About 30 years ago, cannabis researchers started catching up with what many people self-medicating already understood: compounds in cannabis can help some cancer patients cope with symptoms of treatment. THC-based medicines, for example, have been used to address chemotherapy-related nausea and loss of appetite, while medical cannabis has also been studied for cancer pain and reducing reliance on opioids. I was among the first journalists to report on this, interviewing greats like Raphael Mechoulam on his seminal work into cannabis chemistry.
Companies like Pharmos tried to take the mechanisms of chemistry from cannabis into pain medicine without the “high” but failed early on in the game; not because cannabis didn’t work; I can hazard it’s because they got the dosage wrong and the world wasn’t ready. Also all CBD treatments that focus on pain do need some amounts of THC to work effectively, cannabis research Alan Shackelford has told me.
Now researchers are looking at another psychoactive plant-derived drug for a very different reason. And it’s a recreational drug that still gets negative press. Are we ready for it? New research suggests that psilocybin, the psychedelic compound found in so-called magic mushrooms, could help prevent one of chemotherapy’s most debilitating side effects. The study was published in the journal Science.
Psilocybin may protect nerves during chemotherapy
Chemotherapy-induced peripheral neuropathy, or CIPN, can cause burning pain, pins and needles, numbness, cold sensitivity and loss of sensation in the hands and feet. For some cancer patients the nerve damage becomes so severe that doctors have to reduce chemotherapy doses or stop treatment altogether. Sometimes the effects can be permanent.
Researchers found that just two doses of psilocybin given to mice before chemotherapy prevented the animals from developing this neuropathy. Remarkably, the protection continued through repeated chemotherapy cycles and lasted for months.
The finding is particularly interesting when considered alongside decades of research into psychoactive compounds as medicine. Israel’s Raphael Mechoulam helped establish the modern science of medical marijuana, THC and CBD for chronic pain and cancer patients, while a newer generation of scientists is investigating psilocybin, MDMA and LSD-related compounds for their effects on the brain and nervous system.
Research into psychedelics has also explored their potential to change communication and connectivity between neurons. We have previously looked at how psychedelics including psilocybin and LSD may affect the brain, particularly in research related to depression, trauma and neural plasticity. The chemotherapy study, however, points to a different and surprisingly physical mechanism.
Keeping the nerve’s energy supply running
Nerve cells require a tremendous amount of energy. Tiny structures called mitochondria act as the cell’s power plants, and they have to be transported along nerve fibers to supply energy to distant nerve endings.
Chemotherapy can interfere with this mitochondrial transport system. When mitochondria stop moving properly along the nerve, the most distant nerve endings can become starved of energy and eventually become damaged or disappear.
Psilocybin appears to keep that energy-delivery system operating by preserving the movement of mitochondria along sensory nerves. In other words, the drug may do more than change how the brain perceives pain: it appears to help protect the physical nerve itself.
The researchers also found that psilocybin helped normalize activity in areas of the brain involved in processing pain.
Perhaps most intriguing for prospective treatments is that the psychedelic trip associated with magic mushrooms may not be necessary. The researchers traced the protective effect to activation of the serotonin 2A receptor, or 5-HT2A. They then tested a nonhallucinogenic compound that activates the same receptor and found that it produced similar protection.
That raises the possibility of developing a medicine that uses the nerve-protecting mechanism identified in psilocybin without making cancer patients undergo a psychedelic experience.
There is an important hitch: the work is still in preclinical stages: the strongest evidence comes from animal models, and psilocybin has not yet been proven to prevent chemotherapy-induced neuropathy in cancer patients. The researchers did, however, also study human peripheral nerves, human stem cell-derived sensory neurons and patient tissue, finding evidence that the same mitochondrial transport pathway exists in humans.
If those findings eventually translate into clinical trials and patients, psychedelics could offer something considerably more important than temporary pain relief. They could potentially help doctors prevent chemotherapy from permanently damaging sensory nerves in the first place.
