A Comprehensive Review Found THC and Synthetic Cannabinoids Outperformed Placebo for Chemotherapy Nausea | Research

The takeaway

A 1983 review concluded that THC was superior to both placebo and prochlorperazine for chemotherapy-induced nausea, with effectiveness linked to the psychological "high," while synthetic cannabinoids nabilone and levonantradol offered additional options.

Read this if you want a comprehensive picture of the evidence for cannabinoid antiemetics as it stood in the early 1980s.

THC was superior to both placebo and prochlorperazine in controlled trials

What the researchers found

This review synthesized the growing body of evidence on cannabinoid antiemetics. THC, isolated in 1964 and first used for chemotherapy nausea in the 1970s, had accumulated enough clinical trial data for meaningful assessment.

In controlled trials, THC was superior to both placebo and prochlorperazine (a standard antiemetic). A notable finding was that antiemetic effectiveness correlated with the subjective "high" experienced by patients. THC worked across multiple chemotherapy regimens, including high-dose methotrexate and the doxorubicin-cyclophosphamide-fluorouracil combination, though cisplatin-based regimens were more resistant.

Two synthetic alternatives showed promise: nabilone, which was more active than prochlorperazine even against cisplatin regimens, and levonantradol, which could be given intramuscularly as well as orally, offering flexibility for outpatient use. Side effects for all three cannabinoids were generally well tolerated but could be dose-limiting, particularly dysphoria in elderly patients.

Why it matters

This review consolidated the evidence that moved cannabinoid antiemetics from experimental curiosity to clinical reality. The finding that effectiveness correlated with the "high" raised important mechanistic questions about whether the antiemetic and psychoactive effects could be separated.

The numbers in context

THC isolated in 1964, first used for nausea in the 1970s. THC superior to placebo and prochlorperazine. Nabilone more active than prochlorperazine including against cisplatin. Marijuana used medicinally for over 2 centuries.

How the study worked

Narrative review of controlled clinical trials evaluating THC, nabilone, and levonantradol as antiemetics for cancer chemotherapy. Covered mechanisms of action, efficacy data, and side effect profiles.

What this study cannot tell us

Narrative review format means no systematic quality assessment of included studies. The correlation between "high" and efficacy could reflect unblinding rather than a true mechanistic link.

How to read the evidence

A narrative review synthesizing multiple controlled trials. Provides good evidence synthesis but without systematic methodology.

When this study was published

Published in 1983. Modern antiemetic regimens and cannabinoid formulations have evolved substantially.

The bigger picture

This review appeared two years before dronabinol's FDA approval and captured the state of evidence that supported that approval. The question it raised, whether the "high" is inseparable from the antiemetic effect, remains relevant to efforts to develop non-psychoactive cannabinoid medicines.

Questions still open

Can the antiemetic effect be separated from the psychoactive high? Why are cisplatin regimens more resistant to cannabinoid antiemetics? Would combining cannabinoids with other antiemetics produce synergistic effects?

Common questions

Did THC work against all types of chemotherapy nausea?

It worked across many regimens, but cisplatin-based chemotherapy was more resistant to THC. The synthetic cannabinoid nabilone showed better activity against cisplatin regimens.

Is the "high" necessary for the antiemetic effect?

This review found effectiveness correlated with the high, but could not determine whether they are mechanistically linked or just co-occurring effects of the same dose.

Read the original research

Review of cannabinoids and their antiemetic effectiveness.

Drugs, 25 Suppl 1, 52-62

View on PubMed ↗

Citation

Vincent, B J; McQuiston, D J; Einhorn, L H; Nagy, C M; Brames, M J. (1983). Review of cannabinoids and their antiemetic effectiveness.. Drugs, 25 Suppl 1, 52-62.