The NEJM Study That Proved a Synthetic Cannabinoid Was Better Than Standard Anti-Nausea Drugs for Chemo Patients
Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy
Bottom Line
In a 113-patient double-blind crossover trial published in the New England Journal of Medicine, nabilone (a synthetic cannabinoid) was dramatically more effective than prochlorperazine (the standard anti-nausea drug) for chemotherapy-induced nausea — 80% response rate versus 32% — helping pave the way for FDA approval of cannabinoid antiemetics.
Why It Matters
This was among the earliest randomized controlled trials of any cannabinoid for any medical indication, published in the most prestigious medical journal in the world. Co-authored by Lawrence Einhorn — the oncologist who pioneered cisplatin-based chemotherapy for testicular cancer and is one of the most important figures in modern oncology. The study helped establish the evidence base that led to FDA approval of nabilone (Cesamet) and dronabinol (Marinol), which remain the only FDA-approved THC-based drugs besides Epidiolex. It also created the central paradox of American cannabis policy: the federal government classifies cannabis as Schedule I ("no accepted medical use") while simultaneously approving synthetic versions of its active ingredient.
The Backstory
In the 1970s, cancer chemotherapy had a problem that threatened to undermine the entire field. The drugs were working — cisplatin, in particular, was turning testicular cancer from a death sentence into a curable disease. But the nausea and vomiting were so catastrophic that patients sometimes refused further treatment. Up to 20% of patients receiving highly emetogenic drugs postponed or abandoned potentially curative therapy because they couldn't bear the side effects.
The anti-nausea drugs of the era — phenothiazines like prochlorperazine — were inadequate. Ten or more vomiting episodes on the first day of cisplatin was routine. Oncologists were watching their patients die from cancer because the treatment that could save them was too miserable to endure.
Into this crisis stepped a molecule that nobody in mainstream medicine was taking seriously as a drug: a synthetic version of THC.
The Trial
In 1979, Terence Herman and a team spanning the University of Arizona and Indiana University published a two-page paper in the New England Journal of Medicine — the most prestigious medical journal in the world. It was a double-blind, crossover trial comparing nabilone, a synthetic cannabinoid, against prochlorperazine, the standard antiemetic, in 113 cancer patients with severe chemotherapy-induced nausea and vomiting.
The crossover design meant each patient served as their own control: they received nabilone during one chemotherapy cycle and prochlorperazine during another, in random order, without knowing which was which. This eliminates nearly all the confounding variables that plague other trial designs.
80% vs 32%
Response rate to nabilone versus prochlorperazine in 113 cancer patients with severe chemotherapy-induced nausea and vomiting (p < 0.001). Both nausea severity and vomiting episodes were significantly lower with the synthetic cannabinoid.
This 2.5-fold advantage was not subtle. Nabilone didn't slightly edge out the standard drug — it demolished it. Eighty of every hundred patients responded, versus fewer than a third on the existing treatment.
Herman et al. (1979), N Engl J Med 300(23):1295-7
The result was unambiguous. Nabilone was dramatically superior. Patients preferred it. Both nausea and vomiting were significantly reduced. The p-value was less than 0.001 — as close to certainty as clinical trials get.
The Co-Author Who Changed Oncology
The second name on the paper is Lawrence H. Einhorn — and if you know oncology, that name stops you cold.
“Before 1974, if a man was diagnosed with disseminated testicular cancer, he was given a death sentence.”
— Lawrence Einhorn, MD
Indiana University School of Medicine
Einhorn developed the cisplatin-based chemotherapy regimen (BEP) that turned metastatic testicular cancer from 95% fatal to 95% curable — one of the greatest achievements in the history of cancer medicine
Einhorn had joined the Indiana University School of Medicine in 1973 as its first medical oncologist. In 1974, he introduced a cisplatin-based combination regimen for testicular cancer that would eventually cure upward of 95% of patients with the disease — including cyclist Lance Armstrong decades later. It remains one of the most important developments in the history of cancer treatment.
But cisplatin had a price. It caused devastating nausea and vomiting. Einhorn's patients were being cured of cancer and then refusing to finish their treatment because the vomiting was unbearable. When Terence Herman proposed testing a synthetic cannabinoid as an antiemetic, Einhorn was invested in the answer. His patients' lives depended on them staying on their chemotherapy.
The fact that Larry Einhorn co-authored this paper gave it a weight that no cannabis researcher could have achieved alone. This wasn't a marijuana advocate making claims. This was the oncologist who invented modern testicular cancer treatment saying: this cannabinoid works better than what we have.
The Drug
Nabilone is a synthetic cannabinoid — a molecule designed in a laboratory to mimic THC's interaction with cannabinoid receptors, but with chemical modifications intended to optimize therapeutic effects. It was developed by Eli Lilly and Company. Unlike plant-derived THC, nabilone can be manufactured to pharmaceutical specifications: exact dose, consistent potency, predictable pharmacokinetics.
This matters because pharmaceutical standardization was the path through the FDA. Whole-plant cannabis — with its variable cannabinoid ratios, batch-to-batch inconsistency, and uncontrolled growing conditions — was and remains incompatible with the regulatory framework that governs drug approval. A synthetic cannabinoid, manufactured under GMP conditions and delivered in a capsule with a precise dose, is a drug in the way the FDA understands the word.
The Side Effects
The trial was honest about nabilone's drawbacks. Side effects were about twice as frequent and more severe compared to prochlorperazine:
- Somnolence — the most common complaint
- Dry mouth — characteristic of cannabinoid receptor activation
- Dizziness — expected with a CNS-active compound
More concerning: four patients (3%) had adverse events requiring medical attention. Three experienced hallucinations. One had significant hypotension.
These side effects were manageable and resolved, but they foreshadowed a persistent challenge with cannabinoid therapeutics: you can't fully separate the antiemetic effect from the psychoactive effects. Both work through CB1 receptors in the brain. The drug that stops the nausea also makes you dizzy and drowsy — and occasionally hallucinate.
This trade-off was acceptable in the context of severe chemotherapy nausea, where patients were vomiting ten or more times a day. It was less acceptable as a general antiemetic for milder situations. The side effect profile is one reason cannabinoid antiemetics eventually took a back seat to 5-HT3 antagonists like ondansetron (Zofran), which became available in the early 1990s and controlled nausea without psychoactive effects.
The FDA Paradox
Herman's trial was part of a wave of cannabinoid antiemetic studies in the late 1970s and early 1980s. The evidence accumulated rapidly, and in 1985, the FDA did two things:
It approved dronabinol (Marinol) — synthetic THC — for chemotherapy-induced nausea and vomiting. And it approved nabilone (Cesamet) for the same indication.
At the same time, cannabis — the plant from which THC was isolated — remained classified as Schedule I under the Controlled Substances Act: "a high potential for abuse and no currently accepted medical use."
The federal government was now simultaneously saying that THC has accepted medical use (in synthetic, pharmaceutical form) and that the plant containing THC has no accepted medical use. This contradiction has been a central argument in cannabis policy debates for four decades and has never been satisfactorily resolved.
The FDA's position was technically defensible: it approves specific pharmaceutical products, not plants. Marinol and Cesamet met the requirements for drug approval — controlled clinical trials, standardized dosing, consistent manufacturing. Cannabis did not. But the practical result — that a patient could legally take synthetic THC by prescription while being arrested for possessing the plant containing natural THC — struck many observers as absurd.
What This Study Built
The evidence from Herman's trial and others like it established chemotherapy-induced nausea and vomiting as the founding medical use for cannabinoid drugs. When the NASEM committee reviewed the evidence in 2017, they rated cannabinoids for chemotherapy nausea as "conclusive or substantial evidence" — the highest evidence grade in their framework, and one of only three indications to receive that rating.
Dronabinol and nabilone remain the only FDA-approved THC-based drugs besides Epidiolex (CBD for epilepsy). They are still prescribed for refractory chemotherapy nausea — cases where modern antiemetics are insufficient. They also carry the historical distinction of being the medical use that first forced the federal government to acknowledge that a cannabinoid compound had therapeutic value, even as it maintained that the plant from which that compound came had none.
Key Takeaways
Cite this study
Herman, T S; Einhorn, L H; Jones, S E; Nagy, C; Chester, A B; Dean, J C; Furnas, B; Williams, S D; Leigh, S A; Dorr, R T; Moon, T E. (1979). Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. New England Journal of Medicine, 300(23), 1295-1297. https://doi.org/10.1056/NEJM197906073002302