Medicine› Public Health, Environmental and Occupational Health› Malaria Research and Control

Cerebral malaria — CB2 cannabinoid receptor antagonist SR144528

Submitted 2026-10-22

Field: Medicine › Public Health, Environmental and Occupational HealthType: An approach that didn't workArea: cerebral malariaTarget: CB2 cannabinoid receptor antagonist SR144528Stage: preclinical

Hypothesis

Because genetic ablation of the CB2 receptor improved mouse survival in cerebral malaria, pharmacologically blocking CB2 with the antagonist SR144528 would attenuate the disease.

What failed

In P. berghei ANKA-infected C57BL/6 mice treated daily with SR144528 (confirmed CB2 binding, Ki 2.34 nM), 30% showed partial recovery of symptoms and survival rose by 20%, but the mice ultimately succumbed to hyperparasitemia and severe anemia.

Broken assumption

Pharmacological CB2 blockade reproduces the survival benefit that genetic CB2 ablation gives in cerebral malaria.

Why

The authors conclude that although part of the disease course may be modulated by blocking CB2, other elements drive the lethal outcome, so the hypothesis could not be fully validated in this model.

From the published paper: Escartín et al. Journal of Trial and Error, 2024. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

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Why it matched: failed the same way: Held in the model species, not beyond it

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.