Chili Peppers, MJ, and Cone Snails: Recipes for a New Effective Painkiller
Due to the rising death rates and fatal overdoses, American pharmaceutical companies are actively searching for a medication that could serve as an effective and safe alternative to opioid-based painkillers. The presence of such an alternative on the market could allow the company holding its rights to capture a significant share of the $4 billion annual profit of the opioid painkiller industry. Additionally, the federal government has shown interest in finding alternatives, as it has been struggling for years to combat the illegal distribution of dangerous prescription drugs.
Among medical professionals, substances like morphine, oxycodone, and fentanyl are popular because of their rapid action: even a small dose of one of these analgesics is enough to completely block pain signals in the brain, quickly and effectively relieving patients of discomfort. This makes such drugs convenient to prescribe, as they address chronic pain at its root. However, since these substances achieve their effect by activating the brain’s pleasure centers, frequent use leads to deep physiological and psychological dependence.
“I remember back in medical school, my classmates and I had a joke ‘game’ where we’d assemble a ‘first aid kit’ of five drugs we’d want to have on a deserted island. Any doctor would agree that morphine has to be one of them, as it’s a universal and effective painkiller,” says Morgan Sheng, vice chairman of neuroscience and biochemistry at Genentech, part of Roche Holding.
New Approaches to Pain Relief
Since different types of pain are perceived through different biological mechanisms, scientists are studying a wide range of substances to find the most effective ones for specific symptoms. One of the most promising combinations in researchers’ eyes is extracts of MJ and chili peppers, both of which have notable pain-relieving effects. Scientists are also studying the human genome, searching for DNA mutations that make people less sensitive to pain. One group of researchers has even proposed a drug synthesized from the toxin of the cone snail.
Most developments are focused on treating pain caused by osteoarthritis, a common condition among older Americans that causes joint swelling. To address this, Centrexion Therapeutics Corp is developing an injection with synthetic capsaicin, the active ingredient in chili peppers. Limited trials of the prototype have shown impressive results: a single injection into the knee joint relieved pain and muscle swelling for up to six months in test subjects.
Randall Stevens, head of scientific development at Centrexion, explains that capsaicin can reduce the sensitivity of nerve endings at the injection site, thereby decreasing swelling and pain. “Essentially, the substance ‘trims’ overactive receptors,” he says. Over time, the deactivated nerve endings return to normal function. Unlike opioids, capsaicin only affects pain receptors and does not impact the patient’s sense of touch. According to company director Jeffrey Kindler, the new drug will allow patients to remain fully alert and aware while completely blocking pain signals.
Other Promising Painkillers
Another promising category of painkillers under development are nerve growth factor inhibitors. These substances completely block the perception of pain signals in muscles and skin. Doctors say these drugs suppress pain so effectively that some patients accidentally overexert their affected joints, forgetting about their condition. For this reason, the U.S. health authorities temporarily suspended trials to assess potential risks. Developers at Pfizer and Eli Lilly have identified an effective therapeutic dose, and the first drug in this category, called Tanezumab, was approved for prescription sale on June 13 of this year.
Genentech researchers have taken a different approach: their project is based on a rare genetic mutation that reduces natural pain sensitivity. By studying people with this mutation, scientists discovered a new receptor responsible for pain perception and intensity, called Nav 1.7. They are now working on a tablet that can effectively block this receptor.
The project is still in its early stages. Only one trial drug, GDC-0310, has passed the first phase of safety testing. According to Dr. Sheng, the new drug targeting Nav 1.7 is unlikely to have serious side effects, except for temporary loss of smell, which is typical for people with this mutation. He says the new substance will be especially effective for musculoskeletal pain, such as lower back pain. Another company, Amgen Inc., is also working on a drug that blocks Nav 1.7.
Other interesting experiments, conducted outside clinical settings, involve experimental drugs from Cara Therapeutics Inc. and Centrexion that interact with cannabinoid receptors, as well as work by scientists at Hunter College in New York, who are developing a painkiller from cone snail toxins.
Improving Existing Opioids
The search for new drugs does not mean that medicine will completely abandon the use of opium. Despite its dangers, it remains a fast and effective painkiller, widely used in therapy and surgery. Some companies are working to make existing formulas safer rather than inventing entirely new drugs. For example, Nektar Therapeutics is developing an opioid-based substance that is absorbed very slowly, significantly reducing the euphoria and, therefore, the risk of psychological and physical dependence. Naturally, such a drug would not be effective for acute pain due to its slow action. The company is developing it as a treatment for chronic back pain.
Meanwhile, Trevena Inc. is working on an opioid painkiller that does not suppress patients’ breathing, unlike many “classic” opioids. Company director Maxine Gowen says, “We all hope that soon we’ll enter an era where drugs won’t cause dependence. However, I want to point out that even in that future, there will still be a place for opioid painkillers, as no other category of substances has such a powerful and fast effect on the human body.”