Two doses of psilocybin protected mouse nerves through six rounds of cisplatin

A mouse study on psilocybin and chemotherapy-induced peripheral neuropathy was published Thursday, Sept. 3, in the journal Science.

The Science paper is titled "Psilocybin prevents chemotherapy-induced peripheral neuropathy through mitochondrial trafficking preservation" and was co-led by Moran Amit, professor of Head and Neck Surgery, and Patrick Dougherty, professor of Pain Medicine, at The University of Texas MD Anderson Cancer Center.

Two doses of psilocybin, given nine days and two days before the first chemotherapy session, completely prevented mice from developing hypersensitivity, and also reduced cold sensitivity and preserved nerve endings in the skin.

In experiments with human neurons, cisplatin depleted mitochondria and ATP from the wires extending from nerves; psilocybin did not restore the mitochondria's overall energy-producing capacity but preserved their ability to travel and maintained normal ATP production specifically within the nerve projections.

The researchers plan to begin a randomised controlled trial in November of about 80 people with breast, colorectal or head and neck cancer, testing two doses of psilocybin before chemotherapy, with results expected in about five years.

TBG, a compound designed to activate 5-HT2A without causing hallucinations, also protected mice from neuropathy, producing protection similar to psilocybin's.

Established nerve injury from CIPN is often irreversible, existing treatments offer limited benefit, and the authors state that no proven preventive strategy exists.

CIPN is usually treated with duloxetine, an antidepressant that provides moderate pain relief, and no drug had been shown to prevent CIPN, according to Amit at the briefing.

The effect depended on the serotonin receptor 5-HT2A, which is also responsible for many of psilocybin's psychedelic effects, and blocking the 5-HT2A pathway reversed the neuroprotective effects.

Amit said his team was not initially looking for a neuropathy treatment but investigating whether compounds that promote neuroplasticity might protect nerves; after testing several psychedelics they focused on psilocybin as the most effective for relieving neuropathy symptoms.

In severe cases CIPN can force doctors to reduce or stop chemotherapy, and it can contribute to mobility problems that raise the risk of falls and fractures.

Amit cautioned that psilocybin's psychedelic effects may also be playing a neuroprotective role that is not yet understood, so it is unclear whether that effect should be avoided in humans.

Amit compared the microtubules along which mitochondria are transported to a railroad system, noting that chemotherapy can damage both the mitochondria and the tracks they travel along.

Human donor sensory neurons and patient skin biopsies independently confirmed the serotonin 2A-mitochondrial findings.

An 80-person trial randomised evenly gives about 40 participants per arm.

Amit said people with cancer should not take psilocybin without medical supervision: "Please don't take psilocybin at home for chemotherapy-related pain. It hasn't been shown to be safe or effective in patients undergoing chemotherapy. It can interact dangerously with cancer medications."

Psilocybin is currently under investigation for neuropsychiatric and neurological disorders.

The team studied mice with abdominal tumours, half given two doses of psilocybin, each equivalent to a 25-milligram dose in people, by injection into the abdomen one week apart, while the rest had saline injections; all then received daily cisplatin injections for one week.

In pain-sensitivity tests using a thin plastic filament, mice that received psilocybin before cisplatin responded similarly to a third group of mice with cancer that received neither cisplatin nor psilocybin, while mice given cisplatin without psilocybin were much more sensitive to touch.

Maria Maiaru at the University of Reading, who was not involved in the research, said that if the findings can be replicated in clinical trials the implications could be substantial, and that if nerve damage can be prevented, fewer patients may need dose reductions or interruptions of chemotherapy.

CIPN affects roughly one-third to one-half of people receiving certain chemotherapies, according to Dr. Thomas Strouse, a professor of clinical psychiatry and neuropathy researcher at UCLA who was not involved in the study.

The study authors write that CIPN is a common complication of platinum-based chemotherapies such as cisplatin and can affect up to 60% of patients.

Patrick Dougherty said at a press briefing that CIPN affects about 75 per cent of cancer patients who undergo the treatment to some extent.

Amit said about two out of three patients will develop some sort of neuropathic pain requiring either dose adjustments or treatment breaks, which will negatively affect survival.

The lowest and highest incidence figures in the coverage, one-third of patients and 75 per cent, are 42 percentage points apart.