. The product has been exported from the UK to a total of 28 countries to date.
In February 2007, GW and Otsuka Pharmaceutical announced an exclusive agreement for Otsuka to develop and market the drug in the United States. The first large scale US Phase IIb trial, Spray Trial, for people with cancer reported positive results in March 2010. GW and Otsuka have now commenced the Phase III development of nabiximols in cancer pain.
In December 2012, Sativex was approved in Poland.[14]
In 2013, France legalized the use of cannabinoids in medicine, Sativex is the first one to be sold under prescription.[15] Nevertheless, as of June 2016 this drug had still not actually been sold in pharmacies there.[16]
EffectivenessEdit
Of the two preliminary Phase III studies investigating the treatment of people with MS, one showed a reduction of spasticity of 1.2 points on the 0–10 points rating scale (versus 0.6 points under placebo), the other showed a reduction of 1.0 versus 0.8 points. Only the first study reached statistical significance. The Phase III approval study consisted of a run-in phase where the response of individuals to the drug was determined. The responders (42% of subjects) showed a significant effect in the second, placebo controlled, phase of the trial.[17] A 2009 meta-analysis of six studies found large variations of effectiveness, with a – statistically non-significant – trend towards a reduction of spasticity.[18] A systematic review in 2014 by the American Academy of Neurology found that nabiximols was 'probably effective' for spasticity, pain, and urinary dysfunction, but wasn't supported for tremor.[19] A 2021 study, however, showed “clinically relevant symptomatic results”[20]
Nabiximols has also been studied for cancer pain resistant to opioids. While adjuvant use of nabiximols was safe in 3 trials for cancer pain,[21][22][23] data regarding efficacy were mixed, and the drug failed to meet its primary endpoint for this purpose in its first Phase III trial.[24]
Side effectsEdit
In early clinical trials, nabiximols has generally been well tolerated.[25][26][27] The most common adverse effects in Phase III trials were dizziness (25%), drowsiness (8%) and disorientation (4%); 12% of subjects stopped taking the drug because of the side effects. No investigations regarding the potential for dependence are available, but such a potential is unlikely considering the pharmacological properties of the two components.[17] A systematic review has shown no evidence is available about the negative effect of Nabiximols on cognition ability [28]
LicensingEdit
GW Pharmaceuticals were issued a license to cultivate cannabis for the manufacturing of Sativex in the United Kingdom (UK), granting them the sole legal right to research in aerosolized cannabis derived therapeutics, which became commercially viable in April 2013, when the UK Government scheduled the Sativex formulation to part IV of the UK Drugs Act.[29]
^"Statement on a non-proprietary name" (PDF). United States Adopted Names Council.
^"Nabiximols". UK Medicines Online.[permanent dead link] Page accessed Feb 3, 2016
^"Sativex (nabiximols) - factsheet". Multiple Sclerosis Trust. October 2014.
^Itin C, Barasch D, Domb AJ, Hoffman A (May 2020). "Prolonged oral transmucosal delivery of highly lipophilic drug cannabidiol". International Journal of Pharmaceutics. 581: 119276. doi:10.1016/j.ijpharm.2020.119276. PMID 32243971. S2CID 214785913.
^Itin C, Domb AJ, Hoffman A (October 2019). "A meta-opinion: cannabinoids delivered to oral mucosa by a spray for systemic absorption are rather ingested into gastro-intestinal tract: the influences of fed / fasting states". Expert Opinion on Drug Delivery. 16 (10): 1031–1035. doi:10.1080/17425247.2019.1653852. PMID 31393180. S2CID 199505274.
^"GW signs Sativex cannabis-based drug deal with Novartis". The Telegraph. 11 April 2011. Retrieved 12 July 2012.
^Ryan S (4 June 2011). "Sussex MS sufferers call for drug funding". Argus (Sussex, UK). Retrieved 8 June 2011.
^. Lincolnshire. 20 June 2011. Archived from the original on 22 June 2011. Retrieved 20 June 2011.
^"Wales NHS to offer MS cannabis drug Sativex". 15 August 2014. Retrieved 18 August 2014.
^. Swedish Medical Products Agency. Archived from the original on 2014-01-01.
^. GW Pharmaceuticals\. Archived from the original on 2011-08-11. Retrieved 24 July 2011.
^. GW Pharmaceuticals. Archived from the original on 2011-09-27. Retrieved 24 July 2011.
^ "Sativex - Investigational Cannabis-Based Treatment for Pain and Multiple Sclerosis Drug Development Technology". www.drugdevelopment-technology.com. Retrieved 2008-08-08.
^Olszewska D, Kidawa M. "Sativex - lek z marihuany". Krajowe Biuro Do Spraw Przeciwdziałania Narkomanii.
^"France Legalizes Marijuana-Based Drug To Treat Multiple Sclerosis". HunffingtonPost. Retrieved 4 June 2015.
^. Sciences et Avenir. Archived from the original on 2016-05-10. Retrieved 6 June 2016.
^ abSchubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2011/2012(in German)
^Lakhan SE, Rowland M (December 2009). "Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review". BMC Neurology. 9: 59. doi:10.1186/1471-2377-9-59. PMC2793241. PMID 19961570.
^Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, Gloss D (April 2014). "Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology". Neurology. 82 (17): 1556–1563. doi:10.1212/WNL.0000000000000363. PMC4011465. PMID 24778283.
^D'hooghe M, Willekens B, Delvaux V, D'haeseleer M, Guillaume D, Laureys G, et al. (June 2021). "Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience". BMC Neurology. 21 (1): 227. doi:10.1186/s12883-021-02246-0. PMC8218396. PMID 34157999. S2CID 235496708.
^Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, et al. (May 2012). "Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial". The Journal of Pain. 13 (5): 438–449. doi:10.1016/j.jpain.2012.01.003. PMID 22483680.
^Lynch ME, Cesar-Rittenberg P, Hohmann AG (January 2014). "A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain". Journal of Pain and Symptom Management. 47 (1): 166–173. doi:10.1016/j.jpainsymman.2013.02.018. PMID 23742737.
^Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT (August 2013). "An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics". Journal of Pain and Symptom Management. 46 (2): 207–218. doi:10.1016/j.jpainsymman.2012.07.014. PMID 23141881.
^Underwood G (9 January 2015). "Last stage failure for Otsuka and GW Cancer Pain Drug". Pharmafile. Retrieved 2016-12-07.
^Wade DT, Makela P, Robson P, House H, Bateman C (August 2004). "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". Multiple Sclerosis. 10 (4): 434–441. doi:10.1191/1352458504ms1082oa. PMID 15327042. S2CID 1378674.
^Wade DT, Makela PM, House H, Bateman C, Robson P (October 2006). "Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis". Multiple Sclerosis. 12 (5): 639–645. doi:10.1177/1352458505070618. PMID 17086911. S2CID 16175440.
^Wade DT, Robson P, House H, Makela P, Aram J (February 2003). "A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms". Clinical Rehabilitation. 17 (1): 21–29. doi:10.1191/0269215503cr581oa. PMID 12617376. S2CID 1414988.
^Motaghi E, Ghasemi-Pirbaluti M, Rashidi M, Alasvand M, Di Ciano P, Bozorgi H (March 2023). "The effect of tetrahydrocannabinol:cannabidiol oromucosal spray on cognition: a systematic review". European Journal of Clinical Pharmacology. 79 (3): 371–381. doi:10.1007/s00228-023-03454-y. PMID 36700997. S2CID 256273374.
^. Archived from the original on 2013-10-29. Retrieved 2013-11-27.
External linksEdit
Official website
October 15, 2023
nabiximols, usan, trade, name, sativex, specific, cannabis, extract, that, approved, 2010, botanical, drug, united, kingdom, sold, mouth, spray, intended, alleviate, neuropathic, pain, spasticity, overactive, bladder, other, symptoms, multiple, sclerosis, deve. Nabiximols USAN 1 trade name Sativex is a specific Cannabis extract that was approved in 2010 as a botanical drug in the United Kingdom Nabiximols is sold as a mouth spray intended to alleviate neuropathic pain spasticity overactive bladder and other symptoms of multiple sclerosis it was developed by the UK company GW Pharmaceuticals 2 3 In 2019 it was proposed that following application of the spray nabiximols is washed away from the oral mucosa by the saliva flow and ingested into the stomach with subsequent absorption from the gastro intestinal tract 4 5 Nabiximols is a combination drug standardized in composition formulation and dose Its principal active components are the cannabinoids tetrahydrocannabinol THC and cannabidiol CBD Each spray delivers a dose of 2 7 mg THC and 2 5 mg CBD NabiximolsChemical structures of tetrahydrocannabinol top and cannabidiol bottom Combination ofTetrahydrocannabinolCannabinoidCannabidiolCannabinoidClinical dataTrade namesSativexRoutes ofadministrationOromucosal sprayATC codeN02BG10 WHO Legal statusLegal statusAU S8 Controlled drug In general Prescription only IdentifiersCAS Number56575 23 6 NPubChem CID44148067UNIIK4H93P747OCompTox Dashboard EPA DTXSID40972015 N Y what is this verify Canadian packaging of a case of Sativex vialsIn 2003 GW Pharmaceuticals partnered with Bayer to market the drug under the brand name Sativex In 2011 GW licensed the rights to commercialise nabiximols to Novartis for Asia excluding China and Japan Africa and the Middle East excluding Israel 6 Contents 1 Availability 2 Effectiveness 3 Side effects 4 Licensing 5 See also 6 References 7 External linksAvailability EditIn June 2010 the Medicines and Healthcare products Regulatory Agency of the United Kingdom licensed nabiximols as a prescription only medicine for the treatment of spasticity due to multiple sclerosis This regulatory authorization represents the world s first full regulatory approval for the medicine The spray is being marketed in the UK by Bayer Schering Pharma Many people with MS cannot receive nabiximols due to local National Health Service NHS resistance to its funding 7 8 but in August 2014 the NHS in Wales agreed to fund Sativex for people with multiple sclerosis 9 Nabiximols was also approved in Spain for MS spasticity in the second half of 2010 and was launched in that country in March 2011 It was approved in the Czech Republic in April 2011 in Germany in May 2011 in Denmark in June 2011 and in Sweden in January 2012 to people with MS who have not responded adequately to other medication for spasticity 10 It has also been recommended for approval in Italy and Austria with formal approvals expected in these countries during 2011 In Spain and other European markets excluding the UK nabiximols will be marketed by Almirall In Canada nabiximols has been approved by Health Canada for the treatment of MS spasticity It has also received a licence with conditions NOC c for two additional uses as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis 11 and also for pain due to cancer 12 13 Nabiximols is available in a number of countries as an unlicensed medicine which enables doctors to prescribe the product to people who they consider may benefit The product has been exported from the UK to a total of 28 countries to date In February 2007 GW and Otsuka Pharmaceutical announced an exclusive agreement for Otsuka to develop and market the drug in the United States The first large scale US Phase IIb trial Spray Trial for people with cancer reported positive results in March 2010 GW and Otsuka have now commenced the Phase III development of nabiximols in cancer pain In December 2012 Sativex was approved in Poland 14 In 2013 France legalized the use of cannabinoids in medicine Sativex is the first one to be sold under prescription 15 Nevertheless as of June 2016 this drug had still not actually been sold in pharmacies there 16 Effectiveness EditOf the two preliminary Phase III studies investigating the treatment of people with MS one showed a reduction of spasticity of 1 2 points on the 0 10 points rating scale versus 0 6 points under placebo the other showed a reduction of 1 0 versus 0 8 points Only the first study reached statistical significance The Phase III approval study consisted of a run in phase where the response of individuals to the drug was determined The responders 42 of subjects showed a significant effect in the second placebo controlled phase of the trial 17 A 2009 meta analysis of six studies found large variations of effectiveness with a statistically non significant trend towards a reduction of spasticity 18 A systematic review in 2014 by the American Academy of Neurology found that nabiximols was probably effective for spasticity pain and urinary dysfunction but wasn t supported for tremor 19 A 2021 study however showed clinically relevant symptomatic results 20 Nabiximols has also been studied for cancer pain resistant to opioids While adjuvant use of nabiximols was safe in 3 trials for cancer pain 21 22 23 data regarding efficacy were mixed and the drug failed to meet its primary endpoint for this purpose in its first Phase III trial 24 Side effects EditIn early clinical trials nabiximols has generally been well tolerated 25 26 27 The most common adverse effects in Phase III trials were dizziness 25 drowsiness 8 and disorientation 4 12 of subjects stopped taking the drug because of the side effects No investigations regarding the potential for dependence are available but such a potential is unlikely considering the pharmacological properties of the two components 17 A systematic review has shown no evidence is available about the negative effect of Nabiximols on cognition ability 28 Licensing EditGW Pharmaceuticals were issued a license to cultivate cannabis for the manufacturing of Sativex in the United Kingdom UK granting them the sole legal right to research in aerosolized cannabis derived therapeutics which became commercially viable in April 2013 when the UK Government scheduled the Sativex formulation to part IV of the UK Drugs Act 29 See also EditMedical cannabis Nabilone Dronabinol Hortapharm B V References Edit Statement on a non proprietary name PDF United States Adopted Names Council Nabiximols UK Medicines Online permanent dead link Page accessed Feb 3 2016 Sativex nabiximols factsheet Multiple Sclerosis Trust October 2014 Itin C Barasch D Domb AJ Hoffman A May 2020 Prolonged oral transmucosal delivery of highly lipophilic drug cannabidiol International Journal of Pharmaceutics 581 119276 doi 10 1016 j ijpharm 2020 119276 PMID 32243971 S2CID 214785913 Itin C Domb AJ Hoffman A October 2019 A meta opinion cannabinoids delivered to oral mucosa by a spray for systemic absorption are rather ingested into gastro intestinal tract the influences of fed fasting states Expert Opinion on Drug Delivery 16 10 1031 1035 doi 10 1080 17425247 2019 1653852 PMID 31393180 S2CID 199505274 GW signs Sativex cannabis based drug deal with Novartis The Telegraph 11 April 2011 Retrieved 12 July 2012 Ryan S 4 June 2011 Sussex MS sufferers call for drug funding Argus Sussex UK Retrieved 8 June 2011 Sativex rejected by healthcare provider Lincolnshire 20 June 2011 Archived from the original on 22 June 2011 Retrieved 20 June 2011 Wales NHS to offer MS cannabis drug Sativex 15 August 2014 Retrieved 18 August 2014 Sativex nabiximols Swedish Medical Products Agency Archived from the original on 2014 01 01 Multiple Sclerosis GW Pharmaceuticals Archived from the original on 2011 08 11 Retrieved 24 July 2011 Cancer Pain GW Pharmaceuticals Archived from the original on 2011 09 27 Retrieved 24 July 2011 Sativex Investigational Cannabis Based Treatment for Pain and Multiple Sclerosis Drug Development Technology www drugdevelopment technology com Retrieved 2008 08 08 Olszewska D Kidawa M Sativex lek z marihuany Krajowe Biuro Do Spraw Przeciwdzialania Narkomanii France Legalizes Marijuana Based Drug To Treat Multiple Sclerosis HunffingtonPost Retrieved 4 June 2015 Cannabis therapeutique pourquoi le Sativex n est il toujours pas vendu en France Sciences et Avenir Archived from the original on 2016 05 10 Retrieved 6 June 2016 a b Schubert Zsilavecz M Wurglics M Neue Arzneimittel 2011 2012 in German Lakhan SE Rowland M December 2009 Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis a systematic review BMC Neurology 9 59 doi 10 1186 1471 2377 9 59 PMC 2793241 PMID 19961570 Koppel BS Brust JC Fife T Bronstein J Youssof S Gronseth G Gloss D April 2014 Systematic review efficacy and safety of medical marijuana in selected neurologic disorders report of the Guideline Development Subcommittee of the American Academy of Neurology Neurology 82 17 1556 1563 doi 10 1212 WNL 0000000000000363 PMC 4011465 PMID 24778283 D hooghe M Willekens B Delvaux V D haeseleer M Guillaume D Laureys G et al June 2021 Sativex nabiximols cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity the Belgian experience BMC Neurology 21 1 227 doi 10 1186 s12883 021 02246 0 PMC 8218396 PMID 34157999 S2CID 235496708 Portenoy RK Ganae Motan ED Allende S Yanagihara R Shaiova L Weinstein S et al May 2012 Nabiximols for opioid treated cancer patients with poorly controlled chronic pain a randomized placebo controlled graded dose trial The Journal of Pain 13 5 438 449 doi 10 1016 j jpain 2012 01 003 PMID 22483680 Lynch ME Cesar Rittenberg P Hohmann AG January 2014 A double blind placebo controlled crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy induced neuropathic pain Journal of Pain and Symptom Management 47 1 166 173 doi 10 1016 j jpainsymman 2013 02 018 PMID 23742737 Johnson JR Lossignol D Burnell Nugent M Fallon MT August 2013 An open label extension study to investigate the long term safety and tolerability of THC CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer related pain refractory to strong opioid analgesics Journal of Pain and Symptom Management 46 2 207 218 doi 10 1016 j jpainsymman 2012 07 014 PMID 23141881 Underwood G 9 January 2015 Last stage failure for Otsuka and GW Cancer Pain Drug Pharmafile Retrieved 2016 12 07 Wade DT Makela P Robson P House H Bateman C August 2004 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 Multiple Sclerosis 10 4 434 441 doi 10 1191 1352458504ms1082oa PMID 15327042 S2CID 1378674 Wade DT Makela PM House H Bateman C Robson P October 2006 Long term use of a cannabis based medicine in the treatment of spasticity and other symptoms in multiple sclerosis Multiple Sclerosis 12 5 639 645 doi 10 1177 1352458505070618 PMID 17086911 S2CID 16175440 Wade DT Robson P House H Makela P Aram J February 2003 A preliminary controlled study to determine whether whole plant cannabis extracts can improve intractable neurogenic symptoms Clinical Rehabilitation 17 1 21 29 doi 10 1191 0269215503cr581oa PMID 12617376 S2CID 1414988 Motaghi E Ghasemi Pirbaluti M Rashidi M Alasvand M Di Ciano P Bozorgi H March 2023 The effect of tetrahydrocannabinol cannabidiol oromucosal spray on cognition a systematic review European Journal of Clinical Pharmacology 79 3 371 381 doi 10 1007 s00228 023 03454 y PMID 36700997 S2CID 256273374 GWPharma GW Pharmaceuticals cannabinoid medicine Sativex moved to Schedule 4 of UK Drugs Act Archived from the original on 2013 10 29 Retrieved 2013 11 27 External links EditOfficial website Retrieved from https en wikipedia org w index php title Nabiximols amp oldid 1168091353, wikipedia, wiki, book, books, library,
