Clinical question
Do tetrahydrocannabinol (THC), cannabidiol (CBD), or THC-CBD combined have differing benefits or harms?
Bottom line
Of 4 RCTs, 1 found THC-CBD superior to THC but this was inconsistent within the study and with other studies. Adverse events are prevalent with THC, CBD, and THC-CBD. While some early poor-quality research in healthy users suggests CBD attenuates some psychiatric effects of THC, better research in real patients is needed to verify any benefits of specific components.
Evidence
Four RCTs compared THC, CBD, or both combined.
One RCT (N = 243 terminal cancer and weight loss patients) compared THC-CBD, THC, and placebo for 6 weeks.1 There was no statistical difference in appetite or adverse events for THC-CBD versus THC.
- An RCT in 177 patients with refractory cancer pain taking strong opioids (about 270 mg of morphine) compared THC-CBD, THC, and placebo for 2 weeks.2
- -A pain reduction of 30% or more was seen in 38% of the THC-CBD group versus 21% in the THC group (number needed to treat = 6). There was no difference for pain reductions of 10% or more or 50% or more.
- -There was no difference in adverse events with THCCBD versus THC.
- An RCT in 48 patients with brachial nerve injury compared THC-CBD, THC, and placebo over 2 weeks.3
- -Baseline pain score was 7.5 of 10. The THC-CBD and THC groups’ pain reduced by about 1.3 points, statistically significantly more than 0.6 points with placebo.
- -Adverse events were not significantly different between THC-CBD and THC.
- N of 1 studies in 34 chronic pain patients (24 completed) who benefited from THC-CBD compared THCCBD, THC, CBD, and placebo over 8 weeks.4
- -Versus starting THC-CBD, patients’ pain management was the same or better in 38% with repeat THC-CBD, 33% with THC, and 17% with CBD (no statistical difference).
Context
- An RCT in 120 pediatric patients with Dravet syndrome showed CBD reduced seizure frequency by about 22% over placebo at 14 weeks.5
- -Adverse events included somnolence (number needed to harm [NNH] = 4), diarrhea (NNH = 5), and appetite loss (NNH = 5). A recent RCT of adults with Lennox-Gastaut (seizure) syndrome found similar results.6
One guideline recommends low THC or a high CBD-to-THC ratio to reduce THC adverse events based on small studies of healthy volunteers (some with history of other drug use) examined with magnetic resonance imaging or short-term scale changes.7
Implementation
A Canadian guideline recommends cannabinoids (pharmaceutically derived first) only in refractory neuropathic pain, palliative cancer pain, nausea and vomiting from chemotherapy, and spasticity.8 Current guidance for smoked dried cannabis for pain recommends titrating up to 400 mg/d of 9% THC.9 Health Canada permits patients with a prescription for medical cannabis to legally possess up to 150 g, a 1-month’s maximum supply, equating to 5 g/d.10 A content analysis of Canadian licensed producers found that 58% of THC-predominant products had concentrations of 15% THC.11 Thus, patients might be using much higher doses than studied or recommended.
Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.
Footnotes
Competing interests
None declared
The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.
References
- 1.Strasser F, Luftner D, Possinger L, Ernst G, Ruhstaller T, Meissner W, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-in-Cachexia-Study-Group. J Clin Oncol. 2006;24(21):3394–400. doi: 10.1200/JCO.2005.05.1847. [DOI] [PubMed] [Google Scholar]
- 2.Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan E, Potts R, Fallon M. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39(2):167–79. doi: 10.1016/j.jpainsymman.2009.06.008. [DOI] [PubMed] [Google Scholar]
- 3.Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004;112(3):299–306. doi: 10.1016/j.pain.2004.09.013. [DOI] [PubMed] [Google Scholar]
- 4.Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies. Anaesthesia. 2004;59(5):440–52. doi: 10.1111/j.1365-2044.2004.03674.x. [DOI] [PubMed] [Google Scholar]
- 5.Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011–20. doi: 10.1056/NEJMoa1611618. [DOI] [PubMed] [Google Scholar]
- 6.Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085–96. doi: 10.1016/S0140-6736(18)30136-3. [DOI] [PubMed] [Google Scholar]
- 7.Fischer B, Russell C, Sabioni P, van den Brink W, Le Foll B, Hall W, et al. Lower-risk cannabis use guidelines: a comprehensive update of evidence and recommendations. Am J Public Health. 2017;107(8):e1–12. doi: 10.2105/AJPH.2017.303818. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Allan GM, Ramji J, Perry D, Ton J, Beahm NP, Crisp N, et al. Simplified guideline for prescribing medical cannabinoids in primary care. Can Fam Physician. 2018;64:111–20. (Eng), e64–75 (Fr). [PMC free article] [PubMed] [Google Scholar]
- 9.Kahan M, Srivastava A, Spithoff S, Bromley L. Prescribing smoked cannabis for chronic noncancer pain. Preliminary recommendations. Can Fam Physician. 2014;60:1083–90. (Eng), e562–70 (Fr). [PMC free article] [PubMed] [Google Scholar]
- 10.Health Canada. Controlled Drugs and Substances Act. Access to cannabis for medical purposes regulations. Ottawa, ON: Government of Canada; 2016. [Google Scholar]
- 11.Mammen G, de Freitas L, Rehm J, Rueda S. Cannabinoid concentrations in Canada’s regulated medical cannabis industry. Addiction. 2017;112(4):730–2. doi: 10.1111/add.13738. [DOI] [PubMed] [Google Scholar]