Cancer

DGS PraxisLeitlinie v2.0 on cannabis in pain medicine; includes tumor-associated pain as an indication, recommendation grade B for palliative pain situations in cancer (opioid-refractory or intolerance), THC:CBD combinations preferred.

Two double-blind, randomized, placebo-controlled phase 3 trials of Sativex (THC:CBD oromucosal spray) as add-on therapy in advanced cancer patients with chronic pain insufficiently relieved despite optimized opioid therapy. The primary efficacy endpoint (improvement in average daily pain NRS) was not met in EITHER of the two studies. Only a post-hoc subgroup analysis (US patients under 65 years) showed a statistically favorable effect. Overall no evidence of pain reduction beyond placebo.

Cannabis-based medicines (nabiximols, THC, nabilone, CBD) show no clinically relevant advantages over placebo in pain relief in cancer patients with opioid-refractory or chemotherapy-associated pain.

Cochrane SR, k=14 RCTs (n=1.823), cannabis-based medicines vs. placebo for moderate to severe cancer pain despite opioid therapy. Moderate evidence: nabiximols/THC no clinically relevant efficacy; PGIC improvement RD=0,06 (95%-CI 0,01–0,12; NNTB=16); pain intensity SMD=-0,19 (95%-CI -0,40 to 0,02). Low evidence: CBD no additional benefit over palliative care alone (1 study, n=144). Conclusion: moderate evidence for ineffectiveness of oral/oromucosal cannabinoids in opioid-refractory cancer pain.

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive SR across 79 RCTs (n=6.462) on medical cannabis; moderate evidence for chemotherapy-induced nausea/vomiting (CINV), weak evidence for appetite stimulation in HIV/cancer cachexia; nabilone/dronabinol superior vs. placebo (OR=3.82 for CINV control, 95%-CI 1.55–9.42).

Medical cannabis showed no clinically significant effects on depression, anxiety and stress in cancer patients; higher THC doses even increased anxiety risk, while only appetite was improved.

Systematic review and meta-analysis (k=15 studies, of which 11 RCTs; N=1.898 cancer patients): Medical cannabis (THC, CBD, plant extracts) showed no clinically relevant effect on depression, anxiety or stress as primary endpoints. Higher synthetic THC increased anxiety risk vs. low dose (OR=2,0; 95%-CI: 1,4–2,9; p<0,001; confidence: very low). Secondarily, medical cannabis improved appetite (OR=12,3; 95%-CI: 3,5–45,5; p<0,001; confidence: moderate). Conclusion: Insufficient evidence for efficacy on psychiatric symptoms; well-designed studies required.

Cannabinoids showed no significant advantage over placebo in cancer patients for caloric intake, appetite, nausea/vomiting, pain or sleep problems; in HIV patients a benefit for weight gain and appetite was demonstrable, but overall no convincing high-quality evidence was found for the benefit of cannabinoids in anorexia or cachexia.

Systematic review and meta-analysis on cannabinoids in palliative medicine; k=9 RCTs (n=1.561). In cancer patients no significant differences vs. placebo for caloric intake (SMD: 0.2, 95% CI [-0.66, 1.06], p=0.65), appetite (SMD: 0.81, 95% CI [-1.14, 2.75], p=0.42), nausea/vomiting (SMD: 0.21, 95% CI [-0.10, 0.52], p=0.19), >30% pain reduction (RD: 0.07, 95% CI [-0.01, 0.16], p=0.07) or sleep problems (SMD: -0.09, 95% CI [-0.62, 0.43], p=0.72). In HIV patients cannabinoids superior for weight gain (SMD: 0.57, 95% CI [0.22, 0.92], p=0.001) and appetite (SMD: 0.57, 95% CI [0.11, 1.03], p=0.02). Evidence quality (GRADE): low to very low.

Nabiximols and THC did not reduce cancer pain better than placebo, but caused more adverse events.

SR+MA k=5 RCTs (4 in MA), n=1.534 cancer pain patients with insufficient opioid analgesia; oromucosal nabiximols/THC vs. placebo: no significant difference in pain intensity, sleep problems or opioid dose; patient global assessment improved NNT=16 (95% CI 8-∞); NNTH adverse event=20 (95% CI 11-100); NNTH nervous system adverse event=10 (95% CI 7-25); GRADE quality of evidence: very low.

Cannabinoids showed no significant difference from placebo in pain relief (Numeric Rating Scale), but an increased risk of adverse effects such as somnolence and dizziness.

Systematic review with meta-analysis on cannabinoids in cancer-associated pain; k=5 RCTs (n=1442, all low risk of bias). No difference between cannabinoids+opioids vs. placebo+opioids in average NRS pain reduction (MD -0,21 [95% CI -0,48 to 0,07], p=0,14); phase III subanalysis: MD -0,02 (95% CI -0,21 to 0,16, p=0,80). Cannabinoids with higher risk of somnolence (OR 2,69 [95% CI 1,54–4,71], p<0,001) and dizziness (OR 1,58 [95% CI 0,99–2,51], p=0,05); no treatment-associated deaths.

Cannabinoids showed superior antiemetic efficacy compared to conventional medications and placebo, but were associated with more intense and more frequent side effects.

SR/MA (k=30 RCTs); cannabinoids (dronabinol, nabilone, levonantradol) vs. placebo or neuroleptics for chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Dronabinol vs. neuroleptics: RR=0,67 (CI 0,47–0,96), NNT=3,4; patient preference cannabinoids vs. other agents: n=1138, RR=0,33 (CI 0,24–0,44), NNT=1,8. Superiority of antiemetic efficacy of cannabinoids over placebo and neuroleptics confirmed.

Cannabinoids show mixed results: megestrol acetate was more effective than dronabinol; nabilone 0,5 mg showed no superiority over placebo, but at double the dose (1,0 mg after 6 weeks) a significant increase in caloric intake; THC showed weight gain ≥10% in 17,6% of patients and improved appetite at 2,5 mg doses.

Systematic review (k=6: 5 RCTs + 1 prospective study, n=869) on cannabinoids in tumor-related anorexia in older adults. Megestrol 800 mg/d superior to dronabinol 2,5 mg/d for appetite increase. Nabilone 0,5 mg/d: no significant superiority vs. placebo; nabilone 1,0 mg over 6 weeks: significant increase in caloric intake and carbohydrate intake vs. placebo. THC 5–10 mg/d: weight gain ≥10% in 17,6% of patients, without relevant side effects.

Cannabinoids increased appetite, but worsened quality of life and led to frequent side effects.

SR+MA of k=3 RCTs (n=592) on cannabinoids in cancer cachexia; appetite improvement versus placebo (MD=0,27, 95% CI −0,51 to 1,04; n=3 studies), not statistically significant; quality of life significantly worse under cannabinoid (MD=−12,39, 95% CI −24,21 to −0,57; n=2 studies); 607 adverse events in 441 patients (496 cannabinoid group vs. 111 placebo group).

Cannabis and cannabinoids may improve refractory chemotherapy-induced nausea and vomiting, but should not be used as cancer treatment; evidence quality is low to very low.

ASCO guideline on cannabis/cannabinoids in adult cancer patients; evidence base: 13 systematic reviews + 5 primary studies (4 RCTs, 1 cohort study), predominantly low/very low evidence certainty. Recommendation: cannabis/cannabinoids MAY improve refractory chemotherapy-induced nausea/vomiting (in addition to guideline-concordant antiemetics); AGAINST use as tumor-directed therapy outside of studies. Other supportive outcomes (pain, sleep, appetite) unclear.

Oral cannabinoids were more effective than placebo in prophylactic treatment against nausea and vomiting combined, but equivalent to other antiemetics in isolated control of vomiting or nausea; however, increased dysphoria, euphoria and sedation.

SR+MA of RCTs on oral cannabinoids (dronabinol, nabilone) for chemotherapy-induced nausea and vomiting (CINV) in oncology. For the combined endpoint (no vomiting + no nausea) superior to placebo/other antiemetics (Mantel-Haenszel random effects, OR with 95% CI). For isolated single endpoints (nausea only or vomiting only) equivalent to comparator treatments. More frequent dysphoria, euphoria and sedation under cannabinoids.

High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic for cancer pain.

MASCC guideline on cannabis for cancer-associated pain; based on 34 systematic reviews and RCTs (7 RCTs with cancer pain patients, of which 2 with positive primary endpoint — not reproducible in follow-up studies). High-quality systematic reviews with meta-analyses found little evidence for efficacy of cannabinoids as adjuvant analgesics in cancer pain. The MASCC panel recommends AGAINST the use of cannabinoids as adjuvant analgesia; potential harms and side effects (inconsistent evidence) should be carefully weighed, especially in the context of checkpoint inhibitor therapy.

Meta-analysis shows no significant benefits of cannabinoids for appetite, weight gain and quality of life in cancer-associated cachexia; moderate-quality evidence even suggests significantly worse quality of life.

Systematic review + meta-analysis on cannabinoids in cancer-associated cachexia (CAC); k=10 studies (4 RCTs, 6 NRSIs). Meta-analysis (very low quality of evidence): no significant effect on appetite vs. control (SMD=-0.02; 95% CI [-0.51, 0.46]; p=0.93). Moderate evidence: cannabinoids significantly less effective than control on quality of life (SMD=-0.25; 95% CI [-0.43, -0.07]; p=0.007). Conclusion: cannabinoids alone show no convincing benefits in CAC; higher-quality studies within multimodal therapy approaches are recommended.

THC and nabilone were more effective than placebo against chemotherapy-induced nausea and vomiting, but not more effective than other antiemetics; insufficient evidence for other gastrointestinal symptoms.

Systematic review (MASCC guideline development) of k=36 RCTs on cannabinoids for gastrointestinal symptoms in cancer patients (31 CINV, 1 radiotherapy-induced nausea, 4 anorexia-cachexia). THC/nabilone more effective than placebo for CINV (11/36 RCTs positive vs. placebo), but not superior to other antiemetics (only 11/21 comparative studies in favor of cannabis). MASCC conclusion: insufficient evidence for recommending cannabinoids for CINV, advanced cancer-related nausea, anorexia-cachexia and taste disorders.

Cannabinoids reduced tumor growth and promoted apoptosis and autophagy in melanoma cells in vivo.

Systematic review on cannabinoids in melanoma; k=6 in vivo studies from 622 identified papers. Cannabinoids (individually or in combination) reduced tumor growth and promoted apoptosis and autophagy in melanoma cells. Recommendation for further preclinical and animal studies as well as randomized clinical trials before therapeutic application.

No high-quality evidence for cannabis in the treatment of psychological symptoms in cancer patients; only 6 of 15 RCTs suggested benefit, but no studies assessed cannabis efficacy as a primary outcome.

MASCC guideline on cannabis for psychological symptoms (insomnia, anxiety, depression) in cancer patients. Systematic review of k=15 RCTs and 2 SR (search period until November 2021); 18% of cancer patients use cannabis for symptom management. No study evaluated psychological symptoms as a primary endpoint. 6/15 RCTs showed benefit (5 for sleep, 1 for mood). Conclusion: no high-quality evidence for a recommendation until further studies are available.

Majority of participants reported symptom-relieving effect (pain, nausea, sleep, anxiety), but discontinuation due to lack of improvement, side effects (fatigue, paranoia), costs and social stigmatisation.

Systematic review on cannabis use among cancer patients and survivors in the USA; k=27 studies (74% cross-sectional design) from 1162 identified papers, intercoder agreement 0.81. Prevalence 4,8–22% (national samples); most common forms of application: topical (80%), smoking (73%), vaping (12%), edibles (10%). Main motives: symptom management (pain, nausea, insomnia, anxiety); majority reported symptom improvement. Reasons for discontinuation: lack of effect, side effects (fatigue, paranoia), costs, social stigma.

Cannabinoids show anticancer potential against glioma cells, but effects vary depending on combination and dosage; evidence is based mainly on in-vitro and animal studies.

Systematic review on the efficacy of cannabinoids against glioblastoma multiforme; k=14 studies (5 in vitro, 2 in vivo, 7 in vitro+in vivo) out of 302 identified papers. Cannabinoids (CBD, THC, alone or combined with TMZ/radiotherapy) showed inhibition of tumor growth, induction of apoptosis and autophagy in glioma cells. Effect varies with dosage and combination; studies primarily in cell cultures and mice, small number of human studies.

Cannabinoids reduced pain and anxiety, showed trends toward improvement in appetite and nausea/vomiting, but had no effect on constipation, depression, fatigue, mobility or quality of life; THC-dominant formulations increased the risk of psychiatric, neurological and gastrointestinal adverse events.

Systematic review and meta-analysis on symptom control in cancer patients; k=98 studies (interventional + observational). Cannabinoids significantly reduced pain vs. baseline (MD=-1,22; 95% CI: -1,92; -0,52) and anxiety (MD=-1,30; 95% CI: -2,22; -0,39). Appetite, chemotherapy-induced nausea/vomiting (OR=2,18; 95% CI: 0,79; 6,00) and insomnia (MD=-1,08; 95% CI: -2,48; 0,33) showed a trend toward improvement. No effect on constipation, depression, fatigue, mobility or quality of life. THC-dominant formulations increased the risk of psychiatric (OR=10,62; 95% CI: 1,35; 83,57), neurological (OR=2,24; 95% CI: 1,15; 4,35) and gastrointestinal (OR=2,69; 95% CI: 0,73; 9,90) adverse events. PROSPERO CRD42023479375.

Cannabinoids showed superiority over placebo (RR 2,65), but no difference to active comparator treatments; a recent THC:CBD trial showed promising results as add-on therapy.

Systematic review and meta-analysis (k=26 RCTs) on cannabinoids as prophylaxis for chemotherapy-induced nausea and vomiting (CINV). Cannabinoids showed significantly superior CINV control versus placebo (RR 2,65; 95%-CI 1,70–4,12; I²=0,00%). No significant difference versus active comparator arms (predominantly older single-agent antiemetic regimens). 23 of 26 studies date from before 2000; evidence for use alongside modern triple/quadruple antiemetics remains sparse. A recent phase II/III trial showed superiority of THC:CBD as add-on therapy for secondary CINV prevention.

Cannabis showed no clinically meaningful changes in immune parameters in patients with and without cancer; immune markers relevant to ICI function were not associated with cannabis use.

Systematic review on immunomodulatory effects of cannabis in patients with/without cancer; k=40 clinical studies (including 9 RCTs). No meaningful changes in cytokines, T-cell counts or CRP under cannabis exposure in most studies; in autoimmune patients, clinical symptom improvement without objective laboratory changes. No evidence for cannabis-related immunosuppression that could impair ICI function.

Cannabinoids were frequently used for symptom control (58% for nausea/vomiting), but showed more frequent side effects in controlled trials (drowsiness, dizziness, dry mouth, discontinuation) without serious adverse events.

Systematic review on cannabinoids in children with cancer; k=19 studies (n=1.927): 8 retrospective chart reviews, 7 RCTs, 2 open-label studies, 2 case reports. Main indication: chemotherapy-induced nausea/vomiting (11/19 studies, 58%). Controlled trials showed somnolence, dizziness, dry mouth, treatment discontinuation due to side effects more frequently under cannabinoids; no serious cannabis-associated adverse events reported. Evidence for symptom management exists, but there is a lack of rigorous evidence on dosing, safety and efficacy in children with cancer.

Cannabis showed inhibitory effects on sperm parameters, mixed effects on sexual function (possible improvement in subjective sensation, but dose-dependent ED risk), and organ-dependent varying effects on malignancy (increased testicular cancer risk, contradictory data on bladder cancer, anti-neoplastic effects in prostate cancer).

Systematic review on cannabis and male urology; k=91 articles (in vitro, animal models, case series, case-control/cohort studies), of which 25 on urological neoplasias. Cannabis exposure identified as independent risk factor for testicular cancer; contradictory data on bladder cancer; anti-neoplastic effects of cannabinoids reported in prostate cancer.

High evidence for cannabis benefit in MS spasticity and pain; low evidence for small effect in neuropathic pain; unclear evidence for nausea/vomiting in chemotherapy patients.

Systematic review on cannabis efficacy and safety in three indications (MS spasticity, neuropathic pain, chemotherapy-induced nausea); k=41 RCTs (n=4.550), of which 14 studies on cancer patients under chemotherapy. Publication period 1975–2015, majority European studies. Quality assessment according to Cochrane/GRADE standard.

Nabilone showed significant superiority over prochlorperazine: 80% vs. 32% response rate (P<0,001), significantly less nausea and vomiting, but with twice as frequent and in part serious side effects.

n=113 cancer patients under chemotherapy (double-blind crossover RCT, NEJM 1979); response rate nabilone 80% vs. prochlorperazine 32% (p<0,001); nausea (p<0,01) and vomiting (p<0,001) each significantly less frequent under nabilone; patients preferred nabilone for continuation (p<0,001).

Nabiximols was not superior to placebo on the primary endpoint (10,7% vs. 4,5% pain improvement, p=0,0854), but showed advantages on several secondary endpoints, especially in US patients and on quality-of-life measures.

Phase III RCT of nabiximols (THC 27mg/mL + CBD 25mg/mL) vs. placebo in advanced cancer with chronic pain despite optimised opioid therapy; n=397 (nabiximols n=199, placebo n=198). ITT population: median 10,7% vs. 4,5% pain reduction (p=0,0854, primary endpoint not significant). Per-protocol population: 15,5% vs. 6,3% (p=0,0378). Nabiximols significantly superior on 2/3 quality-of-life instruments (week 3) and 3/3 (week 5). Post-hoc analysis: US patients showed significant advantages on multiple secondary endpoints.

THC and prochlorperazine were equally effective against nausea and vomiting from chemotherapy, but THC showed side effects such as reduced concentration, less social interaction and less activity.

n=214 cancer patients (double-blind, crossover RCT); oral THC equally effective as prochlorperazine for chemotherapy-related nausea and vomiting; significant side effects under THC (ability to concentrate p<0,01, social interaction p<0,05, physical activity p<0,05); no significant difference in appetite or food intake between the groups.

THC:CBD showed statistically significant pain relief versus placebo (NRS -1,37 vs. -0,69), but with worsening of nausea and vomiting; THC alone did not differ significantly from placebo.

Multicentre phase II RCT in n=177 patients with refractory tumor pain despite opioid therapy; THC:CBD extract vs. THC extract vs. placebo over 2 weeks. THC:CBD significantly superior vs. placebo (NRS reduction -1.37 vs. -0.69, p<0.05); 43% vs. 21% achieved >30% pain reduction (OR significant). THC extract alone not significant vs. placebo (-1.01 vs. -0.69). Adverse effects mild/moderate; THC:CBD showed worsening of nausea/vomiting vs. placebo (p=0.02).

THC:CBD improved the complete response rate (no vomiting/retching and no rescue medication) from 8% to 24% (absolute difference 16%, p=0,01) with similar effects on absence of significant nausea and improvement in quality of life, but with increased adverse events such as sedation, dizziness and transient anxiety.

Phase II/III RCT (n=147); oral THC:CBD extract (2,5 mg THC + 2,5 mg CBD, 3×/day) vs. placebo as an addition to guideline antiemetic prophylaxis for refractory chemotherapy-related nausea/vomiting. Complete response rate rose from 8% to 24% (absolute difference 16%, 95% CI 4–28; p=0,01). More frequent adverse events: sedation (18% vs. 7%), dizziness (10% vs. 0%), transient anxiety (4% vs. 1%). No serious adverse events under THC:CBD.

THC showed more complete responses (36 of 79 courses) than prochlorperazine (16 of 78 courses) in chemotherapy patients with prior therapy resistance.

n=79 chemotherapy cycles (THC) vs. 78 (prochlorperazine); complete antiemesis: 36/79 (THC) vs. 16/78 (prochlorperazine); patient preference for THC 20/25 (p=0,005); in patients <20 years complete remission 15/20 vs. 21/59 in older patients (p=0,004).

THC showed superior antiemetic efficacy compared to prochlorperazine and placebo: nausea was absent in 40/55 patients under THC, 8/55 under prochlorperazine and 5/55 under placebo.

Randomized, double-blind crossover RCT (n=55 cancer patients with chemotherapy-related nausea/vomiting). THC showed clearly superior antiemetic effect: nausea completely absent in 40/55 patients under THC vs. 8/55 under prochlorperazine vs. 5/55 under placebo. THC effective in particular with cyclophosphamide-, fluorouracil- and doxorubicin-containing regimens.

CBD in addition to standard prophylaxis significantly reduced the incidence of acute GVHD compared with historical controls (HR 0,3; p=0,0002).

n=48 alloHCT patients (79 % acute leukemia/MDS), CBD 300 mg/day orally (day −7 to +30) in addition to standard GVHD prophylaxis; cumulative incidence of acute GVHD grade II–IV by day 100: 12,1 %, grade III–IV: 5 %; no patient developed acute GVHD while taking CBD. Hazard ratio for grade II–IV GVHD vs. 101 historical controls: HR=0,3 (p=0,0002). Non-relapse mortality at day 100: 8,6 %; no CBD-associated grade 3–4 adverse events.

Delta-9-tetrahydrocannabinol showed significant antiemetic effect in 14 of 20 treatment cycles versus 0 of 22 placebo cycles (P < 0,001).

Randomised, double-blind crossover RCT; n=20 evaluable cancer patients under chemotherapy. Oral THC antiemetically effective in 14/20 course sequences vs. 0/22 under placebo (p<0,001). No patient vomited during a subjective "high". First RCT evidence for THC as an antiemetic in chemotherapy-induced vomiting.

Levonantradol 0,5 mg showed better antiemetic effect than chlorpromazine, but is not recommended due to unacceptable CNS side effects.

n=108 cancer patients undergoing highly emetogenic cytostatic therapy; cannabinoid antiemetic levonantradol 0,5 mg superior to chlorpromazine 25 mg; dysphoric adverse effects in 22% (0,5 mg) and 50% (higher doses); efficacy limited with cisplatin regimens. Clinically relevant antiemetic control at the lowest dose.

The 1:1 ratio of medical cannabis significantly improved sleep, physical and functional capacity without serious adverse effects.

Phase 2 RCT n=88 patients with high-grade glioma; 1:1 THC:CBD ratio significantly improved physical capacity (p=0,025), functional wellbeing (p=0,014) and sleep (p=0,009) after 12 weeks; 11% disease reduction, 34% stable disease; no serious adverse events.

43,6% of patients reached the primary endpoint definition (≥2-point reduction in pain); across all patients, worst pain improved by an average of 1,95 points over 15 weeks, and by 2,36 points among study completers; 28% of patients discontinued due to toxicity or preference.

Phase 2 pilot study (n=39) of CBD (Epidiolex, 100 mg BID) in breast cancer patients (stages 0–3) with aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). 43,6 % (95 % CI [28 %, 60 %]) reached the primary endpoint (≥2-point reduction in worst-pain score). Worst pain improved by 0,13 points/week (p<0,001); mean reduction at study completion (n=28) 2,36 points (95 % CI [-3,22; -1,49]). CBD was safe and well tolerated.

Higher proportion of early cannabis patients achieved reduction in opioid use and improved pain control; no serious safety issues reported.

Pilot RCT in n=30 patients with stage IV cancer under opioid therapy, randomized 1:1 to early cannabis (EC) vs. delayed start (DC). Estimated mean daily THC/CBD doses after 3 months: 34 mg THC and 17 mg CBD. Higher proportion of the EC group achieved opioid reduction and improved pain control (numerical values not specified in the abstract). No serious safety issues; high patient satisfaction. Feasibility study for RCTs in state cannabis programs.

THC significantly improved chemosensory perception, taste of food, pre-meal appetite, and protein intake compared to placebo in cancer patients with chemosensory alterations.

n=21 completed treatments (THC n=24, placebo n=22), 18-day double-blind pilot study; THC improved chemosensory perception (P=0.026) and taste intensity (P<0.001), meal appetite (P=0.05) and protein proportion of calories (P=0.008); sleep quality (P=0.025) and relaxation (P=0.045) also significantly improved vs. placebo.

All levonantradol doses significantly reduced chemotherapy-induced emesis compared to placebo (p<0,01) without a demonstrable dose-response effect.

n=20 patients with advanced cancer and refractory chemotherapy-induced emesis; synthetic cannabinoid levonantradol 0,5–2,0 mg i.m. vs. placebo; antiemetic activity significant for all doses versus placebo (p<0,01); tolerability acceptable up to 2,0 mg. No efficacy advantage with cisplatin-containing regimens.

Oral THC (15-20 mg) reduces tumor pain significantly better than placebo, but is accompanied by pronounced sedation and mental clouding.

Pilot study (n=10, cancer patients with tumor pain), oral THC (5/10/15/20 mg) vs. placebo double-blind: significant pain relief compared to placebo at high doses (15 mg and 20 mg); substantial sedation and mental clouding were reported at these doses.

Nabiximols was safe and tolerable; 1-year survival was numerically higher than under placebo, however progression-free rate at 6 months was identical.

Phase 1b RCT, n=21 (nabiximols n=12 + placebo n=9) in first glioblastoma recurrence + dose-intensified temozolomide; progression-free rate at 6 months 33% in both arms; 1-year survival 83% (nabiximols) vs. 44% (placebo), p=0.042; acceptable safety profile, no drug-drug interaction with TMZ; most common AEs vomiting, dizziness, fatigue (grade 2-3).

CBD oil provided no additional benefit over placebo for symptom burden in palliative care patients with advanced cancer.

n=144 advanced cancer patients (palliative care), CBD oil titrated up to 2 mL 3×/day vs. placebo over 28 days; primary endpoint ESAS-TSDS day 14: CBD −3,0 vs. placebo −6,2 points (p=0,24); responders 44,8% (CBD) vs. 58,7% (placebo) (p=0,13); no evidence of added benefit of CBD beyond specialised palliative care.

Nabilone was not superior to placebo with regard to quality of life and treatment-related symptoms during head and neck radiotherapy.

n=56 head and neck carcinoma patients undergoing radiotherapy, nabilone vs. placebo. No significant difference in time to QoL deterioration (p=0,4279), pain reduction (p=0,6048), nausea (p=0,7105), loss of appetite (p=0,3295), body weight (p=0,1454) or sleep (p=0,4438). Negative finding: nabilone at the dosage used was not more effective than placebo for symptom control during head and neck carcinoma radiotherapy.

Benzopyranoperidine showed no analgesic effect versus placebo and was inferior to codeine; both doses tended to increase pain perception.

n=35 cancer patients with malignancy-related pain; THC analogue benzopyranoperidine (2 mg / 4 mg) showed no consistent superiority over placebo in pain relief; codeine 120 mg achieved clinically significant pain reduction (p-value not explicit, comparison clinically meaningful). Negative finding for this THC congener in cancer pain.

Levonantradol was not more effective as an antiemetic than prochlorperazine, but showed a higher rate of side effects.

RCT crossover (n=16 cancer patients undergoing chemotherapy); synthetic cannabinoid levonantradol 1 mg i.m. vs. prochlorperazine 10 mg i.m. for antiemesis; no statistically significant difference in antiemetic response. Levonantradol showed more frequent adverse effects than prochlorperazine. Negative study; historical finding on cannabinoid antiemesis in oncology (n<60).

Clinical study with oral THC (single dose) in patients with cancer pain: THC showed a mild analgesic effect. 20 mg THC caused treatment-limiting side effects (somnolence, dizziness, ataxia, visual disturbances) and in some cases alarming reactions; 10 mg was well tolerated and was analgesically effective despite its sedative effect. Caveat: very small, old single-dose study, narrow therapeutic window.

Intratumoral THC was safely applicable and showed initial antiproliferative indications, without formal proof of efficacy.

First clinical pilot study (n=9, recurrent glioblastoma), intratumoral THC administration after failure of standard therapy. Primary endpoint safety: cannabis delivery safe, no obvious psychoactive effects. Median survival from start of therapy 24 weeks (95% CI: 15-33). THC inhibited tumor cell proliferation in vitro; Ki67 immunostaining reduced in 2 patients. No control arm; phase I without proof of efficacy.

Supervised medical cannabis was associated with treatment success and improved quality of life in 70,6% of patients after 6 months.

Israeli prospective study with approx. n=10.000 patients on prescribed medical cannabis; cancer was the most common primary indication at 49,1%; 70,6% of patients achieved treatment success after 6 months; most common side effects: dizziness (8,2%), dry mouth (6,7%), increased appetite (4,7%); 1.938 (19,4%) patients died during the observation period.

Cannabis use during nivolumab therapy significantly reduced the response rate (37,5% vs. 15,9%, p=0,016), with no effect on progression-free survival or overall survival.

Retrospective cohort study n=140 (89 nivolumab mono, 51 nivolumab+cannabis) in advanced melanoma/NSCLC/renal cell carcinoma; cannabis use significantly reduced tumor response rate (37,5% vs. 15,9%, p=0.016, OR=3.13, 95% CI 1.24–8.1), with no effect on PFS or OS. THC/CBD percentages had no influence on RR (p=0.393/0.116).

Cannabis use during immunotherapy was associated with significantly shorter time to progression and lower overall survival.

Prospective observational study (n=102: 68 immunotherapy, 34 immunotherapy+cannabis) in patients with advanced cancer. Cannabis use during immunotherapy correlated with significantly shortened time to tumour progression and decreased overall survival. Cannabis reduced treatment-related immune-mediated adverse effects. Endocannabinoid levels before immunotherapy did not differ between groups; four eCB compounds were associated with overall survival time. Finding: concomitant cannabis use during immunotherapy associated with increased clinical risk.

Chronic cannabinoid users showed significantly higher postoperative pain scores and increased morphine consumption, but had no increased complication rate.

Prospective cohort study in n=64 patients (24 chronic cannabinoid users, 40 non-users) after abdominal cancer surgery. Chronic users with detectable cannabinoid levels showed significantly higher pain scores and increased morphine-equivalent consumption (8h postoperative: 28,8 vs. 9,8 MME, p=0,036; total hospitalization: 273 vs. 202,1 MME, p=0,046; prescribed: 150 vs. 100 MME, p=0,047; taken by day 30: 67,5 vs. 5 MME, p=0,03). Chronic users had fewer overall complications (22% vs. 51%, p=0,025), but similar rate of severe complications (8,7% vs. 9,8%, p=0,33).

23% of respondents currently use cannabis mainly for medical purposes for symptom control (pain, insomnia, nausea, anxiety); this is a descriptive prevalence study without intervention comparison or effectiveness measurement.

Cross-sectional survey among n=821 cancer patients in British Columbia (response rate 27,4%); 23% currently use cannabis products (mostly medically), 28% were former users (mostly recreational). Symptom targets among current users: pain, insomnia, nausea, anxiety; many also hoped for additional anticancerogenic effects. Only 31% of current users had medical authorisation.

Cannabis-exposed patients showed significantly lower rates of CIPN grade 2-3 (15,3% vs. 27,9%, p<0,001), with a stronger protective effect with prior cannabis exposure.

Retrospective analysis of n=513 patients with oxaliplatin-based chemotherapy (2015-2018); cannabis-exposed patients (n=248) vs. controls (n=265). CIPN grade 2-3 significantly less frequent with cannabis exposure (15.3% vs. 27.9%, p<0.001). Protective effect stronger with cannabis-before-oxaliplatin (cannabis-first, n=116) vs. oxaliplatin-first (n=132): 75% vs. 46.2% protection (p<0.001). Median cumulative oxaliplatin dose higher with cannabis-first (545 mg/m² vs. 340 mg/m² vs. 425 mg/m², p<0.001).

MMJ use improved symptom scores and stabilized opioid consumption, while non-users showed a significant increase in opioid consumption.

n=232 oncological patients (95 MMJ−, 137 MMJ+); MMJ(+) stabilized opioid consumption (45→45 mg/day MME, p=0,522) while MMJ(−) increased by 23% (97,5→120 mg/day MME, p=0,004); only MMJ(+) significantly improved emotional ESAS score; MMJ recommended as adjuvant palliative therapy for cancer-related pain.

Cannabis use had no significant main effect on pain, but reduced the race-related pain disparity between African American and white cancer patients.

Observational study (n=136 cancer patients, 49 African Americans/87 whites) on cannabis use and pain relief (BPI "least pain"): no significant main effect of cannabis (p=0.28); however significant moderation effect — racial pain disparity (African American vs. white: difference 1.63±0.5, p=0.001) was no longer significant under cannabis use (difference 0.59±0.59, p=0.32). Indication of a possible role of cannabis in cancer pain and reduction of health disparities.

Study documents frequency of patient inquiries about cannabis-based products (84% of physicians reported this) and knowledge gaps among oncologists; this is a descriptive observational study without measurement of an intervention effect.

Cross-sectional survey among n=45 physicians (response rate 85%) in 4 New Zealand oncology departments, November 2019–January 2020. 37/44 (84%, 95% CI: 70–93%) reported patient inquiries about cannabis products; 43/44 (98%, 95% CI: 88–100%) reported patient use of illegal cannabis for medical symptoms. Reasons for inquiries: pain, nausea/vomiting, cancer treatment. 36/44 (82%, 95% CI: 67–92%) expressed concerns about future prescribing, all were willing to use products with traditional medical provenance.

Cannabis was used by 42% of breast cancer patients for symptom control, predominantly during active treatment and without physician consultation.

Online survey (n=612 US breast cancer patients): 42% (n=257) used cannabis for symptom control. Most common indications: pain (78%), insomnia (70%), anxiety (57%), nausea (46%). Among users: 81% reported improvement in pain, 77.3% increased appetite, 73% reduced anxiety; 54.5% improved treatment tolerance. Limitation: self-report without control group; 79% used cannabis during active treatment.

MC users predominantly reported symptom improvement in pain, appetite and anxiety; the most frequent side effect reported was cloudy thinking.

Survey (n=188 cancer patients, oncology practice Michigan); MC use 24,5% (n=46). Symptom improvement among users: pain 81% (34/42), appetite 77,3% (34/44), anxiety 73% (32/44); improved treatment tolerance 54,5% (24/44). Baseline symptom score significantly higher in MC users vs. non-users (17,5 vs. 14,4, p<0.001). Adverse effects: impaired thinking 16,7%, lack of energy 9,8%.

After discontinuation of cannabidiol, the methadone serum level decreased from 271 to 125 ng/mL, which correlated with improvement of somnolence and fatigue.

Single case report of a 13-year-old patient with metastatic cancer and chronic pain; CBD-methadone interaction led to an increased methadone serum level (271 ng/mL, reduction to 125 ng/mL after CBD discontinuation) with sedation/fatigue. Mechanism: CBD inhibits CYP3A4/CYP2C19.

Cannabis shows reasonable evidence for nausea/vomiting, loss of appetite and pain as a supplement; promising but limited evidence for chemotherapy-induced peripheral neuropathy, gastrointestinal complaints and sleep disorders; sparse evidence for cognitive impairment, anxiety, depression and fatigue.

Narrative review on cannabis in supportive cancer therapy; qualitative review of data ranging from preclinical to clinical across multiple indications (cancer, HIV, MS, PTSD among others). Conclusions: adequate evidence for cannabis as a supplement for nausea/vomiting, loss of appetite and pain; promising but limited evidence for CIPN, GI complaints, sleep disorders. Side effects documented, mostly mild. No systematic data extraction or meta-analysis.

Limited evidence for efficacy in cancer pain and gastrointestinal symptoms; mixed results for insomnia and mood disorders; side effects documented.

Narrative review on medical cannabis products in palliative care for cancer; summarizing discussion on symptom management (pain, nausea, appetite, sleep), no systematic meta-analysis, primarily mechanistic and best-practice perspective.