WEBVTT NOTE duration:"01:08:03.4600000" NOTE recognizability:0.846 NOTE language:en-us NOTE Confidence: 0.923249985 00:00:22.240 --> 00:00:24.288 Hi everyone, good to see so many people. NOTE Confidence: 0.768989222857143 00:00:59.630 --> 00:01:01.177 It's a minute or two after Cyril. NOTE Confidence: 0.874192625 00:01:01.190 --> 00:01:02.050 You're ready to go. NOTE Confidence: 0.826122286 00:01:05.360 --> 00:01:07.340 Yeah, I I am. Thanks. NOTE Confidence: 0.826122286 00:01:07.340 --> 00:01:10.580 Thanks everyone for for coming. NOTE Confidence: 0.826122286 00:01:10.580 --> 00:01:12.332 Actually, I'm going to. NOTE Confidence: 0.826122286 00:01:12.332 --> 00:01:14.960 Have most of the talking done NOTE Confidence: 0.826122286 00:01:15.045 --> 00:01:17.810 by Shariful Syed Sharif is a. NOTE Confidence: 0.719258558333333 00:01:19.880 --> 00:01:21.704 The research fellow. NOTE Confidence: 0.719258558333333 00:01:21.704 --> 00:01:26.870 In our lab. And he has been. NOTE Confidence: 0.719258558333333 00:01:26.870 --> 00:01:30.468 He has really worked closely with me. NOTE Confidence: 0.719258558333333 00:01:30.470 --> 00:01:33.067 In doing this study and so I'm NOTE Confidence: 0.719258558333333 00:01:33.067 --> 00:01:35.711 going to hand it over to him and NOTE Confidence: 0.719258558333333 00:01:35.711 --> 00:01:37.890 I may interject every now and NOTE Confidence: 0.719258558333333 00:01:37.890 --> 00:01:39.711 then just add a few details. NOTE Confidence: 0.719258558333333 00:01:39.711 --> 00:01:40.953 So should we take it away? NOTE Confidence: 0.82117255 00:01:50.540 --> 00:01:54.330 Hi everyone. My screen. NOTE Confidence: 0.859236944 00:01:56.760 --> 00:01:57.780 Can you share your screen? NOTE Confidence: 0.81935513 00:02:00.750 --> 00:02:01.520 Yes. NOTE Confidence: 0.9351113 00:02:04.520 --> 00:02:05.390 OK, NOTE Confidence: 0.875694222 00:02:06.820 --> 00:02:10.140 OK. Can we see this? Looks good. NOTE Confidence: 0.875694222 00:02:10.140 --> 00:02:13.584 OK. All right, I'll begin. NOTE Confidence: 0.875694222 00:02:13.584 --> 00:02:15.712 Hello everyone. So I'm sheriff. NOTE Confidence: 0.875694222 00:02:15.712 --> 00:02:18.680 Nice to thank you all for coming NOTE Confidence: 0.875694222 00:02:18.772 --> 00:02:21.067 and listening to me today. NOTE Confidence: 0.875694222 00:02:21.070 --> 00:02:23.974 So today I'm going to present to NOTE Confidence: 0.875694222 00:02:23.974 --> 00:02:26.476 you the results from our exploratory NOTE Confidence: 0.875694222 00:02:26.476 --> 00:02:29.140 study of the dose related safety, NOTE Confidence: 0.875694222 00:02:29.140 --> 00:02:32.260 tolerability and efficacy of NOTE Confidence: 0.875694222 00:02:32.260 --> 00:02:34.363 Dimethyltryptamine DMT in healthy NOTE Confidence: 0.875694222 00:02:34.363 --> 00:02:36.568 volunteers and major depressive disorder. NOTE Confidence: 0.772492442222222 00:02:40.580 --> 00:02:44.570 So, so why DMT so to start NOTE Confidence: 0.772492442222222 00:02:44.570 --> 00:02:46.250 with context? Because I. NOTE Confidence: 0.703508133333333 00:02:48.270 --> 00:02:48.978 Does the time NOTE Confidence: 0.779810362727273 00:02:48.990 --> 00:02:50.628 to get in and get away sign NOTE Confidence: 0.779810362727273 00:02:50.628 --> 00:02:54.790 and tribe and all, I think. NOTE Confidence: 0.880489668 00:02:54.790 --> 00:02:57.890 So circumstances being right now, NOTE Confidence: 0.880489668 00:02:57.890 --> 00:03:00.458 silybin LSD more so. NOTE Confidence: 0.880489668 00:03:00.458 --> 00:03:03.668 Psilocybin is the main psychedelic NOTE Confidence: 0.880489668 00:03:03.668 --> 00:03:08.239 drug being used and to treat NOTE Confidence: 0.880489668 00:03:08.239 --> 00:03:09.767 neuropsychiatric diseases. NOTE Confidence: 0.880489668 00:03:09.770 --> 00:03:13.781 It raises some concerns in terms of NOTE Confidence: 0.880489668 00:03:13.781 --> 00:03:16.361 implementation and sustainability as a NOTE Confidence: 0.880489668 00:03:16.361 --> 00:03:19.585 potential treatment option if the goal NOTE Confidence: 0.880489668 00:03:19.585 --> 00:03:22.496 is to expand treatments and provide NOTE Confidence: 0.880489668 00:03:22.496 --> 00:03:25.310 them to as many people as possible. NOTE Confidence: 0.880489668 00:03:25.310 --> 00:03:28.100 And and so you know what it has to do NOTE Confidence: 0.880489668 00:03:28.183 --> 00:03:30.979 with that is first the administration NOTE Confidence: 0.880489668 00:03:30.980 --> 00:03:33.200 psilocybin is usually given orally. NOTE Confidence: 0.880489668 00:03:33.200 --> 00:03:35.760 I did help with the our SILYBIN trial NOTE Confidence: 0.880489668 00:03:35.760 --> 00:03:38.498 with the doctor slower doctor Desouza. NOTE Confidence: 0.880489668 00:03:38.500 --> 00:03:40.980 So is able to kind of experience you NOTE Confidence: 0.880489668 00:03:40.980 --> 00:03:43.039 know first hand what the silybin NOTE Confidence: 0.880489668 00:03:43.039 --> 00:03:45.097 effects were like and you know NOTE Confidence: 0.880489668 00:03:45.163 --> 00:03:47.144 it's a very slow onset takes an NOTE Confidence: 0.880489668 00:03:47.144 --> 00:03:50.195 hour to get to peak and you know NOTE Confidence: 0.880489668 00:03:50.195 --> 00:03:52.390 affects Slash report 6 hours. NOTE Confidence: 0.880489668 00:03:52.390 --> 00:03:54.326 Absorption is naturally variable. NOTE Confidence: 0.880489668 00:03:54.326 --> 00:03:56.746 And in terms of pharmacodynamics, NOTE Confidence: 0.880489668 00:03:56.750 --> 00:03:58.370 you know, the psychedelic effects, NOTE Confidence: 0.880489668 00:03:58.370 --> 00:04:00.045 you know they're very potent NOTE Confidence: 0.880489668 00:04:00.045 --> 00:04:01.385 and and and they, NOTE Confidence: 0.880489668 00:04:01.390 --> 00:04:03.598 they sustained for quite some time. NOTE Confidence: 0.880489668 00:04:03.600 --> 00:04:06.176 And and it's these effects that impart, NOTE Confidence: 0.880489668 00:04:06.180 --> 00:04:10.100 you know require the need of you know NOTE Confidence: 0.880489668 00:04:10.100 --> 00:04:13.828 the current FDA guidelines requires 2 NOTE Confidence: 0.880489668 00:04:13.828 --> 00:04:17.282 clinicians to be supporting a patient NOTE Confidence: 0.880489668 00:04:17.282 --> 00:04:19.287 if they're receiving a psychedelic. NOTE Confidence: 0.880489668 00:04:19.290 --> 00:04:22.041 And so that's actually kind of a NOTE Confidence: 0.880489668 00:04:22.041 --> 00:04:24.810 large use of resources in terms of NOTE Confidence: 0.880489668 00:04:24.810 --> 00:04:28.087 you know 6 to 8 hours to clinicians NOTE Confidence: 0.880489668 00:04:28.087 --> 00:04:31.349 for one session for for a patient. NOTE Confidence: 0.880489668 00:04:31.350 --> 00:04:33.877 And so the other aspect is that NOTE Confidence: 0.880489668 00:04:33.877 --> 00:04:37.049 you know the the use of therapy to NOTE Confidence: 0.880489668 00:04:37.049 --> 00:04:39.644 scaffold you know the psychedelic NOTE Confidence: 0.880489668 00:04:39.644 --> 00:04:42.697 treatment encounter is also quite a NOTE Confidence: 0.880489668 00:04:42.697 --> 00:04:45.630 large endeavor in terms of many trials NOTE Confidence: 0.880489668 00:04:45.630 --> 00:04:49.010 include eight weeks of twice a week sessions. NOTE Confidence: 0.880489668 00:04:49.010 --> 00:04:50.610 And so all these things NOTE Confidence: 0.880489668 00:04:50.610 --> 00:04:52.210 taken together you know it, NOTE Confidence: 0.880489668 00:04:52.210 --> 00:04:54.085 it certainly raises some concerns NOTE Confidence: 0.880489668 00:04:54.085 --> 00:04:55.960 in terms of scalability and NOTE Confidence: 0.880489668 00:04:56.029 --> 00:04:58.798 accessibility and as it pertains NOTE Confidence: 0.880489668 00:04:58.798 --> 00:05:01.302 to financial high cost insurance. NOTE Confidence: 0.880489668 00:05:01.302 --> 00:05:03.430 Coverage being certainly something NOTE Confidence: 0.880489668 00:05:03.430 --> 00:05:05.558 that's influenced by that. NOTE Confidence: 0.880489668 00:05:05.560 --> 00:05:08.170 So I so for all those reasons I I NOTE Confidence: 0.880489668 00:05:08.170 --> 00:05:11.080 think it it does actually make DMT NOTE Confidence: 0.880489668 00:05:11.080 --> 00:05:13.880 seem like an interesting option NOTE Confidence: 0.880489668 00:05:13.880 --> 00:05:17.724 and so so and part of that another NOTE Confidence: 0.880489668 00:05:17.724 --> 00:05:20.886 dimension of why DMT we would argue NOTE Confidence: 0.880489668 00:05:20.886 --> 00:05:23.272 is that something that's kind of NOTE Confidence: 0.880489668 00:05:23.272 --> 00:05:25.212 assumed about psychedelics is that NOTE Confidence: 0.880489668 00:05:25.212 --> 00:05:27.696 you know the effects are necessary NOTE Confidence: 0.880489668 00:05:27.696 --> 00:05:29.726 to their therapeutic effects that's NOTE Confidence: 0.880489668 00:05:29.797 --> 00:05:31.397 not proven yet but that's. NOTE Confidence: 0.880489668 00:05:31.400 --> 00:05:33.784 By and large what a lot of people NOTE Confidence: 0.880489668 00:05:33.784 --> 00:05:36.090 think and you know the magnitude NOTE Confidence: 0.880489668 00:05:36.090 --> 00:05:37.934 of psychedelic effects that's you NOTE Confidence: 0.880489668 00:05:37.934 --> 00:05:40.188 know seems to be you know part NOTE Confidence: 0.880489668 00:05:40.188 --> 00:05:41.840 of just the process. NOTE Confidence: 0.880489668 00:05:41.840 --> 00:05:43.310 People kind of lose themselves. NOTE Confidence: 0.880489668 00:05:43.310 --> 00:05:45.290 They experience you like oceanic NOTE Confidence: 0.880489668 00:05:45.290 --> 00:05:47.654 boundlessness and you know that's again NOTE Confidence: 0.880489668 00:05:47.654 --> 00:05:49.922 you know these effects are part of NOTE Confidence: 0.880489668 00:05:49.922 --> 00:05:51.602 what requires close medical monitoring NOTE Confidence: 0.880489668 00:05:51.602 --> 00:05:54.113 and you know for our study we always NOTE Confidence: 0.880489668 00:05:54.113 --> 00:05:55.328 have to have rescue medication. NOTE Confidence: 0.880489668 00:05:55.330 --> 00:05:57.310 We were taking blood pressures NOTE Confidence: 0.880489668 00:05:57.310 --> 00:05:59.290 and likely those things would NOTE Confidence: 0.880489668 00:05:59.363 --> 00:06:01.350 be required and and practice. NOTE Confidence: 0.880489668 00:06:01.350 --> 00:06:03.030 So you know it. NOTE Confidence: 0.880489668 00:06:03.030 --> 00:06:04.330 It begs the question actually. NOTE Confidence: 0.880489668 00:06:04.330 --> 00:06:06.490 So you know how much psychedelic NOTE Confidence: 0.880489668 00:06:06.490 --> 00:06:09.109 effect is needed if they are indeed, NOTE Confidence: 0.880489668 00:06:09.110 --> 00:06:09.722 you know, NOTE Confidence: 0.880489668 00:06:09.722 --> 00:06:11.252 necessary in terms of duration NOTE Confidence: 0.880489668 00:06:11.252 --> 00:06:13.228 and as well as the magnitude. NOTE Confidence: 0.880489668 00:06:13.230 --> 00:06:15.918 Because in theory. NOTE Confidence: 0.880489668 00:06:15.920 --> 00:06:17.846 If there was a minimum threshold NOTE Confidence: 0.880489668 00:06:17.846 --> 00:06:18.809 that was needed, NOTE Confidence: 0.880489668 00:06:18.810 --> 00:06:20.892 well then it would make sense NOTE Confidence: 0.880489668 00:06:20.892 --> 00:06:22.280 to try and you NOTE Confidence: 0.906474854285714 00:06:22.364 --> 00:06:25.964 know reach that and so that we could NOTE Confidence: 0.906474854285714 00:06:25.964 --> 00:06:28.130 potentially optimize administration. NOTE Confidence: 0.906474854285714 00:06:28.130 --> 00:06:31.748 So again, DMT, it's a tryptamine, NOTE Confidence: 0.906474854285714 00:06:31.750 --> 00:06:33.156 serotonergic, psychedelic. NOTE Confidence: 0.906474854285714 00:06:33.156 --> 00:06:38.780 We have psilocybin here and DMT and LSD, NOTE Confidence: 0.906474854285714 00:06:38.780 --> 00:06:40.376 which you know as a molecule NOTE Confidence: 0.906474854285714 00:06:40.376 --> 00:06:42.110 is a little bit different. NOTE Confidence: 0.906474854285714 00:06:42.110 --> 00:06:45.086 But notice that psilocybin is actually. NOTE Confidence: 0.906474854285714 00:06:45.090 --> 00:06:47.825 You know, and then Dimethyltryptamine NOTE Confidence: 0.906474854285714 00:06:47.825 --> 00:06:50.013 with just that phosphorus NOTE Confidence: 0.906474854285714 00:06:50.013 --> 00:06:52.410 phosphoryl group on the 4th carbon. NOTE Confidence: 0.906474854285714 00:06:52.410 --> 00:06:54.885 OK, so concretely, NOTE Confidence: 0.906474854285714 00:06:54.885 --> 00:06:59.010 DMT is normally administered either NOTE Confidence: 0.906474854285714 00:06:59.010 --> 00:07:03.570 intravenously or smoked intranasal intra. NOTE Confidence: 0.906474854285714 00:07:03.570 --> 00:07:05.335 Inhalation only and so it NOTE Confidence: 0.906474854285714 00:07:05.335 --> 00:07:07.100 has a very rapid onset, NOTE Confidence: 0.906474854285714 00:07:07.100 --> 00:07:09.014 you know within minutes and it's NOTE Confidence: 0.906474854285714 00:07:09.014 --> 00:07:10.700 duration of effects is short. NOTE Confidence: 0.906474854285714 00:07:10.700 --> 00:07:12.488 It's effect usually resolved NOTE Confidence: 0.906474854285714 00:07:12.488 --> 00:07:14.276 by about 30 minutes. NOTE Confidence: 0.906474854285714 00:07:14.280 --> 00:07:18.039 Now some of it's in in the. NOTE Confidence: 0.906474854285714 00:07:18.040 --> 00:07:18.388 Informally, NOTE Confidence: 0.906474854285714 00:07:18.388 --> 00:07:20.602 it's been called the businessman's trip. NOTE Confidence: 0.906474854285714 00:07:20.602 --> 00:07:24.519 And so the reason it has to be given NOTE Confidence: 0.906474854285714 00:07:24.519 --> 00:07:28.320 IV or intra intranasally is because the NOTE Confidence: 0.906474854285714 00:07:28.320 --> 00:07:30.640 oral bioavailability is quite poor. NOTE Confidence: 0.906474854285714 00:07:30.640 --> 00:07:32.776 And that's related to the fact that if NOTE Confidence: 0.906474854285714 00:07:32.776 --> 00:07:35.520 it's if it reaches the peripheral metabolism, NOTE Confidence: 0.906474854285714 00:07:35.520 --> 00:07:38.264 it gets metabolized very quickly by money, NOTE Confidence: 0.906474854285714 00:07:38.270 --> 00:07:44.718 by monoamine oxidase and by by those enzymes. NOTE Confidence: 0.906474854285714 00:07:44.720 --> 00:07:47.267 And so actually the DMT is not able to NOTE Confidence: 0.906474854285714 00:07:47.267 --> 00:07:49.472 reach brain and so that's that limit NOTE Confidence: 0.906474854285714 00:07:49.472 --> 00:07:51.740 its ability to be given that way. NOTE Confidence: 0.906474854285714 00:07:51.740 --> 00:07:54.476 And so iasca is, you know, NOTE Confidence: 0.906474854285714 00:07:54.480 --> 00:07:56.104 it's a ceremonial brew, NOTE Confidence: 0.906474854285714 00:07:56.104 --> 00:07:58.540 it's a tea that you know, NOTE Confidence: 0.906474854285714 00:07:58.540 --> 00:08:00.520 DMT is known to be, NOTE Confidence: 0.906474854285714 00:08:00.520 --> 00:08:01.302 you know, NOTE Confidence: 0.906474854285714 00:08:01.302 --> 00:08:03.257 a very active constituent in NOTE Confidence: 0.906474854285714 00:08:03.260 --> 00:08:05.840 and it's used in the Amazonian NOTE Confidence: 0.906474854285714 00:08:05.840 --> 00:08:07.560 regions of South America. NOTE Confidence: 0.906474854285714 00:08:07.560 --> 00:08:09.070 There's a long tradition and NOTE Confidence: 0.906474854285714 00:08:09.070 --> 00:08:10.580 history associated with it in NOTE Confidence: 0.906474854285714 00:08:10.633 --> 00:08:12.295 terms of some of these cultures, NOTE Confidence: 0.906474854285714 00:08:12.300 --> 00:08:14.799 Brazil in particular I think is 1. NOTE Confidence: 0.906474854285714 00:08:14.800 --> 00:08:17.200 And, you know, looking at iasca, NOTE Confidence: 0.906474854285714 00:08:17.200 --> 00:08:19.318 you know, having DMT in it, NOTE Confidence: 0.906474854285714 00:08:19.320 --> 00:08:21.456 it also has other, you know, NOTE Confidence: 0.906474854285714 00:08:21.460 --> 00:08:22.664 serotonergic potentiating NOTE Confidence: 0.906474854285714 00:08:22.664 --> 00:08:23.868 compounds including, NOTE Confidence: 0.906474854285714 00:08:23.868 --> 00:08:27.941 you know harmaline and other other NOTE Confidence: 0.906474854285714 00:08:27.941 --> 00:08:33.246 SSRI acting components and ayahuasca. NOTE Confidence: 0.906474854285714 00:08:33.250 --> 00:08:34.124 You know, NOTE Confidence: 0.906474854285714 00:08:34.124 --> 00:08:36.309 when ingested orally it's associated NOTE Confidence: 0.906474854285714 00:08:36.309 --> 00:08:38.310 with pretty profound hallucinations, NOTE Confidence: 0.906474854285714 00:08:38.310 --> 00:08:39.690 perceptual alteration, NOTE Confidence: 0.906474854285714 00:08:39.690 --> 00:08:42.462 spiritual insights, euphoria, anxiety. NOTE Confidence: 0.906474854285714 00:08:42.462 --> 00:08:45.246 It also it's relatively. NOTE Confidence: 0.906474854285714 00:08:45.250 --> 00:08:47.746 Associated with often nausea, NOTE Confidence: 0.906474854285714 00:08:47.746 --> 00:08:50.960 vomiting, diarrhea. NOTE Confidence: 0.906474854285714 00:08:50.960 --> 00:08:53.160 So, so then the question is, NOTE Confidence: 0.906474854285714 00:08:53.160 --> 00:08:55.020 well, does DMT, you know, NOTE Confidence: 0.906474854285714 00:08:55.020 --> 00:08:56.460 maybe in the form of ayahuasca, NOTE Confidence: 0.906474854285714 00:08:56.460 --> 00:08:58.580 does that have antidepressant effects? NOTE Confidence: 0.906474854285714 00:08:58.580 --> 00:08:59.820 And you know, interestingly, NOTE Confidence: 0.906474854285714 00:08:59.820 --> 00:09:01.616 you know, I was trying to look at the NOTE Confidence: 0.906474854285714 00:09:01.616 --> 00:09:03.056 history and to see what, you know, NOTE Confidence: 0.906474854285714 00:09:03.056 --> 00:09:05.200 if if that was something on anyone's radar. NOTE Confidence: 0.906474854285714 00:09:05.200 --> 00:09:08.840 And you know there was this psychiatrist NOTE Confidence: 0.906474854285714 00:09:08.840 --> 00:09:12.700 Raymond Prince who wrote this article about, NOTE Confidence: 0.906474854285714 00:09:12.700 --> 00:09:13.390 you know, NOTE Confidence: 0.906474854285714 00:09:13.390 --> 00:09:15.460 his observations of iowaska and how, NOTE Confidence: 0.906474854285714 00:09:15.460 --> 00:09:17.716 you know, shamans used it as you know, NOTE Confidence: 0.906474854285714 00:09:17.720 --> 00:09:19.755 for a therapeutic like purposes NOTE Confidence: 0.906474854285714 00:09:19.755 --> 00:09:20.976 and I thought. NOTE Confidence: 0.906474854285714 00:09:20.980 --> 00:09:22.800 This was interesting because, NOTE Confidence: 0.906474854285714 00:09:22.800 --> 00:09:25.065 you know, I actually want you to NOTE Confidence: 0.906474854285714 00:09:25.065 --> 00:09:27.290 read this part and so referring to, NOTE Confidence: 0.906474854285714 00:09:27.290 --> 00:09:28.370 you know, ayahuasca, NOTE Confidence: 0.906474854285714 00:09:28.370 --> 00:09:30.170 it is a fearsome thing. NOTE Confidence: 0.906474854285714 00:09:30.170 --> 00:09:32.050 I was very much afraid. NOTE Confidence: 0.906474854285714 00:09:32.050 --> 00:09:32.974 And Tarner, NOTE Confidence: 0.906474854285714 00:09:32.974 --> 00:09:35.746 reporting his own initiation into shamanism, NOTE Confidence: 0.906474854285714 00:09:35.750 --> 00:09:38.010 describes the terrifying images he NOTE Confidence: 0.906474854285714 00:09:38.010 --> 00:09:40.989 experienced after taking a species of Natura. NOTE Confidence: 0.906474854285714 00:09:40.990 --> 00:09:42.706 There are two types of terror NOTE Confidence: 0.906474854285714 00:09:42.706 --> 00:09:43.850 involved in psychedelic youth, NOTE Confidence: 0.906474854285714 00:09:43.850 --> 00:09:45.461 specific hallucinatory images NOTE Confidence: 0.906474854285714 00:09:45.461 --> 00:09:48.683 such as giant snakes or Jaguars, NOTE Confidence: 0.906474854285714 00:09:48.690 --> 00:09:50.600 and the general terror of NOTE Confidence: 0.906474854285714 00:09:50.600 --> 00:09:51.746 impending ego dissolution. NOTE Confidence: 0.906474854285714 00:09:51.750 --> 00:09:53.178 Both could conceivably related NOTE Confidence: 0.906474854285714 00:09:53.178 --> 00:09:54.963 to endorphin response as part NOTE Confidence: 0.906474854285714 00:09:54.963 --> 00:09:56.909 of their therapeutic efficacy. NOTE Confidence: 0.906474854285714 00:09:56.910 --> 00:09:59.364 So already there is some observation NOTE Confidence: 0.906474854285714 00:09:59.364 --> 00:10:01.528 or thinking about you know NOTE Confidence: 0.906474854285714 00:10:01.528 --> 00:10:03.788 these psychedelic effects as you NOTE Confidence: 0.906474854285714 00:10:03.788 --> 00:10:05.596 know having some potential NOTE Confidence: 0.890212765652174 00:10:05.666 --> 00:10:08.016 efficacy and curiously in terms NOTE Confidence: 0.890212765652174 00:10:08.016 --> 00:10:10.404 of the you know the distressing NOTE Confidence: 0.890212765652174 00:10:10.404 --> 00:10:12.425 elements seem to be actually NOTE Confidence: 0.890212765652174 00:10:12.425 --> 00:10:15.106 important for that effect in in this. NOTE Confidence: 0.890212765652174 00:10:15.110 --> 00:10:17.216 And in that perspective and so NOTE Confidence: 0.890212765652174 00:10:17.216 --> 00:10:19.818 there are some, there are some NOTE Confidence: 0.890212765652174 00:10:19.818 --> 00:10:22.398 clinical trials that looked at. NOTE Confidence: 0.890212765652174 00:10:22.400 --> 00:10:24.955 Iasca, you know, in a rigorous way NOTE Confidence: 0.890212765652174 00:10:24.955 --> 00:10:26.968 relatively speaking the left we have NOTE Confidence: 0.890212765652174 00:10:26.968 --> 00:10:29.270 here is an open label trial that was, NOTE Confidence: 0.890212765652174 00:10:29.270 --> 00:10:31.188 you know just done in a sample NOTE Confidence: 0.890212765652174 00:10:31.188 --> 00:10:32.010 of three individuals. NOTE Confidence: 0.890212765652174 00:10:32.010 --> 00:10:34.970 We have here on the X axis time and the NOTE Confidence: 0.890212765652174 00:10:35.048 --> 00:10:37.952 Y axis is their Madras score, which is, NOTE Confidence: 0.890212765652174 00:10:37.952 --> 00:10:39.707 you know, depression rating scale. NOTE Confidence: 0.890212765652174 00:10:39.710 --> 00:10:43.196 And so you see here you know NOTE Confidence: 0.890212765652174 00:10:43.196 --> 00:10:45.728 the peak effects, this is our, NOTE Confidence: 0.890212765652174 00:10:45.728 --> 00:10:47.804 our minutes and this is days. NOTE Confidence: 0.890212765652174 00:10:47.810 --> 00:10:50.468 So you have baseline before administration, NOTE Confidence: 0.890212765652174 00:10:50.470 --> 00:10:52.242 you have relatively higher. NOTE Confidence: 0.890212765652174 00:10:52.242 --> 00:10:54.457 Depression score and you know, NOTE Confidence: 0.890212765652174 00:10:54.460 --> 00:10:55.844 it, it comes down, NOTE Confidence: 0.890212765652174 00:10:55.844 --> 00:10:57.920 but it goes through an interesting NOTE Confidence: 0.890212765652174 00:10:57.987 --> 00:11:00.324 kind of ups and downs and to remember NOTE Confidence: 0.890212765652174 00:11:00.324 --> 00:11:02.436 the peak effects around 2 hours. NOTE Confidence: 0.890212765652174 00:11:02.440 --> 00:11:04.940 And so curiously, you know, NOTE Confidence: 0.890212765652174 00:11:04.940 --> 00:11:06.750 you see this actually uptick NOTE Confidence: 0.890212765652174 00:11:06.750 --> 00:11:07.836 in depressive symptoms. NOTE Confidence: 0.890212765652174 00:11:07.840 --> 00:11:09.328 So that you know, NOTE Confidence: 0.890212765652174 00:11:09.328 --> 00:11:11.188 actually lends itself towards well NOTE Confidence: 0.890212765652174 00:11:11.188 --> 00:11:12.993 what does the psychedelic experience NOTE Confidence: 0.890212765652174 00:11:12.993 --> 00:11:16.079 need to be for it to be therapeutic. NOTE Confidence: 0.890212765652174 00:11:16.080 --> 00:11:18.929 So I mean that's a question that NOTE Confidence: 0.890212765652174 00:11:18.929 --> 00:11:21.286 certainly will need to be answered NOTE Confidence: 0.890212765652174 00:11:21.286 --> 00:11:23.450 and probably will be looked at. NOTE Confidence: 0.890212765652174 00:11:23.450 --> 00:11:24.980 In the in the future, NOTE Confidence: 0.890212765652174 00:11:24.980 --> 00:11:27.276 the right is a a clinical trial, NOTE Confidence: 0.890212765652174 00:11:27.280 --> 00:11:28.704 randomized clinical trial where NOTE Confidence: 0.890212765652174 00:11:28.704 --> 00:11:31.184 you know we had a placebo control NOTE Confidence: 0.890212765652174 00:11:31.184 --> 00:11:33.432 and so again this is using the AMD NOTE Confidence: 0.890212765652174 00:11:33.432 --> 00:11:36.311 we see at by seven days after one NOTE Confidence: 0.890212765652174 00:11:36.311 --> 00:11:38.102 administration of ayahuasca you see NOTE Confidence: 0.890212765652174 00:11:38.102 --> 00:11:40.910 a change of from 25 to about 10 NOTE Confidence: 0.890212765652174 00:11:41.005 --> 00:11:44.155 that's a quite a large effect size. NOTE Confidence: 0.890212765652174 00:11:44.160 --> 00:11:45.906 I'd say that's comparable to you NOTE Confidence: 0.890212765652174 00:11:45.906 --> 00:11:47.858 know what some of the psilocybin NOTE Confidence: 0.890212765652174 00:11:47.858 --> 00:11:50.024 studies have shown in terms of NOTE Confidence: 0.890212765652174 00:11:50.024 --> 00:11:52.116 their impressive effects but and NOTE Confidence: 0.890212765652174 00:11:52.116 --> 00:11:54.122 so while ayahuasca. Contains DMT. NOTE Confidence: 0.890212765652174 00:11:54.122 --> 00:11:56.439 It contains all the other things as NOTE Confidence: 0.890212765652174 00:11:56.439 --> 00:11:58.550 we mentioned, and so as a result, NOTE Confidence: 0.890212765652174 00:11:58.550 --> 00:12:01.772 you know we can't really extrapolate NOTE Confidence: 0.890212765652174 00:12:01.772 --> 00:12:04.941 about DMT itself because it has NOTE Confidence: 0.890212765652174 00:12:04.941 --> 00:12:07.266 not been studied in isolation. NOTE Confidence: 0.890212765652174 00:12:07.270 --> 00:12:10.175 So. You know it. It really does. NOTE Confidence: 0.890212765652174 00:12:10.180 --> 00:12:10.840 You know, NOTE Confidence: 0.890212765652174 00:12:10.840 --> 00:12:12.820 the question really arises for all NOTE Confidence: 0.890212765652174 00:12:12.820 --> 00:12:14.612 these psychedelics of, you know, NOTE Confidence: 0.890212765652174 00:12:14.612 --> 00:12:16.917 are these effects long lasting? NOTE Confidence: 0.890212765652174 00:12:16.920 --> 00:12:19.314 And you know there is some suggestion NOTE Confidence: 0.890212765652174 00:12:19.314 --> 00:12:21.716 that you know psilocybin does have NOTE Confidence: 0.890212765652174 00:12:21.716 --> 00:12:23.624 effects that seem to last for NOTE Confidence: 0.890212765652174 00:12:23.624 --> 00:12:25.698 maybe one month or even longer. NOTE Confidence: 0.890212765652174 00:12:25.700 --> 00:12:27.278 And then the so the natural NOTE Confidence: 0.890212765652174 00:12:27.278 --> 00:12:28.719 question is well how do we, NOTE Confidence: 0.890212765652174 00:12:28.720 --> 00:12:31.420 how is that happening now? NOTE Confidence: 0.890212765652174 00:12:31.420 --> 00:12:33.200 Depression to be associated NOTE Confidence: 0.890212765652174 00:12:33.200 --> 00:12:34.980 with dendritic spine loss, NOTE Confidence: 0.890212765652174 00:12:34.980 --> 00:12:38.058 decrease number inside the glial cells. NOTE Confidence: 0.890212765652174 00:12:38.060 --> 00:12:39.828 These things have ramifications NOTE Confidence: 0.890212765652174 00:12:39.828 --> 00:12:42.038 for brain regions such as NOTE Confidence: 0.890212765652174 00:12:42.038 --> 00:12:43.959 hippocampus and prefrontal cortex. NOTE Confidence: 0.890212765652174 00:12:43.960 --> 00:12:45.196 And as a result, you know, NOTE Confidence: 0.890212765652174 00:12:45.200 --> 00:12:47.256 you get ultimately impaired. NOTE Confidence: 0.890212765652174 00:12:47.256 --> 00:12:47.770 Activity. NOTE Confidence: 0.890212765652174 00:12:47.770 --> 00:12:49.330 And these things correlate with, NOTE Confidence: 0.890212765652174 00:12:49.330 --> 00:12:50.954 you know, NOTE Confidence: 0.890212765652174 00:12:50.954 --> 00:12:52.578 depressive symptomatology. NOTE Confidence: 0.890212765652174 00:12:52.580 --> 00:12:55.694 And so in terms of the basis of how NOTE Confidence: 0.890212765652174 00:12:55.700 --> 00:12:58.700 these psychedelics work and this, NOTE Confidence: 0.890212765652174 00:12:58.700 --> 00:13:01.916 it seems to be that they are impacting NOTE Confidence: 0.890212765652174 00:13:01.920 --> 00:13:04.335 neuroplasticity insofar as we define NOTE Confidence: 0.890212765652174 00:13:04.335 --> 00:13:08.185 it to refer to the connectivity between NOTE Confidence: 0.890212765652174 00:13:08.185 --> 00:13:11.920 neurons and their actual, you know, NOTE Confidence: 0.890212765652174 00:13:11.920 --> 00:13:13.480 their, their neurotransmission, NOTE Confidence: 0.890212765652174 00:13:13.480 --> 00:13:17.004 you know, looking at the, at the. NOTE Confidence: 0.890212765652174 00:13:17.004 --> 00:13:19.530 Post synaptic numbering. NOTE Confidence: 0.890212765652174 00:13:19.530 --> 00:13:22.850 OK, so all taken together, NOTE Confidence: 0.890212765652174 00:13:22.850 --> 00:13:26.574 these things guided our study designing to. NOTE Confidence: 0.844688713333333 00:13:26.580 --> 00:13:28.440 In terms of any specific aims NOTE Confidence: 0.844688713333333 00:13:28.440 --> 00:13:30.347 and hypothesis where we wanted to NOTE Confidence: 0.844688713333333 00:13:30.347 --> 00:13:31.885 test the safety, tolerability, NOTE Confidence: 0.844688713333333 00:13:31.885 --> 00:13:34.385 efficacy and potential mechanisms NOTE Confidence: 0.844688713333333 00:13:34.385 --> 00:13:37.510 involved with DMT and major NOTE Confidence: 0.844688713333333 00:13:37.593 --> 00:13:40.257 depression and healthy controls. NOTE Confidence: 0.844688713333333 00:13:40.260 --> 00:13:42.980 So our initial study design NOTE Confidence: 0.844688713333333 00:13:42.980 --> 00:13:45.156 was a double-blind randomized NOTE Confidence: 0.844688713333333 00:13:45.156 --> 00:13:46.960 placebo control trial. NOTE Confidence: 0.844688713333333 00:13:46.960 --> 00:13:48.919 And you know. NOTE Confidence: 0.844688713333333 00:13:48.919 --> 00:13:52.184 But we actually ran into NOTE Confidence: 0.844688713333333 00:13:52.184 --> 00:13:54.349 a roadblock of sorts. NOTE Confidence: 0.844688713333333 00:13:54.349 --> 00:13:58.536 The IRB told us that we had to NOTE Confidence: 0.844688713333333 00:13:58.536 --> 00:14:02.428 first do a fixed order open label NOTE Confidence: 0.844688713333333 00:14:02.428 --> 00:14:04.958 dose escalation study to determine NOTE Confidence: 0.844688713333333 00:14:04.958 --> 00:14:07.262 the safety of the highest dose NOTE Confidence: 0.844688713333333 00:14:07.262 --> 00:14:09.868 of DMT that was tolerable and NOTE Confidence: 0.844688713333333 00:14:09.868 --> 00:14:12.058 safe in depressed subjects as NOTE Confidence: 0.844688713333333 00:14:12.058 --> 00:14:14.657 well as health healthy controls. NOTE Confidence: 0.93417254375 00:14:16.860 --> 00:14:19.516 And those are the results of this study, NOTE Confidence: 0.93417254375 00:14:19.520 --> 00:14:23.224 is what we shall be going over today. NOTE Confidence: 0.93417254375 00:14:23.230 --> 00:14:25.606 The doses, as I mentioned up to .3, NOTE Confidence: 0.93417254375 00:14:25.610 --> 00:14:28.634 so we had two doses that was our .1 NOTE Confidence: 0.93417254375 00:14:28.634 --> 00:14:31.205 milligram per kilogram and then the .3. NOTE Confidence: 0.93417254375 00:14:31.210 --> 00:14:34.242 These doses are based off of the work NOTE Confidence: 0.93417254375 00:14:34.242 --> 00:14:37.359 done by Rick Strassman who actually was NOTE Confidence: 0.93417254375 00:14:37.359 --> 00:14:39.900 someone that was cited in the literature. NOTE Confidence: 0.93417254375 00:14:39.900 --> 00:14:42.843 And some of this, you know from the previous, NOTE Confidence: 0.93417254375 00:14:42.850 --> 00:14:44.425 you know, old article I showed you. NOTE Confidence: 0.93417254375 00:14:44.430 --> 00:14:45.850 There was others like that NOTE Confidence: 0.93417254375 00:14:45.850 --> 00:14:48.172 where he was actually, you know, NOTE Confidence: 0.93417254375 00:14:48.172 --> 00:14:51.127 co-author, but he has specifically NOTE Confidence: 0.93417254375 00:14:51.127 --> 00:14:52.900 studied intravenous DMT. NOTE Confidence: 0.93417254375 00:14:52.900 --> 00:14:54.545 Looking to understand more about NOTE Confidence: 0.93417254375 00:14:54.545 --> 00:14:56.606 human consciousness and so the and NOTE Confidence: 0.93417254375 00:14:56.606 --> 00:14:58.766 with healthy controls which were you NOTE Confidence: 0.93417254375 00:14:58.766 --> 00:15:00.220 know experienced psychedelic users. NOTE Confidence: 0.93417254375 00:15:00.220 --> 00:15:02.524 He has a few clinical trials where you NOTE Confidence: 0.93417254375 00:15:02.524 --> 00:15:04.884 know he established a paradigm and you NOTE Confidence: 0.93417254375 00:15:04.884 --> 00:15:07.722 know proof of concept of the safety and NOTE Confidence: 0.93417254375 00:15:07.722 --> 00:15:09.822 and psychedelic effects of these doses NOTE Confidence: 0.93417254375 00:15:09.822 --> 00:15:12.838 to .1 being a sub psychedelic dose. NOTE Confidence: 0.93417254375 00:15:12.840 --> 00:15:16.744 Meaning that .1 make per cake dose is NOTE Confidence: 0.93417254375 00:15:16.744 --> 00:15:19.344 not associated with over perceptual NOTE Confidence: 0.93417254375 00:15:19.344 --> 00:15:22.893 changes while the .3 you know is. NOTE Confidence: 0.93417254375 00:15:22.900 --> 00:15:24.310 Quite so robustly. NOTE Confidence: 0.93417254375 00:15:24.310 --> 00:15:27.130 One of the words that captures, NOTE Confidence: 0.93417254375 00:15:27.130 --> 00:15:27.730 you know, NOTE Confidence: 0.93417254375 00:15:27.730 --> 00:15:29.230 how people describe the intensity NOTE Confidence: 0.93417254375 00:15:29.230 --> 00:15:31.189 of it because it's known to be NOTE Confidence: 0.93417254375 00:15:31.189 --> 00:15:32.950 quite intense as you know, knowing, NOTE Confidence: 0.93417254375 00:15:32.950 --> 00:15:34.450 knowing its pharmacokinetics NOTE Confidence: 0.93417254375 00:15:34.450 --> 00:15:36.950 being very rapid and onset. NOTE Confidence: 0.93417254375 00:15:36.950 --> 00:15:38.970 You know that also suggestive, NOTE Confidence: 0.93417254375 00:15:38.970 --> 00:15:40.559 but one of the words that uses, NOTE Confidence: 0.93417254375 00:15:40.560 --> 00:15:41.098 you know, NOTE Confidence: 0.93417254375 00:15:41.098 --> 00:15:43.250 it feels like a breakthrough of sorts and NOTE Confidence: 0.93417254375 00:15:43.309 --> 00:15:45.528 that that initial induction of effects is, NOTE Confidence: 0.93417254375 00:15:45.530 --> 00:15:47.644 you know, referred to with words like NOTE Confidence: 0.93417254375 00:15:47.644 --> 00:15:50.066 that and the actual administration NOTE Confidence: 0.93417254375 00:15:50.066 --> 00:15:53.240 of the drug is done intravenously. NOTE Confidence: 0.93417254375 00:15:53.240 --> 00:15:57.353 And over 30 to 60 seconds as a bolus. NOTE Confidence: 0.93417254375 00:15:57.360 --> 00:15:58.836 And so that was doctor Dsouza, NOTE Confidence: 0.93417254375 00:15:58.840 --> 00:15:59.988 you know, NOTE Confidence: 0.93417254375 00:15:59.988 --> 00:16:02.858 administering those to our subjects. NOTE Confidence: 0.93417254375 00:16:02.860 --> 00:16:03.355 OK. NOTE Confidence: 0.93417254375 00:16:03.355 --> 00:16:07.183 So in terms of how we measured all NOTE Confidence: 0.93417254375 00:16:07.183 --> 00:16:09.361 these things that we discussed is NOTE Confidence: 0.93417254375 00:16:09.361 --> 00:16:12.860 very was our aims in terms of safety. NOTE Confidence: 0.93417254375 00:16:12.860 --> 00:16:15.410 Physiologically we had we measure NOTE Confidence: 0.93417254375 00:16:15.410 --> 00:16:17.930 blood pressures, heart rates, NOTE Confidence: 0.93417254375 00:16:17.930 --> 00:16:20.555 oxygen saturation and you know, NOTE Confidence: 0.93417254375 00:16:20.560 --> 00:16:22.260 heart rate oxygen being continuous NOTE Confidence: 0.93417254375 00:16:22.260 --> 00:16:23.896 blood pressure, you know, NOTE Confidence: 0.93417254375 00:16:23.896 --> 00:16:26.286 we measured at numerous time NOTE Confidence: 0.93417254375 00:16:26.286 --> 00:16:29.160 points adverse events. NOTE Confidence: 0.93417254375 00:16:29.160 --> 00:16:30.976 You know we were very careful you know NOTE Confidence: 0.93417254375 00:16:30.976 --> 00:16:32.797 this being you know the first clinical NOTE Confidence: 0.93417254375 00:16:32.797 --> 00:16:34.720 trial using DMT and depressed individuals. NOTE Confidence: 0.93417254375 00:16:34.720 --> 00:16:36.673 You know we really wanted to make NOTE Confidence: 0.93417254375 00:16:36.673 --> 00:16:38.714 sure we captured any and all potential NOTE Confidence: 0.93417254375 00:16:38.714 --> 00:16:41.211 adverse events that to any of the the NOTE Confidence: 0.93417254375 00:16:41.211 --> 00:16:43.684 subject experience and in terms of. NOTE Confidence: 0.93417254375 00:16:43.684 --> 00:16:46.300 Rescue medications based off the work NOTE Confidence: 0.93417254375 00:16:46.381 --> 00:16:49.000 done in healthy controls, you know, NOTE Confidence: 0.93417254375 00:16:49.000 --> 00:16:50.500 temporal increases in heart rate, NOTE Confidence: 0.93417254375 00:16:50.500 --> 00:16:53.176 blood pressure, anxiety, confusion. NOTE Confidence: 0.93417254375 00:16:53.176 --> 00:16:56.521 We selected a rescue medications NOTE Confidence: 0.93417254375 00:16:56.521 --> 00:16:58.979 to serve those needs, NOTE Confidence: 0.93417254375 00:16:58.980 --> 00:17:00.355 but we actually didn't need NOTE Confidence: 0.93417254375 00:17:00.355 --> 00:17:02.160 to use any in our study. NOTE Confidence: 0.93417254375 00:17:02.160 --> 00:17:04.400 And of course the need for the study NOTE Confidence: 0.93417254375 00:17:04.400 --> 00:17:07.004 to be aborted or if subjects dropping NOTE Confidence: 0.93417254375 00:17:07.004 --> 00:17:09.579 out after receiving the the .1 dose, NOTE Confidence: 0.93417254375 00:17:09.580 --> 00:17:11.990 those things also certainly would NOTE Confidence: 0.93417254375 00:17:11.990 --> 00:17:14.400 inform how we understood safety. NOTE Confidence: 0.93417254375 00:17:14.400 --> 00:17:14.777 OK. NOTE Confidence: 0.93417254375 00:17:14.777 --> 00:17:15.908 As for tolerability, NOTE Confidence: 0.93417254375 00:17:15.908 --> 00:17:18.965 so we use what's called a which I'm NOTE Confidence: 0.93417254375 00:17:18.965 --> 00:17:21.805 sure many of you know a visual analog NOTE Confidence: 0.93417254375 00:17:21.883 --> 00:17:24.781 scale measure which is basically a NOTE Confidence: 0.93417254375 00:17:24.781 --> 00:17:27.291 horizontal line anchored with vertical NOTE Confidence: 0.93417254375 00:17:27.291 --> 00:17:30.717 lines that's you know prompt the, NOTE Confidence: 0.93417254375 00:17:30.720 --> 00:17:31.173 the, NOTE Confidence: 0.93417254375 00:17:31.173 --> 00:17:31.626 the, NOTE Confidence: 0.93417254375 00:17:31.626 --> 00:17:35.250 the individual to answer on that spectrum and NOTE Confidence: 0.871317273888889 00:17:35.341 --> 00:17:38.557 you know make a dash to indicate where. NOTE Confidence: 0.871317273888889 00:17:38.560 --> 00:17:41.320 So you know for example tolerability was you NOTE Confidence: 0.871317273888889 00:17:41.320 --> 00:17:44.460 know was one of those things and actually. NOTE Confidence: 0.871317273888889 00:17:44.460 --> 00:17:46.740 You know something about. NOTE Confidence: 0.871317273888889 00:17:46.740 --> 00:17:49.490 Just nomenclature or maybe semantics, NOTE Confidence: 0.871317273888889 00:17:49.490 --> 00:17:50.506 safety. Tolerability. NOTE Confidence: 0.871317273888889 00:17:50.506 --> 00:17:53.046 Those words seem to often. NOTE Confidence: 0.871317273888889 00:17:53.050 --> 00:17:54.386 They seem to have a lot of overlap, NOTE Confidence: 0.871317273888889 00:17:54.390 --> 00:17:56.946 but it seems to be this. NOTE Confidence: 0.871317273888889 00:17:56.950 --> 00:17:59.542 There are some important distinctions between NOTE Confidence: 0.871317273888889 00:17:59.542 --> 00:18:05.540 the two that I wanted to raise, and that's. NOTE Confidence: 0.871317273888889 00:18:05.540 --> 00:18:09.230 You know, go away based off. NOTE Confidence: 0.871317273888889 00:18:09.230 --> 00:18:13.940 Now the FDA looks at these things, so. NOTE Confidence: 0.871317273888889 00:18:13.940 --> 00:18:14.680 I'm sorry. NOTE Confidence: 0.803428058636364 00:18:18.910 --> 00:18:21.822 So do you at the FDA defines tolerability NOTE Confidence: 0.803428058636364 00:18:21.822 --> 00:18:24.787 as the degree to which overt adverse NOTE Confidence: 0.803428058636364 00:18:24.787 --> 00:18:27.709 effects can be tolerated by a patient NOTE Confidence: 0.803428058636364 00:18:27.710 --> 00:18:29.859 while safety is defined as the risk NOTE Confidence: 0.803428058636364 00:18:29.859 --> 00:18:32.526 to the subject or patient from a drug NOTE Confidence: 0.803428058636364 00:18:32.526 --> 00:18:34.678 or biologic assist by laboratory test NOTE Confidence: 0.803428058636364 00:18:34.678 --> 00:18:36.673 vital signs clinical adverse events NOTE Confidence: 0.803428058636364 00:18:36.673 --> 00:18:38.580 and other special safety tests. NOTE Confidence: 0.803428058636364 00:18:38.580 --> 00:18:41.370 So you know we keeping that in mind we NOTE Confidence: 0.803428058636364 00:18:41.443 --> 00:18:43.879 we try to distinguish between safety NOTE Confidence: 0.803428058636364 00:18:43.879 --> 00:18:46.339 and how we interpreted safety and. NOTE Confidence: 0.803428058636364 00:18:46.340 --> 00:18:49.580 Capability so a psychedelic effects. NOTE Confidence: 0.803428058636364 00:18:49.580 --> 00:18:53.096 We also used AVAS visual analog NOTE Confidence: 0.803428058636364 00:18:53.096 --> 00:18:55.808 scale version of the altered states NOTE Confidence: 0.803428058636364 00:18:55.808 --> 00:18:58.740 of consciousness. This was 23 items. NOTE Confidence: 0.803428058636364 00:18:58.740 --> 00:19:02.190 We also use the psycho psychotomimetic NOTE Confidence: 0.803428058636364 00:19:02.296 --> 00:19:03.710 effects scale. NOTE Confidence: 0.803428058636364 00:19:03.710 --> 00:19:07.028 And then we measured anxiety and NOTE Confidence: 0.803428058636364 00:19:07.028 --> 00:19:08.687 drug reinforcing effects. NOTE Confidence: 0.803428058636364 00:19:08.690 --> 00:19:11.805 You know, being a schedule one substance, NOTE Confidence: 0.803428058636364 00:19:11.810 --> 00:19:13.598 the psychedelic compounds NOTE Confidence: 0.803428058636364 00:19:13.598 --> 00:19:16.282 necessarily have been, you know, NOTE Confidence: 0.803428058636364 00:19:16.282 --> 00:19:18.512 viewed by the federal government NOTE Confidence: 0.803428058636364 00:19:18.512 --> 00:19:20.650 as highly addictive compounds. NOTE Confidence: 0.803428058636364 00:19:20.650 --> 00:19:21.890 That's part of the definition NOTE Confidence: 0.803428058636364 00:19:21.890 --> 00:19:23.130 of a schedule one substance. NOTE Confidence: 0.803428058636364 00:19:23.130 --> 00:19:24.222 So, you know, NOTE Confidence: 0.803428058636364 00:19:24.222 --> 00:19:26.406 naturally it's very important to assess, NOTE Confidence: 0.803428058636364 00:19:26.410 --> 00:19:29.580 you know, potential drug reinforcement. NOTE Confidence: 0.803428058636364 00:19:29.580 --> 00:19:31.800 And in terms of efficacy being NOTE Confidence: 0.803428058636364 00:19:31.800 --> 00:19:34.160 a clinical trial for depression, NOTE Confidence: 0.803428058636364 00:19:34.160 --> 00:19:36.416 we utilize the grid AMD which is you NOTE Confidence: 0.803428058636364 00:19:36.416 --> 00:19:38.814 know a well validated scale that's NOTE Confidence: 0.803428058636364 00:19:38.814 --> 00:19:41.454 used in clinical trials for depression, NOTE Confidence: 0.803428058636364 00:19:41.460 --> 00:19:46.280 our cutoff score being 17. NOTE Confidence: 0.803428058636364 00:19:46.280 --> 00:19:47.064 All right. NOTE Confidence: 0.803428058636364 00:19:47.064 --> 00:19:50.680 And so just to go over some of our, NOTE Confidence: 0.803428058636364 00:19:50.680 --> 00:19:53.544 our pertinent inclusion exclusion NOTE Confidence: 0.803428058636364 00:19:53.544 --> 00:19:56.585 criteria for the and overall it's NOTE Confidence: 0.803428058636364 00:19:56.585 --> 00:19:58.910 very consistent with the psychedelic NOTE Confidence: 0.803428058636364 00:19:58.995 --> 00:20:00.138 trials to date. NOTE Confidence: 0.803428058636364 00:20:00.140 --> 00:20:03.532 You know in our depressed group we we NOTE Confidence: 0.803428058636364 00:20:03.532 --> 00:20:05.731 define treatment refractory as you NOTE Confidence: 0.803428058636364 00:20:05.731 --> 00:20:08.699 know having at least one failed SSRI NOTE Confidence: 0.803428058636364 00:20:08.700 --> 00:20:10.980 treatment in the current episode. NOTE Confidence: 0.803428058636364 00:20:10.980 --> 00:20:12.930 You know we also appropriately and NOTE Confidence: 0.803428058636364 00:20:12.930 --> 00:20:14.634 that's really kind of required NOTE Confidence: 0.803428058636364 00:20:14.634 --> 00:20:16.329 patients not be taking it. NOTE Confidence: 0.803428058636364 00:20:16.330 --> 00:20:18.694 Depressants because of the NOTE Confidence: 0.803428058636364 00:20:18.694 --> 00:20:21.180 potential concerns of, you know, NOTE Confidence: 0.803428058636364 00:20:21.180 --> 00:20:23.310 an excess of serotonin such as, NOTE Confidence: 0.803428058636364 00:20:23.310 --> 00:20:23.844 you know, NOTE Confidence: 0.803428058636364 00:20:23.844 --> 00:20:25.446 leading to something like serotonin syndrome. NOTE Confidence: 0.803428058636364 00:20:25.450 --> 00:20:26.467 So, you know, NOTE Confidence: 0.803428058636364 00:20:26.467 --> 00:20:29.452 no one could be on a medication that NOTE Confidence: 0.803428058636364 00:20:29.452 --> 00:20:32.046 was potentiating their serotonin. NOTE Confidence: 0.803428058636364 00:20:32.046 --> 00:20:34.350 Likewise for supplements, NOTE Confidence: 0.803428058636364 00:20:34.350 --> 00:20:35.890 everyone had to begin treatment. NOTE Confidence: 0.803428058636364 00:20:35.890 --> 00:20:37.666 We excluded anyone with psychotic disorders, NOTE Confidence: 0.803428058636364 00:20:37.670 --> 00:20:38.213 history, NOTE Confidence: 0.803428058636364 00:20:38.213 --> 00:20:41.668 mania and in terms of suicide risk because, NOTE Confidence: 0.803428058636364 00:20:41.668 --> 00:20:43.746 you know a lot of these patients being NOTE Confidence: 0.803428058636364 00:20:43.746 --> 00:20:46.340 treated or resistant, you know, I had a. NOTE Confidence: 0.803428058636364 00:20:46.340 --> 00:20:50.638 Appreciable risk of suicide if not previous. NOTE Confidence: 0.803428058636364 00:20:50.640 --> 00:20:52.744 So we we've been really based it off NOTE Confidence: 0.803428058636364 00:20:52.744 --> 00:20:55.658 if we temporarily had recent elevated risk, NOTE Confidence: 0.803428058636364 00:20:55.660 --> 00:20:58.525 you know we excluded those NOTE Confidence: 0.803428058636364 00:20:58.525 --> 00:21:00.279 individuals for healthy controls. NOTE Confidence: 0.803428058636364 00:21:00.279 --> 00:21:03.668 We just wanted to be careful to minimize NOTE Confidence: 0.803428058636364 00:21:03.668 --> 00:21:08.380 their psychedelic use as a specific point. NOTE Confidence: 0.803428058636364 00:21:08.380 --> 00:21:12.738 OK, so here we have our consort chart NOTE Confidence: 0.803428058636364 00:21:12.740 --> 00:21:16.500 and you'll see that we we assessed 52. NOTE Confidence: 0.803428058636364 00:21:16.500 --> 00:21:18.859 People that called in a lot of NOTE Confidence: 0.803428058636364 00:21:18.859 --> 00:21:21.330 them you know found this online, NOTE Confidence: 0.803428058636364 00:21:21.330 --> 00:21:24.375 people looking for DMT to help themselves NOTE Confidence: 0.803428058636364 00:21:24.375 --> 00:21:27.289 with their with their mental health. NOTE Confidence: 0.803428058636364 00:21:27.290 --> 00:21:29.555 Many were deemed ineligible for NOTE Confidence: 0.803428058636364 00:21:29.555 --> 00:21:32.570 a variety of the normal reasons, NOTE Confidence: 0.803428058636364 00:21:32.570 --> 00:21:34.619 not meeting criteria, NOTE Confidence: 0.803428058636364 00:21:34.619 --> 00:21:36.668 having excluding diagnosis, NOTE Confidence: 0.803428058636364 00:21:36.670 --> 00:21:37.930 living too far away, NOTE Confidence: 0.803428058636364 00:21:37.930 --> 00:21:39.190 not being in treatments. NOTE Confidence: 0.803428058636364 00:21:39.190 --> 00:21:42.004 So we ultimately brought in 14 people, NOTE Confidence: 0.803428058636364 00:21:42.010 --> 00:21:43.516 two failed screening, NOTE Confidence: 0.803428058636364 00:21:43.516 --> 00:21:46.026 one didn't meet the minimum NOTE Confidence: 0.803428058636364 00:21:46.026 --> 00:21:47.030 depression severity. NOTE Confidence: 0.803428058636364 00:21:47.030 --> 00:21:49.760 Which was 17 and another head NOTE Confidence: 0.803428058636364 00:21:49.760 --> 00:21:51.580 ongoing substance use disorder. NOTE Confidence: 0.803428058636364 00:21:51.580 --> 00:21:54.359 So we enrolled 12 and we technically NOTE Confidence: 0.803428058636364 00:21:54.359 --> 00:21:56.819 had two dropouts and these were NOTE Confidence: 0.803428058636364 00:21:56.819 --> 00:21:59.598 individuals that did not you know even NOTE Confidence: 0.840802431538461 00:21:59.676 --> 00:22:02.051 really start the any of our testing NOTE Confidence: 0.840802431538461 00:22:02.051 --> 00:22:04.157 those sessions because you know one NOTE Confidence: 0.840802431538461 00:22:04.157 --> 00:22:06.154 didn't complete the paper so they NOTE Confidence: 0.840802431538461 00:22:06.154 --> 00:22:07.924 couldn't proceed and then the other NOTE Confidence: 0.840802431538461 00:22:07.924 --> 00:22:09.730 you know schedule wise wasn't able NOTE Confidence: 0.840802431538461 00:22:09.730 --> 00:22:11.820 to to connect and you know make NOTE Confidence: 0.840802431538461 00:22:11.820 --> 00:22:14.380 it make it in for the test days. NOTE Confidence: 0.840802431538461 00:22:14.380 --> 00:22:17.845 And so we had 1010 subjects complete. NOTE Confidence: 0.840802431538461 00:22:17.850 --> 00:22:19.402 The first Test day, NOTE Confidence: 0.840802431538461 00:22:19.402 --> 00:22:21.342 remember everyone got and at NOTE Confidence: 0.840802431538461 00:22:21.342 --> 00:22:23.569 first the .1 make per cake and NOTE Confidence: 0.840802431538461 00:22:23.569 --> 00:22:25.758 then the .3 make per kig dose. NOTE Confidence: 0.840802431538461 00:22:25.760 --> 00:22:27.638 And usually the time between those NOTE Confidence: 0.840802431538461 00:22:27.638 --> 00:22:29.569 two doses was usually a few days, NOTE Confidence: 0.840802431538461 00:22:29.570 --> 00:22:33.310 at least 72 hours overall. NOTE Confidence: 0.840802431538461 00:22:33.310 --> 00:22:35.165 And so out of these 10 subjects, NOTE Confidence: 0.840802431538461 00:22:35.170 --> 00:22:39.018 we had three healthy controls and 7th press. NOTE Confidence: 0.840802431538461 00:22:39.020 --> 00:22:41.550 This here is yes. NOTE Confidence: 0.838743591428571 00:22:42.060 --> 00:22:44.209 Do you want to say how we? NOTE Confidence: 0.838743591428571 00:22:44.210 --> 00:22:47.078 Decided whether someone would go from. NOTE Confidence: 0.838743591428571 00:22:47.080 --> 00:22:48.700 Oh yes, yes to another. NOTE Confidence: 0.876091802 00:22:49.450 --> 00:22:51.683 Right, right. So. You know we were NOTE Confidence: 0.876091802 00:22:51.683 --> 00:22:54.759 as I was kind of saying before being NOTE Confidence: 0.876091802 00:22:54.759 --> 00:22:57.296 very careful you wanted and this NOTE Confidence: 0.876091802 00:22:57.296 --> 00:22:59.384 being you know opponent substance. NOTE Confidence: 0.876091802 00:22:59.384 --> 00:23:02.352 We you know we asked every every NOTE Confidence: 0.876091802 00:23:02.352 --> 00:23:05.125 subject if you know they if they NOTE Confidence: 0.876091802 00:23:05.125 --> 00:23:07.431 were willing to come back for NOTE Confidence: 0.876091802 00:23:07.431 --> 00:23:09.717 a second dose after the first. NOTE Confidence: 0.876091802 00:23:09.720 --> 00:23:11.682 You know there was no there NOTE Confidence: 0.876091802 00:23:11.682 --> 00:23:12.990 was no pressure whatsoever. NOTE Confidence: 0.876091802 00:23:12.990 --> 00:23:15.105 You know just naturally them NOTE Confidence: 0.876091802 00:23:15.105 --> 00:23:17.760 being here voluntary but also this NOTE Confidence: 0.876091802 00:23:17.760 --> 00:23:20.060 independent to their their willingness NOTE Confidence: 0.876091802 00:23:20.060 --> 00:23:22.398 to return we also looked at. NOTE Confidence: 0.876091802 00:23:22.400 --> 00:23:24.619 Of a variety of things and assessing NOTE Confidence: 0.876091802 00:23:24.619 --> 00:23:26.668 whether we felt it was appropriate NOTE Confidence: 0.876091802 00:23:26.668 --> 00:23:28.383 for subjects to come back. NOTE Confidence: 0.876091802 00:23:28.390 --> 00:23:30.950 So we would look at together all their NOTE Confidence: 0.876091802 00:23:30.950 --> 00:23:33.197 readings of their blood pressures or NOTE Confidence: 0.876091802 00:23:33.197 --> 00:23:35.182 heart rate, their subjective effects. NOTE Confidence: 0.876091802 00:23:35.182 --> 00:23:35.990 You know, NOTE Confidence: 0.876091802 00:23:35.990 --> 00:23:39.266 during the acute session and you know, NOTE Confidence: 0.876091802 00:23:39.270 --> 00:23:41.028 during the entire session, you know, NOTE Confidence: 0.876091802 00:23:41.030 --> 00:23:42.486 there was three or four of us, NOTE Confidence: 0.876091802 00:23:42.490 --> 00:23:43.570 doctor Dsouza, myself, NOTE Confidence: 0.876091802 00:23:43.570 --> 00:23:46.216 a research nurse in RA, you know, NOTE Confidence: 0.876091802 00:23:46.216 --> 00:23:48.360 observing, writing down notes, etcetera. NOTE Confidence: 0.876091802 00:23:48.360 --> 00:23:50.610 So taken together, you know, NOTE Confidence: 0.876091802 00:23:50.610 --> 00:23:52.584 we we, we came to a consensus. NOTE Confidence: 0.876091802 00:23:52.590 --> 00:23:55.846 As a team for each subject and you NOTE Confidence: 0.876091802 00:23:55.846 --> 00:23:58.524 know whether to ultimately deem NOTE Confidence: 0.876091802 00:23:58.524 --> 00:24:01.971 appropriate to proceed and yes question. NOTE Confidence: 0.876091802 00:24:01.971 --> 00:24:02.528 So NOTE Confidence: 0.881829585 00:24:02.540 --> 00:24:04.308 in the most places NOTE Confidence: 0.793397974074074 00:24:04.320 --> 00:24:06.065 that are doing therapeutic psilocybin NOTE Confidence: 0.793397974074074 00:24:06.065 --> 00:24:08.140 or following the protocol that Johns NOTE Confidence: 0.793397974074074 00:24:08.140 --> 00:24:09.802 Hopkins developed 20 years ago where NOTE Confidence: 0.793397974074074 00:24:09.802 --> 00:24:11.858 you got the two people sitting and NOTE Confidence: 0.793397974074074 00:24:11.858 --> 00:24:13.733 providing her and sounds like you're NOTE Confidence: 0.793397974074074 00:24:13.733 --> 00:24:16.050 setting is sort of more just straight NOTE Confidence: 0.793397974074074 00:24:16.112 --> 00:24:18.416 observational and kind of more medicalized NOTE Confidence: 0.793397974074074 00:24:18.416 --> 00:24:20.489 and not providing that kind of. NOTE Confidence: 0.793397974074074 00:24:20.490 --> 00:24:21.630 Psychological support? What? NOTE Confidence: 0.793397974074074 00:24:21.630 --> 00:24:23.873 What? How do you, how do you, NOTE Confidence: 0.793397974074074 00:24:23.873 --> 00:24:25.319 how did you think about that? NOTE Confidence: 0.824778443636364 00:24:25.730 --> 00:24:27.225 Yeah. So that's exactly what NOTE Confidence: 0.824778443636364 00:24:27.225 --> 00:24:29.110 I was going to say here. NOTE Confidence: 0.824778443636364 00:24:29.110 --> 00:24:31.630 So perfect timing. NOTE Confidence: 0.824778443636364 00:24:31.630 --> 00:24:33.622 That's actually quite nice. NOTE Confidence: 0.824778443636364 00:24:33.622 --> 00:24:36.058 So, so this is our test day, NOTE Confidence: 0.824778443636364 00:24:36.060 --> 00:24:37.956 the test days happened in the NOTE Confidence: 0.824778443636364 00:24:37.956 --> 00:24:40.420 you know in the bio studies unit NOTE Confidence: 0.824778443636364 00:24:40.420 --> 00:24:42.877 BA which is on the 9th floor. NOTE Confidence: 0.824778443636364 00:24:42.880 --> 00:24:45.816 We we ran these and in terms of NOTE Confidence: 0.824778443636364 00:24:45.816 --> 00:24:48.349 the concept that was driving us, NOTE Confidence: 0.824778443636364 00:24:48.350 --> 00:24:51.129 we wanted, we you know we really NOTE Confidence: 0.824778443636364 00:24:51.129 --> 00:24:53.619 wanted to see you know what? NOTE Confidence: 0.824778443636364 00:24:53.620 --> 00:24:57.428 What effects? Are due to the medication, NOTE Confidence: 0.824778443636364 00:24:57.430 --> 00:24:59.530 the biology of what they're doing. NOTE Confidence: 0.824778443636364 00:24:59.530 --> 00:25:02.514 And so unlike philosophy, which, you know, NOTE Confidence: 0.824778443636364 00:25:02.514 --> 00:25:04.524 does, which are soliciting trial. NOTE Confidence: 0.824778443636364 00:25:04.530 --> 00:25:07.362 We had a very we had a dedicated NOTE Confidence: 0.824778443636364 00:25:07.362 --> 00:25:09.530 dosing room for just silybin. NOTE Confidence: 0.824778443636364 00:25:09.530 --> 00:25:12.347 It had it had nice artwork on the walls. NOTE Confidence: 0.824778443636364 00:25:12.350 --> 00:25:16.585 It had, you know, nice lighting plants. NOTE Confidence: 0.824778443636364 00:25:16.590 --> 00:25:18.585 No no lava lamp. NOTE Confidence: 0.824778443636364 00:25:18.585 --> 00:25:19.100 Are NOTE Confidence: 0.874826147142857 00:25:19.110 --> 00:25:20.167 we allowed to have those I'm not NOTE Confidence: 0.799214128666667 00:25:20.180 --> 00:25:23.978 even sure but but we had we had nice NOTE Confidence: 0.799214128666667 00:25:23.978 --> 00:25:26.692 lighting but no love the land and NOTE Confidence: 0.799214128666667 00:25:26.692 --> 00:25:28.946 and and background music you know we NOTE Confidence: 0.799214128666667 00:25:28.946 --> 00:25:31.437 had a very actually a very doctor NOTE Confidence: 0.799214128666667 00:25:31.437 --> 00:25:33.639 Sunshower had a very specific playlist NOTE Confidence: 0.799214128666667 00:25:33.639 --> 00:25:36.052 that he designed for the trial which NOTE Confidence: 0.799214128666667 00:25:36.052 --> 00:25:37.930 was well received by everyone but NOTE Confidence: 0.799214128666667 00:25:37.997 --> 00:25:40.221 you know so that was silybin for DMT NOTE Confidence: 0.799214128666667 00:25:40.221 --> 00:25:41.970 being that we wanted to really try NOTE Confidence: 0.799214128666667 00:25:41.970 --> 00:25:44.232 and start to get at well you know if NOTE Confidence: 0.799214128666667 00:25:44.232 --> 00:25:46.150 you don't have that those all those. NOTE Confidence: 0.799214128666667 00:25:46.150 --> 00:25:48.460 Setting dimensions present what happened. NOTE Confidence: 0.799214128666667 00:25:48.460 --> 00:25:50.585 So we specifically and intentionally NOTE Confidence: 0.799214128666667 00:25:50.585 --> 00:25:53.848 wanted to make it as very, you know, NOTE Confidence: 0.799214128666667 00:25:53.848 --> 00:25:56.256 not these words sterile but very simple, NOTE Confidence: 0.799214128666667 00:25:56.260 --> 00:25:57.848 very hospitalized. You know, NOTE Confidence: 0.799214128666667 00:25:57.848 --> 00:26:00.562 similar to how ketamine treatments are done. NOTE Confidence: 0.799214128666667 00:26:00.562 --> 00:26:03.180 And I can make some comparison because NOTE Confidence: 0.799214128666667 00:26:03.248 --> 00:26:05.718 I work in the the TRD service at the VA NOTE Confidence: 0.799214128666667 00:26:05.787 --> 00:26:08.278 we're giving ketamine to our veterans. NOTE Confidence: 0.799214128666667 00:26:08.278 --> 00:26:10.958 So you know, it was we did this and NOTE Confidence: 0.799214128666667 00:26:10.958 --> 00:26:12.779 then one of our EEG booths, NOTE Confidence: 0.799214128666667 00:26:12.780 --> 00:26:15.090 which is a square enclosed space, NOTE Confidence: 0.799214128666667 00:26:15.090 --> 00:26:16.802 you know, that's soundproof. NOTE Confidence: 0.799214128666667 00:26:16.802 --> 00:26:18.942 There was a hospital grade NOTE Confidence: 0.799214128666667 00:26:18.942 --> 00:26:21.140 reclining chair in it, you know, NOTE Confidence: 0.799214128666667 00:26:21.140 --> 00:26:23.870 kind of dim overhead fluorescent lighting NOTE Confidence: 0.799214128666667 00:26:23.870 --> 00:26:26.684 and no art on the walls, no music, you know, NOTE Confidence: 0.799214128666667 00:26:26.684 --> 00:26:29.289 just doctor D'souza and myself and you know, NOTE Confidence: 0.799214128666667 00:26:29.290 --> 00:26:32.450 the IV lines and you know, NOTE Confidence: 0.799214128666667 00:26:32.450 --> 00:26:34.550 and that that was the entire setup and, NOTE Confidence: 0.799214128666667 00:26:34.550 --> 00:26:36.486 you know, and so we stayed with them, NOTE Confidence: 0.799214128666667 00:26:36.490 --> 00:26:37.346 you know, NOTE Confidence: 0.799214128666667 00:26:37.346 --> 00:26:40.770 to be a source of support if needed. NOTE Confidence: 0.799214128666667 00:26:40.770 --> 00:26:42.880 But, you know, our, our, our, NOTE Confidence: 0.799214128666667 00:26:42.880 --> 00:26:45.580 our focus was to let subjects, NOTE Confidence: 0.799214128666667 00:26:45.580 --> 00:26:47.700 you know, experience the effects. NOTE Confidence: 0.799214128666667 00:26:47.700 --> 00:26:49.026 You know entirely. NOTE Confidence: 0.799214128666667 00:26:49.026 --> 00:26:52.120 On their own and not really guide. NOTE Confidence: 0.799214128666667 00:26:52.120 --> 00:26:54.630 So it was a very it was a very non NOTE Confidence: 0.799214128666667 00:26:54.705 --> 00:26:57.655 directed approach by design and NOTE Confidence: 0.799214128666667 00:26:57.655 --> 00:27:00.480 that and that's how we. NOTE Confidence: 0.799214128666667 00:27:00.480 --> 00:27:02.590 When about conducting the doses, NOTE Confidence: 0.848524062142857 00:27:03.010 --> 00:27:06.846 we decided. That he would not speak NOTE Confidence: 0.848524062142857 00:27:06.846 --> 00:27:10.649 to the subjects for the first five. NOTE Confidence: 0.848524062142857 00:27:10.650 --> 00:27:15.306 Minutes, because we were concerned that. NOTE Confidence: 0.848524062142857 00:27:15.310 --> 00:27:17.842 Interacting them with them NOTE Confidence: 0.848524062142857 00:27:17.842 --> 00:27:20.374 might disrupt the experience. NOTE Confidence: 0.848524062142857 00:27:20.380 --> 00:27:23.556 So unless the subject reached out to us. NOTE Confidence: 0.848524062142857 00:27:23.560 --> 00:27:25.920 And wanted to engage us. NOTE Confidence: 0.848524062142857 00:27:25.920 --> 00:27:27.520 We kind of remain. NOTE Confidence: 0.848524062142857 00:27:27.520 --> 00:27:29.120 Silent in the background, NOTE Confidence: 0.848524062142857 00:27:29.120 --> 00:27:31.415 we were standing a few feet away from them. NOTE Confidence: 0.848524062142857 00:27:31.420 --> 00:27:33.634 Even the instruction we gave the NOTE Confidence: 0.848524062142857 00:27:33.634 --> 00:27:35.580 subject was to indicate to us, NOTE Confidence: 0.848524062142857 00:27:35.580 --> 00:27:37.440 either by raising their hand, NOTE Confidence: 0.848524062142857 00:27:37.440 --> 00:27:39.822 the first change that they noticed NOTE Confidence: 0.848524062142857 00:27:39.822 --> 00:27:41.670 after the administration of PM. NOTE Confidence: 0.848524062142857 00:27:41.670 --> 00:27:45.158 But otherwise we we we didn't say anything. NOTE Confidence: 0.848524062142857 00:27:45.160 --> 00:27:47.862 I I guess the first interruption would NOTE Confidence: 0.848524062142857 00:27:47.862 --> 00:27:50.540 have been the the blood pressure cuff NOTE Confidence: 0.848524062142857 00:27:50.540 --> 00:27:52.820 being inflated at about 5 minutes. NOTE Confidence: 0.848524062142857 00:27:52.820 --> 00:27:54.180 But otherwise we kept quiet NOTE Confidence: 0.848524062142857 00:27:54.180 --> 00:27:55.540 because we can see anything. NOTE Confidence: 0.848524062142857 00:27:55.540 --> 00:27:57.220 So there was just to be clear, NOTE Confidence: 0.848524062142857 00:27:57.220 --> 00:27:59.465 no psychotherapy the way that NOTE Confidence: 0.848524062142857 00:27:59.465 --> 00:28:02.360 psychotherapy is done for psychic studies. NOTE Confidence: 0.821002704666667 00:28:02.370 --> 00:28:04.580 Yeah it it is worth I mean this is of NOTE Confidence: 0.821002704666667 00:28:04.642 --> 00:28:06.609 course a super active issue in the NOTE Confidence: 0.821002704666667 00:28:06.609 --> 00:28:09.091 in the field in which about which I NOTE Confidence: 0.821002704666667 00:28:09.091 --> 00:28:10.852 don't have strong opinions but but NOTE Confidence: 0.821002704666667 00:28:10.852 --> 00:28:12.056 it's with sure even what you just NOTE Confidence: 0.821002704666667 00:28:12.056 --> 00:28:13.043 noticed they're two different things NOTE Confidence: 0.821002704666667 00:28:13.043 --> 00:28:14.255 that you're trying to keep neutral. NOTE Confidence: 0.821002704666667 00:28:14.260 --> 00:28:16.040 There's the environment and NOTE Confidence: 0.821002704666667 00:28:16.040 --> 00:28:17.794 there's the guidance, right. NOTE Confidence: 0.821002704666667 00:28:17.794 --> 00:28:20.692 So you could have an unmet actualized NOTE Confidence: 0.821002704666667 00:28:20.692 --> 00:28:22.410 environment with no guidance. NOTE Confidence: 0.821002704666667 00:28:22.410 --> 00:28:24.438 Have a medicalized environment with guidance. NOTE Confidence: 0.821002704666667 00:28:24.440 --> 00:28:25.970 And so it's just you know, NOTE Confidence: 0.821002704666667 00:28:25.970 --> 00:28:28.364 in think trying to wrap our heads NOTE Confidence: 0.821002704666667 00:28:28.364 --> 00:28:30.305 around what matters and what doesn't NOTE Confidence: 0.821002704666667 00:28:30.305 --> 00:28:32.368 and I have no idea and I'm just, NOTE Confidence: 0.821002704666667 00:28:32.368 --> 00:28:33.448 I'm trying to keep these NOTE Confidence: 0.821002704666667 00:28:33.448 --> 00:28:34.369 things straight in my head, NOTE Confidence: 0.821002704666667 00:28:34.370 --> 00:28:35.520 but thank you for that, NOTE Confidence: 0.821002704666667 00:28:35.520 --> 00:28:36.399 for that clarification. NOTE Confidence: 0.821002704666667 00:28:36.399 --> 00:28:37.278 That's really helpful. NOTE Confidence: 0.815396619166667 00:28:38.040 --> 00:28:40.020 Yes, I continue to struggle NOTE Confidence: 0.815396619166667 00:28:40.020 --> 00:28:42.870 to keep them in my head too. NOTE Confidence: 0.815396619166667 00:28:42.870 --> 00:28:45.640 And so just at 30 minutes we we gave them NOTE Confidence: 0.815396619166667 00:28:45.715 --> 00:28:48.284 scales to you know assess the effects. NOTE Confidence: 0.815396619166667 00:28:48.290 --> 00:28:50.486 So remember by about 30 minutes NOTE Confidence: 0.815396619166667 00:28:50.486 --> 00:28:52.310 they basically resolved but you NOTE Confidence: 0.815396619166667 00:28:52.310 --> 00:28:54.354 know they they were able to kind NOTE Confidence: 0.815396619166667 00:28:54.354 --> 00:28:56.265 of capture what they felt were NOTE Confidence: 0.815396619166667 00:28:56.265 --> 00:28:58.465 the peak effects and then again 2 NOTE Confidence: 0.815396619166667 00:28:58.465 --> 00:29:00.825 hour at the two hour mark and this NOTE Confidence: 0.815396619166667 00:29:00.825 --> 00:29:03.634 is where we assess tolerability 2 NOTE Confidence: 0.815396619166667 00:29:03.634 --> 00:29:06.340 hours after receiving drug. OK. NOTE Confidence: 0.858331661818182 00:29:06.390 --> 00:29:07.566 So we just just one other NOTE Confidence: 0.858331661818182 00:29:07.566 --> 00:29:08.770 thing I wanted to mention. NOTE Confidence: 0.858331661818182 00:29:08.770 --> 00:29:12.984 We chose to administer all those scales. NOTE Confidence: 0.858331661818182 00:29:12.990 --> 00:29:15.924 When we were confident that the NOTE Confidence: 0.858331661818182 00:29:15.924 --> 00:29:18.830 acute effects of BMD would be. NOTE Confidence: 0.858331661818182 00:29:18.830 --> 00:29:20.916 Would have faded away because we were NOTE Confidence: 0.858331661818182 00:29:20.916 --> 00:29:22.888 concerned that while under the influence, NOTE Confidence: 0.858331661818182 00:29:22.890 --> 00:29:24.941 people may not be able to accurately NOTE Confidence: 0.858331661818182 00:29:24.941 --> 00:29:27.109 describe or report what they were feeling. NOTE Confidence: 0.858331661818182 00:29:27.110 --> 00:29:29.040 So we waited to yeah. NOTE Confidence: 0.9151664 00:29:30.450 --> 00:29:34.040 Yes. OK, so let's start NOTE Confidence: 0.9151664 00:29:34.040 --> 00:29:35.620 to present the results. NOTE Confidence: 0.9151664 00:29:35.620 --> 00:29:37.852 Here's our demographic table. NOTE Confidence: 0.9151664 00:29:37.852 --> 00:29:41.200 Notice that our our first three. NOTE Confidence: 0.9151664 00:29:41.200 --> 00:29:43.300 Rows are healthy control subjects NOTE Confidence: 0.9151664 00:29:43.300 --> 00:29:45.400 and then the remaining seven NOTE Confidence: 0.9151664 00:29:45.468 --> 00:29:47.500 are are depressed individuals. NOTE Confidence: 0.9151664 00:29:47.500 --> 00:29:53.060 Overall, there are subjects had about NOTE Confidence: 0.9151664 00:29:53.060 --> 00:29:56.533 an illness burden of at least 20 NOTE Confidence: 0.9151664 00:29:56.533 --> 00:29:59.795 years and most of them were educated, NOTE Confidence: 0.9151664 00:29:59.800 --> 00:30:02.808 quite educated graduate degrees. NOTE Confidence: 0.9151664 00:30:02.810 --> 00:30:04.370 Previous academic use was, NOTE Confidence: 0.9151664 00:30:04.370 --> 00:30:05.848 you know, very limited. NOTE Confidence: 0.9151664 00:30:05.848 --> 00:30:07.942 You know, there was one or NOTE Confidence: 0.9151664 00:30:07.942 --> 00:30:09.963 two discrete at the uses for NOTE Confidence: 0.9151664 00:30:09.963 --> 00:30:11.533 for maybe half of subjects. NOTE Confidence: 0.873526786 00:30:13.570 --> 00:30:16.100 And notably in terms of, you know, NOTE Confidence: 0.873526786 00:30:16.100 --> 00:30:17.625 what makes them treatment resistant, NOTE Confidence: 0.873526786 00:30:17.630 --> 00:30:19.150 looking at the, you know, NOTE Confidence: 0.873526786 00:30:19.150 --> 00:30:21.740 past past antidepressant trials failed, NOTE Confidence: 0.873526786 00:30:21.740 --> 00:30:23.434 you know, we had quite a few NOTE Confidence: 0.873526786 00:30:23.434 --> 00:30:25.168 subjects that you know did not have, NOTE Confidence: 0.873526786 00:30:25.170 --> 00:30:27.170 you know, relief with ketamine, NOTE Confidence: 0.873526786 00:30:27.170 --> 00:30:30.850 ECT, RTMS and you know, NOTE Confidence: 0.873526786 00:30:30.850 --> 00:30:33.490 really the most robust NOTE Confidence: 0.873526786 00:30:33.490 --> 00:30:35.854 treatments that are offered. NOTE Confidence: 0.873526786 00:30:35.854 --> 00:30:38.372 So you know, so these are pretty, NOTE Confidence: 0.873526786 00:30:38.372 --> 00:30:39.562 these were pretty ill patients. NOTE Confidence: 0.828734964 00:30:42.130 --> 00:30:45.434 And in terms of our healthy controls and NOTE Confidence: 0.828734964 00:30:45.434 --> 00:30:48.994 to also note no one had used DMT before NOTE Confidence: 0.828734964 00:30:48.994 --> 00:30:52.457 that that we were also made certain of. NOTE Confidence: 0.828734964 00:30:52.460 --> 00:30:54.266 OK. So next we'll be going through NOTE Confidence: 0.828734964 00:30:54.266 --> 00:30:56.289 the results in the order of the NOTE Confidence: 0.828734964 00:30:56.289 --> 00:30:57.700 outcome measures, as I said. NOTE Confidence: 0.828734964 00:30:57.700 --> 00:31:00.616 So say in terms of safety, looking at our, NOTE Confidence: 0.828734964 00:31:00.616 --> 00:31:02.776 our cardiac parameters going from NOTE Confidence: 0.828734964 00:31:02.776 --> 00:31:05.998 left to right just to Orient everyone, NOTE Confidence: 0.828734964 00:31:06.000 --> 00:31:08.856 the red lines are going to represent NOTE Confidence: 0.828734964 00:31:08.860 --> 00:31:11.478 the blue lines represent the .1 dose, NOTE Confidence: 0.828734964 00:31:11.480 --> 00:31:13.783 so the the the first session and NOTE Confidence: 0.828734964 00:31:13.783 --> 00:31:15.870 then the red lines present. NOTE Confidence: 0.828734964 00:31:15.870 --> 00:31:19.082 The .3 dose the second session and NOTE Confidence: 0.828734964 00:31:19.082 --> 00:31:21.406 so going and the green arrows here, NOTE Confidence: 0.828734964 00:31:21.410 --> 00:31:24.476 they represent the time point at which NOTE Confidence: 0.828734964 00:31:24.476 --> 00:31:28.842 the DMT I bolus was given over 30 to 60 NOTE Confidence: 0.828734964 00:31:28.842 --> 00:31:31.406 seconds just just so everyone is clear. NOTE Confidence: 0.828734964 00:31:31.410 --> 00:31:34.470 And so going from left to right we see, NOTE Confidence: 0.828734964 00:31:34.470 --> 00:31:37.718 we see an expected increase in all three NOTE Confidence: 0.828734964 00:31:37.718 --> 00:31:39.741 measures, systolic blood pressure, NOTE Confidence: 0.828734964 00:31:39.741 --> 00:31:42.963 diastolic blood pressure and heart rates, NOTE Confidence: 0.828734964 00:31:42.970 --> 00:31:46.600 the magnitude of the increase. NOTE Confidence: 0.828734964 00:31:46.600 --> 00:31:47.182 I would say, NOTE Confidence: 0.828734964 00:31:47.182 --> 00:31:49.100 and you know I know there are many experts NOTE Confidence: 0.828734964 00:31:49.100 --> 00:31:50.892 here in the audience and know better. NOTE Confidence: 0.828734964 00:31:50.900 --> 00:31:51.644 You know, NOTE Confidence: 0.828734964 00:31:51.644 --> 00:31:52.760 comparing to ketamine, NOTE Confidence: 0.828734964 00:31:52.760 --> 00:31:55.060 it's also associated with a NOTE Confidence: 0.828734964 00:31:55.060 --> 00:31:57.360 transient increase in blood pressure. NOTE Confidence: 0.828734964 00:31:57.360 --> 00:31:59.286 It seems about similar from what NOTE Confidence: 0.828734964 00:31:59.286 --> 00:32:01.620 I get from my understanding. NOTE Confidence: 0.890006884705882 00:32:03.900 --> 00:32:05.745 But, you know, one of the one thing I NOTE Confidence: 0.890006884705882 00:32:05.745 --> 00:32:07.716 think that is different is the heart rate. NOTE Confidence: 0.890006884705882 00:32:07.720 --> 00:32:11.600 That was pretty impressively increased NOTE Confidence: 0.890006884705882 00:32:11.600 --> 00:32:14.704 acutely after administering DMT. NOTE Confidence: 0.890006884705882 00:32:14.710 --> 00:32:18.010 Not of that being more. NOTE Confidence: 0.890006884705882 00:32:18.010 --> 00:32:20.749 That being dose. NOTE Confidence: 0.890006884705882 00:32:20.750 --> 00:32:22.622 Difference between doses for NOTE Confidence: 0.890006884705882 00:32:22.622 --> 00:32:24.962 the other for blood pressure, NOTE Confidence: 0.890006884705882 00:32:24.970 --> 00:32:26.738 they were fairly similar. NOTE Confidence: 0.890006884705882 00:32:26.738 --> 00:32:28.506 Heart rate still wasn't NOTE Confidence: 0.890006884705882 00:32:28.506 --> 00:32:29.802 statistically significant overall NOTE Confidence: 0.890006884705882 00:32:29.802 --> 00:32:31.567 given all these time points, NOTE Confidence: 0.890006884705882 00:32:31.570 --> 00:32:34.585 but you know at at this one time point NOTE Confidence: 0.890006884705882 00:32:34.585 --> 00:32:37.298 certainly that was significantly different. NOTE Confidence: 0.890006884705882 00:32:37.300 --> 00:32:40.219 OK, so next here we have a NOTE Confidence: 0.890006884705882 00:32:40.219 --> 00:32:42.200 graphic illustration of our NOTE Confidence: 0.890006884705882 00:32:42.200 --> 00:32:44.138 psychedelic affect ratings. NOTE Confidence: 0.890006884705882 00:32:44.140 --> 00:32:47.636 So this this is our modified AC scale. NOTE Confidence: 0.890006884705882 00:32:47.640 --> 00:32:50.832 These are the 23 items that query NOTE Confidence: 0.890006884705882 00:32:50.832 --> 00:32:52.960 that the psychedelic effects. NOTE Confidence: 0.890006884705882 00:32:52.960 --> 00:32:54.480 And you'll notice, you know, NOTE Confidence: 0.890006884705882 00:32:54.480 --> 00:32:57.640 the red is quite long and so right NOTE Confidence: 0.890006884705882 00:32:57.640 --> 00:33:00.278 there more intense the .3 dose. NOTE Confidence: 0.890006884705882 00:33:00.280 --> 00:33:02.220 The the bars here represent NOTE Confidence: 0.890006884705882 00:33:02.220 --> 00:33:04.160 standard errors of the mean. NOTE Confidence: 0.890006884705882 00:33:04.160 --> 00:33:05.812 And I guess I'd like to bring NOTE Confidence: 0.890006884705882 00:33:05.812 --> 00:33:07.228 your attention to a few of the. NOTE Confidence: 0.890006884705882 00:33:07.230 --> 00:33:09.450 Items here. NOTE Confidence: 0.890006884705882 00:33:09.450 --> 00:33:11.460 You know the last item here, NOTE Confidence: 0.890006884705882 00:33:11.460 --> 00:33:13.410 how intense was the drug NOTE Confidence: 0.890006884705882 00:33:13.410 --> 00:33:14.580 experience on average? NOTE Confidence: 0.890006884705882 00:33:14.580 --> 00:33:16.530 You know, people found the .3 NOTE Confidence: 0.890006884705882 00:33:16.530 --> 00:33:18.897 dose to be about 95 out of 100. NOTE Confidence: 0.890006884705882 00:33:18.900 --> 00:33:21.960 So that that does seem to be quite telling NOTE Confidence: 0.890006884705882 00:33:21.960 --> 00:33:25.490 of just how intense the the experience was. NOTE Confidence: 0.890006884705882 00:33:25.490 --> 00:33:28.140 Also subjects found that the NOTE Confidence: 0.890006884705882 00:33:28.140 --> 00:33:31.139 experience was much more challenging, NOTE Confidence: 0.890006884705882 00:33:31.140 --> 00:33:32.740 but the .3 dose, NOTE Confidence: 0.890006884705882 00:33:32.740 --> 00:33:36.020 you know about 65 versus. NOTE Confidence: 0.890006884705882 00:33:36.020 --> 00:33:39.140 You know 25. NOTE Confidence: 0.890006884705882 00:33:39.140 --> 00:33:40.355 But they also, NOTE Confidence: 0.890006884705882 00:33:40.355 --> 00:33:43.190 you see they found the those the NOTE Confidence: 0.890006884705882 00:33:43.285 --> 00:33:46.480 experience being much more meaningful NOTE Confidence: 0.890006884705882 00:33:46.480 --> 00:33:49.176 and so the ones with the asterisks here, NOTE Confidence: 0.890006884705882 00:33:49.180 --> 00:33:51.116 these are all significantly NOTE Confidence: 0.890006884705882 00:33:51.116 --> 00:33:54.020 different between those the the two NOTE Confidence: 0.890006884705882 00:33:54.103 --> 00:33:56.545 stars means you know it's greater NOTE Confidence: 0.890006884705882 00:33:56.545 --> 00:33:59.231 smaller P value and this was NOTE Confidence: 0.890006884705882 00:33:59.231 --> 00:34:03.350 corrected for false discovery rates. NOTE Confidence: 0.890006884705882 00:34:03.350 --> 00:34:04.310 And, you know, NOTE Confidence: 0.890006884705882 00:34:04.310 --> 00:34:06.452 there's only so much that, you know, NOTE Confidence: 0.890006884705882 00:34:06.452 --> 00:34:07.536 these, the graphic illustrations NOTE Confidence: 0.890006884705882 00:34:07.536 --> 00:34:08.800 and scales can tell us. NOTE Confidence: 0.890006884705882 00:34:08.800 --> 00:34:11.299 So included here we have one of NOTE Confidence: 0.890006884705882 00:34:11.299 --> 00:34:13.070 our healthy control subjects. NOTE Confidence: 0.890006884705882 00:34:13.070 --> 00:34:14.930 Now that, you know, went, NOTE Confidence: 0.890006884705882 00:34:14.930 --> 00:34:17.346 I was able to draw for us what NOTE Confidence: 0.890006884705882 00:34:17.346 --> 00:34:19.509 what their experience was like. NOTE Confidence: 0.890006884705882 00:34:19.510 --> 00:34:23.166 So I'll show you a few drawings so, NOTE Confidence: 0.890006884705882 00:34:23.166 --> 00:34:26.054 you know, it's written here, you know, NOTE Confidence: 0.890006884705882 00:34:26.054 --> 00:34:28.166 this turns into a cavernous room NOTE Confidence: 0.890006884705882 00:34:28.166 --> 00:34:29.850 that's depicted in the drawing. NOTE Confidence: 0.890006884705882 00:34:29.850 --> 00:34:30.603 It was domed, NOTE Confidence: 0.890006884705882 00:34:30.603 --> 00:34:32.360 and the ceiling and walls had the NOTE Confidence: 0.890006884705882 00:34:32.414 --> 00:34:34.066 same sort of look as the mucks. NOTE Confidence: 0.890006884705882 00:34:34.070 --> 00:34:36.220 Filling in the attached picture, NOTE Confidence: 0.890006884705882 00:34:36.220 --> 00:34:37.720 the main difference is that NOTE Confidence: 0.890006884705882 00:34:37.720 --> 00:34:39.909 everything was made out of light and NOTE Confidence: 0.890006884705882 00:34:39.909 --> 00:34:42.514 was moving quite quickly and so. NOTE Confidence: 0.890006884705882 00:34:42.514 --> 00:34:43.858 So yeah. NOTE Confidence: 0.60237566 00:34:46.270 --> 00:34:49.130 It's smooth solids, tiled shapes, NOTE Confidence: 0.60237566 00:34:49.130 --> 00:34:53.310 tiled shapes, interesting puzzle like. NOTE Confidence: 0.60237566 00:34:53.310 --> 00:34:58.378 Things. Looks like a double Helix there. NOTE Confidence: 0.60237566 00:34:58.380 --> 00:35:01.216 And so this was the mosque picture NOTE Confidence: 0.60237566 00:35:01.216 --> 00:35:02.480 that they're referring to. NOTE Confidence: 0.60237566 00:35:02.480 --> 00:35:04.204 So apparently, you know, NOTE Confidence: 0.60237566 00:35:04.204 --> 00:35:07.812 their experience was a light. You know, NOTE Confidence: 0.60237566 00:35:07.812 --> 00:35:11.280 complex that looks something like this. NOTE Confidence: 0.60237566 00:35:11.280 --> 00:35:14.940 Seems pretty impressive to me. NOTE Confidence: 0.60237566 00:35:14.940 --> 00:35:17.192 Then more more details. NOTE Confidence: 0.60237566 00:35:17.192 --> 00:35:20.007 So this then gave way NOTE Confidence: 0.60237566 00:35:20.007 --> 00:35:22.759 depicted in the entity space, NOTE Confidence: 0.60237566 00:35:22.760 --> 00:35:25.154 drawing what felt like a different NOTE Confidence: 0.60237566 00:35:25.154 --> 00:35:27.818 a temporal realm with its own order. NOTE Confidence: 0.60237566 00:35:27.820 --> 00:35:30.564 Here all surfaces were smooth and uniform in NOTE Confidence: 0.60237566 00:35:30.564 --> 00:35:33.516 color as as as if they were enamel painted. NOTE Confidence: 0.60237566 00:35:33.520 --> 00:35:35.794 The two flying beings pictured had NOTE Confidence: 0.60237566 00:35:35.794 --> 00:35:38.381 round bodies that were smooth but Matt NOTE Confidence: 0.60237566 00:35:38.381 --> 00:35:40.680 gun metal Gray as per the back wings. NOTE Confidence: 0.60237566 00:35:40.680 --> 00:35:43.104 Their color and texture were like that of NOTE Confidence: 0.60237566 00:35:43.104 --> 00:35:45.288 those glossy dark red KitchenAid mixers. NOTE Confidence: 0.60237566 00:35:45.290 --> 00:35:46.952 I don't remember the color of NOTE Confidence: 0.60237566 00:35:46.952 --> 00:35:48.690 their front winglets or appendages, NOTE Confidence: 0.60237566 00:35:48.690 --> 00:35:50.266 but I do remember that they were vague, NOTE Confidence: 0.60237566 00:35:50.270 --> 00:35:51.206 being vaguely there. NOTE Confidence: 0.60237566 00:35:51.206 --> 00:35:53.078 They had no eyes or faces, NOTE Confidence: 0.60237566 00:35:53.080 --> 00:35:55.738 but were somehow looking at me. NOTE Confidence: 0.60237566 00:35:55.740 --> 00:35:58.629 So I mean that's what these are referring to. NOTE Confidence: 0.883705195714286 00:35:59.020 --> 00:36:01.428 One of the reasons we thought we NOTE Confidence: 0.883705195714286 00:36:01.428 --> 00:36:03.938 would share this with you is because. NOTE Confidence: 0.883705195714286 00:36:03.940 --> 00:36:06.499 Anecdotally, at least. NOTE Confidence: 0.883705195714286 00:36:06.500 --> 00:36:09.220 There are a number of reports of people. NOTE Confidence: 0.883705195714286 00:36:09.220 --> 00:36:13.100 To claim. To see entities or NOTE Confidence: 0.883705195714286 00:36:13.100 --> 00:36:15.700 feel the presence of entities. NOTE Confidence: 0.883705195714286 00:36:15.700 --> 00:36:17.500 After the CPMT. NOTE Confidence: 0.840820142272727 00:36:19.940 --> 00:36:21.669 And so I think this was the NOTE Confidence: 0.840820142272727 00:36:21.669 --> 00:36:23.163 only subject in our entire NOTE Confidence: 0.840820142272727 00:36:23.163 --> 00:36:25.233 subject list of 10 subjects who NOTE Confidence: 0.840820142272727 00:36:25.233 --> 00:36:26.560 reported anything like this, NOTE Confidence: 0.840820142272727 00:36:26.560 --> 00:36:30.760 but what it highlighted for me is. NOTE Confidence: 0.840820142272727 00:36:30.760 --> 00:36:33.328 What you bring to the occasion NOTE Confidence: 0.840820142272727 00:36:33.330 --> 00:36:34.800 is likely what's going to. NOTE Confidence: 0.86801729 00:36:37.280 --> 00:36:38.246 Influence your experience. NOTE Confidence: 0.86801729 00:36:38.246 --> 00:36:39.856 So this is a subject NOTE Confidence: 0.86801729 00:36:39.856 --> 00:36:41.479 from the Divinity school. NOTE Confidence: 0.86801729 00:36:41.480 --> 00:36:45.084 So no, no surprise that he saw NOTE Confidence: 0.86801729 00:36:45.084 --> 00:36:47.408 the inside of a mosque and that's NOTE Confidence: 0.86801729 00:36:47.408 --> 00:36:49.760 how he described it and and many NOTE Confidence: 0.86801729 00:36:49.760 --> 00:36:51.861 of many of his interpretations NOTE Confidence: 0.86801729 00:36:51.861 --> 00:36:54.757 of these perceptual alterations. NOTE Confidence: 0.86801729 00:36:54.760 --> 00:36:57.490 Had religious connotations. NOTE Confidence: 0.871832387333333 00:36:59.790 --> 00:37:03.038 Yeah, it it was remarkable just to mention NOTE Confidence: 0.871832387333333 00:37:03.038 --> 00:37:05.576 anecdotally that a lot of the perceptual. NOTE Confidence: 0.871832387333333 00:37:05.580 --> 00:37:08.148 Changes that subject experience did have, NOTE Confidence: 0.871832387333333 00:37:08.150 --> 00:37:09.726 you know, temporal relation NOTE Confidence: 0.871832387333333 00:37:09.726 --> 00:37:12.090 to things they had seen and. NOTE Confidence: 0.871832387333333 00:37:12.090 --> 00:37:13.945 Recent like the day before the experience NOTE Confidence: 0.871832387333333 00:37:13.945 --> 00:37:15.740 or you know something actually, NOTE Confidence: 0.871832387333333 00:37:15.740 --> 00:37:17.420 you know, long standing and you know NOTE Confidence: 0.871832387333333 00:37:17.420 --> 00:37:19.367 maybe in their subconscious so to speak, NOTE Confidence: 0.871832387333333 00:37:19.370 --> 00:37:20.710 but that's, you know, NOTE Confidence: 0.871832387333333 00:37:20.710 --> 00:37:22.960 for another sort of talk. OK. NOTE Confidence: 0.871832387333333 00:37:22.960 --> 00:37:26.380 So move back to our results. NOTE Confidence: 0.871832387333333 00:37:26.380 --> 00:37:30.433 So these are the the assessments of NOTE Confidence: 0.871832387333333 00:37:30.433 --> 00:37:33.600 using the psychotomimetic effects scale. NOTE Confidence: 0.871832387333333 00:37:33.600 --> 00:37:36.144 So as you can see there was an NOTE Confidence: 0.871832387333333 00:37:36.144 --> 00:37:38.792 acute elevation much that in the NOTE Confidence: 0.871832387333333 00:37:38.792 --> 00:37:41.307 with both doses the difference NOTE Confidence: 0.871832387333333 00:37:41.307 --> 00:37:44.657 being more significant than the .3. NOTE Confidence: 0.871832387333333 00:37:44.660 --> 00:37:46.754 Notably you see at baseline they're NOTE Confidence: 0.871832387333333 00:37:46.754 --> 00:37:49.226 being you know it's it wasn't a NOTE Confidence: 0.871832387333333 00:37:49.226 --> 00:37:51.242 negligible you know baseline and the NOTE Confidence: 0.871832387333333 00:37:51.242 --> 00:37:53.832 next slide look if we break it down into NOTE Confidence: 0.871832387333333 00:37:53.832 --> 00:37:55.928 its six subscales we can understand. NOTE Confidence: 0.871832387333333 00:37:55.928 --> 00:37:58.626 A little bit better you know what NOTE Confidence: 0.871832387333333 00:37:58.626 --> 00:38:00.719 what what the PSI was picking up NOTE Confidence: 0.871832387333333 00:38:00.719 --> 00:38:03.464 and so the only two scales that NOTE Confidence: 0.871832387333333 00:38:03.464 --> 00:38:05.539 were significant were the perceptual NOTE Confidence: 0.871832387333333 00:38:05.540 --> 00:38:07.704 distortion and cognitive disorganization. NOTE Confidence: 0.871832387333333 00:38:07.704 --> 00:38:11.719 The other four were not and you know NOTE Confidence: 0.871832387333333 00:38:11.719 --> 00:38:14.620 I guess this here tells us what you NOTE Confidence: 0.871832387333333 00:38:14.620 --> 00:38:17.140 saw before which was that baseline NOTE Confidence: 0.871832387333333 00:38:17.140 --> 00:38:19.608 our depressed subjects reported more NOTE Confidence: 0.871832387333333 00:38:19.608 --> 00:38:22.027 Antonia makes sense but that also NOTE Confidence: 0.871832387333333 00:38:22.027 --> 00:38:23.472 you know brings really important NOTE Confidence: 0.871832387333333 00:38:23.472 --> 00:38:25.480 point to stand that now it's really NOTE Confidence: 0.871832387333333 00:38:25.480 --> 00:38:26.850 important to look at the. NOTE Confidence: 0.871832387333333 00:38:26.850 --> 00:38:28.968 Change in the effects because if NOTE Confidence: 0.871832387333333 00:38:28.968 --> 00:38:31.702 one just looks at the objective one NOTE Confidence: 0.871832387333333 00:38:31.702 --> 00:38:34.198 time point that may miss something, NOTE Confidence: 0.871832387333333 00:38:34.200 --> 00:38:36.839 especially when we're talking about you know, NOTE Confidence: 0.871832387333333 00:38:36.840 --> 00:38:39.068 depressed individuals who are NOTE Confidence: 0.871832387333333 00:38:39.068 --> 00:38:41.853 experiencing symptoms that are affecting, NOTE Confidence: 0.871832387333333 00:38:41.860 --> 00:38:42.808 you know, NOTE Confidence: 0.871832387333333 00:38:42.808 --> 00:38:44.704 their experiences including you NOTE Confidence: 0.871832387333333 00:38:44.704 --> 00:38:46.600 know their perception etcetera. NOTE Confidence: 0.871832387333333 00:38:46.600 --> 00:38:47.580 Sharif. NOTE Confidence: 0.871832387333333 00:38:47.580 --> 00:38:48.045 Yes. NOTE Confidence: 0.871832387333333 00:38:48.045 --> 00:38:48.510 So NOTE Confidence: 0.836401929 00:38:48.520 --> 00:38:50.832 that what you have is the 30 minute NOTE Confidence: 0.836401929 00:38:50.832 --> 00:38:52.885 time point that's the scale is NOTE Confidence: 0.836401929 00:38:52.885 --> 00:38:54.645 administered at 30 minutes after NOTE Confidence: 0.836401929 00:38:54.645 --> 00:38:57.388 the acute effects have dissipated. NOTE Confidence: 0.836401929 00:38:57.390 --> 00:38:59.922 Yes. And are they asked to rate NOTE Confidence: 0.836401929 00:38:59.922 --> 00:39:02.125 their memory of the maximum effect NOTE Confidence: 0.836401929 00:39:02.125 --> 00:39:05.553 within the last 30 minutes? Yes. OK. NOTE Confidence: 0.836401929 00:39:05.553 --> 00:39:07.497 And then at the 120 minute time point NOTE Confidence: 0.836401929 00:39:07.497 --> 00:39:09.254 and at the -, 60 minute time point, NOTE Confidence: 0.836401929 00:39:09.254 --> 00:39:11.035 I presume they're asked to rate how NOTE Confidence: 0.836401929 00:39:11.035 --> 00:39:13.240 they're feeling right now. Yes. NOTE Confidence: 0.691046962 00:39:13.490 --> 00:39:14.962 So just to clarification, NOTE Confidence: 0.691046962 00:39:14.962 --> 00:39:16.620 so at mine, at baseline, NOTE Confidence: 0.691046962 00:39:16.620 --> 00:39:18.470 they asked about how they're NOTE Confidence: 0.691046962 00:39:18.470 --> 00:39:20.302 feeling at that moment at NOTE Confidence: 0.691046962 00:39:20.302 --> 00:39:22.492 30 minutes, they're asking, NOTE Confidence: 0.691046962 00:39:22.492 --> 00:39:25.736 they're asked to integrate. NOTE Confidence: 0.691046962 00:39:25.740 --> 00:39:27.847 At the time from from the time NOTE Confidence: 0.691046962 00:39:27.847 --> 00:39:29.764 they received the injection and NOTE Confidence: 0.691046962 00:39:29.764 --> 00:39:32.452 then at the 120 minute time point NOTE Confidence: 0.691046962 00:39:32.452 --> 00:39:34.640 they asked about what happened NOTE Confidence: 0.691046962 00:39:34.640 --> 00:39:37.310 between plus 30 and plus 1/20. NOTE Confidence: 0.691046962 00:39:37.310 --> 00:39:39.050 To report the maximal effects. NOTE Confidence: 0.767725240909091 00:39:40.570 --> 00:39:42.313 So, OK. And and at at the NOTE Confidence: 0.767725240909091 00:39:42.313 --> 00:39:43.290 30 minutes they're at, NOTE Confidence: 0.767725240909091 00:39:43.290 --> 00:39:44.340 they're not asking for the peak, NOTE Confidence: 0.767725240909091 00:39:44.340 --> 00:39:45.424 to report the peak, NOTE Confidence: 0.767725240909091 00:39:45.424 --> 00:39:46.508 they're asked to integrate, NOTE Confidence: 0.74101996 00:39:47.250 --> 00:39:49.320 integrate, but report the highest. NOTE Confidence: 0.768173591 00:39:50.910 --> 00:39:52.261 Which is. And if you do ask NOTE Confidence: 0.768173591 00:39:52.261 --> 00:39:53.116 people to integrate, they NOTE Confidence: 0.768173591 00:39:53.116 --> 00:39:54.496 usually report the peak anyways. NOTE Confidence: 0.714977084 00:39:56.070 --> 00:39:58.510 So that that missed that, yeah, NOTE Confidence: 0.714977084 00:39:58.510 --> 00:39:59.870 that's important point. Thanks. NOTE Confidence: 0.5219478 00:40:01.920 --> 00:40:03.590 And that is that NOTE Confidence: 0.656839003333333 00:40:03.590 --> 00:40:05.682 increase in anhedonia 30 minutes NOTE Confidence: 0.656839003333333 00:40:05.682 --> 00:40:06.926 that was not significant. NOTE Confidence: 0.81636779 00:40:08.410 --> 00:40:09.990 No, it was not OK, NOTE Confidence: 0.80190595 00:40:10.040 --> 00:40:12.488 but it's kind of. It's if NOTE Confidence: 0.80190595 00:40:12.488 --> 00:40:14.468 it's real, it's odd, but NOTE Confidence: 0.773068446666667 00:40:14.530 --> 00:40:16.679 it is. Yes, it is odd. Yes. NOTE Confidence: 0.773068446666667 00:40:16.679 --> 00:40:18.422 And that's going to show up again NOTE Confidence: 0.773068446666667 00:40:18.422 --> 00:40:20.338 actually in another scale. Good. NOTE Confidence: 0.773068446666667 00:40:20.338 --> 00:40:23.010 Good catch, doctor fenninger. NOTE Confidence: 0.773068446666667 00:40:23.010 --> 00:40:26.384 OK, so next we have our last, NOTE Confidence: 0.773068446666667 00:40:26.390 --> 00:40:29.070 our second to last result related to safety. NOTE Confidence: 0.773068446666667 00:40:29.070 --> 00:40:32.490 And this is our AE or adverse event table. NOTE Confidence: 0.773068446666667 00:40:32.490 --> 00:40:36.474 So again, here we have all 10 subjects. NOTE Confidence: 0.773068446666667 00:40:36.480 --> 00:40:39.384 You know. Grossly speaking, NOTE Confidence: 0.773068446666667 00:40:39.384 --> 00:40:42.920 overall the effect the adverse events NOTE Confidence: 0.773068446666667 00:40:42.920 --> 00:40:46.040 that are subject experience were mild NOTE Confidence: 0.773068446666667 00:40:46.127 --> 00:40:49.361 and they most often occurred during the NOTE Confidence: 0.773068446666667 00:40:49.361 --> 00:40:52.899 onset of effects being in that zero to 10, NOTE Confidence: 0.773068446666667 00:40:52.900 --> 00:40:56.330 zero to 20 time point. NOTE Confidence: 0.773068446666667 00:40:56.330 --> 00:40:59.065 Qualitatively, the actual effects that NOTE Confidence: 0.773068446666667 00:40:59.065 --> 00:41:01.800 they experienced were relatively varied. NOTE Confidence: 0.773068446666667 00:41:01.800 --> 00:41:04.248 There wasn't really any specific thing NOTE Confidence: 0.773068446666667 00:41:04.248 --> 00:41:06.969 that seemed to really ring true for NOTE Confidence: 0.773068446666667 00:41:06.969 --> 00:41:09.349 for the most more subjects than not. NOTE Confidence: 0.773068446666667 00:41:09.350 --> 00:41:11.710 So we had not anxiety, NOTE Confidence: 0.773068446666667 00:41:11.710 --> 00:41:15.730 hypertension, nausea, NOTE Confidence: 0.773068446666667 00:41:15.730 --> 00:41:17.010 those were the main things. NOTE Confidence: 0.773068446666667 00:41:17.010 --> 00:41:18.978 Some Lightheadedness kind of goes a NOTE Confidence: 0.773068446666667 00:41:18.978 --> 00:41:21.489 little bit with the nausea and anxiety, NOTE Confidence: 0.773068446666667 00:41:21.490 --> 00:41:23.900 but very important to emphasize NOTE Confidence: 0.773068446666667 00:41:23.900 --> 00:41:26.890 now is that we did have. NOTE Confidence: 0.773068446666667 00:41:26.890 --> 00:41:29.402 One serious adverse event. NOTE Confidence: 0.773068446666667 00:41:29.402 --> 00:41:34.700 And that was related to subject #5 here. NOTE Confidence: 0.773068446666667 00:41:34.700 --> 00:41:36.989 So this is one of our depressed NOTE Confidence: 0.773068446666667 00:41:36.989 --> 00:41:39.450 subjects and we're actually going to go NOTE Confidence: 0.773068446666667 00:41:39.450 --> 00:41:41.900 through that in some detail right now. NOTE Confidence: 0.773068446666667 00:41:41.900 --> 00:41:44.357 So this this table here is the NOTE Confidence: 0.773068446666667 00:41:44.357 --> 00:41:47.330 is the time points and the the NOTE Confidence: 0.773068446666667 00:41:47.330 --> 00:41:49.625 details of exactly what happened NOTE Confidence: 0.773068446666667 00:41:49.625 --> 00:41:52.430 for this serious adverse event. NOTE Confidence: 0.773068446666667 00:41:52.430 --> 00:41:54.008 So, you know, NOTE Confidence: 0.773068446666667 00:41:54.008 --> 00:41:57.690 basically this at from the five minute NOTE Confidence: 0.773068446666667 00:41:57.799 --> 00:42:01.747 time point after administering the DMT, NOTE Confidence: 0.773068446666667 00:42:01.750 --> 00:42:05.782 we noticed the the blood pressure NOTE Confidence: 0.773068446666667 00:42:05.782 --> 00:42:10.130 and pulse in tandem start to drop. NOTE Confidence: 0.773068446666667 00:42:10.130 --> 00:42:13.790 And so we see here at the zero time point, NOTE Confidence: 0.773068446666667 00:42:13.790 --> 00:42:15.435 their baseline is their blood NOTE Confidence: 0.773068446666667 00:42:15.435 --> 00:42:17.450 pressure is on the lower side, NOTE Confidence: 0.773068446666667 00:42:17.450 --> 00:42:19.570 108 / 60 heart rate, NOTE Confidence: 0.773068446666667 00:42:19.570 --> 00:42:21.545 54 individual is someone that NOTE Confidence: 0.773068446666667 00:42:21.545 --> 00:42:24.289 does exercise a lot is very fit. NOTE Confidence: 0.773068446666667 00:42:24.290 --> 00:42:26.180 So those things you know seemed NOTE Confidence: 0.773068446666667 00:42:26.180 --> 00:42:28.056 you know within normal limits for NOTE Confidence: 0.773068446666667 00:42:28.056 --> 00:42:30.002 them and as per history as well. NOTE Confidence: 0.773068446666667 00:42:30.010 --> 00:42:32.618 But you know at at the plus 5 NOTE Confidence: 0.773068446666667 00:42:32.618 --> 00:42:35.120 minute time point it dropped quite NOTE Confidence: 0.773068446666667 00:42:35.120 --> 00:42:37.928 precipitously to about 70 / 40, NOTE Confidence: 0.773068446666667 00:42:37.928 --> 00:42:40.918 the pulse went to 42. NOTE Confidence: 0.773068446666667 00:42:40.920 --> 00:42:42.332 And actually, you know, NOTE Confidence: 0.773068446666667 00:42:42.332 --> 00:42:44.895 still went down further at the a NOTE Confidence: 0.773068446666667 00:42:44.895 --> 00:42:47.139 minute later and another minute later. NOTE Confidence: 0.773068446666667 00:42:47.140 --> 00:42:48.660 And so this, you know, NOTE Confidence: 0.773068446666667 00:42:48.660 --> 00:42:50.400 when we saw this change, NOTE Confidence: 0.773068446666667 00:42:50.400 --> 00:42:52.692 which was not expected. NOTE Confidence: 0.773068446666667 00:42:52.692 --> 00:42:56.533 Because all the literature to date of NOTE Confidence: 0.773068446666667 00:42:56.533 --> 00:42:59.230 DMT remember being in healthy control NOTE Confidence: 0.773068446666667 00:42:59.230 --> 00:43:01.645 showed very consistently increase in NOTE Confidence: 0.773068446666667 00:43:01.645 --> 00:43:04.930 blood pressure and increase in heart rate, NOTE Confidence: 0.773068446666667 00:43:04.930 --> 00:43:05.782 not decrease. NOTE Confidence: 0.773068446666667 00:43:05.782 --> 00:43:08.764 So this was you know quite surprising NOTE Confidence: 0.773068446666667 00:43:08.764 --> 00:43:12.347 but you know we we adapted accordingly we NOTE Confidence: 0.773068446666667 00:43:12.347 --> 00:43:15.988 were prepared but so you know we see by. NOTE Confidence: 0.773068446666667 00:43:15.990 --> 00:43:19.490 The plus 10 time .5 minutes later, NOTE Confidence: 0.773068446666667 00:43:19.490 --> 00:43:21.800 the blood pressure and pulse NOTE Confidence: 0.773068446666667 00:43:21.800 --> 00:43:25.213 starts to trend back or get back NOTE Confidence: 0.773068446666667 00:43:25.213 --> 00:43:27.229 to their normal baseline. NOTE Confidence: 0.773068446666667 00:43:27.230 --> 00:43:28.940 And so while that was, NOTE Confidence: 0.773068446666667 00:43:28.940 --> 00:43:30.809 you know quite scary in real time, NOTE Confidence: 0.773068446666667 00:43:30.810 --> 00:43:33.190 I still remember that I guess relatively NOTE Confidence: 0.773068446666667 00:43:33.190 --> 00:43:35.968 well-being quite junior in my experience NOTE Confidence: 0.773068446666667 00:43:35.968 --> 00:43:38.770 as a clinician and researcher. NOTE Confidence: 0.773068446666667 00:43:38.770 --> 00:43:40.075 It was very, NOTE Confidence: 0.773068446666667 00:43:40.075 --> 00:43:42.250 it was very interesting that NOTE Confidence: 0.773068446666667 00:43:42.250 --> 00:43:44.690 the subject in terms of their, NOTE Confidence: 0.773068446666667 00:43:44.690 --> 00:43:47.210 their subjective experience of what was NOTE Confidence: 0.773068446666667 00:43:47.210 --> 00:43:51.144 going on and remember this is the .3 dose. NOTE Confidence: 0.773068446666667 00:43:51.150 --> 00:43:53.868 You know they didn't report any NOTE Confidence: 0.773068446666667 00:43:53.868 --> 00:43:55.680 distress actually they were NOTE Confidence: 0.829763180909091 00:43:55.759 --> 00:43:57.925 coherent, they were they were actually NOTE Confidence: 0.829763180909091 00:43:57.925 --> 00:44:00.442 kind of puzzled by us you know because NOTE Confidence: 0.829763180909091 00:44:00.442 --> 00:44:02.717 the interventions we made where we we, NOTE Confidence: 0.829763180909091 00:44:02.720 --> 00:44:05.498 we placed her in a closer NOTE Confidence: 0.829763180909091 00:44:05.498 --> 00:44:06.887 to Trendelenburg position. NOTE Confidence: 0.829763180909091 00:44:06.890 --> 00:44:08.780 We increased the fluids which NOTE Confidence: 0.829763180909091 00:44:08.780 --> 00:44:09.914 were already running. NOTE Confidence: 0.829763180909091 00:44:09.920 --> 00:44:12.454 At baseline at a drip rate we NOTE Confidence: 0.829763180909091 00:44:12.454 --> 00:44:15.240 increased it to the Max normal flow. NOTE Confidence: 0.829763180909091 00:44:15.240 --> 00:44:17.018 So as you were doing those things NOTE Confidence: 0.829763180909091 00:44:17.018 --> 00:44:18.290 the subject actually asked us NOTE Confidence: 0.829763180909091 00:44:18.290 --> 00:44:19.664 like you know what's going on. NOTE Confidence: 0.829763180909091 00:44:19.670 --> 00:44:22.246 Why are you like doing doing all NOTE Confidence: 0.829763180909091 00:44:22.246 --> 00:44:24.979 this because you know we were we were NOTE Confidence: 0.829763180909091 00:44:24.979 --> 00:44:26.909 responding to these numbers because NOTE Confidence: 0.829763180909091 00:44:26.909 --> 00:44:29.364 they were were were concerning but NOTE Confidence: 0.829763180909091 00:44:29.364 --> 00:44:31.308 luckily you know again after after NOTE Confidence: 0.829763180909091 00:44:31.308 --> 00:44:33.523 the effects had resolved you know we NOTE Confidence: 0.829763180909091 00:44:33.523 --> 00:44:36.160 we asked again and they said you know NOTE Confidence: 0.829763180909091 00:44:36.160 --> 00:44:38.175 they didn't experience any discomfort, NOTE Confidence: 0.829763180909091 00:44:38.180 --> 00:44:39.702 distress, anxiety, NOTE Confidence: 0.829763180909091 00:44:39.702 --> 00:44:40.463 Lightheadedness. NOTE Confidence: 0.829763180909091 00:44:40.463 --> 00:44:42.746 Loss of consciousness, NOTE Confidence: 0.829763180909091 00:44:42.750 --> 00:44:45.162 they remember they were verbal the NOTE Confidence: 0.829763180909091 00:44:45.162 --> 00:44:47.246 entire time and what was really NOTE Confidence: 0.829763180909091 00:44:47.246 --> 00:44:49.509 important that came out after was this NOTE Confidence: 0.829763180909091 00:44:49.509 --> 00:44:52.101 subject told us that they had a history of, NOTE Confidence: 0.829763180909091 00:44:52.110 --> 00:44:55.386 you know of fainting many times in the past, NOTE Confidence: 0.829763180909091 00:44:55.390 --> 00:44:56.230 of syncope basically. NOTE Confidence: 0.829763180909091 00:44:56.230 --> 00:44:58.540 And they've had maybe 30 to 50 lifetime NOTE Confidence: 0.829763180909091 00:44:58.540 --> 00:45:00.570 events to the point that you know, NOTE Confidence: 0.829763180909091 00:45:00.570 --> 00:45:03.307 they have adapted their lifestyle around it. NOTE Confidence: 0.829763180909091 00:45:03.310 --> 00:45:05.655 And so this was not something that NOTE Confidence: 0.829763180909091 00:45:05.655 --> 00:45:07.681 was revealed to us until until NOTE Confidence: 0.829763180909091 00:45:07.681 --> 00:45:09.270 this and so that you know, NOTE Confidence: 0.829763180909091 00:45:09.270 --> 00:45:11.195 that helped us under make sense of. NOTE Confidence: 0.829763180909091 00:45:11.200 --> 00:45:12.970 Why this may have happened, NOTE Confidence: 0.829763180909091 00:45:12.970 --> 00:45:14.356 but you know, that being said, NOTE Confidence: 0.829763180909091 00:45:14.360 --> 00:45:17.769 it was still quite concerning and something NOTE Confidence: 0.829763180909091 00:45:17.769 --> 00:45:21.450 to adapt all future protocols for. NOTE Confidence: 0.829763180909091 00:45:21.450 --> 00:45:25.860 And obviously do very rigorous screening. NOTE Confidence: 0.829763180909091 00:45:25.860 --> 00:45:26.343 So. NOTE Confidence: 0.829763180909091 00:45:26.343 --> 00:45:29.724 Then you know in terms of desirability, NOTE Confidence: 0.829763180909091 00:45:29.730 --> 00:45:32.844 in terms of the drug reinforcement NOTE Confidence: 0.829763180909091 00:45:32.844 --> 00:45:34.920 aspect of of safety. NOTE Confidence: 0.829763180909091 00:45:34.920 --> 00:45:36.929 With people basically if they asked how NOTE Confidence: 0.829763180909091 00:45:36.929 --> 00:45:39.208 much they would pay for it from 0 to $100, NOTE Confidence: 0.829763180909091 00:45:39.210 --> 00:45:42.252 they said about $2425 for both NOTE Confidence: 0.829763180909091 00:45:42.252 --> 00:45:44.734 doses and in terms of how likely NOTE Confidence: 0.829763180909091 00:45:44.734 --> 00:45:47.444 they were to use the drug if they NOTE Confidence: 0.829763180909091 00:45:47.444 --> 00:45:49.418 could of from zero to 100, NOTE Confidence: 0.829763180909091 00:45:49.420 --> 00:45:52.297 again about the similar in the 20s. NOTE Confidence: 0.829763180909091 00:45:52.300 --> 00:45:55.980 So it didn't really seem like people enjoy, NOTE Confidence: 0.829763180909091 00:45:55.980 --> 00:45:59.868 really enjoyed or took pleasure out NOTE Confidence: 0.829763180909091 00:45:59.868 --> 00:46:04.549 of the the actual dose experience. NOTE Confidence: 0.829763180909091 00:46:04.550 --> 00:46:08.078 This figure is this is the measure NOTE Confidence: 0.829763180909091 00:46:08.078 --> 00:46:10.596 of tolerability as we assessed NOTE Confidence: 0.829763180909091 00:46:10.596 --> 00:46:13.308 it 2 hours after the dose. NOTE Confidence: 0.829763180909091 00:46:13.310 --> 00:46:16.130 Was given after they were completely NOTE Confidence: 0.829763180909091 00:46:16.130 --> 00:46:18.900 back to baseline on the we'll see NOTE Confidence: 0.829763180909091 00:46:18.900 --> 00:46:21.350 here it goes from zero to 100. NOTE Confidence: 0.829763180909091 00:46:21.350 --> 00:46:23.898 We have each subjects scores for each NOTE Confidence: 0.829763180909091 00:46:23.898 --> 00:46:26.920 of those we have the 1st 3 being NOTE Confidence: 0.829763180909091 00:46:26.920 --> 00:46:29.387 the healthy controls and then the NOTE Confidence: 0.829763180909091 00:46:29.387 --> 00:46:32.047 remaining seven are depressed subjects. NOTE Confidence: 0.829763180909091 00:46:32.050 --> 00:46:35.026 And you see here at the end the NOTE Confidence: 0.829763180909091 00:46:35.026 --> 00:46:38.359 aggregate means and so unsurprisingly NOTE Confidence: 0.829763180909091 00:46:38.359 --> 00:46:42.006 we see the the tolerability for NOTE Confidence: 0.829763180909091 00:46:42.006 --> 00:46:43.766 the higher dose was lower. NOTE Confidence: 0.829763180909091 00:46:43.770 --> 00:46:46.400 The average approximately was 90 NOTE Confidence: 0.829763180909091 00:46:46.400 --> 00:46:49.792 out of 100 for tolerability of the NOTE Confidence: 0.829763180909091 00:46:49.792 --> 00:46:52.456 low dose and then 70 out of 100 NOTE Confidence: 0.829763180909091 00:46:52.550 --> 00:46:54.130 for the high dose. NOTE Confidence: 0.829763180909091 00:46:54.130 --> 00:46:56.422 But something that is also worth NOTE Confidence: 0.829763180909091 00:46:56.422 --> 00:46:59.308 noting here is just kind of looking NOTE Confidence: 0.829763180909091 00:46:59.308 --> 00:47:01.864 at the the variability in the NOTE Confidence: 0.829763180909091 00:47:01.864 --> 00:47:03.987 tolerability for the low dose where NOTE Confidence: 0.829763180909091 00:47:03.987 --> 00:47:06.582 we actually had a few subjects that NOTE Confidence: 0.829763180909091 00:47:06.582 --> 00:47:09.984 rated the tolerability as low as 30, NOTE Confidence: 0.829763180909091 00:47:09.990 --> 00:47:13.626 so which is sounds quite difficult NOTE Confidence: 0.829763180909091 00:47:13.626 --> 00:47:14.838 to tolerate. NOTE Confidence: 0.829763180909091 00:47:14.840 --> 00:47:16.128 But overall, you know, NOTE Confidence: 0.829763180909091 00:47:16.128 --> 00:47:18.060 70 was what it came out NOTE Confidence: 0.89892185 00:47:18.130 --> 00:47:18.550 to be. NOTE Confidence: 0.823452592272727 00:47:20.950 --> 00:47:23.792 So again it it's clearly not something NOTE Confidence: 0.823452592272727 00:47:23.792 --> 00:47:26.807 that you know is 1 size fits all NOTE Confidence: 0.823452592272727 00:47:26.807 --> 00:47:29.389 the dose even the effects et cetera. NOTE Confidence: 0.823452592272727 00:47:29.390 --> 00:47:32.414 OK and so Doctor Pittinger your point NOTE Confidence: 0.823452592272727 00:47:32.414 --> 00:47:34.458 about the depression curious finding NOTE Confidence: 0.823452592272727 00:47:34.458 --> 00:47:37.450 well it came up again here as we NOTE Confidence: 0.823452592272727 00:47:37.529 --> 00:47:40.139 we measured both anxiety depression NOTE Confidence: 0.823452592272727 00:47:40.139 --> 00:47:43.191 separately on top of everything else NOTE Confidence: 0.823452592272727 00:47:43.191 --> 00:47:45.962 to assess for the acute impact on NOTE Confidence: 0.823452592272727 00:47:45.962 --> 00:47:50.700 by the by DMT and so we we asked. NOTE Confidence: 0.823452592272727 00:47:50.700 --> 00:47:53.330 About anxiety for both groups. NOTE Confidence: 0.823452592272727 00:47:53.330 --> 00:47:55.815 The only depression in our NOTE Confidence: 0.823452592272727 00:47:55.815 --> 00:47:56.809 depressed subjects. NOTE Confidence: 0.823452592272727 00:47:56.810 --> 00:47:59.698 So in all ten we asked for anxiety NOTE Confidence: 0.823452592272727 00:47:59.698 --> 00:48:02.024 and they did report elevated NOTE Confidence: 0.823452592272727 00:48:02.024 --> 00:48:04.544 anxiety and the higher dose. NOTE Confidence: 0.823452592272727 00:48:04.550 --> 00:48:07.753 But again notice that on on objectively NOTE Confidence: 0.823452592272727 00:48:07.753 --> 00:48:11.026 speaking 50 out of 100, you know, NOTE Confidence: 0.823452592272727 00:48:11.026 --> 00:48:13.294 that's not 100 being you know, NOTE Confidence: 0.823452592272727 00:48:13.300 --> 00:48:17.035 the very anxious or the most anxious or NOTE Confidence: 0.823452592272727 00:48:17.035 --> 00:48:19.635 more more anxious than usual is what the NOTE Confidence: 0.823452592272727 00:48:19.635 --> 00:48:22.867 100 anchor stood for more anxious than usual? NOTE Confidence: 0.823452592272727 00:48:22.870 --> 00:48:23.544 Much more. NOTE Confidence: 0.823452592272727 00:48:23.544 --> 00:48:27.319 So they rated at 50 for the high dose and NOTE Confidence: 0.823452592272727 00:48:27.319 --> 00:48:30.313 then similarly the wording for depression, NOTE Confidence: 0.823452592272727 00:48:30.320 --> 00:48:32.780 we saw that you know the NOTE Confidence: 0.823452592272727 00:48:32.780 --> 00:48:34.420 .3 dose subjects felt, NOTE Confidence: 0.823452592272727 00:48:34.420 --> 00:48:35.328 you know, NOTE Confidence: 0.823452592272727 00:48:35.328 --> 00:48:37.598 more more depressed during during NOTE Confidence: 0.823452592272727 00:48:37.598 --> 00:48:38.960 the peak effects. NOTE Confidence: 0.823452592272727 00:48:38.960 --> 00:48:42.656 So that and this this was statistically NOTE Confidence: 0.823452592272727 00:48:42.656 --> 00:48:45.650 significant in terms of the effects. NOTE Confidence: 0.823452592272727 00:48:45.650 --> 00:48:48.338 And so our main finding which NOTE Confidence: 0.823452592272727 00:48:48.338 --> 00:48:51.124 again is curious given you know we NOTE Confidence: 0.823452592272727 00:48:51.124 --> 00:48:53.880 see this increase in depression. NOTE Confidence: 0.823452592272727 00:48:53.880 --> 00:48:55.398 Depression endorsement acutely. NOTE Confidence: 0.823452592272727 00:48:55.398 --> 00:48:57.928 You know the day after, NOTE Confidence: 0.823452592272727 00:48:57.930 --> 00:49:01.290 you know we do see reduction and NOTE Confidence: 0.823452592272727 00:49:01.290 --> 00:49:05.790 So what we have here is a the graph NOTE Confidence: 0.823452592272727 00:49:05.790 --> 00:49:08.390 showing the change in Hamilton NOTE Confidence: 0.823452592272727 00:49:08.390 --> 00:49:10.544 depression scores starting at NOTE Confidence: 0.823452592272727 00:49:10.544 --> 00:49:13.610 baseline and showing the trend for NOTE Confidence: 0.823452592272727 00:49:13.610 --> 00:49:16.808 each subject being a different color. NOTE Confidence: 0.823452592272727 00:49:16.810 --> 00:49:19.175 The black line represents the NOTE Confidence: 0.823452592272727 00:49:19.175 --> 00:49:21.003 mean for the group. NOTE Confidence: 0.823452592272727 00:49:21.003 --> 00:49:23.258 And so we we put, NOTE Confidence: 0.823452592272727 00:49:23.260 --> 00:49:26.860 we show here one day after the low dose when NOTE Confidence: 0.823452592272727 00:49:26.948 --> 00:49:32.870 we measured the Hamilton, the change was. NOTE Confidence: 0.823452592272727 00:49:32.870 --> 00:49:34.199 Not too much. NOTE Confidence: 0.823452592272727 00:49:34.199 --> 00:49:36.857 One day after the .3 dose, NOTE Confidence: 0.823452592272727 00:49:36.860 --> 00:49:37.912 you know, we see, NOTE Confidence: 0.823452592272727 00:49:37.912 --> 00:49:39.227 we see an interesting spread. NOTE Confidence: 0.823452592272727 00:49:39.230 --> 00:49:42.285 We see some subjects report NOTE Confidence: 0.823452592272727 00:49:42.285 --> 00:49:43.507 significant improvement, NOTE Confidence: 0.823452592272727 00:49:43.510 --> 00:49:46.426 you know change of nine points NOTE Confidence: 0.823452592272727 00:49:46.426 --> 00:49:48.889 on their Hamilton and then NOTE Confidence: 0.823452592272727 00:49:48.889 --> 00:49:51.230 some may not maybe one point. NOTE Confidence: 0.823452592272727 00:49:51.230 --> 00:49:56.064 So you know so some people seem to NOTE Confidence: 0.823452592272727 00:49:56.064 --> 00:49:58.699 experience reduction of in their NOTE Confidence: 0.823452592272727 00:49:58.699 --> 00:50:01.400 depression symptoms while some did not. NOTE Confidence: 0.823452592272727 00:50:01.400 --> 00:50:04.070 This is also somewhat contrasting, NOTE Confidence: 0.823452592272727 00:50:04.070 --> 00:50:04.920 or at least, you know, NOTE Confidence: 0.823452592272727 00:50:04.920 --> 00:50:07.350 juxtaposed against silybin where you NOTE Confidence: 0.823452592272727 00:50:07.350 --> 00:50:11.349 know you get a much more homogeneous, NOTE Confidence: 0.823452592272727 00:50:11.350 --> 00:50:11.988 you know, NOTE Confidence: 0.823452592272727 00:50:11.988 --> 00:50:12.626 positive response. NOTE Confidence: 0.823452592272727 00:50:12.626 --> 00:50:14.540 I haven't seen these sort of NOTE Confidence: 0.823452592272727 00:50:14.602 --> 00:50:16.552 spreads in terms of the depression NOTE Confidence: 0.823452592272727 00:50:16.552 --> 00:50:18.762 scores when they looked at their NOTE Confidence: 0.823452592272727 00:50:18.762 --> 00:50:20.040 acute antidepressant effects. NOTE Confidence: 0.823452592272727 00:50:20.040 --> 00:50:21.530 Most subjects tend to respond, NOTE Confidence: 0.809065381111111 00:50:22.120 --> 00:50:24.199 but that may be because of our small sample. NOTE Confidence: 0.876677282 00:50:24.970 --> 00:50:26.330 Right, right, right. Of course. NOTE Confidence: 0.876677282 00:50:26.330 --> 00:50:30.256 Sorry. And so our effect size is .75 NOTE Confidence: 0.876677282 00:50:30.256 --> 00:50:34.430 reported that is, is G and and Oh yeah, NOTE Confidence: 0.876677282 00:50:34.430 --> 00:50:37.311 of course to mention that the the NOTE Confidence: 0.876677282 00:50:37.311 --> 00:50:40.221 analysis we did was comparing the NOTE Confidence: 0.876677282 00:50:40.221 --> 00:50:43.190 change from baseline to each test day. NOTE Confidence: 0.876677282 00:50:43.190 --> 00:50:46.342 So the change between baseline and one day NOTE Confidence: 0.876677282 00:50:46.342 --> 00:50:49.410 after the low dose was not significant, NOTE Confidence: 0.876677282 00:50:49.410 --> 00:50:51.996 but the change between the day NOTE Confidence: 0.876677282 00:50:51.996 --> 00:50:55.340 after the .3 dose and baseline was. NOTE Confidence: 0.876677282 00:50:55.340 --> 00:50:58.430 And so that affects size was .75. NOTE Confidence: 0.876677282 00:50:58.430 --> 00:51:01.130 We use hedges G that's calculated NOTE Confidence: 0.876677282 00:51:01.130 --> 00:51:05.272 as the the change in the mean over NOTE Confidence: 0.876677282 00:51:05.272 --> 00:51:07.722 the standard deviation pooled and NOTE Confidence: 0.876677282 00:51:07.722 --> 00:51:09.978 so that is how we arrived at that. NOTE Confidence: 0.876677282 00:51:09.980 --> 00:51:12.724 This is the table that just shows NOTE Confidence: 0.876677282 00:51:12.724 --> 00:51:15.538 our means for the depression scores NOTE Confidence: 0.876677282 00:51:15.538 --> 00:51:17.176 and the differences. NOTE Confidence: 0.876677282 00:51:17.180 --> 00:51:21.473 So you see here our average is near 24 NOTE Confidence: 0.876677282 00:51:21.473 --> 00:51:24.896 baseline Hamilton score and you know. NOTE Confidence: 0.876677282 00:51:24.900 --> 00:51:26.385 One day after. NOTE Confidence: 0.876677282 00:51:26.385 --> 00:51:29.850 The low dose you know about point NOTE Confidence: 0.876677282 00:51:29.958 --> 00:51:33.070 difference and one day after the NOTE Confidence: 0.876677282 00:51:33.070 --> 00:51:35.600 higher dose about a 4.5 difference NOTE Confidence: 0.876677282 00:51:35.600 --> 00:51:38.180 and so this this was statistically NOTE Confidence: 0.876677282 00:51:38.180 --> 00:51:40.663 significant for what for what it for NOTE Confidence: 0.876677282 00:51:40.663 --> 00:51:42.615 whatever it means which is limited NOTE Confidence: 0.876677282 00:51:42.615 --> 00:51:45.398 by a variety of things which you know NOTE Confidence: 0.876677282 00:51:45.398 --> 00:51:48.513 will comment on now and then kind of NOTE Confidence: 0.876677282 00:51:48.513 --> 00:51:51.713 open up to you know thoughts and questions. NOTE Confidence: 0.876677282 00:51:51.720 --> 00:51:54.954 So this study is the the NOTE Confidence: 0.876677282 00:51:54.954 --> 00:51:57.110 first to demonstrate no. NOTE Confidence: 0.876677282 00:51:57.110 --> 00:52:01.485 Safety, tolerability and DMT are most novel. NOTE Confidence: 0.876677282 00:52:01.490 --> 00:52:05.130 Finding is that we did see a reduction, NOTE Confidence: 0.876677282 00:52:05.130 --> 00:52:09.060 a significant reduction in depressive NOTE Confidence: 0.876677282 00:52:09.060 --> 00:52:11.418 depressive symptomatology after NOTE Confidence: 0.876677282 00:52:11.418 --> 00:52:14.922 subject received .3 milligram per NOTE Confidence: 0.876677282 00:52:14.922 --> 00:52:17.374 kilogram of DMT intravenously. NOTE Confidence: 0.876677282 00:52:17.380 --> 00:52:19.720 Of notes. NOTE Confidence: 0.876677282 00:52:19.720 --> 00:52:21.504 Confounding this potential effect, NOTE Confidence: 0.876677282 00:52:21.504 --> 00:52:22.396 you know, NOTE Confidence: 0.876677282 00:52:22.400 --> 00:52:24.764 besides being open label and you NOTE Confidence: 0.876677282 00:52:24.764 --> 00:52:26.340 know fixed dose etcetera, NOTE Confidence: 0.876677282 00:52:26.340 --> 00:52:29.434 I mean there we cannot say that NOTE Confidence: 0.876677282 00:52:29.434 --> 00:52:32.895 the .1 dose was non contributory NOTE Confidence: 0.876677282 00:52:32.895 --> 00:52:36.088 to that potential effect, you know, NOTE Confidence: 0.876677282 00:52:36.088 --> 00:52:36.820 as a carryover. NOTE Confidence: 0.876677282 00:52:36.820 --> 00:52:37.964 And that's you know, NOTE Confidence: 0.876677282 00:52:37.964 --> 00:52:40.319 again one of the other challenges with doing, NOTE Confidence: 0.876677282 00:52:40.320 --> 00:52:42.672 you know multiple dose studies with NOTE Confidence: 0.876677282 00:52:42.672 --> 00:52:44.680 the psychedelics because you know NOTE Confidence: 0.876677282 00:52:44.680 --> 00:52:46.565 it's very difficult to separate, NOTE Confidence: 0.876677282 00:52:46.570 --> 00:52:48.652 you know what what they're doing NOTE Confidence: 0.876677282 00:52:48.652 --> 00:52:49.693 and how they. NOTE Confidence: 0.876677282 00:52:49.700 --> 00:52:53.810 Interact or accumulatively act in general. NOTE Confidence: 0.876677282 00:52:53.810 --> 00:52:57.354 So in the study we did not provide NOTE Confidence: 0.876677282 00:52:57.354 --> 00:52:58.240 any psychotherapy. NOTE Confidence: 0.876677282 00:52:58.240 --> 00:53:01.452 There was no special setting and so NOTE Confidence: 0.876677282 00:53:01.452 --> 00:53:03.948 taken together I think this study NOTE Confidence: 0.876677282 00:53:03.948 --> 00:53:07.337 raises a lot of interesting questions. NOTE Confidence: 0.876677282 00:53:07.340 --> 00:53:09.769 Naturally the next step is you know NOTE Confidence: 0.876677282 00:53:09.769 --> 00:53:12.283 we have the approval to proceed NOTE Confidence: 0.876677282 00:53:12.283 --> 00:53:14.608 with our randomized clinical trial NOTE Confidence: 0.876677282 00:53:14.608 --> 00:53:17.538 which is which is what our plan is. NOTE Confidence: 0.876677282 00:53:17.540 --> 00:53:20.046 You know there are still very much NOTE Confidence: 0.876677282 00:53:20.046 --> 00:53:22.105 questions about what is you know NOTE Confidence: 0.876677282 00:53:22.105 --> 00:53:23.017 an optimal dose, NOTE Confidence: 0.876677282 00:53:23.020 --> 00:53:26.344 you know in terms of reducing NOTE Confidence: 0.876677282 00:53:26.344 --> 00:53:28.958 depression severity. What duration? NOTE Confidence: 0.876677282 00:53:28.958 --> 00:53:31.016 And, you know, NOTE Confidence: 0.876677282 00:53:31.020 --> 00:53:33.480 by having IV administration we NOTE Confidence: 0.876677282 00:53:33.480 --> 00:53:36.870 do have the ability to, you know, NOTE Confidence: 0.876677282 00:53:36.870 --> 00:53:39.195 exquisitely control the the level, NOTE Confidence: 0.876677282 00:53:39.200 --> 00:53:41.190 the concentration and the duration NOTE Confidence: 0.876677282 00:53:41.190 --> 00:53:41.986 of effects. NOTE Confidence: 0.800525858421053 00:53:44.310 --> 00:53:47.088 And you know something that's intrinsically NOTE Confidence: 0.800525858421053 00:53:47.088 --> 00:53:50.657 a challenge to these clinical trials is to NOTE Confidence: 0.800525858421053 00:53:50.657 --> 00:53:53.740 how to control for expectancy given that NOTE Confidence: 0.800525858421053 00:53:53.740 --> 00:53:56.830 you know many placebo effect etcetera. NOTE Confidence: 0.800525858421053 00:53:56.830 --> 00:54:00.102 These things you know really do seem to NOTE Confidence: 0.800525858421053 00:54:00.102 --> 00:54:03.466 impact you know the changes associated with NOTE Confidence: 0.800525858421053 00:54:03.466 --> 00:54:06.821 with these with these drugs and there's no, NOTE Confidence: 0.800525858421053 00:54:06.821 --> 00:54:09.277 there's no easy answers at the there was NOTE Confidence: 0.800525858421053 00:54:09.277 --> 00:54:11.475 a site there was the first psychedelic NOTE Confidence: 0.800525858421053 00:54:11.475 --> 00:54:13.312 NIH workshop in January and these NOTE Confidence: 0.800525858421053 00:54:13.312 --> 00:54:15.028 were some of the things that. NOTE Confidence: 0.800525858421053 00:54:15.030 --> 00:54:17.118 You know, they were also contemplating NOTE Confidence: 0.800525858421053 00:54:17.118 --> 00:54:19.382 and kind of discussing and that, NOTE Confidence: 0.800525858421053 00:54:19.382 --> 00:54:21.806 you know there really aren't any NOTE Confidence: 0.800525858421053 00:54:21.806 --> 00:54:24.574 easy solutions but you know certainly NOTE Confidence: 0.800525858421053 00:54:24.574 --> 00:54:27.070 there seems to be some interesting NOTE Confidence: 0.800525858421053 00:54:27.143 --> 00:54:29.765 potential that needs to be explored. NOTE Confidence: 0.800525858421053 00:54:29.770 --> 00:54:31.414 Something I'm very curious NOTE Confidence: 0.800525858421053 00:54:31.414 --> 00:54:33.469 about to you know ask, NOTE Confidence: 0.800525858421053 00:54:33.470 --> 00:54:35.528 you know the experts in the audience NOTE Confidence: 0.800525858421053 00:54:35.528 --> 00:54:37.616 that have much more robotic experience NOTE Confidence: 0.800525858421053 00:54:37.616 --> 00:54:39.521 with you know the depression NOTE Confidence: 0.800525858421053 00:54:39.521 --> 00:54:41.494 treatments as you know where are NOTE Confidence: 0.800525858421053 00:54:41.494 --> 00:54:43.448 people think how we should move from NOTE Confidence: 0.800525858421053 00:54:43.448 --> 00:54:45.192 here in terms of study design if the. NOTE Confidence: 0.800525858421053 00:54:45.200 --> 00:54:47.490 People have thoughts or recommendations. NOTE Confidence: 0.800525858421053 00:54:47.490 --> 00:54:50.914 I'm I'm quite curious and trying to you NOTE Confidence: 0.800525858421053 00:54:50.914 --> 00:54:53.282 know isolate and you know question, NOTE Confidence: 0.800525858421053 00:54:53.282 --> 00:54:56.026 you know the five HT 2A component NOTE Confidence: 0.800525858421053 00:54:56.026 --> 00:54:58.406 of you know the mechanism. NOTE Confidence: 0.800525858421053 00:54:58.410 --> 00:55:00.362 You know to see if we can actually NOTE Confidence: 0.800525858421053 00:55:00.362 --> 00:55:02.390 kind of prove that because it doesn't NOTE Confidence: 0.800525858421053 00:55:02.390 --> 00:55:05.093 seem to be that study today really have NOTE Confidence: 0.800525858421053 00:55:05.093 --> 00:55:07.415 discerned that you know very definitively. NOTE Confidence: 0.854736058 00:55:09.500 --> 00:55:12.926 So, so yeah, I mean. Thoughts. NOTE Confidence: 0.854736058 00:55:12.926 --> 00:55:15.790 Comments. Feel free to. NOTE Confidence: 0.854736058 00:55:15.790 --> 00:55:19.190 Umm. London. Thank you. NOTE Confidence: 0.843705639285714 00:55:21.170 --> 00:55:22.562 Thank you sheriff. This is really NOTE Confidence: 0.843705639285714 00:55:22.562 --> 00:55:24.347 cool work and I do know how much. NOTE Confidence: 0.843705639285714 00:55:24.350 --> 00:55:25.570 Well maybe, I probably don't. NOTE Confidence: 0.843705639285714 00:55:25.570 --> 00:55:27.262 I probably still underestimate how much NOTE Confidence: 0.843705639285714 00:55:27.262 --> 00:55:29.109 work goes into getting this off the NOTE Confidence: 0.843705639285714 00:55:29.109 --> 00:55:30.900 ground and doing the first DMT study and. NOTE Confidence: 0.843705639285714 00:55:30.900 --> 00:55:32.770 So it's really impressive to NOTE Confidence: 0.843705639285714 00:55:32.770 --> 00:55:34.640 have gotten to this point. NOTE Confidence: 0.843705639285714 00:55:34.640 --> 00:55:36.420 With the the controlled study, NOTE Confidence: 0.843705639285714 00:55:36.420 --> 00:55:38.142 are you going to stick with the NOTE Confidence: 0.843705639285714 00:55:38.142 --> 00:55:39.916 three group Saline point 1.3 or do NOTE Confidence: 0.843705639285714 00:55:39.916 --> 00:55:41.392 these pilot results make you think NOTE Confidence: 0.843705639285714 00:55:41.445 --> 00:55:42.831 that maybe you could go straight NOTE Confidence: 0.843705639285714 00:55:42.831 --> 00:55:45.148 to a two group just say Linden .3? NOTE Confidence: 0.79631792125 00:55:46.810 --> 00:55:50.226 If between the two, more likely the latter, NOTE Confidence: 0.79631792125 00:55:50.230 --> 00:55:53.394 I think we're also really curious about NOTE Confidence: 0.79631792125 00:55:53.394 --> 00:55:56.649 the idea of potentially a constant NOTE Confidence: 0.79631792125 00:55:56.649 --> 00:56:00.255 infusion to maybe prolong the effects. NOTE Confidence: 0.79631792125 00:56:00.260 --> 00:56:02.689 Maybe a lower dose because the .3 NOTE Confidence: 0.79631792125 00:56:02.689 --> 00:56:06.035 seems to be right as we saw kind NOTE Confidence: 0.79631792125 00:56:06.035 --> 00:56:08.340 of varied in its tolerability. NOTE Confidence: 0.79631792125 00:56:08.340 --> 00:56:11.247 It's you know, we we thought the .3 for NOTE Confidence: 0.79631792125 00:56:11.247 --> 00:56:13.950 depressed subjects seem to be less tolerable. NOTE Confidence: 0.79631792125 00:56:13.950 --> 00:56:16.085 I mean it will be really important NOTE Confidence: 0.79631792125 00:56:16.085 --> 00:56:18.494 to see differences if there are any NOTE Confidence: 0.79631792125 00:56:18.494 --> 00:56:20.284 between controls and depressed objects. NOTE Confidence: 0.79631792125 00:56:20.290 --> 00:56:21.942 I mean if there may be that NOTE Confidence: 0.79631792125 00:56:21.942 --> 00:56:23.310 wouldn't be too surprising. NOTE Confidence: 0.79631792125 00:56:23.310 --> 00:56:24.744 So I'm thinking we may need NOTE Confidence: 0.79631792125 00:56:24.744 --> 00:56:26.270 to adapt for things like that. NOTE Confidence: 0.79631792125 00:56:26.270 --> 00:56:28.526 But I think, you know we'll have to NOTE Confidence: 0.79631792125 00:56:28.526 --> 00:56:31.118 do more studies to get get at it. NOTE Confidence: 0.817436771428571 00:56:31.810 --> 00:56:33.945 The other reason we are thinking about. NOTE Confidence: 0.817436771428571 00:56:33.950 --> 00:56:36.946 Ways of doing a. Both this and NOTE Confidence: 0.817436771428571 00:56:36.946 --> 00:56:38.780 constant confusion which would. NOTE Confidence: 0.817436771428571 00:56:38.780 --> 00:56:40.705 Produce effects that are not NOTE Confidence: 0.817436771428571 00:56:40.705 --> 00:56:43.500 as intense as the .3 milligram. NOTE Confidence: 0.817436771428571 00:56:43.500 --> 00:56:47.440 Still is if psychotherapy is NOTE Confidence: 0.817436771428571 00:56:47.440 --> 00:56:52.940 supposed to be a key component in in. NOTE Confidence: 0.817436771428571 00:56:52.940 --> 00:56:55.705 In this approach. In half an hour. NOTE Confidence: 0.865180626428572 00:56:58.000 --> 00:56:59.352 Of such intense effects. NOTE Confidence: 0.865180626428572 00:56:59.352 --> 00:57:01.380 I don't think people can actually NOTE Confidence: 0.865180626428572 00:57:01.440 --> 00:57:03.480 engage in meaningful psychotherapy, NOTE Confidence: 0.865180626428572 00:57:03.480 --> 00:57:04.520 at least in our hands, NOTE Confidence: 0.865180626428572 00:57:04.520 --> 00:57:07.139 what we saw at this point 3 milligram dose, NOTE Confidence: 0.865180626428572 00:57:07.140 --> 00:57:11.276 but it's conceivable that at a lower dose. NOTE Confidence: 0.865180626428572 00:57:11.280 --> 00:57:12.815 People might be able to NOTE Confidence: 0.865180626428572 00:57:12.815 --> 00:57:13.736 engage in psychotherapy, NOTE Confidence: 0.865180626428572 00:57:13.740 --> 00:57:16.557 again based on the if we make the assumption NOTE Confidence: 0.865180626428572 00:57:16.557 --> 00:57:18.814 that psychotherapy is an essential NOTE Confidence: 0.865180626428572 00:57:18.814 --> 00:57:21.159 ingredient to people getting better. NOTE Confidence: 0.865180626428572 00:57:21.160 --> 00:57:22.835 I don't think that's been NOTE Confidence: 0.865180626428572 00:57:22.835 --> 00:57:23.505 clearly demonstrated, NOTE Confidence: 0.865180626428572 00:57:23.510 --> 00:57:27.032 though that is how most groups NOTE Confidence: 0.865180626428572 00:57:27.032 --> 00:57:28.793 are actually approaching. NOTE Confidence: 0.865180626428572 00:57:28.800 --> 00:57:30.432 Use of psychedelic drugs. NOTE Confidence: 0.865180626428572 00:57:30.432 --> 00:57:30.840 So. NOTE Confidence: 0.865180626428572 00:57:30.840 --> 00:57:33.290 So we are looking at ways of NOTE Confidence: 0.865180626428572 00:57:33.290 --> 00:57:35.365 of extending the infusion but NOTE Confidence: 0.865180626428572 00:57:35.365 --> 00:57:38.635 at but with the idea of having NOTE Confidence: 0.865180626428572 00:57:38.635 --> 00:57:40.087 less intense effects. NOTE Confidence: 0.83105517 00:57:42.040 --> 00:57:42.730 Makes sense? NOTE Confidence: 0.847742898 00:57:44.360 --> 00:57:45.360 May I ask a question? NOTE Confidence: 0.84051284375 00:57:47.530 --> 00:57:50.370 Thank you so much Terry for the presentation. NOTE Confidence: 0.84051284375 00:57:50.370 --> 00:57:53.135 Speaking of dosing, I noticed that in NOTE Confidence: 0.84051284375 00:57:53.135 --> 00:57:56.529 the table that you had or it was a graph NOTE Confidence: 0.84051284375 00:57:56.529 --> 00:57:59.690 that about the effects of .1 and .3, NOTE Confidence: 0.84051284375 00:57:59.690 --> 00:58:02.510 a good number of individuals also NOTE Confidence: 0.84051284375 00:58:02.510 --> 00:58:05.469 reported intense experience with .1. NOTE Confidence: 0.84051284375 00:58:05.470 --> 00:58:08.865 I don't remember what was the number, NOTE Confidence: 0.84051284375 00:58:08.870 --> 00:58:10.562 but that was interesting to me NOTE Confidence: 0.84051284375 00:58:10.562 --> 00:58:12.413 that what was the intensity of NOTE Confidence: 0.84051284375 00:58:12.413 --> 00:58:14.393 the experience they had with .1. NOTE Confidence: 0.77284918 00:58:16.350 --> 00:58:20.438 Yeah, yeah, they scored it as well. NOTE Confidence: 0.77284918 00:58:20.440 --> 00:58:23.338 45 out of 100 right for NOTE Confidence: 0.77284918 00:58:23.338 --> 00:58:25.700 the intensity for the .1. NOTE Confidence: 0.786223688 00:58:26.450 --> 00:58:28.320 I I think what people? NOTE Confidence: 0.847160215 00:58:31.330 --> 00:58:33.970 What what many subjects may be NOTE Confidence: 0.847160215 00:58:33.970 --> 00:58:37.750 reporting is the initial rush. NOTE Confidence: 0.847160215 00:58:37.750 --> 00:58:40.180 That you get when it's administered NOTE Confidence: 0.847160215 00:58:40.180 --> 00:58:42.301 intravenously as a bolus that NOTE Confidence: 0.847160215 00:58:42.301 --> 00:58:44.029 rushes like being launched, NOTE Confidence: 0.847160215 00:58:44.030 --> 00:58:45.978 you know, into space, NOTE Confidence: 0.847160215 00:58:45.978 --> 00:58:48.413 kind of that initial joke. NOTE Confidence: 0.847160215 00:58:48.420 --> 00:58:51.514 And whereas with the .3 milligram dose, NOTE Confidence: 0.847160215 00:58:51.520 --> 00:58:53.596 that effects may last a little NOTE Confidence: 0.847160215 00:58:53.596 --> 00:58:55.620 longer and be more intense, NOTE Confidence: 0.847160215 00:58:55.620 --> 00:58:58.212 at .1 it kind of tapers off pretty quickly. NOTE Confidence: 0.892589244545455 00:58:59.180 --> 00:59:02.001 So does it mean that .1 also NOTE Confidence: 0.892589244545455 00:59:02.001 --> 00:59:03.960 has some psychedelic effects? NOTE Confidence: 0.892589244545455 00:59:03.960 --> 00:59:05.525 Like do they have altered NOTE Confidence: 0.892589244545455 00:59:05.525 --> 00:59:07.597 perception and some type of like NOTE Confidence: 0.892589244545455 00:59:07.597 --> 00:59:09.827 those feelings that people really NOTE Confidence: 0.892589244545455 00:59:09.827 --> 00:59:11.165 experience with psychedelics? NOTE Confidence: 0.897659772727273 00:59:12.570 --> 00:59:14.936 As you can see on this graph NOTE Confidence: 0.897659772727273 00:59:14.936 --> 00:59:16.962 itself there was some, you know, NOTE Confidence: 0.897659772727273 00:59:16.962 --> 00:59:19.054 obviously this is not placebo-controlled. NOTE Confidence: 0.897659772727273 00:59:19.054 --> 00:59:22.990 But some subjects reported. NOTE Confidence: 0.897659772727273 00:59:22.990 --> 00:59:26.966 You know, I felt unusual bodily sensations. NOTE Confidence: 0.897659772727273 00:59:26.970 --> 00:59:30.410 I saw geometric pattern, so so for example, NOTE Confidence: 0.897659772727273 00:59:30.410 --> 00:59:32.252 some of the effects that subjects NOTE Confidence: 0.897659772727273 00:59:32.252 --> 00:59:34.490 reported on the .1 milligram doses. NOTE Confidence: 0.897659772727273 00:59:34.490 --> 00:59:35.834 I don't know if you've seen NOTE Confidence: 0.897659772727273 00:59:35.834 --> 00:59:37.230 the inside of the EEG boot, NOTE Confidence: 0.897659772727273 00:59:37.230 --> 00:59:40.849 but it's it's covered with copper mesh. NOTE Confidence: 0.897659772727273 00:59:40.850 --> 00:59:43.786 And it's the the the IT has a NOTE Confidence: 0.897659772727273 00:59:43.786 --> 00:59:45.619 geometric pattern that's there, NOTE Confidence: 0.897659772727273 00:59:45.620 --> 00:59:47.594 but it's almost you're oblivious to it NOTE Confidence: 0.897659772727273 00:59:47.594 --> 00:59:50.187 most of the time because it's really trap. NOTE Confidence: 0.897659772727273 00:59:50.190 --> 00:59:52.950 But what subjects reported was that NOTE Confidence: 0.897659772727273 00:59:52.950 --> 00:59:55.549 geometric pattern came to the fore? NOTE Confidence: 0.897659772727273 00:59:55.550 --> 00:59:58.850 And the lines start shimmering, NOTE Confidence: 0.897659772727273 00:59:58.850 --> 01:00:00.930 uh, and assuming different colors. NOTE Confidence: 0.897659772727273 01:00:00.930 --> 01:00:02.688 And they were previously unaware of NOTE Confidence: 0.897659772727273 01:00:02.688 --> 01:00:04.778 those kinds of, but it wasn't disturbing. NOTE Confidence: 0.897659772727273 01:00:04.778 --> 01:00:05.986 It was just that. NOTE Confidence: 0.897659772727273 01:00:05.990 --> 01:00:07.810 Yeah, so those are the kinds of NOTE Confidence: 0.897659772727273 01:00:07.810 --> 01:00:09.638 things that people with other subjects NOTE Confidence: 0.897659772727273 01:00:09.638 --> 01:00:11.608 reported feeling like they were. NOTE Confidence: 0.897659772727273 01:00:11.610 --> 01:00:15.416 The entire chair was kind of floating in, NOTE Confidence: 0.897659772727273 01:00:15.416 --> 01:00:16.362 you know, NOTE Confidence: 0.897659772727273 01:00:16.362 --> 01:00:19.200 those were the kinds of experiences. NOTE Confidence: 0.885798666666667 01:00:19.990 --> 01:00:20.839 OK. Thank you. NOTE Confidence: 0.895041320833333 01:00:24.440 --> 01:00:28.166 I was hoping to comment on the on the NOTE Confidence: 0.895041320833333 01:00:28.166 --> 01:00:32.630 mention of the of of the worsening. NOTE Confidence: 0.895041320833333 01:00:32.630 --> 01:00:34.955 Worsening depression measures NOTE Confidence: 0.895041320833333 01:00:34.955 --> 01:00:38.055 acutely and the anhedonia. NOTE Confidence: 0.895041320833333 01:00:38.060 --> 01:00:41.308 So in the in the headache studies that NOTE Confidence: 0.895041320833333 01:00:41.308 --> 01:00:44.656 I've been doing in the in the same lab, NOTE Confidence: 0.895041320833333 01:00:44.660 --> 01:00:49.280 a lot of patients get headaches. NOTE Confidence: 0.895041320833333 01:00:49.280 --> 01:00:51.114 Not necessarily on the test day but NOTE Confidence: 0.895041320833333 01:00:51.114 --> 01:00:53.136 maybe later on that evening or the NOTE Confidence: 0.895041320833333 01:00:53.136 --> 01:00:54.900 following day and these are headache NOTE Confidence: 0.895041320833333 01:00:54.955 --> 01:00:56.765 patients so they're they're getting NOTE Confidence: 0.895041320833333 01:00:56.765 --> 01:00:58.842 headaches anyways but some people but NOTE Confidence: 0.895041320833333 01:00:58.842 --> 01:01:00.676 we we let patients know that these NOTE Confidence: 0.895041320833333 01:01:00.676 --> 01:01:02.630 drugs are known to cause headaches. NOTE Confidence: 0.895041320833333 01:01:02.630 --> 01:01:04.750 So just you know be be ready for NOTE Confidence: 0.895041320833333 01:01:04.750 --> 01:01:06.777 that and it's not official because NOTE Confidence: 0.895041320833333 01:01:06.777 --> 01:01:09.307 I haven't done like this like the NOTE Confidence: 0.895041320833333 01:01:09.307 --> 01:01:11.129 the analysis but it almost seemed NOTE Confidence: 0.895041320833333 01:01:11.130 --> 01:01:13.344 like the patients who had more NOTE Confidence: 0.895041320833333 01:01:13.344 --> 01:01:15.198 had worsening headaches did did NOTE Confidence: 0.895041320833333 01:01:15.198 --> 01:01:17.070 better ultimately and I tell them NOTE Confidence: 0.895041320833333 01:01:17.070 --> 01:01:19.469 you know in my non scientific way. NOTE Confidence: 0.895041320833333 01:01:19.470 --> 01:01:20.904 So it's probably just shaking up NOTE Confidence: 0.895041320833333 01:01:20.904 --> 01:01:22.469 the system to help turn it off. NOTE Confidence: 0.895041320833333 01:01:22.470 --> 01:01:24.780 So it needs to generate the headache NOTE Confidence: 0.895041320833333 01:01:24.780 --> 01:01:27.787 for it to to turn off the the system. NOTE Confidence: 0.895041320833333 01:01:27.790 --> 01:01:29.554 So I tell patients don't worry about NOTE Confidence: 0.895041320833333 01:01:29.554 --> 01:01:31.140 an extra headache or two because NOTE Confidence: 0.895041320833333 01:01:31.140 --> 01:01:32.445 it actually probably means that NOTE Confidence: 0.895041320833333 01:01:32.445 --> 01:01:33.668 it's it's going to work. NOTE Confidence: 0.895041320833333 01:01:33.670 --> 01:01:35.644 So I probably shouldn't do that because NOTE Confidence: 0.895041320833333 01:01:35.644 --> 01:01:37.520 then I guess their expectations NOTE Confidence: 0.642201595 01:01:37.530 --> 01:01:40.506 out if they're having headaches. NOTE Confidence: 0.642201595 01:01:40.506 --> 01:01:42.558 But so I actually wonder if there's NOTE Confidence: 0.919220025 01:01:42.570 --> 01:01:45.282 something similar going on here where NOTE Confidence: 0.919220025 01:01:45.282 --> 01:01:47.955 the system is being activated so NOTE Confidence: 0.919220025 01:01:47.955 --> 01:01:51.067 that it can be it can be suppressed. NOTE Confidence: 0.919220025 01:01:51.070 --> 01:01:52.720 And that's that's a non NOTE Confidence: 0.919220025 01:01:52.720 --> 01:01:53.380 scientific hypothesis. NOTE Confidence: 0.88817352 01:01:54.780 --> 01:01:57.646 No, it is aligned with, you know, NOTE Confidence: 0.88817352 01:01:57.646 --> 01:02:02.075 the 1972 article from Doctor Francis NOTE Confidence: 0.88817352 01:02:02.075 --> 01:02:04.700 Raymond who's who seems to again NOTE Confidence: 0.88817352 01:02:04.700 --> 01:02:07.579 suggest as well that some of this NOTE Confidence: 0.88817352 01:02:07.579 --> 01:02:09.959 intensity of this negative affective. NOTE Confidence: 0.88817352 01:02:09.960 --> 01:02:12.820 Experience seems to be relevant, NOTE Confidence: 0.88817352 01:02:12.820 --> 01:02:15.380 but you know, so I think it is NOTE Confidence: 0.88817352 01:02:15.380 --> 01:02:16.788 very interesting, it's very, NOTE Confidence: 0.88817352 01:02:16.788 --> 01:02:19.092 it's very interesting in terms of NOTE Confidence: 0.88817352 01:02:19.092 --> 01:02:20.596 predicting response and hopefully NOTE Confidence: 0.88817352 01:02:20.596 --> 01:02:22.948 that's something we're going to try and NOTE Confidence: 0.88817352 01:02:22.948 --> 01:02:25.388 do moving forward with some level of. NOTE Confidence: 0.88817352 01:02:25.390 --> 01:02:25.840 Record. NOTE Confidence: 0.842993931666667 01:02:27.400 --> 01:02:29.976 Yeah. And and and another note is NOTE Confidence: 0.842993931666667 01:02:29.976 --> 01:02:32.728 that in our headache studies we NOTE Confidence: 0.842993931666667 01:02:32.728 --> 01:02:35.333 there is also no psychotherapy, NOTE Confidence: 0.842993931666667 01:02:35.340 --> 01:02:37.605 we're not treating an underlying NOTE Confidence: 0.842993931666667 01:02:37.605 --> 01:02:39.417 underlying depression or anxiety. NOTE Confidence: 0.842993931666667 01:02:39.420 --> 01:02:41.996 So it's a similar the we the patients NOTE Confidence: 0.842993931666667 01:02:41.996 --> 01:02:44.903 are are given the capsule and the nurses NOTE Confidence: 0.842993931666667 01:02:44.903 --> 01:02:47.578 are there to check vitals and such, NOTE Confidence: 0.842993931666667 01:02:47.580 --> 01:02:49.388 but we don't sit with the patients either. NOTE Confidence: 0.842993931666667 01:02:49.390 --> 01:02:53.128 And this this is also supportive of NOTE Confidence: 0.842993931666667 01:02:53.128 --> 01:02:55.784 decades of patients self medicating with NOTE Confidence: 0.842993931666667 01:02:55.784 --> 01:02:58.160 these compounds in their living rooms. NOTE Confidence: 0.842993931666667 01:02:58.160 --> 01:03:00.780 Without, without psychiatry or NOTE Confidence: 0.842993931666667 01:03:00.780 --> 01:03:02.745 medical professionals there. NOTE Confidence: 0.842993931666667 01:03:02.750 --> 01:03:05.615 So there certainly is there NOTE Confidence: 0.842993931666667 01:03:05.615 --> 01:03:07.907 there separating out the, NOTE Confidence: 0.842993931666667 01:03:07.910 --> 01:03:10.255 the effects of the drug versus the NOTE Confidence: 0.842993931666667 01:03:10.255 --> 01:03:13.069 effect of the of of the setting and NOTE Confidence: 0.842993931666667 01:03:13.069 --> 01:03:15.266 of any other procedures like like NOTE Confidence: 0.842993931666667 01:03:15.266 --> 01:03:17.534 therapy have to be separated out. NOTE Confidence: 0.66771406 01:03:18.900 --> 01:03:19.300 Agreed. NOTE Confidence: 0.78598188 01:03:22.720 --> 01:03:26.510 I just, um, I guys, can you hear me? Yes, NOTE Confidence: 0.832813497142857 01:03:26.510 --> 01:03:29.800 I had a quick question about the concept NOTE Confidence: 0.832813497142857 01:03:29.800 --> 01:03:31.624 of individuals like seeing the grading NOTE Confidence: 0.832813497142857 01:03:31.624 --> 01:03:33.660 on the wall even though ordinarily NOTE Confidence: 0.832813497142857 01:03:33.660 --> 01:03:36.022 wouldn't wouldn't attend to it and that NOTE Confidence: 0.832813497142857 01:03:36.022 --> 01:03:37.408 kind of being the underlying basis NOTE Confidence: 0.832813497142857 01:03:37.408 --> 01:03:39.156 for some of the things they perceive. NOTE Confidence: 0.832813497142857 01:03:39.160 --> 01:03:42.394 I'm wondering if you have any knowledge. NOTE Confidence: 0.832813497142857 01:03:42.400 --> 01:03:45.060 And literature on attention NOTE Confidence: 0.832813497142857 01:03:45.060 --> 01:03:47.720 work using these substances, NOTE Confidence: 0.832813497142857 01:03:47.720 --> 01:03:49.502 because a lot of the theories NOTE Confidence: 0.832813497142857 01:03:49.502 --> 01:03:51.099 of attention postulate that the NOTE Confidence: 0.832813497142857 01:03:51.099 --> 01:03:53.199 attention spotlight is not actually an NOTE Confidence: 0.832813497142857 01:03:53.199 --> 01:03:54.979 enhancement of attention on one thing, NOTE Confidence: 0.832813497142857 01:03:54.980 --> 01:03:56.900 but it's the ability to inhibit NOTE Confidence: 0.832813497142857 01:03:56.900 --> 01:03:58.920 things you're not attending to. NOTE Confidence: 0.832813497142857 01:03:58.920 --> 01:04:01.718 And if that is kind of if these NOTE Confidence: 0.832813497142857 01:04:01.718 --> 01:04:03.729 preferences are kind of impairing that NOTE Confidence: 0.832813497142857 01:04:03.729 --> 01:04:06.214 normal capability and if has there been, NOTE Confidence: 0.832813497142857 01:04:06.220 --> 01:04:08.208 you know, attempts to do like Posner NOTE Confidence: 0.832813497142857 01:04:08.208 --> 01:04:10.307 cueing tasks or other attention based NOTE Confidence: 0.832813497142857 01:04:10.307 --> 01:04:12.677 tasks while they're using these substances? NOTE Confidence: 0.903506822 01:04:13.600 --> 01:04:14.932 So I'm not aware of anyone NOTE Confidence: 0.903506822 01:04:14.932 --> 01:04:15.820 has actually done that. NOTE Confidence: 0.903506822 01:04:15.820 --> 01:04:17.818 But I, I, I, I think I agree with NOTE Confidence: 0.903506822 01:04:17.818 --> 01:04:19.666 your hypothesis that what these drugs NOTE Confidence: 0.903506822 01:04:19.666 --> 01:04:22.222 may be doing is basically impairing NOTE Confidence: 0.903506822 01:04:22.222 --> 01:04:25.477 our normal filtering capacity of NOTE Confidence: 0.903506822 01:04:25.477 --> 01:04:28.200 filtering out irrelevant stimuli. NOTE Confidence: 0.903506822 01:04:28.200 --> 01:04:31.552 And so the kinds of things that would NOTE Confidence: 0.903506822 01:04:31.552 --> 01:04:34.380 support that hypothesis is the air NOTE Confidence: 0.903506822 01:04:34.380 --> 01:04:37.215 conditioner that I was previously unaware of. NOTE Confidence: 0.903506822 01:04:37.220 --> 01:04:39.916 I'm now aware of the noise it's making. NOTE Confidence: 0.903506822 01:04:39.920 --> 01:04:41.930 Or I was previously unaware of NOTE Confidence: 0.903506822 01:04:41.930 --> 01:04:44.415 the IV line dripping and now I can NOTE Confidence: 0.903506822 01:04:44.415 --> 01:04:46.430 hear the dripping of the IV line. NOTE Confidence: 0.903506822 01:04:46.430 --> 01:04:49.508 And and so that extends to NOTE Confidence: 0.903506822 01:04:49.508 --> 01:04:51.047 also visual stimuli. NOTE Confidence: 0.903506822 01:04:51.050 --> 01:04:52.967 I think I I saw a lot of that NOTE Confidence: 0.903506822 01:04:52.967 --> 01:04:54.934 with some of the early ketamine NOTE Confidence: 0.903506822 01:04:54.934 --> 01:04:57.105 studies where we were using much NOTE Confidence: 0.903506822 01:04:57.105 --> 01:04:59.170 higher doses of ketamine that's NOTE Confidence: 0.903506822 01:04:59.170 --> 01:05:01.181 current than what's currently used NOTE Confidence: 0.903506822 01:05:01.181 --> 01:05:02.936 in the treatment of depression. NOTE Confidence: 0.903506822 01:05:02.940 --> 01:05:05.976 And we would often notice that NOTE Confidence: 0.903506822 01:05:05.976 --> 01:05:08.490 subjects would would notice seemingly NOTE Confidence: 0.903506822 01:05:08.490 --> 01:05:10.990 irrelevant stimuli in the environment NOTE Confidence: 0.903506822 01:05:10.990 --> 01:05:13.989 that they were previously unaware of. NOTE Confidence: 0.903506822 01:05:13.990 --> 01:05:15.845 So you may be on onto something NOTE Confidence: 0.903506822 01:05:15.845 --> 01:05:17.729 and I'm sure it can be tested. NOTE Confidence: 0.903506822 01:05:17.730 --> 01:05:19.650 In this kind in these kinds NOTE Confidence: 0.903506822 01:05:19.650 --> 01:05:20.610 of laboratory experiments, NOTE Confidence: 0.783896577272727 01:05:20.730 --> 01:05:22.656 yeah. And I'm a quick adding NOTE Confidence: 0.783896577272727 01:05:22.656 --> 01:05:24.810 adding to that they experienced. NOTE Confidence: 0.783896577272727 01:05:24.810 --> 01:05:26.994 So I was curious in this case. NOTE Confidence: 0.783896577272727 01:05:27.000 --> 01:05:28.696 Part of that would be if they're more NOTE Confidence: 0.783896577272727 01:05:28.696 --> 01:05:30.075 aware of like they're interoceptive NOTE Confidence: 0.783896577272727 01:05:30.075 --> 01:05:32.175 processes like body position or met by NOTE Confidence: 0.783896577272727 01:05:32.229 --> 01:05:34.077 explain the body sensations they report. NOTE Confidence: 0.783896577272727 01:05:34.080 --> 01:05:35.832 But in that case you would NOTE Confidence: 0.783896577272727 01:05:35.832 --> 01:05:37.000 think that they would. NOTE Confidence: 0.783896577272727 01:05:37.000 --> 01:05:39.408 Report on like the sudden versus event. NOTE Confidence: 0.783896577272727 01:05:39.410 --> 01:05:40.892 They would report on feeling odd NOTE Confidence: 0.783896577272727 01:05:40.892 --> 01:05:42.860 if they had low blood pressure or, NOTE Confidence: 0.783896577272727 01:05:42.860 --> 01:05:45.330 you know, feeling. More tense. NOTE Confidence: 0.783896577272727 01:05:45.330 --> 01:05:46.830 If they have the physical, NOTE Confidence: 0.783896577272727 01:05:46.830 --> 01:05:48.150 you know the heartbeat going up. NOTE Confidence: 0.783896577272727 01:05:48.150 --> 01:05:50.016 And maybe that could explain the NOTE Confidence: 0.783896577272727 01:05:50.016 --> 01:05:51.900 30 minute sudden anxiety and the NOTE Confidence: 0.783896577272727 01:05:51.900 --> 01:05:53.634 30 minute sudden ledonia if they're NOTE Confidence: 0.783896577272727 01:05:53.634 --> 01:05:55.532 like more aware of potentially NOTE Confidence: 0.783896577272727 01:05:55.532 --> 01:05:56.789 negative body sensations. NOTE Confidence: 0.783896577272727 01:05:56.790 --> 01:05:57.170 But that's NOTE Confidence: 0.853948153333333 01:05:57.180 --> 01:05:57.699 just a thought. NOTE Confidence: 0.837744654285714 01:05:58.930 --> 01:06:00.185 I think that's a really NOTE Confidence: 0.837744654285714 01:06:00.185 --> 01:06:05.070 good thought, yeah. Yeah. I NOTE Confidence: 0.853503579166667 01:06:05.080 --> 01:06:08.544 mean we clearly saw some subjects who were NOTE Confidence: 0.853503579166667 01:06:08.544 --> 01:06:11.060 had significant anticipatory anxiety. NOTE Confidence: 0.853503579166667 01:06:11.060 --> 01:06:15.976 Hmm, which which really influenced the. NOTE Confidence: 0.853503579166667 01:06:15.976 --> 01:06:20.050 Their experience of the first dose, NOTE Confidence: 0.853503579166667 01:06:20.050 --> 01:06:22.290 but then they were able to get over NOTE Confidence: 0.853503579166667 01:06:22.290 --> 01:06:24.516 it and and come back for the 2nd dose. NOTE Confidence: 0.543368206 01:06:27.080 --> 01:06:29.680 Yeah, thanks. This is fascinating. NOTE Confidence: 0.543368206 01:06:29.680 --> 01:06:32.198 Yeah. Remind me how long NOTE Confidence: 0.894283296363636 01:06:32.210 --> 01:06:34.235 was the the the gap between the 1st and NOTE Confidence: 0.894283296363636 01:06:34.235 --> 01:06:36.480 2nd dose? Was that fixed or variable? NOTE Confidence: 0.718875178 01:06:36.750 --> 01:06:38.010 It was variable? It was, NOTE Confidence: 0.718875178 01:06:38.010 --> 01:06:41.034 I think it was three to seven day NOTE Confidence: 0.718875178 01:06:41.034 --> 01:06:43.490 window closer to three days. Thanks. NOTE Confidence: 0.8815278 01:06:49.150 --> 01:06:49.900 OK. NOTE Confidence: 0.9368441 01:06:52.610 --> 01:06:55.198 OK. Well, thank you so NOTE Confidence: 0.9368441 01:06:55.198 --> 01:06:57.008 much both Sharif and Cyril. NOTE Confidence: 0.906912911428571 01:06:57.010 --> 01:06:59.929 This is exciting and exciting new area. NOTE Confidence: 0.906912911428571 01:06:59.930 --> 01:07:01.460 And serial, the point you make NOTE Confidence: 0.906912911428571 01:07:01.460 --> 01:07:03.062 about you know the the rapid NOTE Confidence: 0.906912911428571 01:07:03.062 --> 01:07:04.628 action and short half life mean NOTE Confidence: 0.906912911428571 01:07:04.628 --> 01:07:06.350 that you can adjust the timing. NOTE Confidence: 0.906912911428571 01:07:06.350 --> 01:07:07.934 You know the if you can adjust both NOTE Confidence: 0.906912911428571 01:07:07.934 --> 01:07:09.059 the intensity and the duration, NOTE Confidence: 0.906912911428571 01:07:09.060 --> 01:07:10.836 that opens the door to a lot of NOTE Confidence: 0.906912911428571 01:07:10.836 --> 01:07:11.950 really interesting manipulations. NOTE Confidence: 0.906912911428571 01:07:11.950 --> 01:07:12.859 This is exciting. NOTE Confidence: 0.92712125 01:07:14.220 --> 01:07:16.080 Thank you. Alright, NOTE Confidence: 0.91457969 01:07:16.850 --> 01:07:17.860 thank you all for coming. NOTE Confidence: 0.814838445555556 01:07:18.050 --> 01:07:19.078 We'll have another meeting NOTE Confidence: 0.814838445555556 01:07:19.078 --> 01:07:20.363 at the seminar in April. NOTE Confidence: 0.814838445555556 01:07:20.370 --> 01:07:21.490 I'm not sure who who NOTE Confidence: 0.814838445555556 01:07:21.490 --> 01:07:22.610 will line up for that. NOTE Confidence: 0.814838445555556 01:07:22.610 --> 01:07:24.258 I'm open to suggestions. NOTE Confidence: 0.736011996363636 01:07:25.640 --> 01:07:27.080 It's a great doctor. NOTE Confidence: 0.736011996363636 01:07:27.080 --> 01:07:29.850 Schindler has a number of ongoing studies. NOTE Confidence: 0.736011996363636 01:07:29.850 --> 01:07:33.274 Yes, it was syben and and you know. NOTE Confidence: 0.736011996363636 01:07:33.280 --> 01:07:34.732 Headache disorders. Yep. NOTE Confidence: 0.736011996363636 01:07:34.732 --> 01:07:37.152 And then I think Patrick NOTE Confidence: 0.736011996363636 01:07:37.152 --> 01:07:39.980 has Patrick and Jordan. NOTE Confidence: 0.736011996363636 01:07:39.980 --> 01:07:43.368 We just looked over some of our. NOTE Confidence: 0.736011996363636 01:07:43.370 --> 01:07:46.787 Our EEG findings. Typing. NOTE Confidence: 0.736011996363636 01:07:46.787 --> 01:07:48.972 And one of them could NOTE Confidence: 0.736011996363636 01:07:48.972 --> 01:07:51.300 present to wonderful. OK. NOTE Confidence: 0.840612846666667 01:07:51.690 --> 01:07:54.786 Thank you. I'll be in touch. NOTE Confidence: 0.840612846666667 01:07:54.790 --> 01:07:56.770 All right. Take care, everyone. NOTE Confidence: 0.840612846666667 01:07:56.770 --> 01:07:58.096 Thanks again. Have a good weekend.