What was measured in the mice
The measurement ran like this: half of a group of mice carrying abdominal tumours received two doses of psilocybin a week apart, and the other half received saline. All of them then received cisplatin daily for one week. In a touch test with a thin plastic filament, the mice given psilocybin responded much as tumour-bearing mice that received neither cisplatin nor psilocybin did, while those given cisplatin without psilocybin were far more sensitive to the filament. The same protection appeared in human neurons exposed to cisplatin in the laboratory. The paper's abstract reports that the protection held across platinum- and taxane-based models, including repeated chemotherapy cycles, without impairing antitumor efficacy; for a clinician the second point matters as much as the first, because an agent that prevents pain while weakening the treatment is of no use.[1]
The weight those two results can carry stays at the preclinical level. The evidence comes from an animal model and from human cells treated in a dish; neither carries a numbness, tingling or pain score measured in a patient receiving chemotherapy. The mechanism the team describes is credible: once psilocybin is processed into its active ingredient psilocin, it activates the 5HT2A receptor and keeps up the mitochondrial transport that chemotherapy disrupts, so the nerve endings do not wear out. An alternative reading is also available: nerve metabolism differs between species, so the same transport effect could come out at a different size in patients, and the protection measured in a dish would then not appear to the same degree in people.[1]
The figure that is missing
The size of the problem is clear. Chemotherapy-induced peripheral neuropathy affects about 75 per cent of patients who undergo the treatment to some degree, and it can leave lasting numbness, tingling or pain in the hands and feet. Duloxetine, the drug now available, gives only moderate pain relief and does not prevent the damage; no drug had been shown to prevent it. Maria Maiaru at the University of Reading says that if the findings are replicated in clinical trials, patients could avoid the sensory problems and pain that persist after treatment, and that if nerve damage is prevented, fewer patients may need dose reductions or interruptions of chemotherapy.[1]
This is the second time in one week that the same gap turns up. On 2 September I wrote that semaglutide moved the median lifespan from 742 to 834 days in female C57BL/6 mice, and said the human side held no endpoint followed over time. The shape I see in the psilocybin result is the same: a clear difference measured in an animal model, and an endpoint on the human side that has not yet been measured. What the two share is that no measurement has been made to show at what size the mechanism producing the difference comes out in people.[1], [2]
The trial that will answer it
The team plans to open a randomised controlled trial in November: about 80 people with breast, colorectal or head and neck cancer, given two doses of psilocybin before chemotherapy. Results may not arrive for about five years. Each dose given to the mice was equivalent to 25 milligrams in a person; what the clinical trial will measure is whether the same mechanism changes numbness and pain scores in patients. An arm of about 80 people might be too small to separate that; what decides it is the trial's prespecified endpoint and the size of the effect.[1]
The one practical piece of advice in the meantime also comes from the team. Moran Amit says patients should not take psilocybin at home for chemotherapy-related pain, that it has not been shown to be safe or effective in patients undergoing chemotherapy, and that it can interact dangerously with cancer medications. That is often the first thing a preclinical result asks of a patient: wait.[1]