Psilocybin prevents chemotherapy nerve damage in mice

Researchers gave mice with abdominal tumours two doses of psilocybin, the psychedelic compound in magic mushrooms, before treating them with the chemotherapy drug cisplatin. Cisplatin commonly causes chemotherapy-induced peripheral neuropathy (CIPN), a condition that damages nerve endings in the hands and feet and can cause lasting numbness, tingling or pain. About 75% of cancer patients who undergo chemotherapy experience this side effect to some degree, and no drug had previously been shown to prevent it.

Mice that received psilocybin before cisplatin responded to a touch test with a thin plastic filament in the same way as mice that never received chemotherapy at all. Mice that received cisplatin without psilocybin were far more sensitive to the same touch, a sign of nerve damage. In further mouse experiments, protection held even after as many as six consecutive cycles of chemotherapy, though these results are so far limited to mice and have not been confirmed in people.

The researchers then tested the effect in human neurons grown in the lab, treating them with either psilocybin or a saline solution before exposing them to cisplatin. The psilocybin-treated human nerve cells withstood the toxic effects of the chemotherapy and kept functioning normally, echoing what was seen in the mice.

Chemotherapy drugs like cisplatin enter nerve cells and disrupt microtubules, structures that work like a railway system inside the cell. Nerve endings depend on this railway to receive mitochondria, which are the small structures that supply cells with energy, transported from the main body of the neuron near the spinal cord out to the skin. When cisplatin disrupts the railway, mitochondria stop arriving, so nerve endings run out of energy, wear out and retract, producing the tingling and numbness typical of neuropathy.

Once psilocybin is broken down in the body into its active form, psilocin, it activates a receptor called 5HT2A on nerve cells. That receptor was already known to be involved in psilocybin's psychological effects. The new finding is that activating this receptor also sends signals that stop chemotherapy from disrupting the mitochondria's transport along the microtubule railway, so nerve endings keep their energy supply and stay intact.

No existing treatment prevents CIPN. The standard approach, an antidepressant called duloxetine, only offers moderate pain relief after the damage has already occurred. If psilocybin's protective effect is confirmed in people, researchers say patients could avoid the long-lasting sensory problems and chronic pain that often persist even after cancer treatment succeeds.

There could also be a knock-on benefit for cancer treatment itself. Because CIPN sometimes forces doctors to reduce chemotherapy doses or pause treatment altogether, preventing the nerve damage in the first place could let patients complete more of their planned chemotherapy, which researchers say might improve cancer outcomes. Separately from this nerve-damage research, psilocybin has already been studied for relieving depression and anxiety in cancer patients; several systematic reviews and meta-analyses of small trials report reduced anxiety, improved quality of life, and better pain control following psilocybin-assisted therapy in patients with advanced cancer, though the number of participants across these studies remains modest.

The nerve-protection findings so far come only from mice and from human nerve cells grown in a laboratory dish, not from cancer patients receiving chemotherapy. Researchers caution that people with cancer should not take psilocybin on their own to try to prevent chemotherapy side effects, since it has not been shown to be safe or effective in patients undergoing chemotherapy and could interact dangerously with cancer medications.

A randomised controlled trial is planned to test the idea directly in people. It will involve about 80 patients with breast, colorectal or head and neck cancer, testing two doses of psilocybin before chemotherapy begins, with results expected in around five years. Researchers say they have anecdotal reports of chemotherapy patients enrolled in psilocybin trials for other reasons noticing improvement in nerve-related symptoms too, but this has not been formally tested.

On the psychological side, the existing evidence for psilocybin's benefits in cancer patients also carries hedges. Reviewers note that most supporting studies are small, single-arm, or open-label rather than large placebo-controlled trials, and one review found that while classic psychedelics improved anxiety, depression, spirituality and quality of life in patients with life-threatening illness, the small sample sizes limited how confidently the results could be generalised.