Abstract
Background
Approximately 18% of patients with cancer use cannabis at one time as palliation or treatment for their cancer. We performed a systematic review of randomized cannabis cancer trials to establish a guideline for its use in pain and to summarize the risk of harm and adverse events when used for any indication in cancer patients.
Methods
A systematic review of randomized trials with or without meta-analysis was carried out from MEDLINE, CCTR, Embase, and PsychINFO. The search involved randomized trials of cannabis in cancer patients. The search ended on November 12, 2021. The Jadad grading system was used for grading quality. Inclusion criteria for articles were randomized trials or systematic reviews of randomized trials of cannabinoids versus either placebo or active comparator explicitly in adult patients with cancer.
Results
Thirty-four systematic reviews and randomized trials met the eligibility criteria for cancer pain. Seven were randomized trials involving patients with cancer pain. Two trials had positive primary endpoints, which could not be reproduced in similarly designed trials. High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic to cancer pain. Seven systematic reviews and randomized trials related to harms and adverse events were included. There was inconsistent evidence about the types and levels of harm patients may experience when using cannabinoids.
Conclusion
The MASCC panel recommends against the use of cannabinoids as an adjuvant analgesic for cancer pain and suggests that the potential risk of harm and adverse events be carefully considered for all cancer patients, particularly with treatment with a checkpoint inhibitor.
Similar content being viewed by others
Change history
06 May 2023
A Correction to this paper has been published: https://doi.org/10.1007/s00520-023-07789-1
References
Anderson SP et al (2019) Impact of medical cannabis on patient-reported symptoms for patients with cancer enrolled in Minnesota’s medical cannabis program. J Oncol Pract 15(4):e338–e345
Donovan KA et al (2019) Relationship of cannabis use to patient-reported symptoms in cancer patients seeking supportive/palliative care. J Palliat Med 22(10):1191–1195
Guzmán M (2018) Cannabis for managing cancer symptoms: T.H.C. version 2.0? Cannabis Cannabinoid Res 3(1):117–119
Luckett T et al (2016) Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes, and beliefs among patients willing to consider participation. Intern Med J 46(11):1269–1275
Bar-Lev Schleider L, Abuhasira R, Novack V (2018) Medical cannabis: aligning use to evidence-based medicine approach. Br J Clin Pharmacol 84(11):2458–2462
Bar-Lev Schleider L et al (2018) Prospective analysis of safety and efficacy of medical cannabis in a large unselected population of patients with cancer. Eur J Intern Med 49:37–43
Martell K et al (2018) Rates of cannabis use in patients with cancer. Curr Oncol 25(3):219–225
Zolotov Y, Eshet L, Morag O (2021) Preliminary assessment of medical cannabis consumption by cancer survivors. Complement Ther Med 56:102592
Taneja S et al (2021) Use of Cannabis in urological cancer patients: a review to evaluate the risk for cancer development, therapeutic use, and symptom management. Can Urol Assoc J 15(12):413–419
Malhotra P, Casari I, Falasca M (2021) Therapeutic potential of cannabinoids in combination cancer therapy. Adv Biol Regul 79:100774
Boeri M et al (2021) Green hope: perspectives on Cannabis from people who use opioids. Sociol Inq 91(3):668–695
Imtiaz S, Elton-Marshall T, Rehm J (2021) Cannabis liberalization and the U.S. opioid crisis. B.M.J. 372:n163
Pawasarat IM et al (2020) The Efficacy of medical marijuana in treating cancer-related pain. J Palliat Med 23(6):809–816
Hauser W et al (2019) Efficacy, tolerability, and safety of cannabis-based medicines for cancer pain: a systematic review with meta-analysis of randomized controlled trials. Schmerz 33(5):424–436
Lichtman AH et al (2018) Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. J Pain Symptom Manage 55(2):179–188.e1
Noyes R Jr et al (1975) The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin Pharmacol Ther 18(1):84–89
Noyes R et al (1975) the Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol 15(2-3):139–143
Fallon MT et al (2017) Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies. Br J Pain 11(3):119–133
Portenoy RK et al (2012) Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain 13(5):438–449
Johnson JR et al (2010) Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of T.H.C.:CBD extract and T.H.C. extract in patients with intractable cancer-related pain. J Pain Symptom Manage 39(2):167–179
Cote M et al (2016) Improving the quality of life with nabilone during radiotherapy treatments for head and neck cancers: a randomized, double-blind placebo-controlled trial. Ann Otol Rhinol Laryngol 125(4):317–324
Jochimsen PR et al (1978) Effect of benzopyranoperidine, a Δ-9-THC congener, on pain. Clin Pharmacol Ther 24(2):223–227
Lynch ME, Cesar-Rittenberg P, Hohmann AG (2014) A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for the treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 47(1):166–173
Sreevalsan S et al (2011) Induction of apoptosis by cannabinoids in prostate and colon cancer cells are phosphatase dependent. Anticancer Res 31(11):3799–3807
Sarfaraz S et al (2005) Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res 65(5):1635–1641
Nigro E et al (2021) Cancer initiation, progression and resistance: are phytocannabinoids from Cannabis sativa L. promising compounds? Molecules 26(9):2668
Kampa-Schittenhelm KM et al (2016) Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns. BMC Cancer 16(1):1–12
Gholizadeh F et al (2019) Assessment of cannabinoids agonist and antagonist in invasion potential of K562 cancer cells. Iran Biomed J 23(2):153
Dobovišek L et al (2020) Cannabinoids and hormone receptor-positive breast cancer treatment. Cancers 12(3):525
Massi P, Vaccani A, Parolaro D (2006) Cannabinoids, immune system, and cytokine network. Curr Pharm Des 12(24):3135–3146
Bar-Sela G et al (2020) Cannabis consumption used by cancer patients during immunotherapy correlates with poor clinical outcome. Cancers 12(9):2447
Whitcomb B et al (2020) Use of cannabinoids in cancer patients: a Society of Gynecologic Oncology (S.G.O.) clinical practice statement. Gynecol Oncol 157(2):307–311
Häuser W, Petzke F, Fitzcharles M (2018) Efficacy, tolerability, and safety of cannabis-based medicines for chronic pain management–an overview of systematic reviews. Eur J Pain 22(3):455–470
Rice ASC, Belton J, L. (2021) Arendt Nielsen Presenting the outputs of the IASP Presidential Task Force on Cannabis and Cannabinoid Analgesia. Pain 162(Suppl 1):S3–S4
Thompson JW, Tanzer R, Triska T et al (2021) Evaluation of ‘spin’ in the abstracts and articles of randomized controlled trials in pain literature and general anesthesia. Pain Manag 11(1):23–28
Chiu K, Grundy Q, Bero L (2017) ‘Spin’ in published biomedical literature: a systematic methodological review. PLoS Biol 15(9):e2002173
Boutron I et al (2010) Reporting and interpretation of randomized controlled trials with statistically nonsignificant results for primary outcomes. JAMA 303(20):2058–2064
Caulfield T, Ogbogu U (2015) The commercialization of university-based research: balancing risks and benefits. B.M.C. Medical. Ethics 16(1):1–7
Jadad AR et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12
Harrison AM et al (2015) Systematic review of the use of phytochemicals for management of pain in cancer therapy. Biomed Res Int 2015
Chapman EJ et al (2020) Practice review: evidence-based and effective management of pain in patients with advanced cancer. Palliat Med 34(4):444–453
Johnson JR et al (2013) An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal T.H.C. spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage 46(2):207–218
Darkovska-Serafimovska M et al (2018) Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases. J Pain Res 11:837
Shin S et al (2019) An integrated review of cannabis and cannabinoids in adult oncologic Pain Management. Pain Manag Nurs 20(3):185–191
Chung M, Kim HK, Abdi S (2020) Update on cannabis and cannabinoids for cancer pain. Curr Opin Anaesthesiol 33(6):825–831
Meng H et al (2020) Cannabis and cannabinoids in cancer pain management. Curr Opin Support Palliat Care 14(2):87–93
Aviram J, Samuelly-Leichtag G (2017) Efficacy of cannabis-based medicines for pain management: a systematic review and meta-analysis of randomized controlled trials. Pain Physician 20(6):E755–E796
Rabgay K et al (2020) The effects of Cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: a systematic review and network meta-analysis. J Am Pharm Assoc 60(1):225–234 e6
Yanes JA et al (2019) Effects of cannabinoid administration for pain: a meta-analysis and meta-regression. Exp Clin Psychopharmacol 27(4):370
Nugent SM et al (2017) The effects of Cannabis among adults with chronic pain and an overview of general harms: a systematic review. Ann Intern Med 167(5):319–331
Boland EG et al (2020) Cannabinoids for adult cancer-related pain: systematic review and meta-analysis. BMJ Support Palliat Care 10(1):14–24
Duran M et al (2010) Preliminary Efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 70(5):656–663
Twelves C et al (2021) A phase 1b randomized, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma. Br J Cancer 124(8):1379–1387
Schloss J et al (2021) A phase 2 randomised clinical trial assessing the tolerability of two different ratios of medicinal cannabis in patients wth high grade gliomas. Frontiers. Oncology 11 (no pagination(649555):649555
Chow R et al (2020) Oral cannabinoid for the prophylaxis of chemotherapy-induced nausea and vomiting-a systematic review and meta-analysis. Support Care Cancer 28(5):2095–2103
Smith LA et al (2015) Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev 2015(11) (no pagination)(CD009464):CD009464
Patel J, Marwaha R (2022) Cannabis use disorder. In: StatPearls, StatPearls Publishing Copyright © 2022. StatPearls Publishing L.L.C., Treasure Island (F.L.)
Ahsan S et al (2021) Negative coping styles among individuals with cannabis use disorder and non-users. J Pak Med Assoc 71(7):1757–1760
Cofield SS, Corona RV, Allison DB (2010) Use of causal language in observational studies of obesity and nutrition. Obes Facts 3(6):353–356
Huff J (2007) Industry influence on occupational and environmental public health. Int J Occup Environ Health 13(1):107–117
Thomas O et al (2008) Industry funding and the reporting quality of large long-term weight loss trials. Int J Obes (Lond) 32(10):1531–1536
Ioannidis JP (2008) Why most discovered true associations are inflated. Epidemiology 19(5):640–648
Ioannidis JP (2018) Why replication has more scientific value than original discovery. Behav Brain Sci 41:e137
Pertwee RG (2001) Cannabinoid receptors and pain. Prog Neurobiol 63(5):569–611
Cichewicz DL (2004) Synergistic interactions between cannabinoid and opioid analgesics. Life Sci 74(11):1317–1324
Norwood CS et al (2003) Pre-exposure to the cannabinoid receptor agonist CP 55,940 enhances morphine behavioral sensitization and alters morphine self-administration in Lewis rats. Eur J Pharmacol 465(1-2):105–114
Manzanedo C et al (2004) Cannabinoid agonist-induced sensitisation to morphine place preference in mice. Neuroreport 15(8):1373–1377
Vierke C et al (2021) Buprenorphine–cannabis interaction in patients undergoing opioid maintenance therapy. Eur Arch Psychiatry Clin Neurosci 271(5):847–856
Li J-X et al (2008) Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception. Psychopharmacology 199(2):199–208
Maguire DR, Yang W, France CP (2013) Interactions between μ-opioid receptor agonists and cannabinoid receptor agonists in rhesus monkeys: antinociception, drug discrimination, and drug self-administration. J Pharmacol Exp Ther 345(3):354–362
Maguire DR, France CP (2014) Impact of efficacy at the μ-opioid receptor on antinociceptive effects of combinations of μ-opioid receptor agonists and cannabinoid receptor agonists. J Pharmacol Exp Ther 351(2):383–389
Maguire DR, France CP (2016) Interactions between cannabinoid receptor agonists and mu-opioid receptor agonists in rhesus monkeys discriminating fentanyl. Eur J Pharmacol 784:199–206
Taha T et al (2019) Cannabis impacts tumor response rate to nivolumab in patients with advanced malignancies. Oncologist 24(4):549–554
Reece AS, Hulse GK (2021) Causal inference multiple imputation investigation of the impact of cannabinoids and other substances on ethnic differentials in U.S. testicular cancer incidence. B.M.C. Pharmacol Toxicol 22(1):40
Reece AS, Hulse GK (2022) Geotemporospatial and causal inference epidemiological analysis of U.S. survey and overview of cannabis, cannabidiol and cannabinoid genotoxicity in relation to congenital anomalies 2001-2015. BMC Pediatr 22(1):47
Reece AS, Hulse GK (2021) A spatiotemporal and causal inference epidemiological exploration of substance and cannabinoid exposure as drivers of rising U.S. pediatric cancer rates. B.M.C. Cancer 21(1):197
Reece AS, Hulse GK (2021) Cannabinoid exposure as a major driver of pediatric acute lymphoid leukaemia rates across the U.S.A.: combined geospatial, multiple imputation and causal inference study. BMC Cancer 21(1):984
Vazquez M et al (2020) Potential pharmacokinetic drug-drug interactions between cannabinoids and drugs used for chronic pain. Biomed Res Int 2020:3902740
Velayudhan L, McGoohan K, Bhattacharyya S (2021) Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: a systematic review and meta-analysis. PLoS Med 18(3):e1003524
Pisani S et al (2021) Safety and tolerability of natural and synthetic cannabinoids in older adults: a systematic review and meta-analysis of open-label trials and observational studies. Drugs Aging 38(10):887–910
Velayudhan L, McGoohan KL, Bhattacharyya S (2021) Evaluation of THC-related neuropsychiatric symptoms among adults aged 50 years and older: a systematic review and metaregression analysis. JAMA Netw Open 4(2):e2035913
Pearlson GD, Stevens MC, D'Souza DC (2021) Cannabis and driving. Front Psych 12:689444
Funding
No funding was provided for this guideline.
Author information
Authors and Affiliations
Contributions
Josephine To and Mellar Davis: review of studies derived from the systematic review and writing the manuscript.
Jessica Garsed: the clinical informationist performance of the systematic review.
Andrea Sbrana, Bryony Alderman, David Hui, Sandip Mukhopadhyay, Carole Bouleuc, Amy A. Case, Koji Amano, Gregory P. Crawford, Giulia de Feo, and Kimberson Tanco: reviewed and edited the manuscript and provided consensus as to the recommendations.
Corresponding author
Ethics declarations
Ethics approval
Not applicable.
Competing interests
The authors declare no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The original version of this article was revised. The correct name should be Gregory B. Crawford.
Supplementary information
ESM 1.
(DOCX 17 kb)
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
To, J., Davis, M., Sbrana, A. et al. MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events. Support Care Cancer 31, 202 (2023). https://doi.org/10.1007/s00520-023-07662-1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00520-023-07662-1