Characteristics of included studies (n=18)
| Author-year (country) | Study design | No of participants (% prescribed opioids) | Type of chronic pain (specific condition) | Age mean (SD) | % Female | Baseline opioid dose | Follow-up duration | Medical cannabis dose | Analgesic cointervention | Funding source |
| Fallon, 2017 study I (multicentre trial*)43 | Parallel arm RCT | n=399; nabiximols (n=20), placebo (n=199) (100%) | 100% chronic cancer pain | 59.8 (10.9) | 43% | Receiving opioid therapy of <500 MME/day (nabiximols group: 199 MME/day±131; placebo group: 207 MME/day±135) | 5 weeks | THC 27 mg/mL; CBD 25 mg/mL (maximum allowed daily dosage of 10 sprays) | Patients were excluded if they planned to undergo clinical interventions that would affect pain | Otsuka Pharmaceutical |
| Fallon, 2017 study II (multicentre trial*)43 | Parallel arm RCT | n=206; nabiximols (n=103), placebo=103 (100%) | 100% chronic cancer pain | 61.5 (11.3) | 49% | Receiving opioid therapy of <500 MME/day (nabiximols: 212 MME/day±136; placebo: 209 MME/day±121) | 5 weeks | THC 27 mg/mL; CBD 25 mg/mL (maximum allowed daily dosage of 10 sprays) | Patients were excluded if they planned to undergo clinical interventions that would affect pain | Otsuka Pharmaceutical |
| Johnson, 2010 (multicentre trial*)44 | Parallel arm RCT | n=177; THC: CBD extract (n=60), THC extract (n=58), placebo (n=59) (100%) | 100% chronic cancer pain | 60.2 (12.3) | 46% | Receiving opioid therapy for at least 1 week before enrolment (THC:CBD: 258MME/day±789; THC: 188 MME±234; placebo: 367±886) | 2 weeks | One spray: 2.7 mg THC/2.5 mg CBD. The maximum permitted dose: eight actuations over 3 hours and 48 actuations over 24-hours | Patients were excluded if they planned to undergo clinical interventions that would affect pain | GW Pharmaceuticals |
| Lichtman, 2018 (multicentre*)45 | Parallel arm RCT | n=398; nabiximol (n=199), placebo (n=198) (100%) | 100% chronic cancer pain | 60 (11.5) | 46% | Receiving opioid therapy of <500 MME/day (nabiximols: 193 MME/day±130; placebo: 186 MME/day±131) | 5 weeks | THC 27 mg/mL; CBD 25 mg/mL (maximum allowed daily dosage of 10 sprays per day) | Patients were excluded if they planned to undergo clinical interventions that would affect pain | Otsuka Pharmaceutical |
| Portenoy, 2012 (multicentre*)46 | Parallel arm RCT | n=360; nabiximols low dose (1–4 sprays/day) (n=91), medium dose (6–10 sprays/day) (n=88), high dose (11–16 sprays/day) (n=90), placebo (n=91) (100%) | 100% chronic cancer pain | 58 (12.2) | 48% | Receiving opioid therapy of <500 MME/day (median was 120 MME/day; range 3–16 660) | 5 weeks | THC 27 mg/mL; CBD 25 mg/mL (maximum allowed daily dosage of 10 sprays per day) | Patients were allowed to use breakthrough opioid analgesic as required | GW Pharmaceuticals; Otsuka Pharmaceutical |
| Barlowe, 2019 (USA)47 | Retrospective chart review | Enrolled in MCP (n=34), not enrolled in MCP (n=19) (100%) | 100% CNCP (chronic painful pancreatitis) | 49.9 (10.5) | 45% | Not enrolled in MCP 183 MME/day±284; enrolled in MCP 190 MME/day±273 | Range 4–297 weeks | NR | NR | NR |
| Bellnier, 2018 (USA)48 | One-arm observational study | n=29 (100%) | 90% CNCP; 10% cancer pain | 61 (10) | 65% | Patients were receiving a median opioid dose of 79.94 MME/day | 13 weeks | 10 mg capsules of THC/ CBD in a 1:1 ratio 3-times daily | NR | NR |
| Capano, 2020 (USA)49 | One-arm observational study | n=131 (100%) | 100% chronic pain (cancer and non-cancer) | 56.1 (range: 39– 70) | 68% | Receiving at least 50 MME/day | 8 weeks | 30 mg CBD/1 mg THC | NR | Ananda Professional |
| Haroutounian, 2016 (Israel)50 | One-arm observational study | n=73 (35%) | 93.2% CNCP; 6.8% chronic cancer pain | 51.2 (15.4)† | 38%† | Receiving a median opioid dose of 60 MME/day (range 45–90) | 26 weeks | Cigarettes: 6% to 14% THC, 0.2% to 3.8% CBD; Oral: 11% to 19% THC, 0.5% to 5.5% CBD | All participants were encouraged to attempt gradual dose reduction and possible discontinuation of other analgesics | No-external funding |
| Maida, 2008 (Canada)51 | Prospective cohort | Enrolled in MCP (n=47), not enrolled in MCP (n=65) (100%) | 100% chronic cancer pain | 69.7 (10.1) | 42% | nabilone treated:60 MME/day±64; nabilone untreated: 67 MME/day±101 | 4 weeks | On average 1.79 mg two times daily nabilone | Patients were permitted to use concomitant analgesics | Valeant Pharmaceuticals Canada |
| Narang, 2008 (USA)52 | One-arm observational study | n=30 (100%) | 100% CNCP | Median=43.5 (range=21–67) | 53% | Receiving an average opioid dose of 68 MME/day±57 | 4 weeks | Flexible dose schedule, dronabinol 5–20 mg three times daily | NR | Solvay Pharmaceuticals |
| O’Connell, 2019 (USA)53 | One-arm observational study | n=77 (100%) | 100% CNCP | 54.1 (range=26–76) | 58% | Receiving a mean opioid dose of 140 MME/day±184 | 26 weeks | NR | NR | No industry funding |
| Pritchard, 2020 (USA)54 | Retrospective cohort | cannabis and opioids couse (n=22), opioids only (n=61) (100%) | 100% chronic cancer pain | 53.1 (11.7) | 23% | MCP enrolled: 144 MME/day±129; MCP not enrolled: 119 MME/day±100 | 26 weeks | NR | NR | No industry funding |
| Pawasarat, 2020 (USA)55 | Retrospective chart review | Enrolled in MCP (n=137), not enrolled in MCP (n=95) (100%) | 100% chronic cancer pain | 58 (IQR:14.7) | 56% | MCP enrolled: median 45 MME/day, IQR=135; MCP not enrolled: median 97.5 MME/day, IQR=150 | Between 39 and 52 weeks for MCP enrolled;<26 weeks for not enrolled | NR | NR | No industry funding |
| Rod, 2019 (Canada)56 | One-arm observational study | n=600 | 100% chronic pain (cancer and non-cancer) | NR | NR | Receiving a mean opioid dose of 120 MME/day (range 90–240 MME/day) | 26 weeks | CBD and THC ranged between 4% and 6%. Doses related directly to the opioid taper. | All participants indicated readiness to reduce opioid dose and also received psychological supports (eg, CBT, mindfulness, relaxation) | No external funding |
| Takakuwa, 2020 (USA)57 | One-arm observational study | n=61 (100%) | 100% CNCP (back pain) | 50 (11.4) | 38% | Receiving a median opioid dose of 21 MME/day | Median of 6.4 years among patients who ceased opioids completely | NR | NR | The Society of Cannabis Clinicians |
| Vigil, 2017 (USA)58 | Retrospective chart review | Enrolled in MCP (n=37), not enrolled (n=29)(100%) | 100% CNCP (90% back pain) | 56.3 (11.8) | 36% | Maximum daily dosage of <200 MME/day (enrolled in MCP: mean 24 MME/day±23; not enrolled in MCP: mean 16 MME/day±14) | 52 weeks | NR | NR | University of New Mexico Medical Cannabis Research Fund |
| Yassin, 2019 (Israel)59 | One-arm observational study | n=31 (100%) | 100% CNCP (fibromyalgia) | 33.4 (12.3) | 90% | Receiving oxycodone 5 mg three times/day | 26 weeks | THC to CBD ratio was 1:4; 20 g/month for 3 months, increased up to 30 g/month at the end of 6 months | Patients were permitted to use standardised analgesic therapy (duloxetine 30 mg once daily and Targin 5/2.5 mg two times a day). All other opiates and atypical analgesics were stopped | NR |
*In Belgium, Bulgaria, Czech Republic, Estonia, Germany, Hungary, Latvia, Lithuania, Poland, Romania, the UK and the USA.
†Based on the whole population including opioid users and non-users.
CBD, cannabidiol; CBT, cognitive behavioural therapy; CNCP, chronic non-cancer pain; FU, follow-up; MME, milligram morphine equivalent; NR, not reported; RCT, randomised controlled trial; THC, tetrahydrocannabinol.