Opioids attach to receptors in the brain to quickly relieve pain.  They are effective, but highly addictive, and researchers are busy trying to find an effection solution to curtail the subsequent addiction problem.  According to the Centers for Disease Control and Prevention (CDC), in the United States in 2017, two-thirds of drug overdose deaths involved an opioid.  That same year, 47,000 people died due to opioid overdoses, and prescription opioids were involved in 36% of these deaths.  According to the National Institute on Drug Abuse, in 2017, 1.7 million people in the U.S. had “substance use disorders related to prescription opioid pain relievers.”This data underscores the need for a nonaddictive alternative to pain treatment.  One that is an effective replacement for addictive prescription opioid medications.  Dr. Daniel Kohane, Ph.D., recently led a study at Boston Children’s Hospital in Massachusetts and his research team believes that they might have found a viable solution.  However, their solution involves a lethal toxin derived from the ocean.  The scientists published their most recent findings in Nature Communications.

Photo by Lucas Vasques on Unsplash

Many sea creatures contain tetrodotoxin, a toxin that blocks sodium channels, preventing nerves from carrying impulses.  When consumed, tetrodotoxin can cause headaches, vomiting, and a tingling sensation in the tongue and lips.  If too much is ingested, it can lead to respiratory arrest and death.  In fact, tetrodotoxin is 1,200 times more toxic than cyanide, which, perhaps, makes it difficult to believe the drug is a viable alternative or any less deadly.However, Dr. Kohane said, “Tetrodotoxin and compounds like it are very potent local anesthetics.  Also, unlike conventional local anesthetics, they don’t cause seizures, cardiac arrhythmias, and tissue (nerve and muscle) injury.”  He previously demonstrated in an earlier study that tetrodotoxin produces anesthesia.  In small amounts, pain relief is significant, but in higher quantities, it is lethal.  In his studies, Dr. Kohane has attempted to limit tetrodotoxin’s toxicity while maintaining its analgesia.  If he can accomplish this, the drug has a fighting chance.In an earlier study, Kohane’s team combined tetrodotoxin within a lipid membrane. The study details, “On the surface of the membrane, they added molecules called sonosensitizers that are sensitive to sound.  Next, the researchers placed the tiny sacs under the skin of rats.  Using ultrasound, they triggered the toxin’s release in small doses, relieving pain, and minimizing toxicity.”In another study, Dr. Kohane and his team combined tetrodotoxin and capsaicin, both nerve blockers.  They found that the two increased each other’s nerve blocking properties and offered an effective solution to reduce pain.  The combination was more potent than either by itself.  In his most recent research, he and his team fused tetrodotoxin to a polymer backbone.“In this system, we gave an amount of tetrodotoxin intravenously that would be enough to kill a rat several times over if given in the unbound state, and the animals didn’t even seem to notice it,” he said.Kohane and fellow researchers Chao Zhao, Ph.D., and Andong Liu, Ph.D. trialed a range of polymers.  As Zhao explains, “We can modulate the polymer composition to control the release rate.”They also added a chemical that enhanced the permeability of nerve tissue.  Kohane explains, “With the enhancer, drug concentrations that are ineffective become effective, without increasing systemic toxicity.  Each bit of drug you put in packs the most punch possible.”“Polymer, toxin, and permeability enhancer mixed together and administered in a single injection near the sciatic nerve of rats blocked the nerve for three days with no apparent signs of tissue damage or toxicity,” Kohane said.  He and his colleagues will continue their trials in hopes that tetrodotoxin will one day soon be an effective solution to the crisis.

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How a lethal toxin might help in the opioid crisisOpioid alternative? Taming tetrodotoxin for precise painkilling