Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review
Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuro...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | IBRO Neuroscience Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242121000051 |
| _version_ | 1818437091041738752 |
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| author | Esraa Aly Willias Masocha |
| author_facet | Esraa Aly Willias Masocha |
| author_sort | Esraa Aly |
| collection | DOAJ |
| description | Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP. |
| first_indexed | 2024-12-14T17:19:09Z |
| format | Article |
| id | doaj.art-65ec108119c3424db33aca71fb1e05fb |
| institution | Directory Open Access Journal |
| issn | 2667-2421 |
| language | English |
| last_indexed | 2024-12-14T17:19:09Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj.art-65ec108119c3424db33aca71fb1e05fb2022-12-21T22:53:22ZengElsevierIBRO Neuroscience Reports2667-24212021-06-0110109118Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic reviewEsraa Aly0Willias Masocha1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, KuwaitCorrespondence to: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwai.; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, KuwaitHuman immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP.http://www.sciencedirect.com/science/article/pii/S2667242121000051Human immunodeficiency virusAntiretroviralNeuropathic painCannabisCannabinoidEndocannabinoid |
| spellingShingle | Esraa Aly Willias Masocha Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review IBRO Neuroscience Reports Human immunodeficiency virus Antiretroviral Neuropathic pain Cannabis Cannabinoid Endocannabinoid |
| title | Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review |
| title_full | Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review |
| title_fullStr | Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review |
| title_full_unstemmed | Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review |
| title_short | Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review |
| title_sort | targeting the endocannabinoid system for management of hiv associated neuropathic pain a systematic review |
| topic | Human immunodeficiency virus Antiretroviral Neuropathic pain Cannabis Cannabinoid Endocannabinoid |
| url | http://www.sciencedirect.com/science/article/pii/S2667242121000051 |
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