Cannabinoids: Do They have Clinical Usefulness for Pain Relief?
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Published:
May 6, 2021
Keywords:
cannabinoids, pain relie
Main Article Content
Abstract
Cannabis (marijuana) is the most popular psychoactive substance in the world. Cannabis is now a center of attention in many countries because of its roles for recreational and medicinal purposes. There are at least 500 cannabinoids found in cannabis, of which 104 of them have been identified. Among all cannabinoids, Δ9 tetrahydrocannabinol (THC) is the best known ingredient. THC is the dominant psychoactive component in plant-based marijuana or Cannabis sativa. Cannabidiol (CBD) is a main non-psychoactive (non-intoxicating) and potentially therapeutic component of cannabis. Studies reveal a more favorable analgesic benefit of cannabinoids in animals compared to humans. The benefits of cannabinoids in treating many conditions of chronic pain are uncertain as there is no good evidence to show its favorable analgesic effect.
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Review articles
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References
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administrationof thecannabinoid 2receptoragonisJWH015
canattenuatecancer painand decrease mRNA expression
of the2B subunitof N-methyl-D-asparticacid. Anesh Analg
2011;113:405-11.
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Antinociceptive effect of intrathecal cannabinoid receptor
agonist WIN 55,212-2 in a rat bone tumor pain model.
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12. Curto-Reyes V, Llames S, Hidalgo A, Menéndez L,
Baamonde A. Spinaland peripheralanalgesiceffectsof the
CB2 cannabinoid receptor agonist AM1241 in two models
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A cannabinoid 2 receptor agonist attenuates bone
cancer-induced painand boneloss.Life Sci2010;86:646-53.
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2018;84:955-69.
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role in depression, reward and pain control (Review). Mol
Med Rep 2016;14:2899-903.
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Targeting the endocannabinoid system to treat anxietyrelated disorders. J Basic Clin Physiol Pharmacol 2016;
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Symptom Manage2010;39:167-79.
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open-label extension study to investigate the long-term
safety and tolerability of THC/CBD oromucosal spray and
oromucosalTHCsprayin patientswithterminalcancer-related
painrefractorytostrong opioid analgesics.J Pain Symptom
Manage2013;46:207-18.
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opioids and cannabinoid systems. Brain Res 1999;848:
183-90.
24. Welch SP,Thomas C, Patrick GS.Modulationofcannabinoidinduced antinociceptionafter intracerebroventricularversus
intrathecaladministrationto mice: possible mechanismsfor
interaction with morphine. J Pharmacol Exp Ther 1995;
272:310-21.
25. Kaymakçalan S. Pharmacologicalsimilaritiesand interactions
between cannabis and opioids. Adv Biosci 1978;22-23:
591-604.
26. LynchME, Cesar-Rittenberg P, Hohmann AG. A double-blind,
placebo-controlled,crossover pilot trial withextensionusing
an oral mucosal cannabinoid extract for treatment of
chemotherapy-induced neuropathic pain. J Pain Symptom
Manage2014;47:166-73.
27. Ward SJ,McAllister SD, Kawamura R,Murase R, Neelakantan
H, Walker EA. Cannabidiol inhibits paclitaxel-induced
neuropathic pain through 5-HT(1A) receptors without
diminishing nervous system function or chemotherapy
efficacy. Br J Pharmacol2014;171:636-45.
28. FallonMT, AlbertLux E,McQuade R,etal. Sativexoromucosal
spray as adjunctive therapy in advanced cancer patients
withchronic painunalleviated byoptimized opioid therapy:
two double-blind, randomized, placebo-controlled phase 3
studies. Br J Pain2017;11:119-33.
29. Lichtman AH,Lux EA,McQuade R,etal. Resultsofa doubleblind, randomized, placebo-controlled study of nabiximols
oromucosal spray as an adjunctive Therapy in advanced
cancer patients with chronic uncontrolled pain. J Pain
Symptom Manage2018;55:179-88.
30. Roberts JD, Gennings C, Shih M. Synergistic affective
analgesicinteraction between delta-9-tetrahydrocannabinol
and morphine. Eur J Pharmacol2006;530:54-8.
31. Allan GM, Finley CR, Ton J, et al. Systematic review of
systematicreviews for medicalcannabinoids: pain,nausea
and vomiting, spasticity, and harms. Can Fam Physician
2018;64:e78-94.
32. Stockings E, Campbell G, Hall WD, et al. Cannabis and
cannabinoids for the treatment of people with chronic
noncancer pain conditions: a systematic review and
meta-analysis of controlled and observational studies. Pain
2018;159:1932-54.
33. HäuserW, PetzkeF,Fitzcharles MA. Efficacy, tolerabilityand
safety of cannabis-based medicines for chronic pain
management - Anoverview ofsystematicreviews. EurJ Pain
2018;22:455-70.
34. Häuser W; Finnerup NB, Andrew RA. Systematic reviews
with meta-analysis on cannabis-based medicines for
chronic pain:a methodologicaland political minefield. Pain
2018;159:1906-7.
35. Turri M, Teatini F, Donato F, et al. Pain Modulation after
oromucosal cannabinoid spray (sativex®) in patients with
multiple sclerosis: a study with quantitative sensory testing
and laser-evoked potentials.Medicines(Basel)2018;21;5(3).
pii: E59. doi:10.3390/medicines5030059
36. TurcottJG, Del Rocío Guillen Núñez M,Flores-Estrada D,et
al.Theeffectofnabiloneonappetite,nutritional status,and
qualityof lifeinlung cancer patients:arandomized, doubleblind clinical trial. Support Care Cancer2018;26:3029-38.
37. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study
team. Cannabisfor the managementof pain:assessmentof
safety study (COMPASS). .J Pain2015;16:1233-42.
visionfor theclinician. Eur J Pain2018;22:485-91.
2. Krcevski-Skvarc N, Wells C, Häuser W. Availability and
approval of cannabis-based medicines for chronic pain
management and palliative/supportive care in Europe:
a survey of the status in the chapters of the European Pain
Federation. Eur J Pain2018;22:440-54.
3. Lafaye G, Karila L, Blecha L, Benyamina A. Cannabis,
cannabinoids and health. Dialogues Clin Neurosci 2017;
9:309-16.
4. Mechoulam R, Gaoni Y, HashishIV. HashishIV.Theisolation
andstructureofcannabinolic,cannabidiolicandcannabigerolic
acids.Tetrahedron1965;21:1223-9.
5. Englund A, Freeman TP, Murray RM, McGuire P. Can we
makecannabis safer?Lancet Psychiatry2017;4:643-64.
6. Kraft B. Isthereanyclinicallyrelevantcannabinoid-induced
analgesia? Pharmacology2012;89:237-46.
7. MunroS,ThomasKL,Abu-ShaarM.Molecularcharacterization
of a peripheral receptor for cannabinoids. Nature 1993;
365:61-5.
8. Walter C, Oertel BG, Felden L, et al. Brain mapping-based
model of Δ(9)-tetrahydrocannabinol effects on connectivity
in the pain matrix. Neuropsychopharmacology 2016;41:
1659-69.
9. Lee MC, Ploner M, Wiech K, et al. Amygdala activity
contributes to the dissociative effect of cannabis on pain
perception. Pain2013;154:124-34.
10. Gu X, Mei F, Liu Y, Zhang R, Zhang J, Ma Z. Intrathecal
administrationof thecannabinoid 2receptoragonisJWH015
canattenuatecancer painand decrease mRNA expression
of the2B subunitof N-methyl-D-asparticacid. Anesh Analg
2011;113:405-11.
11. Cui JH, Kim WM, Lee HG, Kim YO, Kim CM, Yoon MH.
Antinociceptive effect of intrathecal cannabinoid receptor
agonist WIN 55,212-2 in a rat bone tumor pain model.
NeurosciLett2011;493:67-71.
12. Curto-Reyes V, Llames S, Hidalgo A, Menéndez L,
Baamonde A. Spinaland peripheralanalgesiceffectsof the
CB2 cannabinoid receptor agonist AM1241 in two models
ofbonecancer-inducedpain.BrJPharmacol2010;160:561-73.
13. Lozano-Ondoua AN, Wright C, Vardanyan A, et al.
A cannabinoid 2 receptor agonist attenuates bone
cancer-induced painand boneloss.Life Sci2010;86:646-53.
14. National Institute on Drug Abuse. 2016 [Internet]. Available
from: https://www.drugabuse.gov/researchers/researchresources/nida-drug-supply-program-dsp/marijuana-plantmaterial-available-nida-drug-supply-program [Cited on 5
March2019].
15. PergolizziJV Jr,Lequang JA,Taylor R Jr, Raffa RB, Colucci
D, NEMA Research Group.Theroleofcannabinoidsin pain
control: the good, the bad,and theugly. Minerva Anestesiol
2018;84:955-69.
16. Huang WJ, Chen WW, Zhang X. Endocannabinoid system:
role in depression, reward and pain control (Review). Mol
Med Rep 2016;14:2899-903.
17. Korem N, Zer-Aviv TM, Ganon-Elazar E, Abush H, Akirav I.
Targeting the endocannabinoid system to treat anxietyrelated disorders. J Basic Clin Physiol Pharmacol 2016;
27:193-202.
18. Babson KA, SottileJ, Morabito D. Cannabis,cannabinoids,
and sleep: a review of the literature. Curr Psychiatry Rep
2017;19:23.
19. Portenoy RK, Ganae-Motan ED, Allende S,etal. Nabiximols
for opioid-treated cancer patients with poorly-controlled
chronic pain:arandomized, placebo-controlled, graded-dose
trial. J Pain2012;13:438-49.
20. JohnsonJR,Burnell-NugentM,LossignolD,GanaeMotan ED,
Potts R, Fallon MT. Multicenter, double-blind, randomized,
placebo-controlled, parallel-group study of the efficacy,
safety,and tolerabilityofTHC:CBD extractand THC extract
in patients with intractable cancer-related pain. J Pain
Symptom Manage2010;39:167-79.
21. Côté M,Trudel M, Wang C,Fortin A. Improving qualityof life
with nabilone during radiotherapy treatments for head and
neck cancers: a randomized double-blind placebocontrolled trial. Ann Otol RhinolLaryngol2016;125:317-24.
22. Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An
open-label extension study to investigate the long-term
safety and tolerability of THC/CBD oromucosal spray and
oromucosalTHCsprayin patientswithterminalcancer-related
painrefractorytostrong opioid analgesics.J Pain Symptom
Manage2013;46:207-18.
23. Welch SP, Eads M. Synergistic interactions of endogenous
opioids and cannabinoid systems. Brain Res 1999;848:
183-90.
24. Welch SP,Thomas C, Patrick GS.Modulationofcannabinoidinduced antinociceptionafter intracerebroventricularversus
intrathecaladministrationto mice: possible mechanismsfor
interaction with morphine. J Pharmacol Exp Ther 1995;
272:310-21.
25. Kaymakçalan S. Pharmacologicalsimilaritiesand interactions
between cannabis and opioids. Adv Biosci 1978;22-23:
591-604.
26. LynchME, Cesar-Rittenberg P, Hohmann AG. A double-blind,
placebo-controlled,crossover pilot trial withextensionusing
an oral mucosal cannabinoid extract for treatment of
chemotherapy-induced neuropathic pain. J Pain Symptom
Manage2014;47:166-73.
27. Ward SJ,McAllister SD, Kawamura R,Murase R, Neelakantan
H, Walker EA. Cannabidiol inhibits paclitaxel-induced
neuropathic pain through 5-HT(1A) receptors without
diminishing nervous system function or chemotherapy
efficacy. Br J Pharmacol2014;171:636-45.
28. FallonMT, AlbertLux E,McQuade R,etal. Sativexoromucosal
spray as adjunctive therapy in advanced cancer patients
withchronic painunalleviated byoptimized opioid therapy:
two double-blind, randomized, placebo-controlled phase 3
studies. Br J Pain2017;11:119-33.
29. Lichtman AH,Lux EA,McQuade R,etal. Resultsofa doubleblind, randomized, placebo-controlled study of nabiximols
oromucosal spray as an adjunctive Therapy in advanced
cancer patients with chronic uncontrolled pain. J Pain
Symptom Manage2018;55:179-88.
30. Roberts JD, Gennings C, Shih M. Synergistic affective
analgesicinteraction between delta-9-tetrahydrocannabinol
and morphine. Eur J Pharmacol2006;530:54-8.
31. Allan GM, Finley CR, Ton J, et al. Systematic review of
systematicreviews for medicalcannabinoids: pain,nausea
and vomiting, spasticity, and harms. Can Fam Physician
2018;64:e78-94.
32. Stockings E, Campbell G, Hall WD, et al. Cannabis and
cannabinoids for the treatment of people with chronic
noncancer pain conditions: a systematic review and
meta-analysis of controlled and observational studies. Pain
2018;159:1932-54.
33. HäuserW, PetzkeF,Fitzcharles MA. Efficacy, tolerabilityand
safety of cannabis-based medicines for chronic pain
management - Anoverview ofsystematicreviews. EurJ Pain
2018;22:455-70.
34. Häuser W; Finnerup NB, Andrew RA. Systematic reviews
with meta-analysis on cannabis-based medicines for
chronic pain:a methodologicaland political minefield. Pain
2018;159:1906-7.
35. Turri M, Teatini F, Donato F, et al. Pain Modulation after
oromucosal cannabinoid spray (sativex®) in patients with
multiple sclerosis: a study with quantitative sensory testing
and laser-evoked potentials.Medicines(Basel)2018;21;5(3).
pii: E59. doi:10.3390/medicines5030059
36. TurcottJG, Del Rocío Guillen Núñez M,Flores-Estrada D,et
al.Theeffectofnabiloneonappetite,nutritional status,and
qualityof lifeinlung cancer patients:arandomized, doubleblind clinical trial. Support Care Cancer2018;26:3029-38.
37. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study
team. Cannabisfor the managementof pain:assessmentof
safety study (COMPASS). .J Pain2015;16:1233-42.