As a pain management physician, Dr. J. Fred Stoner has seen the rise of the opioid epidemic over the past decade with both synthetic and semi-synthetic opioids. Throughout the 90s, pharmaceutical companies assured physicians that the drugs did not exhibit dependence properties and were safe for patients to use long-term. Unfortunately, it was found that these drugs in fact caused high levels of addiction in its users, and patients that were being managed for pain initially would end up with drug seeking habits, many times in the form of heroin. As the epidemic continues, scientists and physicians alike work together to find new methods of treating chronic pain in patients that are both effective, and non-addictive.
Salvinorin A is the main component of the psychoactive plant Salvia divinorum, originating from the Oaxaca region of Mexico, and is also known as sage of the diviners, seer’s sage, or simply as salvia. The name of the plant comes from the Latin word salvia, meaning sage, and divinorum being derived from its historical use in divination. The plant was first officially recorded in 1939, however the Mexican Mazatecs have had a long history of using the plant for both its hallucinogenic effects in divination, as well as in pain control. Dr. J. Fred Stoner explains that the plants hallucinogenic effects are well documented, and because of this it is illegal in many states.
Mechanism of Action
Salvinorin A is an interesting component, as unlike other psychoactive drugs, it does not target the dopamine and serotonin receptors in the brain, but rather targets an opioid receptor like opioid drugs. However, the subtype of receptor differs, as Salvinorin A works on the kappa-opioid receptor. This subtle difference makes a huge difference when looking at abuse potential, as it is known that traditional opioid drugs such as morphine, fentanyl, and heroin act on the mu-opioid receptor, which is responsible for the activation of the reward centers of our brain causing feelings of euphoria and helping to lead to addiction. On the other hand, the kappa-opioid receptor is known to cause the opposite, many times causing distress and aversion. As a molecule acting on an opioid receptor in general however, Salvinorin A has been found to help significantly in reducing levels of pain.
Unfortunately, as good as salvia may sound as a potential drug for pain relief, there are a few disadvantages that work against it being used in the patient population as compared to other pain relief medications. One of the biggest issues with the drug is its hallucinogenic effects, many times causing adverse effects such as depression. Dr. J. Fred Stoner recalls the 2006 Delaware case, where a teenager consumed salvia and later committed suicide, with his parents citing salvia use as the sole cause of his suicide. This brought upon what is called Brett’s Law, making the use of salvia illegal in that state. Another huge disadvantage is the short half-life of the drug; if smoked, effects can last just a few minutes, and even if taken orally, last up to about an hour. For patients with chronic pain, this makes the drug cumbersome to use, as dosing would be needed frequently.
With the knowledge of how the plant elicits its analgesic properties, scientists have come out with a myriad of synthetic analogs to come up with the perfect balance of pain control with minimal side effect profile. Analogs have been made to act on the kappa-opioid receptor that are peripherally selective and do not cross the blood-brain-barrier, to allow for both significant pain control while decreasing the centrally acting hallucinogenic effects. Going forward, Dr. J. Fred Stoner believes that Salvinorin A and many synthetic analogs will play an integral role in pain management.
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