Cannabis for nausea and chemotherapy: Nabilon and Dronabinol
Chemotherapy-induced nausea and vomiting (CINV) are among the most burdensome side effects of cancer treatment. Cannabinoids are the oldest pharmacologically developed antiemetics with approved preparations — and yet they are still underutilized in practice. What Dronabinol and Nabilone achieve and when they are indicated.
CINV: The Problem
Chemotherapy-associated nausea is more complex than a simple stomach reaction:
- Acute CINV: Within hours after the infusion. Due to the direct emetogenic effect of the chemotherapy drug on the intestinal mucosa and the chemoreceptor trigger zone in the brainstem
- Delayed CINV: 24 hours to 5 days after chemotherapy. Substance P/NK1 receptor-mediated, harder to control
- Anticipatory CINV: Conditioned nausea before the actual chemotherapy — smells, places, people trigger nausea. Psychologically conditioned, difficult to treat pharmacologically
- Refractory CINV: Nausea that does not respond to standard antiemetics — often the point at which cannabinoids come into play
Approved Cannabinoid Preparations as Antiemetics
Two synthetic cannabinoids have official approvals:
- Dronabinol (Marinol, Syndros): Synthetic Delta-9-THC. FDA approval in 1985 for CINV in patients who do not respond to conventional antiemetics. Second approval: anorexia/cachexia in HIV patients. In Germany: available as a prescription medication, not as a finished product directly
- Nabilone (Cesamet): Synthetic THC analog. Approved in Germany in 2010 for severe CINV that does not respond sufficiently to conventional antiemetics. Reimbursement by the statutory health insurance is possible in case of failure of other antiemetics
- Nabiximols (Sativex): Not approved for CINV, but may be used off-label in combination with a pain component
Mechanism of Action: How Cannabinoids Reduce Nausea
The antiemetic effect occurs through several pathways simultaneously:
- CB1 in the dorsal vagal complex: CB1 activation inhibits emesis trigger signals in the chemoreceptor trigger zone (CTZ) and the nucleus tractus solitarius
- CB1 in the gastrointestinal tract: THC reduces gastrointestinal motility and secretion — direct antiemetic effect at the gastric level
- 5-HT3 modulation: THC inhibits serotonin-3 receptors (5-HT3) — the same mechanism as Ondansetron (standard antiemetic). Combination of both can have a synergistic effect
- Anandamide mediation: Endocannabinoids in the brainstem modulate nausea and vomiting naturally — THC enhances this endogenous mechanism
- Anticipatory CINV: Cannabinoids reduce anxiety and conditioned responses through amygdala suppression — particularly relevant for the psychogenic component of nausea
Evidence: What studies show
- Meta-analysis Whiting 2015 (JAMA): 3 RCTs on cannabinoids vs. conventional antiemetics — moderate evidence for superiority of cannabinoids in refractory CINV. However, higher rate of psychiatric side effects
- Nabilone vs. Prochlorperazine: Several older studies show Nabilone as comparable or superior to older generations of antiemetics
- Combination with 5-HT3 antagonists: Combination of cannabinoids + ondansetron showed additive antiemetic effects in small studies for severe CINV
- Limitations: Most studies are older (1980s–1990s), compared to outdated antiemetics. There is little comparative data against modern triple therapy (5-HT3 + NK1 + dexamethasone)
In practice: When to use cannabinoids for CINV
- First-Line Standard: Modern antiemetic protocols (5-HT3 antagonists + NK1 antagonists + dexamethasone) are first-line — not cannabis
- Second-Line: Nabilone or dronabinol for refractory CINV after failure of standard protocols
- Anticipatory CINV: Cannabis may be used as an approach — the psychological component and anxiety reduction via CB1 complement standard treatment
- Combination: Cannabis + standard antiemetics can be used simultaneously and is meaningful — additive effect, no known dangerous interactions
- Contraindications: Severe cardiovascular pre-existing conditions, history of psychotic disorders, pregnancy (nausea in the first trimester: no cannabis)
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