Hardy et al.2222 Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:71. Australia |
RCT (dose-escalated placebo, phase IIb). |
Determine whether CBD oil can improve symptomatic distress in patients with advanced cancer receiving palliative care. |
n=144 (52.8% men, age 64.6±12.8 years); advanced cancer (prostate 21.1%, breast 15.5%, colorectal 14.8%, gynecological 12.7%, pulmonary 9.2% and hematological 4.9%); patients received palliative care. |
CBD oil solution (100 mg/mL) oral. |
Dose titration 3/3 days: from 0.5mL 1x/day to 2mL 3x/day for 14 days, according to tolerability. Participants remained on the titrated dose until 28 days. |
Placebo |
Scales: ESAS; SGIC. Under treatment with opioids. |
Clarke et al.2424 Clarke S, Butcher BE, McLachlan AJ, Henson JD, Rutolo D, Hall S, Vitetta L. Pilot clinical and pharmacokinetic study of ∆9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain. PLoS One. 2022;17(10):e0270543. Australia |
Clinical trial |
Assess the safety, tolerability, pharmacokinetics and analgesic effect of a new medicinal cannabis spray in patients with incurable cancer and pain uncontrolled with opioids. |
n=5 in Stage I (which does not fulfil the eligibility criteria for this study). n=25 in Stage II (which is considered in this study); patients (60% women; age 55.9±11.9 years); advanced cancer (28% breast, 16% lung and gastrointestinal, 12% hematological, 8% pancreas and ovaries, 4% melanoma, prostate and central nervous system). |
THC/CBD mouth spray (1.25mg/ 1.25mg per spray). |
Stage I: 1 day with 2 sprays, next day with 6 sprays. Stage II: 1-9 days of dose escalation (1 spray 3 days; 2 sprays 3 days; and 3 sprays 3 days); 10-15 days of treatment with the dose tolerated in the previous stage; 16-30 days of follow-up. |
- |
Scale: EORTC-QLQ-C30-v3 Single-arm study, unblinded for researchers and participants. |
Grimison et al.2525 Grimison P, Mersiades A, Kirby A, Lintzeris N, Morton R, Haber P, Olver I, Walsh A, McGregor I, Cheung Y, Tognela A, Hahn C, Briscoe K, Aghmesheh M, Fox P, Abdi E, Clarke S, Della-Fiorentina S, Shannon J, Gedye C, Begbie S, Simes J, Stockler M. Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomized, placebo-controlled, phase II crossover trial. Ann Oncol. 2020;31(11):1553-60. Australia |
RCT (multicentre, double-blinded, placebo, phase II/III). |
Assess an oral cannabis extract (THC:CBD) for the prevention of refractory nausea and vomiting induced by chemotherapy. |
n=81 (78% women; ages: 18-49 years -30%, 50-69 - 63%, ≥70 years - 6%); cancer at any stage (breast 33%, colorectal 13%, lung 12%, esophageal/gastric 9%, gynecological 9%, pancreatic 9%, hematological 4%, testicular 4%). |
THC/CBD oral capsules (2.5mg/ 2.5mg). |
1st cycle: 1-4 self-titrated capsules 3 times a day, starting 1 day before intravenous chemotherapy, ending on day 5; 2nd cycle: placebo (cross-over between participants); 3rd cycle: treatment preferred by the participants. |
Placebo |
Various centers: New South Wales. 72 participants completed cycles 1 and 2. Scale: AQOL-8D. |
Good et al.2626 Good PD, Greer RM, Huggett GE, Hardy JR. An open-label pilot study testing the feasibility of assessing total symptom burden in trials of cannabinoid medications in palliative care. J Palliat Med. 2020;23(5):650-5. Australia; |
Prospective two-arm open label trial of escalating doses. |
Assess the response to medicinal cannabis, determine tolerated median doses of CBD and THC and document adverse events. |
n=21 (66.7% women, age 57.5±12.4 years); metastatic or locally advanced cancer (breast 33%, prostate 19%, colorectal 14%, gynecological 10%, pancreas 10%, bone and soft tissue 5%, hematological 5%). |
Oral solution of CBC oil (100mg/mL) and THC (10mg/mL). |
1 dose with CBC (50-600mg/day), the other with THC (2.5-30mg/day). Increases every 2/2 days, until symptomatic control or unacceptable side effects. Then the dose was maintained for 14, ideally 28 days. |
- |
Scales: CGIC, DASS-21, EORTC-QLQ-C15-PAL, ESAS, PGIC. Participants were taking opioid therapy. |
Bar-Sela et al.2727 Bar-Sela G, Zalman D, Semenysty V, Ballan E. The effects of dosage-controlled cannabis capsules on cancer-related cachexia and anorexia syndrome in advanced cancer patients: pilot study. Integr Cancer Ther. 2019;18:1534735419881498. Israel |
Clinical Trial |
Asses the effect of dose-controlled cannabis capsules on anorexia-caquexia syndrome in patients with advanced cancer. |
n=24 (62.5% men, average age 66 years); Most common cancers: pancreatic, colon, prostate and lung carcinoma. |
THC/CBD oral capsules (9.5mg/ 0.5mg). |
1 capsule 12/12h for 6 months. If adverse effects occur, reduce the dose by half. |
- |
Scale: EORTC-QLQ-C30. -87.5% of the participants were undergoing chemotherapy. |
Lichtman et al.2828 Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Kornyeyeva E, Fallon MT. 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. 2018;55(2):179-88.e1. Several countries |
RCT (multi-center, double-blind, placebo, phase III). |
Asses the efficacy of nabiximols as adjuvants in advanced cancer patients with chronic pain unrelieved by optimized opioid therapy. |
n=380 (men/age: experimental group 55.8%/59.2±12.0 years; control group 52%/ 60.7±11.1 years); advanced cancer (lung 16.9%, breast 15.6%, colon 10.8%, prostate 9.8%, hematological 6.0%, pancreas 5.8%, head and neck 5.5%); Patients with chronic pain refractory to optimized opioid treatment. |
THC|CBD mouth spray (27mg/mL|25mg/mL). |
On the 1st day, 1 spray, gradually increasing until: acceptable pain relief, unacceptable adverse effects, or maximum of 10 sprays/day. Complete titration at 14 days; then maintain for 3 weeks. |
Placebo |
114 centers from Belgium, Bulgaria, the Czech Republic, Estonia, Germany, Hungary, Latvia, Lithuania, Poland, Romania, the United Kingdom and the United States of America took part. Scales: PGIC, PSQ, SGIC. |
Turcott et al.2929 Turcott JG, Del Rocío Guillen Núñez M, Flores-Estrada D, Oñate-Ocaña LF, Zatarain-Barrón ZL, Barrón F, Arrieta O. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Support Care Cancer. 2018;26(9):3029-38. México |
RCT (pilot, double-blind, placebo). |
Asses the effect of nabilone vs. placebo on appetite, nutritional status and QoL in patients with advanced lung cancer. |
n=65; 47 were randomized (women/age: experimental group 78.9%/61.1±10.6 years; control group 78.6%/52.6±11.8 years); advanced non-small cell lung cancer. |
Oral capsules of synthetic THC (nabilone 0.5mg). |
1 capsule/day for 2 weeks, then 2 capsules/day for 6 weeks. |
Placebo |
Scales: EORTC-QLQ-C30, EORTC-QLQ-LC13, FAACT, PG-SGA. Participants with a good performance status and with anorexia. |
Johnson et al.3030 Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage. 2013;46(2):207-18. United Kingdom |
Long-term, open-label, follow-up study. |
Investigate the long-term safety and tolerability of THC/CBD spray and THC spray for pain relief in patients with advanced cancer. |
n=43 (men/age: THC/CBD group 59%/ 57.5±13.5 years; THC group 25%/ 58.6±6.3 years); advanced cancer (breast 21%, prostate 16%, rectum 16%, lung 7%, bone 5%); Patients with pain refractory to optimized opioid treatment. |
Spray bucal de THC|CBD (27mg/mL|25mg/mL) (n=39); e Spray bucal de THC 27mg/mL (n=4). |
Patients who had previously participated in the 2-week RCT. Self-titration. Visits: at the end of the RCT/screening; after 7-10 days; after 4/4 weeks; at study completion/dropout. |
- |
Centers: 21 in the UK and 1 in Belgium. Scales: BPI-SF, EORTC-QLQ-C30. Average duration of treatment: for THC/CBD - 25 days, for THC - 151.5 days. Participants taking opioid treatment. |
Portenoy et al.3131 Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S, Fallon MT. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13(5):438-49. Several Countries |
RCT (double-blind, placebo graded dose). |
Obtain information on the dose response to analgesia and the safety of nabiximols in a population with cancer and pain not controlled with opioids. |
n=360 (51.7% men, age 58±12.2 years); advanced cancer (gastrointestinal 17.8%, lung 17.8%, breast 15%, prostate 12.2%); patients with pain refractory to optimized opioid treatment. |
Spray bucal de THC|CBD (27mg/mL|25mg/mL); número de pulverizações: dor ligeira: 1-4; dor moderada: 6-10; dor intensa: 11-16. |
A baseline period of 5-14 days, followed by 5 weeks, with titration and treatment (in 4 groups, with 3 doses). After 2 weeks, a post-study was carried out. Maximum duration of 9 weeks. |
Placebo |
A total of 84 centers in North and South America, Europe and South Africa participated. Scales: BPI-SF, EORTC-QLQ-C30-v3, MADRS, PGIC. |
Brisbois et al.3232 Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, MacDonald N, Baracos VE, Wismer WV. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol. 2011;22(9):2086-93. Canadá |
RCT (pilot, double-blind, placebo, phase II). |
Determine whether THC can improve the taste and perception of smell, appetite, calorie intake and QoL of cancer patients with chemosensory alterations. |
n=21 (men/age: experimental group 64%/ 67.0±10.9 years; placebo group 50%/ 65.5+8.0 years); advanced cancer (THC/placebo: lung 45%/50%, genitourinary 27%/20%, gastrointestinal 18%/10%); patients with anorexia and chemosensory alterations. |
Cápsulas orais de THC 2,5mg. |
Treatment: Days 1-3, 1xday; Days 4-18, 3xday; with the option of increasing the dose up to 20mg/day. |
Placebo |
Scales: ESAS, FAACT. Around 33% of patients received chemotherapy. |