Psilocybin could prevent common and debilitating chemotherapy side effect

Psilocybin may prevent a debilitating side effect of chemotherapy: nerve damage that can cause lasting numbness, tingling or pain in the hands and feet. In tests in nerve samples from mice and humans, the psychedelic seemed to maintain the energy supply in nerve endings that is commonly disrupted by chemotherapy, resulting in less damage and fewer complications.

This is the first time a therapy has been shown to prevent this common side effect, which lacks effective treatments and can limit access to cancer drugs.

“If these findings can be replicated in clinical trials, the implications could be substantial,” says Maria Maiaru at the University of Reading in the UK, who wasn’t involved in the research. “Patients could avoid long-lasting sensory problems and chronic pain that often remain after cancer has been successfully treated.”

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What’s more, “if nerve damage can be prevented, fewer patients may need dose reductions or interruptions of chemotherapy, potentially improving cancer outcomes”, she says.

But people with cancer shouldn’t take psilocybin, the psychedelic compound in magic mushrooms, without medical supervision. “Please don’t take psilocybin at home for chemotherapy-related pain,” says team member Moran Amit at the University of Texas MD Anderson Cancer Center in Houston. “It hasn’t been shown to be safe or effective in patients undergoing chemotherapy. It can interact dangerously with cancer medications.”

Chemotherapy-induced peripheral neuropathy (CIPN) affects about 75 per cent of cancer patients who undergo the treatment to some extent, said Patrick Dougherty, also at the University of Texas MD Anderson Cancer Center, in a press briefing. It is usually treated with duloxetine, an antidepressant that provides moderate pain relief. But no drug had been shown to prevent CIPN, said Amit at the briefing.

CIPN occurs when chemotherapy drugs enter nerve cells and disrupt machinery around microtubules. These are railway-like structures that usually transport mitochondria from the main body of neurons, near the spinal cord, to nerve endings in the skin. The mitochondria supply energy to maintain nerve endings, but the disruption means they wear out and retract, causing issues like tingling.

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The researchers wondered whether psilocybin, which has been shown to alter nerve metabolism and growth, could preserve these nerve endings.

To find out, they studied a group of mice with abdominal tumours, half of which were given two doses of psilocybin – each equivalent to a 25-milligram dose in people – via injections into the abdomen, one week apart. The remaining mice had saline injections. All of them then received daily injections of cisplatin, a type of chemotherapy that commonly causes CIPN, for one week.

After receiving cisplatin, the mice underwent pain-sensitivity tests, where they were touched with a thin plastic filament to see how they responded. Those that received psilocybin before cisplatin responded similarly to a third group of mice with cancer that didn’t receive cisplatin or psilocybin. The mice that received cisplatin without psilocybin seemed to be much more sensitive to the filament’s touch.

To explore how psilocybin may be having this effect, the team analysed nerve samples from the mice. This showed that, after the psychedelic is processed to its active ingredient, psilocin, it activates a receptor called 5HT2A, confirming findings from prior studies. But it also revealed that this receptor sends molecular signals that prevent chemotherapy-related disruption of mitochondrial transport.

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Finally, the researchers confirmed the results in human neurons treated with either psilocybin or a saline solution before receiving cisplatin. “Psilocybin seemed to help nerves withstand the toxic effects of chemotherapy and maintain normal function,” says Maiaru.

They now plan to begin a randomised controlled trial in November. This will be made up of about 80 people with breast, colorectal or head and neck cancer, testing two doses of psilocybin before chemotherapy. Results are expected in about five years. 

Psilocybin has already been shown to relieve symptoms of depression and anxiety in people with cancer. Although not a psychedelic, cannabis is also approved to treat cancer-related chronic pain in the UK. The US Food and Drug Administration has also approved two drugs that are made up of chemicals similar to those in cannabis to relieve chemotherapy-related nausea and vomiting.

Science DOI: 10.1126/science.aec6116