The presence of three approved medications apiece for alcohol and opioid dependence hardly qualifies as an abundance of patient options, compared with other disease categories. But that makes up a thriving market when placed against the complete lack of medication treatments for cocaine and other stimulant addiction. Researchers and a specialty pharmaceutical company have taken a longstanding theory about addiction and have used it to develop a novel approach to its treatment with medication, in the hope of creating the breakthrough drug for patients with cocaine dependence.
That journey already has been lengthy, and best-case estimates place the product before the Food and Drug Administration (FDA) no sooner than 2023. But a sustained excitement over this work stems partly from the notion that if this research can prove to maximize the link between stress and addiction, the resulting product could apply to a whole range of addictions—substance or otherwise.
“This may even work for other addictions that I'm not even thinking about yet,” Nicholas E. Goeders, PhD, chair of the Department of Pharmacology, Toxicology and Neuroscience at the Louisiana State University Health Sciences Center in Shreveport, tells Addiction Professional.
Early history of discovery
The “this” in Goeders' comment currently goes by the name EMB-001, but is actually a combination of two federally approved drugs: the benzodiazepine oxazepam and the cortisol synthesis inhibitor metyrapone. Goeders' work in this area draws in part from his own experience as a former smoker. He knew intuitively, as do his smoking brethren, that at a time of stress he would want to smoke a cigarette.
With cocaine known to affect benzodiazepine receptors in areas of the brain that are associated with reward, would it be possible to develop a drug that would affect the stress response activated by cues that influence drug seeking?
With a benzodiazepine alone not serving as a viable option for cocaine dependence treatment, given its potential for generating other harmful effects, the search began for a companion drug and landed on the cortisol synthesis inhibitor category. At doses that by themselves would produce no effect, a combination of oxazepam and metyrapone was found in a study published in 2008 to reduce cocaine self-administration in rats. That research attracted the interest of investors and the establishment of Boston-based pharmaceutical company Embera NeuroTherapeutics, Inc.
The ongoing research received a National Institute on Drug Abuse (NIDA) grant in 2010, and in 2015 the company filed an Investigational New Drug application to begin testing of EMB-001 in humans. In the most recent results, from a Phase 1B cocaine interaction study financed by another NIDA grant awarded last year, no serious adverse events or significant changes in blood pressure or heart rate were found from the drug when it was administered to 18 adults with cocaine use disorder.
That paved the way for Embera to prepare for Phase 2 research that should get under way in the second quarter of next year. Company officials envision the product as an immediate-release oral medication delivered twice daily, with possible dosing of up to 1,440 mg per day of metyrapone and 48 mg per day of oxazepam.
Potential long-term impact
The possibility of introducing the first approved medication for cocaine dependence carries huge importance, especially with growing evidence from current data in some parts of the country that stimulant addiction is quietly experiencing a resurgence in the shadow of the opioid crisis.
Moreover, the ongoing research and development around this product reflects a potential departure from an addiction medication development strategy that has looked either to drugs that mimic the action of the abused substance (agonists) or those that block the high (antagonists). An effective drug acting on stress response could conceivably apply to other substance addictions besides cocaine dependence, as well as process addictions such as pathological gambling.
“This is a novel approach, but it's not something new,” says Goeders. “If we can get it to the point that it helps someone, I can't tell you how rewarding that's going to be.”