So far, we talked about FDA approved agents for insomnia and how well they work. Let's take a second to talk about over the counter agents because these are widely used by individuals who have insomnia. There have been a number of different studies, but many are of relatively poor quality. In a relatively recent study, we evaluated the effects of chamomile compared to placebo in individuals who have primary insomnia over the course of one month. In this particular study we had 30 individuals and we randomized them to either chamomile high grade extract, which they took daily or placebo. You can see the table indicates a variety of different subjects of sleep measures, including sleep latency, that is time to fall asleep. Wake after sleep onset, which is time awake in the middle of the night, the number of awakenings, ratings of sleep quality, score in the insomnia severity index, a validated measure of insomnia. And total score in the Pittsburgh sleep quality index, a validated measure of sleep disturbance. There are a bunch of numbers in the table but they essentially indicate that there was no significant difference on any of these outcomes between the chamomile group and Ppacebo group after four weeks of treatment. Suggesting that when studied under rigorous conditions there seems to be no evidence that chamomile for example has benefits for insomnia relative to placebo medication. So the results of our study found no benefit of chamomile relative to placebo but so many people use over the counter agents for insomnia, there's a great need for additional research looking at the effects of over the counter agents and regulates highly controlled studies. There are a variety of limitations to pharmacotherapy or medication treatments for insomnia. They're generally symptom-focused, they only help people fall asleep or stay asleep or some combination of those things, but they may or may not address the underlying pathophysiology or mechanism associated with the insomnia problem. As I mentioned, there have been few long-term studies on both the efficacy and the safety of using these medications over an extended period of time, with the exception of Lunesta. Tolerance and dependence is a concern for many individuals, and particularly concern maybe among those who have a substance use history. Many people do complain of tolerance at a given dose that the medication becomes less effective over time than it was when they first started it. Side effects can also be an issue for many individuals, although the newer medications have fewer of these side effects associated with them. But many people can still experience residual daytime sedation, and other somatic complaints such as headaches associated with these medications. Some can experience rebound insomnia, that is insomnia that's worse than baseline when they discontinue the medication. Some can experience cognitive or thinking and psychomotor waking impairment. And finally, among some individuals, particularly elderly individuals, there may be an increased fall risk associated with many of these sleep-related medications. So just to summarize this section on pharmacological or medication treatments for insomnia. The non-benzodiazepine, benzodiazepine receptor agonist such as Ambien, Lunesta, Sonata. Research suggest that they offer the best efficacy to safety ratio. With the exception of eszopiclone, there seems to be minimal evidence to date of long-term efficacy when used repeatedly over time, especially on a nightly basis. There are newer hypnotics and agents that are in development and these will focus on systems other than the GABA system, which has been historically the system most focused on to produce sleep effects. So newer agents might focus on orexin, there may be orexin antagonists that are focused on selective H1 antagonists, 5-HT2A antagonists, and CRH antagonists. And finally as I mentioned over the counter have not certainly require more rigorous evaluation given that they're widely used by many people in the population.