Marijuana's uncanny ability to make us feel hungry has long intrigued the medical community. Currently, many states allow marijuana to be prescribed for its therapeutic benefits, especially for patients who have trouble drumming up an appetite.
The link between marijuana use and appetite has also informed us about potential ways to treat the growing obesity epidemic. And this particular use of marijuana may surprise you.
Cannabinoid receptors as an anti-obesity drug target
Because of the link between appetite and the cannabinoid receptor system, clinicians have been attempting to exploit it as a way to combat the growing obesity epidemic. The idea is simple enough: Create a drug that acts as an antagonist for the cannabinoid receptors in our brain, causing us to feel full instead of hungry.
While the concept is straightforward in theory, its application in the real world has proved difficult. In 2008, the French drugmaker Sanofi (NYSE:SNY) pulled its cannabinoid antagonist Acomplia in Europe after the drug was found to be associated with serious psychiatric effects, including a handful of suicides. The problem is that the cannabinoid receptor system also influences mood through cascading effects that are difficult to control. As a result, we've seen researchers move away from cannabinoid receptors as therapeutic targets in recent years, although hope remains that a second generation of drugs can target cannabinoid receptors outside the brain to avoid the unwanted emotional side effects.
Moving on to the serotonin receptor system
Because of these adverse effects associated with stimulating the cannabinoid receptor system, researchers have been looking into a highly similar biochemical pathway known as the serotonin receptor system. These receptors also tend to be G-Protein-coupled receptors and show a high distribution in the hypothalamus as well.
Arena Pharmaceuticals (NASDAQ:ARNA) successfully developed an obesity med using this system recently, gaining Food and Drug Administration approval for its 5-HT2C agonist lorcaserin in 2012. Like Acomplia, lorcaserin promotes weight loss by making a person feel full, causing the person to eat less. While clinical trials showed that lorcaserin is a moderately effective weight-loss pill, some researchers have nonetheless raised the specter of potential serious psychiatric effects in this drug as well. Although we haven't seen evidence of any major side effects with lorcaserin since the drug's commercial launch, its relatively slow uptake into the obesity market is perhaps at least partially explained by safety concerns stemming from obesity drugs past.
Doctors are hoping to one day have access to a safe and effective pharmacotherapy for chronic obesity. And despite promising insights from the cannabinoid receptor system, the sheer complexity of the human nervous and endocrine systems has blunted our best efforts so far.
Looking ahead, there is reason to believe that some pharma companies could reprise their efforts to develop an obesity med that targets the cannabinoid receptor system. Namely, recent work has shown that cannabinoid receptors are more widely distributed than previously thought, raising the potential to target them in tissues outside the central nervous system, hopefully lessening their influence on a person's mood. Besides the potential commercial implications, there are therapeutic reasons to go this route as well. Specifically, preclinical studies in rats have shown that a dual stimulation of the cannabinoid and serotonin pathways leads to a synergistic effect that appears to modify feeding behavior. In short, we could one day see lorcaserin used in conjunction with a next-generation cannabinoid receptor in the fight against obesity.
That being said, pharma companies haven't exactly been lining up to develop new cannabinoid receptor-based obesity meds. In 2008, Merck (NYSE:MRK) shuttered one of the last efforts by a large pharma following problematic psychiatric effects arising in its clinical candidate taranabant. Whether these recent insights into cannabinoid receptors and obesity will prove enough to entice a company to follow up remains to be seen. Understand, however, that the field hasn't been entirely abandoned and progress is being made on how to best exploit this system without altering a patient's mental state.
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