Nausea

Prospective randomized double-blind cross-over study in children (10 months to 17 years) undergoing emetogenic chemotherapy: the synthetic cannabinoid nabilone was compared with oral domperidone. 18 of 23 children completed the study; significantly less vomiting and nausea under nabilone, two thirds preferred nabilone. Nabilone was superior to domperidone. Most common side effects: somnolence and dizziness (one patient with hallucinations). Conclusion: Nabilone is an effective antiemetic in childhood chemotherapy. Small sample size.

Cannabinoids were more effective than standard antiemetics against chemotherapy-induced nausea and vomiting, but showed considerable side effects (dizziness, dysphoria, hallucinations, paranoia) and higher discontinuation rates.

Systematic review of k=30 RCTs (n=1.366) on cannabinoids in chemotherapy-induced nausea. Cannabinoids (nabilone, dronabinol, levonantradol oral/i.m.) vs. conventional antiemetics (prochlorperazine, metoclopramide, among others): RR=1.38 (95% CI 1.18-1.62, NNT=6) for complete control of nausea; RR=1.28 (1.08-1.51, NNT=8) for complete control of vomiting. Patient preference for cannabinoids: RR=2.39 (2.05-2.78, NNT=3). More frequent side effects: dizziness NNT=3, dysphoria NNT=8, hallucinations NNT=17, paranoia NNT=20, hypotension NNT=7. Discontinuation due to side effects: RR=4.67 (3.07-7.09, NNT=11).

Cannabinoids show advantages over placebo for nausea/vomiting (RR 2,9-5,7), but markedly increased adverse events (RR 6,9 for discontinuation); vs. prochlorperazine no difference in efficacy, but more side effects (dizziness, dysphoria, sedation).

Cochrane SR of k=23 RCTs (1975-1991) on cannabinoids for chemotherapy-induced nausea and vomiting. Cannabinoids (nabilone, dronabinol, levonantradol) vs. conventional antiemetics: RR=1.38 (95% CI 1.18-1.62, NNT=6) for complete control of nausea; RR=1.28 (1.08-1.51, NNT=8) for complete control of vomiting. Patients preferred cannabinoids for future cycles: RR=2.39 (2.05-2.78, NNT=3). More frequent side effects: dizziness RR=2.97 (NNT=3), euphoria NNT=7, hallucinations NNT=17, paranoia NNT=20.

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): cannabinoids vs. placebo showed significant superiority (OR=3.82, 95% CI 1.55–9.42), comparable efficacy to conventional antiemetics with a higher side effect rate.

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

Systematic review + meta-analysis (k=30 RCTs) on the antiemetic efficacy of cannabinoids in chemotherapy-induced nausea/vomiting (CINV). Dronabinol vs. neuroleptics: RR=0,67 (95% CI 0,47–0,96), NNT=3,4; patient preference for cannabinoids vs. other antiemetics: RR=0,33 (95% CI 0,24–0,44), NNT=1,8. Cannabinoids showed superior antiemetic efficacy, but more frequent and more intense side effects.

Strong evidence for chemotherapy-induced nausea/vomiting and increasing evidence for epilepsy; insufficient evidence for spasticity, neuropathic pain, PTSD and Tourette syndrome.

Systematic review on medical cannabinoids in children/adolescents; k=22 studies (5 RCTs, 5 retrospective, 5 case reports, 4 open-label, 2 surveys, 1 case series), n=795 participants. Strongest evidence for chemotherapy-induced nausea and vomiting (CINV); increasing evidence for epilepsy. Insufficient evidence for spasticity, neuropathic pain, PTSD, Tourette syndrome.

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.

Systematic review + meta-analysis of RCTs on oral cannabinoids for chemotherapy-induced nausea and vomiting (CINV); Mantel-Haenszel method, random-effects model. Oral cannabinoids were more effective than placebo or other antiemetics in the combined endpoint analysis (no vomiting + no nausea) (OR >1, 95% CI reported); for isolated nausea or vomiting no significant difference versus comparator treatments was found. More frequent side effects: dysphoria, euphoria, sedation.

Cannabinoids were more effective against chemotherapy-induced nausea and vomiting than placebo and slightly better than conventional antiemetics.

Systematic review on cannabinoids in chemotherapy-induced nausea and vomiting (CINV); vs. placebo: absence of vomiting in 3 RCTs (n=168), absence of nausea+vomiting in 3 RCTs (n=288); vs. conventional antiemetics: no nausea in 5 RCTs (n=258), no vomiting in 4 RCTs (n=209). Cannabinoids more effective than placebo and slightly superior to conventional antiemetics; pediatric data for nabilone/dronabinol as adjuvant antiemetics also reported.

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 across k=26 RCTs on cannabinoids as prophylaxis for chemotherapy-induced nausea and vomiting (CINV). Cannabinoids showed superior CINV control versus placebo (RR=2,65; 95% CI 1,70–4,12; I²=0%). No significant difference versus active comparators (predominantly outdated single-agent antiemetic regimens). THC:CBD showed superiority as add-on to modern antiemetic regimens in a recent phase II/III trial. Evidence for modern triple/quadruple antiemetic combinations remains limited.

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 + meta-analysis on cannabinoids for pediatric cancer symptom control (PROSPERO CRD42020187433); k=19 studies (7 RCTs, 8 retrospective, 2 open-label, 2 case reports), n=1927 participants. Main indication: chemotherapy-induced nausea/vomiting (11/19 [58%]). Most common side effects in controlled trials: somnolence, dizziness, dry mouth, discontinuation due to side effects; no serious cannabis-associated events. Evidence insufficient for pediatric dosing/safety/efficacy.

Two double-blind comparative studies examined delta-9-THC in children undergoing cancer chemotherapy against metoclopramide syrup and prochlorperazine tablets. THC was significantly more effective against nausea and vomiting, however not all patients achieved relief. In some children THC increased appetite. Side effects: significantly more frequent tiredness, in two cases a reported "high". Limitation: small, older studies without exact patient numbers in the abstract.

Randomized controlled trial (pilot + RCT) in cancer patients undergoing palliative single-dose radiotherapy to emetogenic regions. The cannabinoid levonantradol (0,5 and 0,75 mg) was compared with the standard antiemetic chlorpromazine. Both substances were well tolerated, but the frequency of vomiting was similar in all three groups, i.e. the cannabinoid showed no advantage over chlorpromazine. Small sample size, old design (1982), negative result.

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, double-blind crossover RCT; oral THC vs. prochlorperazine for chemotherapy-induced nausea/vomiting — comparable antiemetic efficacy in both groups; THC: reduced ability to concentrate (p<0,01), social interaction (p<0,05) and physical activity (p<0,05); patient preference for THC not diminished despite side effects.

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 evaluable), oral THC:CBD 2,5mg/2,5mg 3x daily (day −1 to +5) vs. placebo as an addition to guideline-directed antiemesis in moderately/highly emetogenic chemotherapy; complete response rate (no vomiting + no rescue medication, 0–120h) 24% vs. 8% (absolute difference +16%, 95% CI 4–28, p=0,01).

75% of patients reported that nabilone was more effective than prochlorperazine against nausea and vomiting; 46 of these 60 patients continued nabilone as their antiemetic of choice.

n=80 cancer patients undergoing cisplatin-containing chemotherapy; double-blind crossover RCT: 75 % (60/80) preferred nabilone over prochlorperazine for control of nausea and vomiting; 46 of the 60 responders chose nabilone permanently as their antiemetic of choice.

THC:CBD improved the complete response rate from 14% to 25% (RR 1,77, P=0,041) in refractory chemotherapy-induced nausea and vomiting, with similar improvements in absence of emesis and reduction of nausea, however with moderate to severe adverse events in 31% of participants.

n=72 (multicenter, randomized, double-blind, placebo-controlled, crossover RCT phase II; oral THC 2,5 mg/CBD 2,5 mg 3×/day): complete response (0–120 h after chemotherapy) increased from 14% (placebo) to 25% (THC:CBD); RR 1,77 (90% CI 1,12–2,79; p=0,041); 83% of participants preferred THC:CBD over placebo; 31% experienced moderate/severe cannabinoid-related adverse events (sedation, dizziness, disorientation).

Combination therapy (dronabinol + prochlorperazine) was significantly more effective at controlling chemotherapy-induced nausea and vomiting than either monotherapy alone.

Multicenter RCT (n not explicitly stated), double-blind, parallel; dronabinol 10 mg + prochlorperazine 10 mg vs. monotherapies. Nausea after chemotherapy: combination 29 % vs. dronabinol alone 47 % vs. prochlorperazine alone 60 %. Vomiting: 35 % (combination) vs. 55 % (dronabinol) vs. 41 % (prochlorperazine). Combination therapy significantly superior (p<0,05); median episode duration of both symptoms shorter under combination.

THC reduces nausea comparably to prochlorperazine, but is associated with more side effects (sedation), yet is preferred by patients.

n=139 cancer patients undergoing chemotherapy; double-blind crossover comparison THC vs. prochlorperazine (Compazine); nausea reduction was the main preference factor; ~2/3 of patients preferred THC. THC with more side effects (especially sedation); no significant age effect (<50 vs. ≥50 years) on preference or nausea reduction.

THC reduced nausea/vomiting versus placebo, but offered no advantage over prochlorperazine and was associated with considerably more CNS side effects.

n=116, chemo-induced nausea/vomiting in gastrointestinal carcinoma (5-FU + semustine), THC 15 mg 3x daily vs. prochlorperazine vs. placebo; THC superior vs. placebo for antiemesis, no advantage vs. prochlorperazine; CNS side effects significantly more frequent and severe with THC (older patient population, median age 61 years).

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 chemotherapy; levonantradol 0,5 mg vs. chlorpromazine 25 mg (active comparator); levonantradol 0,5 mg superior to chlorpromazine as an antiemetic; dysphoric reactions in 22% (0,5 mg) to 50% (higher doses). No sufficient protection against emesis with cisplatin-containing regimens.

Metoclopramide/dexamethasone was objectively superior, however carboplatin patients preferred nabilone/prochlorperazine due to better tolerability.

n=80 chemotherapy patients (cisplatin/cisplatin analogues), nabilone 2 mg + prochlorperazine 5 mg orally vs. metoclopramide i.v. + dexamethasone; complete control of nausea and vomiting: 19% (nabilone arm) vs. 32% (metoclopramide arm), overall emesis p=0.02 in favour of metoclopramide. Carboplatin subgroup: patient preference for nabilone (16 vs. 5, p=0.013). Nabilone was better tolerated and preferred in carboplatin regimens.

Dronabinol and ondansetron showed similar efficacy with higher response rates (47-58%) compared to placebo (20%), while combination therapy was not superior.

Double-blind, placebo-controlled RCT (n=61) on dronabinol vs. ondansetron vs. combination therapy for delayed chemotherapy-induced nausea and vomiting (CINV). Total Response: dronabinol 54%, ondansetron 58%, combination 47%, placebo 20%. Absence of nausea significantly higher under active treatment (dronabinol 71%, ondansetron 64%, combination 53%) vs. placebo 15% (p<0,05 for all vs. placebo). Dronabinol was equivalent to ondansetron; combination therapy showed no additional benefit.

THC showed a markedly superior antiemetic effect (40/55 patients without nausea) compared to prochlorperazine (8/55) and placebo (5/55), with statistical significance (P < 0,005).

Double-blind, randomized crossover study (n=55 cancer patients with chemo-induced nausea): THC suppressed nausea in 40/55 patients (73%), prochlorperazine in 8/55 (15%), placebo in 5/55 (9%). THC significantly superior to prochlorperazine (p<0,005).

Nabilone did not significantly reduce postoperative nausea and vomiting compared with metoclopramide.

n=53 evaluable patients after total abdominal hysterectomy; nabilone 2mg vs. metoclopramide 10mg preoperatively; nausea incidence 73% vs. 70%, vomiting 54% vs. 67% — no significant differences between groups.

THC and haloperidol were equally effective in controlling nausea and vomiting, but the side effects of THC were less well tolerated than those of haloperidol.

n=52 cancer patients under strongly emetogenic chemotherapy (cisplatin/nitrogen mustard/doxorubicin), THC vs. haloperidol (randomised, double-blind, crossover); both agents equally effective for nausea and vomiting: ~10% complete control of emesis, approx. one third <5 emesis episodes; patients who did not respond to one antiemetic had good control with the other in ~50% of cases. THC toxicity less well tolerated than haloperidol, though mostly no severe side effects.

Nabilone offers no efficacy advantage over metoclopramide, but causes more side effects.

n=40 patients with radiation-induced nausea/vomiting; nabilone vs. metoclopramide; no difference in efficacy (p not significant); ADR rate significantly higher with nabilone than with metoclopramide.

The combination of nabilone and dexamethasone was superior to nabilone alone in reducing vomiting episodes, with less hypotension and better patient preference (67% vs. 47%).

n=40 lung cancer patients under chemotherapy (crossover RCT); nabilone + dexamethasone (DXM) significantly superior to nabilone alone in reducing vomiting (p&lt;0.05); approx. 63% vs. 47% without side effects; two thirds of patients preferred the combination.

Nabilone significantly reduced the number of vomiting episodes compared to domperidone.

n=38 cancer patients under highly emetogenic chemotherapy (70% cisplatin); nabilone 1 mg every 8 hours vs. domperidone 20 mg; mean vomiting episodes cycle 1: nabilone 4,76 vs. domperidone 12,95 (p<0,02); cycles 1+2 combined: 4,53 vs. 10,81 (p<0,01); nabilone significantly superior.

THC reduced nausea and vomiting in 64% of patients (23/36) compared to 3% under prochlorperazine (1/36).

Randomised crossover study (n=36) in cancer patients with refractory chemotherapy-induced nausea: oral THC (15 mg/m²) reduced nausea and vomiting in 23/36 (64%) of patients vs. 1/36 (3%) under prochlorperazine. All patients reported transient sensory changes; dysphoria occurred in 17/36 cases. Recommended starting dose 5 mg/m².

Nabilone showed significantly better symptom scores for nausea, retching and vomiting as well as fewer vomiting episodes compared to prochlorperazine, without the need for additional parenteral antiemetics.

n=34 lung cancer patients, double-blind crossover study; nabilone (synthetic cannabinoid) vs. prochlorperazine during 3-day chemotherapy (CAE). Symptom scores for nausea, retching and vomiting significantly better under nabilone (p<0,05). Fewer patients vomited under nabilone (p=0,05); more patients preferred nabilone as antiemetic (p<0,005).

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): Oral THC showed an antiemetic effect in 14/20 course sequences versus 0/22 under placebo; at study completion 12/15 vs. 0/14 (p<0,001). No patient vomited during the subjective "high".

Nabilone reduced emesis episodes and nausea duration significantly better than alizapride during cisplatin chemotherapy.

n=20 testicular cancer patients (cisplatin, low-dose), nabilone 2×2 mg/day vs. alizapride 3×150 mg/day, crossover RCT; nabilone significantly superior: vomiting median 1,1 vs. 2,9 episodes (p<0,01), complete nausea control 65% vs. 30% (p<0,01), nausea duration 1,3 h vs. 5,1 h (p<0,01). More side effects with nabilone; dose reduction recommended.

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

n=20 cancer patients with refractory chemotherapy-induced emesis; levonantradol 0,5–2,0 mg i.m. vs. placebo; significant antiemetic effect for all doses versus placebo (p<0,01); no dose-response effect. Dose-limiting side effects: somnolence and hypotension; psychomimetic effects tolerable.

Dronabinol (alone or combined) showed significantly better efficacy against nausea and vomiting than prochlorperazine alone, but was associated with more CNS side effects.

n=19 (6+6+5 evaluable), double-blind multicenter RCT; dronabinol 10 mg vs. prochlorperazine 10 mg vs. combination in chemotherapy-induced nausea/vomiting; median duration and severity of nausea and vomiting episodes significantly lower in dronabinol groups vs. prochlorperazine alone; only 1/5 patients in the combination group vs. 3/6 each in the single-therapy groups suffered from nausea; side effects (sedation, dizziness) more frequent in dronabinol groups, but not significantly different.

Cannabis-based medicine showed a higher complete response rate against delayed chemotherapy-induced nausea and vomiting (71,4% vs. 22,2% with placebo) and was well tolerated.

Pilot RCT of cannabis-based medicine (THC+CBD oromucosal) vs. placebo for chemotherapy-induced nausea/vomiting (CINV) despite standard antiemetics; n=16 (7 CBM, 9 placebo). Complete response in 71,4% (CBM) vs. 22,2% (placebo), difference 49,2% (95% CI 1%–75%), primarily in the delayed phase. Only 1 discontinuation due to adverse effects (CBM group). Mean daily dose 4,8 sprays.

Both antiemetics provided good control of nausea/vomiting, with day-dependent differences, but no clear overall superiority of one regimen.

n=106 evaluable cancer patients (high-dose chemotherapy + autologous BMT); dronabinol 5 mg/m² as add-on to prochlorperazine or metoclopramide showed no significant additional benefit on the final day of treatment (no difference between dronabinol and placebo add-on arms, p>0.05); metoclopramide significantly better on day 1 (p<0.002), prochlorperazine significantly better on day 3 (p<0.002).

Intramuscular levonantradol achieved an antiemetic effect in 89 % of patients at low doses starting from 0,5 mg.

n=28 cancer patients refractory to conventional antiemetic therapy, intramuscular levonantradol (synthetic THC derivative) 0,5–1,5 mg; 25/28 (89%) complete or partial antiemetic response; dose-limiting dysphoria in 5 patients (16%) at 1,0–1,5 mg; most common side effects somnolence (48%) and dry mouth (32%).

Nabilone was significantly more effective antiemetically than prochlorperazine, but was associated with considerably more side effects.

Crossover RCT (n=24 lung cancer patients undergoing chemotherapy); nabilone 2 mg vs. prochlorperazine 15 mg orally; nabilone significantly superior in reducing episodes of vomiting (p<0.05); two thirds of patients preferred nabilone. Side effects (dizziness/coordination disturbances) in approx. 50% of patients on nabilone; 3 discontinuations due to CNS side effects.

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.; no statistically significant difference in antiemetic response between groups. More frequent side effects under levonantradol (somnolence, dry mouth, dizziness, tachycardia, orthostatic hypotension, visual disturbances) vs. prochlorperazine (somnolence, dry mouth, tachycardia). Negative study (n<60).

THC significantly reduces nausea and vomiting under high-dose methotrexate compared to placebo (p<0,001).

RCT n=15 osteosarcoma patients under high-dose methotrexate chemotherapy; oral/inhaled THC vs. placebo. 14/15 patients showed reduction of nausea and vomiting under THC vs. placebo (p<0,001). Plasma THC >10 ng/mL: only 6% nausea/vomiting incidence vs. 72% under placebo.

THC showed no significant antiemetic effect compared to placebo for Adriamycin/Cytoxan-induced emesis.

RCT (n=8 sarcoma patients, adjuvant Adriamycin/Cytoxan chemotherapy); oral and inhaled THC vs. placebo; no significant difference in vomiting episodes, emesis volume or nausea severity between THC and placebo (SPID 6h: placebo 7,9 vs. THC 4,3 cm·h on movement, 95% CI –1,8 to 9,0; p not significant). Negative RCT: antiemetic THC effect not demonstrable in Adriamycin/Cytoxan chemotherapy.

Double-blind, randomized cross-over study (n=32) compared oral nabilone with intravenous metoclopramide for the treatment of cisplatin-induced nausea and vomiting. No difference in overall incidence or severity of vomiting between the two treatments; a subgroup benefited more from metoclopramide. Side effects corresponded to the pharmacological profile of the substances. Limitation: small sample size, no superiority of nabilone.

Levonantradol produced a substantial antiemetic effect in 15 of 20 refractory patients.

n=20 cancer patients refractory to standard antiemetics; oral levonantradol (THC analogue): 15/20 patients (75%) experienced substantial nausea relief, 10/20 preferred the medication for further chemotherapy cycles.

Acute vomiting control under nabilone was insufficient at approx. 50%, side effects were frequent but of little clinical significance.

n=110 pediatric cancer patients (median 14 years); nabilone (cannabinoid) + 5-HT3 antagonist for acute CINV prophylaxis; complete acute vomiting control: 50,6% (42/83) with highly emetogenic, 53,8% (14/26) with moderately emetogenic chemotherapy; side effects in 34% (37/110), all CTCAE grade ≤2; sedation 20%, dizziness 10%, euphoria 3,6%; discontinuation due to adverse drug reactions in 10 patients.

Positive effects were reported in 80% of cases, but with isolated side effects, particularly among smokers.

Retrospective case series (n=50 children/adolescents with cancer, 2010–2017) on medical cannabis as supportive therapy; main indication nausea/vomiting; positive effect in 80% of cases (parent-/patient-reported); well tolerated, rarely toxicity (most common adverse effects: throat burning, anxiety attacks in smokers).

Delta-8-THC completely prevented chemotherapy-induced vomiting in all treated children.

n=8 children (3–13 years) with hematological cancers, Delta-8-THC (18 mg/m² p.o.) prophylactically 2h before each antineoplastic cycle, 480 treatment administrations over up to 8 months; vomiting completely prevented in 100% of treatments (480/480); side effects negligible.

Narrative review on the role of cannabinoids and the endocannabinoid system in the regulation of nausea and vomiting; no primary study results reported.

Narrative overview on the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. Discusses central CB1/CB2 mechanisms and therapeutic potential in chemotherapy-induced and other nausea. Qualitative synthesis without systematic data extraction.

Narrative review on dronabinol (synthetic delta-9-THC) in chemotherapy-induced nausea/vomiting (CINV), unresponsive to standard antiemetics. Evaluates evidence for dronabinol as monotherapy as well as in combination with ondansetron and prochlorperazine. Cannabinoids show lower efficacy and more side effects than serotonin/neurokinin antagonists, and belong among alternative CINV options.