Callaghan RC, Allebeck P, Sidorchuk A. Marijuana use and risk of lung cancer: a 40-year cohort study. Cancer Causes Control. 2013;24:1811–20.
Moon AS, Smith W, Mullen S, Ponce BA, McGwin G, Shah A, et al. Marijuana use and mortality following orthopedic surgical procedures. Subst Abus. 2018:1–5 Self-reported use of cannabinoids has increased since legalization of recreational and medical use, with over 22 million Americans over age 12 using marijuana in 2016. A decreased inpatient mortality rate has been seen in orthopedic patients who used marijuana compared with non-users.
Jennings JM, Angerame MR, Eschen CL, Phocas AJ, Dennis DA. Cannabis use does not affect outcomes after total knee arthroplasty. J Arthroplast. 2019;34:1667–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S088354031930347X. Self-reported use of cannabinoids has increased since legalization of recreational and medical use.
Wilkinson ST, Yarnell S, Radhakrishnan R, Ball SA, D’Souza DC. Marijuana legalization: impact on physicians and public health. Annu Rev Med. 2016;67:453–66 Available from: http://www.annualreviews.org/doi/10.1146/annurev-med-050214-013454.
Ayers JW, Caputi TL, Leas EC. The need for federal regulation of marijuana marketing. JAMA. 2019;321:2163. Available from: https://jamanetwork.com/journals/jama/fullarticle/2734209. Aggressive advertising for marijuana and CBD products has likely impacted increasing consumption by orthopedic patients during the perioperative period.
Leas EC, Nobles AL, Caputi TL, Dredze M, Smith DM, Ayers JW. Trends in Internet searches for cannabidiol (CBD) in the United States. JAMA Netw Open. 2019;2:e1913853. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753393. It is estimated that many orthopedic patients consume cannabinoid products during the perioperative period.
Gowran A, McKayed K, Campbell VA. The cannabinoid receptor type 1 is essential for mesenchymal stem cell survival and differentiation: implications for bone health. Stem Cells Int. 2013;2013:1–8 Available from: http://www.hindawi.com/journals/sci/2013/796715/.
Van Der Stelt M, Di Marzo V. Cannabinoid receptors and their role in neuroprotection. NeuroMolecular Med. 2005;7:37–50.
Lamontagne D, Lépicier P, Lagneux C, Bouchard JF. The endogenous cardiac cannabinoid system: a new protective mechanism against myocardial ischemia. Arch Mal Coeur Vaiss. 2006;99:242–6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16618028.
Pertwee RG. The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes. 2006:S13–8.
Wang X, Galaj E, Bi G, Zhang C, He Y, Zhan J, et al. Different receptor mechanisms underlying phytocannabinoid- versus synthetic cannabinoid-induced tetrad effects: opposite roles of CB1/CB2 versus GPR55 receptors. Br J Pharmacol. 2019;bph.14958. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.14958.
Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ, et al. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci U S A. 2009;106:16511–6 Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.0902743106.
Sophocleous A, Robertson R, Ferreira NB, McKenzie J, Fraser WD, Ralston SH. Heavy cannabis use is associated with low bone mineral density and an increased risk of fractures. Am J Med. 2017;130:214–21.
Idris AI, Sophocleous A, Landao-Bassonga E, Van’t Hof RJ, Ralston SH, Greig IR, et al. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Endocrinology. 2005;11:774–9 Available from: http://www.nature.com/articles/nm1255.
Idris AI, Van’t Hof RJ, Greig IR, Ridge SA, Baker D, Ross RA, et al. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med. 2005;11:774–9 Available from: http://www.nature.com/articles/nm1255.
Idris AI, Sophocleous A, Landao-Bassonga E, Canals M, Milligan G, Baker D, et al. Cannabinoid receptor type 1 protects against age- related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells. Cell Metab. 2009;10:139–47 Available from: https://linkinghub.elsevier.com/retrieve/pii/S1550413109002022.
Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K, et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci U S A. 2006;103:696–701 Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.0504187103.
Idris AI, Sophocleous A, Landao-Bassonga E, Van’t Hof RJ, Ralston SH. Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology. 2008;149:5619–26 Available from: https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2008-0150.
Scutt A, Williamson EM. Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors. Calcif Tissue Int. 2007;80:50–9 Available from: http://link.springer.com/10.1007/s00223-006-0171-7.
Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002;54:161–202 Available from: http://pharmrev.aspetjournals.org/cgi/doi/10.1124/pr.54.2.161.
Gowran A, McKayed K, Kanichai M, White C, Hammadi N, Campbell V. Tissue engineering of cartilage; can cannabinoids help? Pharmaceuticals. 2010;3:2970–85 Available from: http://www.mdpi.com/1424-8247/3/9/2970.
Leas EC, Nobles AL, Caputi TL, Dredze M, Smith DM, Ayers JW. Trends in Internet searches for cannabidiol (CBD) in the United States. JAMA Netw Open. 2019;2:e1913853.
Gowran A, Campbell VA. A role for p53 in the regulation of lysosomal permeability by Δ 9 -tetrahydrocannabinol in rat cortical neurones: implications for neurodegeneration. J Neurochem. 2008;105:1513–24 Available from: http://doi.wiley.com/10.1111/j.1471-4159.2008.05278.x.
Greenhough A, Patsos HA, Williams AC, Paraskeva C. The cannabinoid Δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int J Cancer. 2007;121:2172–80 Available from: http://doi.wiley.com/10.1002/ijc.22917.
Salazar M, Carracedo A, Salanueva ÍJ, Hernández-Tiedra S, Lorente M, Egia A, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009;119:1359–72 Available from: http://www.jci.org/articles/view/37948.
Caffarel MM, Sarrió D, Palacios J, Guzmán M, Sánchez C. Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006;66:6615–21 Available from: http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-05-4566.
Nogueira-Filho GDR, Cadide T, Rosa BT, Neiva TG, Tunes R, Peruzzo D, et al. Cannabis sativa smoke inhalation decreases bone filling around titanium implants: a histomorphometric study in rats. Implant Dent. 2008;17:461–70 Available from: https://insights.ovid.com/crossref?an=00008505-200812000-00013.
Kogan NM, Melamed E, Wasserman E, Raphael B, Breuer A, Stok KS, et al. Cannabidiol, a major non-psychotropic cannabis constituent enhances fracture healing and stimulates lysyl hydroxylase activity in osteoblasts. J Bone Miner Res. 2015;30:1905–13 Available from: http://doi.wiley.com/10.1002/jbmr.2513.
Pisanti S, Malfitano AM, Ciaglia E, Lamberti A, Ranieri R, Cuomo G, et al. Cannabidiol: state of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017;175:133–50. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0163725817300657. CBD has been well studied for a number of illnesses including neurodegenerative disease, epilepsy, and immune disorders such as multiple sclerosis, arthritis, and cancer. Currently, it is FDA approved only for the treatment of epilepsy.
Kamali A, Oryan A, Hosseini S, Ghanian MH, Alizadeh M, Baghaban Eslaminejad M, et al. Cannabidiol-loaded microspheres incorporated into osteoconductive scaffold enhance mesenchymal stem cell recruitment and regeneration of critical-sized bone defects. Mater Sci Eng C. 2019;101:64–75. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0928493118303606. Further studies are needed to better evaluate the role of CBD in human bone healing and metabolism, as well as the long-term effects of CBD ingestion.
Best MJ, Buller LT, Klika AK, Barsoum WK. Outcomes following primary total hip or knee arthroplasty in substance misusers. J Arthroplast. 2015;30:1137–41 Available from: https://linkinghub.elsevier.com/retrieve/pii/S0883540315000777.
Law TY, Kurowicki J, Rosas S, Sabeh K, Summers S, Hubbard Z, et al. Cannabis use increases risk for revision after total knee arthroplasty. J Long Term Eff Med Implants. 2018;28:125–30. Available from: http://www.dl.begellhouse.com/journals/1bef42082d7a0fdf,639e402206fa0df3,4c9989d43961247f.html. A retrospective review of the Medicare database on total knee arthroplasty patients evaluating those who used marijuana compared with those who did not found a significant increase in reoperation rate due to infection in the cohort that used marijuana.
Fitzcharles MA, Häuser W. Cannabinoids in the management of musculoskeletal or rheumatic diseases. Curr Rheumatol Rep. 2016;18.
Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE. Triggering myocardial infarction by marijuana. Circulation. 2001;103:2805–9 Available from: https://www.ahajournals.org/doi/10.1161/01.CIR.103.23.2805.
Rumalla K, Reddy AY, Mittal MK. Association of recreational marijuana use with aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2016;25:452–60.
Moussouttas M. Cannabis use and cerebrovascular disease. Neurol Int. 2004;10:47–53 Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00127893-200401000-00005.
Thomas G, Kloner RA, Rezkalla S. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know. Am J Cardiol. 2014;113:187–90 Available from: https://linkinghub.elsevier.com/retrieve/pii/S0002914913019760.
Rumalla K, Reddy AY, Mittal MK. Recreational marijuana use and acute ischemic stroke: a population-based analysis of hospitalized patients in the United States. J Neurol Sci. 2016;364:191–6 Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022510X16300661.
Madden K, van der Hoek N, Chona S, George A, Dalchand T, Baldawi H, et al. Cannabinoids in the management of musculoskeletal pain. JBJS Rev. 2018;6:1. Available from: http://insights.ovid.com/crossref?an=01874474-900000000-99892. Cannabinoids, if effective for pain relief, could potentially reduce the opioid burden.
Lötsch J, Weyer-Menkhoff I, Tegeder I. Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings. Eur J Pain (United Kingdom). 2018;22:471–84. Available from: http://doi.wiley.com/10.1002/ejp.1148. Δ9-THC has also been shown to have euphoric and psychoactive effects, both of which have a role in pain modulation and experience. Clinical evidence has not demonstrated similar findings in human experiments.
Häuser W, Fitzcharles MA, Radbruch L, Petzke F. Cannabinoids in pain management and palliative medicine. Dtsch Arztebl Int. 2017;114:627–34. Available from: https://www.aerzteblatt.de/10.3238/arztebl.2017.0627. No clear benefit from the use of cannabinoids has been shown to be better than placebo, due in part to a lack of high-quality evidence to support the use of medical marijuana therapy for acute or chronic pain indications. There is a lack of evidence supporting the common use of marijuana for chronic rheumatologic, oncologic, or arthritic pain.