Therapeutic potential of cannabinoids for stroke: scoping review protocol


  • Iván Pérez-Neri Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez
  • M. Dulce Estêvão Escola Superior de Saúde da Universidade do Algarve. Campus de Gambelas
  • Rakesh Mishra Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University
  • Hugo Sandoval General Directorate. National Institute of Rehabilitation Luis Guillermo Ibarra Ibarra
  • Manuel Zárate Universidad Autónoma de Baja California, Campus Mexicali
  • Camilo Ríos Department of Neurochemistry. National Institute of Neurology and Neurosurgery Manuel Velasco Suárez



Phytocannabinoid, Endocannabinoid, Stroke, Ischemia, Artery occlusion


Introduction: Each year, approximately 795,000 people experience a new or recurrent stroke, either ischemic or hemorrhagic. The current therapeutical approach for acute ischemic stroke includes thrombolysis and mechanical thrombectomy; still, no neuroprotective treatment options currently exist to improve its neurological outcome. Some components of the endocannabinoid system are altered after ischemic stroke. It is considered that cannabinoids may exert neuroprotective effects; however, the use of cannabinoid receptor ligands is a major concern due to its psychotropic properties. Regardless that there are many studies describing the benefit of administering cannabinoids for experimental stroke several unanswered questions remain since most of the information point up in non-human species. A previous systematic review detected significant heterogeneity among studies, so it is appropriate to perform a scoping review to evaluate the feasibility of performing an updated systematic review and meta-analysis. This scoping review aims to evaluate the therapeutic potential of modulating the endocannabinoid system for stroke. Methods: Published studies (all publication types) will be retrieved from Web of Science, PubMed, Scopus, Ovid, EBSCOhost, and Google Scholar. Eligibility criteria: Clinical or preclinical studies reporting endocannabinoid levels or their effects, or reporting administration of cannabinoid modulators (stimulating or inhibiting their synthesis or metabolism, phytocannabinoids, or synthetic cannabinoids), in patients or models of stroke will be considered for inclusion. Studies written in languages different than Spanish or English that could not be appropriately translated, or whose full-text files could not be retrieved will be excluded. Data charting: Results will be summarized in tabular form. This protocol complies with PRISMA-P.


1. Crimes UNOODA. World Drug Report 2021. 2021
2. Tournebize J, Gibaja V, Kahn JP. Acute effects of synthetic cannabinoids: Update 2015. Subst Abus. 2017;38(3):344-366. doi: 10.1080/08897077.2016.1219438
3. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, Tsao CW, American HACOEAPSCASSS. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8):e254-e743. doi: 10.1161/CIR.0000000000000950
4. Khavjou O, Phelps D, Leib A. Projections of Cardiovascular Disease Prevalence and Costs: 2015–2035. 2016
5. Zarruk JG, Fernández-López D, García-Yébenes I, García-Gutiérrez MS, Vivancos J, Nombela F, Torres M, Burguete MC, Manzanares J, Lizasoain I, Moro MA. Cannabinoid Type 2 Receptor Activation Downregulates Stroke-Induced Classic and Alternative Brain Macrophage/Microglial Activation Concomitant to Neuroprotection. Stroke. 2012;43(1):211-219. doi: 10.1161/STROKEAHA.111.631044
6. Jouanjus E, Raymond V, Lapeyre-Mestre M, Wolff V. What is the Current Knowledge About the Cardiovascular Risk for Users of Cannabis-Based Products? A Systematic Review. Curr Atheroscler Rep. 2017;19(6):26. doi: 10.1007/s11883-017-0663-0
7. Yoo SGK, Seth M, Vaduganathan M, Ruwende C, Karve M, Shah I, Hill T, Gurm HS, Sukul D, Blue CBSOMCCI. Marijuana Use and In-Hospital Outcomes After Percutaneous Coronary Intervention in Michigan, United States. JACC Cardiovasc Interv. 2021;14(16):1757-1767. doi: 10.1016/j.jcin.2021.06.036
8. Gómez Ochoa SA. Stroke and cannabis use in patients with no cardiovascular risk factors: a systematic review of case reports. Neurologia (Engl Ed). 2021;36(3):222-228. doi: 10.1016/j.nrl.2017.09.016
9. Chiu RG, Fuentes AM, Patil SN, Chiu R, McGuire LS, Mehta AI. Cannabis Abuse and Perioperative Complications After Treatment of Intracranial Aneurysms: A Nationwide Analysis. World Neurosurgery. 2021 doi: 10.1016/j.wneu.2021.10.156
10. Rabat Y, Sibon I, Berthoz S. Implication of problematic substance use in poststroke depression: an hospital-based study. Sci Rep. 2021;11(1):13324. doi: 10.1038/s41598-021-92639-5
11. Gorelick DA, Hermann R. Cannabis use and disorder: Epidemiology, comorbidity, health consequences, and medico-legal status. UpToDate. 2-150.
12. England TJ, Hind WH, Rasid NA, O’Sullivan SE. Cannabinoids in experimental stroke: a systematic review and meta-analysis. J Cereb Blood Flow Metab. 2015;35(3):348-358. doi: 10.1038/jcbfm.2014.218
13. Marinelli L, Balestrino M, Mori L, Puce L, Rosa GM, Giorello L, Currà A, Fattapposta F, Serrati C, Gandolfo C. A randomised controlled cross-over double-blind pilot study protocol on THC: CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity. BMJ open. 2017;7(9):e016843. doi: 10.1136/bmjopen-2017-016843
14. Moser U. Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1: 1 ratio: a therapeutic option for patients with central post-stroke pain syndrome. BMJ Case Reports CP. 2021;14(7):e243072. doi: 10.1136/bcr-2021-243072
15. Hashiesh HM, Jha NK, Sharma C, Gupta PK, Jha SK, Patil CR, Goyal SN, Ojha SK. Pharmacological potential of JWH133, a cannabinoid type 2 receptor agonist in neurodegenerative, neurodevelopmental and neuropsychiatric diseases. Eur J Pharmacol. 2021;909:174398. doi: 10.1016/j.ejphar.2021.174398
16. Sultan SR, Millar SA, England TJ, O’Sullivan SE. A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol. Front Pharmacol. 2017;8:81. doi: 10.3389/fphar.2017.00081
17. Wang LN, Xing MD, Qu WT, Wang CB, Liu ZQ, Han J, Ren W, Qiao YN. Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice. Microvasc Res. 2022;139:104263. doi: 10.1016/j.mvr.2021.104263
18. Davis MP, Behm B, Mehta Z, Fernandez C. The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review. Am J Hosp Palliat Care. 2019;36(12):1134-1154. doi: 10.1177/1049909119850807
19. Annunziata C, Pirozzi C, Lama A, Senzacqua M, Comella F, Bordin A, Monnolo A, Pelagalli A, Ferrante MC, Mollica MP, Iossa A, De Falco E, Mattace Raso G, Cinti S, Giordano A, Meli R. Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α. Pharmaceutics. 2022;14(2):338. doi: 10.3390/pharmaceutics14020338
20. Azar S, Udi S, Drori A, Hadar R, Nemirovski A, Vemuri KV, Miller M, Sherill-Rofe D, Arad Y, Gur-Wahnon D, Li X, Makriyannis A, Ben-Zvi D, Tabach Y, Ben-Dov IZ, Tam J. Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent. Mol Metab. 2020;42:101087. doi: 10.1016/j.molmet.2020.101087
21. Pérez-Neri I, Diéguez-Campaa CE, Sandoval H, Chávez VA, Castro-Martínez E, Ríos C. Therapeutic potential of dehydroepiandrosterone for Parkinson’s disease: scoping review protocol. Arch Neurocien. 2022;in press
22. Rosca EC, Tudor R, Cornea A, Simu M. Parkinson’s Disease in Romania: A Scoping Review Protocol. Brain Sci. 2021;11(2):251. doi: 10.3390/brainsci11020251
23. Polhemus AM, Bergquist R, Bosch de Basea M, Brittain G, Buttery SC, Chynkiamis N, Dalla Costa G, Delgado Ortiz L, Demeyer H, Emmert K, Garcia Aymerich J, Gassner H, Hansen C, Hopkinson N, Klucken J, Kluge F, Koch S, Leocani L, Maetzler W, Micó-Amigo ME, Mikolaizak AS, Piraino P, Salis F, Schlenstedt C, Schwickert L, Scott K, Sharrack B, Taraldsen K, Troosters T, Vereijken B, Vogiatzis I, Yarnall A, Mazza C, Becker C, Rochester L, Puhan MA, Frei A. Walking-related digital mobility outcomes as clinical trial endpoint measures: protocol for a scoping review. BMJ Open. 2020;10(7):e038704. doi: 10.1136/bmjopen-2020-038704
24. Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. JBI; 2020 doi: 10.46658/JBIMES-20-01
25. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, McKenzie JE. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. doi: 10.1136/bmj.n160
26. Beller EM, Glasziou PP, Altman DG, Hopewell S, Bastian H, Chalmers I, Gøtzsche PC, Lasserson T, Tovey D, PRISMA FAG. PRISMA for Abstracts: reporting systematic reviews in journal and conference abstracts. PLoS Med. 2013;10(4):e1001419. doi: 10.1371/journal.pmed.1001419
27. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, PRISMA-P G. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647. doi: 10.1136/bmj.g7647
28. Rethlefsen ML, Kirtley S, Waffenschmidt S, Ayala AP, Moher D, Page MJ, Koffel JB, PRISMA-S G. PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. Syst Rev. 2021;10(1):39. doi: 10.5195/jmla.2021.962
29. Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018;169(7):467-473. doi: 10.7326/M18-0850
30. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc. 2015;13(3):147-153. doi: 10.1097/XEB.0000000000000054
31. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016;75:40-46. doi: 10.1016/j.jclinepi.2016.01.021
32. Improving efficiency and confidence in systematic literature searching. European Association for Health Information and Libraries (EAHIL).
33. Willcox MDP, Walsh K, Nichols JJ, Morgan PB, Jones LW. The ocular surface, coronaviruses and COVID‐19. Clin Exp Optom. 2020;103(4):418-424. doi: 10.1111/cxo.13088
34. Pérez-Neri I, González-Aguilar A, Sandoval H, Pineda C, Ríos C. Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence. Curr Neuropharmacol. 2021;19(3):334-348. doi: 10.2174/1570159X18666200720175253
35. McKeown S, Mir ZM. Considerations for conducting systematic reviews: evaluating the performance of different methods for de-duplicating references. Syst Rev. 2021;10(1):38. doi: 10.1186/s13643-021-01583-y
36. Bozada T, Borden J, Workman J, Del Cid M, Malinowski J, Luechtefeld T. Sysrev: A FAIR Platform for Data Curation and Systematic Evidence Review. Front Artif Intell. 2021;4:685298. doi: 10.3389/frai.2021.685298
37. Garritty C, Gartlehner G, Nussbaumer-Streit B, King VJ, Hamel C, Kamel C, Affengruber L, Stevens A. Cochrane Rapid Reviews Methods Group offers evidence-informed guidance to conduct rapid reviews. J Clin Epidemiol. 2021;130:13-22. doi: 10.1016/j.jclinepi.2020.10.007
38. Usher R, Stapleton T. Approaches for assessing decision-making capacity in older adults: a scoping review protocol. JBI Evidence Synthesis. 2020;18(4):832-840. doi: 10.11124/JBISRIR-D-19-00068



How to Cite

Pérez-Neri, I., Estêvão, M. D., Mishra, R., Sandoval, H., Zárate, M., & Ríos, C. (2022). Therapeutic potential of cannabinoids for stroke: scoping review protocol. Archivos De Neurociencias, 28(2).



Evidence synthesis

Most read articles by the same author(s)

<< < 1 2 3 4