How Opioids Disrupt Quality of Sleep | Dr. Gina Poe & Dr. Andrew Huberman
00:00:00.000 | I'd love for you to tell us about some of the work that you're doing more recently on
00:00:05.440 | the relationship between sleep and opiate use, withdrawal, relapse and craving, just
00:00:14.720 | addiction generally.
00:00:16.440 | I get a lot of questions about people trying to come off benzodiazepines or people's challenges
00:00:23.400 | with benzodiazepine and other types of addiction.
00:00:27.440 | What is the role of sleep in addiction and recovery from addiction and opiates in particular?
00:00:33.680 | This is a very young area.
00:00:35.800 | And in fact, my laboratory has just started.
00:00:37.840 | I have a graduate student who's been in my lab for just one year.
00:00:41.560 | She's done amazing work already, but completely groundbreaking work.
00:00:46.280 | And what she has discovered already, we don't have the paper out yet, but we're working
00:00:50.920 | on it, is that when animals withdraw from opiates, and this has been replicated in other
00:00:58.520 | ways with other types of things, our sleep is disturbed.
00:01:03.040 | Our sleep is terribly disturbed.
00:01:04.560 | And the amount of sleep disturbance predicts relapse behaviors.
00:01:09.360 | And you might think, well, of course, you're going to relapse if you can't sleep because
00:01:13.000 | opiates calm you down.
00:01:14.000 | Well, one of the reasons why opiates calm you down is because the locus aureolus, again,
00:01:18.120 | the blue spot, is covered with opiate receptors that are normally really responsive to our
00:01:23.920 | endogenous opiates.
00:01:26.440 | And so what happens when we are pleased, for example, or laughing, or whatever, our endogenous
00:01:32.640 | opiates activate those receptors in the locus aureolus and calm it down.
00:01:37.440 | And it actually suppresses locus aureolus activity, makes us happy and relaxed.
00:01:43.640 | One of the reasons why opiates are so addictive is because it also calms us down and makes
00:01:48.560 | us relaxed.
00:01:50.680 | But the problem with exogenous opiates is that they really strongly bind these receptors
00:01:57.100 | on our locus aureolus.
00:01:58.800 | And if you take exogenous opiates again and again, like you're recovering from surgery,
00:02:03.440 | for example, take these pain medications, is that our locus aureolus struggles to do
00:02:08.160 | what it's supposed to do, which is keep us awake and learning and concentrating on things.
00:02:13.000 | So it will down-regulate.
00:02:14.000 | It will internalize these receptors that are normally only occupied by endogenous opiates.
00:02:20.040 | And it will do this.
00:02:21.480 | It will change our genes that are associated with producing these receptors, so you actually
00:02:26.040 | have very many fewer receptors.
00:02:27.920 | So the locus aureolus, at least during wakefulness, can fire and help us to do these things, like
00:02:32.640 | learn about our environment.
00:02:34.920 | And so if you long-term reduce the number of receptors out there, then when you withdraw
00:02:40.080 | the exogenous opiates, there is not enough of your endogenous opiates to be able to occupy
00:02:47.640 | those few receptors that are there.
00:02:49.520 | And our locus aureolus has nothing to calm it down anymore, no pacifier.
00:02:53.320 | And it just fires and fires and fires.
00:02:55.440 | And that phasic and tonic high activity stresses us out, because it's normally associated with
00:03:03.400 | stress.
00:03:04.400 | And so any exogenous stressor that adds to that and also activates our locus aureolus,
00:03:09.240 | there's nothing to calm it down again.
00:03:11.200 | And so it just keeps firing.
00:03:13.000 | It disturbs our sleep.
00:03:15.160 | And that's why maybe sleep disturbance is an indicator of a hyperactive locus aureolus
00:03:23.920 | and such a good predictor of relapsed behaviors, because nobody likes to live in that high
00:03:28.960 | stress state.
00:03:30.680 | And they will do anything to get back to normal.
00:03:34.740 | So the problem with taking these drugs is that it leaves you excited-- sorry, excited--
00:03:44.520 | relaxed and happy.
00:03:46.440 | But then when you come off of it, you're worse than when you were at baseline.
00:03:50.880 | You take it again, it only brings you up this far, because you have fewer receptors.
00:03:55.680 | When you come off it, you're down, even more depressed and anxious.
00:04:00.120 | And depressed is a word I use loosely, and that's not what I should say.
00:04:04.360 | Essentially central nervous system depression, I mean sleepier, less motivated, lowered mood.
00:04:09.360 | Yeah.
00:04:10.360 | I mean, our locus aureolus is actually-- it's the anxiety kind of depression, actually,
00:04:15.240 | the anxiety-related depression.
00:04:16.760 | So yeah.
00:04:19.000 | So we don't know yet what-- and there's some good research going on right now-- what could
00:04:23.840 | restore our own endogenous receptors so that our own endogenous opiates can properly calm
00:04:30.680 | our locus aureolus.
00:04:32.680 | It's that they've been tamped down by exogenous opiates, but that would be really one way
00:04:37.720 | that you can access the sleep disturbance.
00:04:40.640 | So we talked about sleep and the importance of sleep in terms of learning and memory,
00:04:44.360 | the importance of the structure of the 90-minute cycle for all of that.
00:04:48.480 | So you can imagine if your sleep is disturbed by too much locus aureolus activity, the structure
00:04:54.820 | and the function of those sleep spindles and that theta during REM sleep, and the lack
00:05:00.280 | of norepinephrine, all of those structures, all those functions for learning, something
00:05:07.040 | new like a new behavior that doesn't involve the drugs, becomes compromised.
00:05:13.520 | And so that's something that Tanya Lu goes in collaboration with Pamela Kennedy at UCLA
00:05:19.240 | that we're looking at.
00:05:20.320 | How is learning and memory affected by the sleep disturbance?
00:05:23.400 | If there are way we can-- in animals that are coming off of opiates, can we restore
00:05:28.240 | their sleep to normal so that then they are less likely to do relapse kinds of behaviors?
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