Sleep Pharmacotherapy, Melatonin, and the Link to Substance Use Disorders

As previously established, the role of sleep health in most psychiatric conditions is both affected and affecting—creating a cyclical burden of worsening symptoms for patients with mental illnesses including post-traumatic stress disorder (PTSD).

Finding adequate interventions for sleep, though, may increase the likelihood of adequately treating the mental illness.

In the second segment of an interview with HCPLive during the American Psychiatric Association (APA) 2022 Annual Meeting last week, Gina Poe, PhD, the Eleanor Leslie Chair for Innovative Brain Research at UCLA, discussed potential sleep pharmacotherapy agents and their ongoing research.

Most prominently, Poe discussed the beta blocker propranolol, that blocks the neurotransmitter receptor of the locus coeruleus—theoretically reducing the overactivity that hinders a patients’ progression to rapid eye movement (REM) sleep and therefore their capability to recover from mental illnesses.

“I think you need to give in combination with melatonin because it actually prevents sleep onset,” Poe explained. “But if you can get people to sleep with the beta blocker onboard, then our preliminary studies show you can get an adaptive sleep again.”

Poe highlighted that, in 8 currently available human clinical trials, propranolol has worked in approximately half to benefit patients with PTSD; she believes the inconsistency is due to investigators not taking into account its impact on patient sleep. In the coming year, her laboratory is looking into propranolol and other agents for the mitigation of overactivity in the locus coeruleus.

She and colleagues will additionally investigate melatonin as a supplement treatment for substance use disorder; however she stressed an understanding from consumers who may come to rely on the popular marketed sleep aide therapy.

“When you buy it over the counter, you don’t know what you’re actually getting,” Poe said. “There might be in some people a placebo effect—but placebo effects are actually strong. Theres a lot of top-down control—if you think you’re getting treated, you begin to feel better.”

Additionally, Poe review the neurobiologic relationship of sleep and substance disorder, highlighted the dynamic impact of addiction on the function of the hypothalamus and locus coerulus—affecting the capability and health benefits of sleep.

“We think that it’s a multifaceted whammy that really perpetuates the drug-seeking behaviors, doesn’t allow us to learn how to do anything differently, doesn’t allow us to feel good and doesn’t allow us to sleep to learn those things,” Poe said. “It’s all wrapped up together in a tangled mess.”

Future clinical research should consider the associations as a target for intervention.

“We don’t know yet if treating sleep can help with treating opioid abuse or any other drug use,” Poe said. “Nobody has tried it, and it would be really interesting.”