1 00:00:05,640 --> 00:00:10,760 >> I'M WIN ARIAS 2 00:00:10,760 --> 00:00:12,480 SENIOR SCIENTIST EMERITUS NIH 3 00:00:12,480 --> 00:00:20,280 HUMAN GENOME INSTITUTE WE 4 00:00:20,280 --> 00:00:23,000 WELCOME YOU TO THE 12TH SESSION 5 00:00:23,000 --> 00:00:24,600 IN THE 23RD YEAR OF THE COURSE 6 00:00:24,600 --> 00:00:27,320 AT THE NATIONAL INSTITUTES OF 7 00:00:27,320 --> 00:00:31,080 HEALTH CALLED DEMYSTIFYING 8 00:00:31,080 --> 00:00:34,960 MEDICINE PURPOSE OF COURSE IS 9 00:00:34,960 --> 00:00:36,560 BRIDGING EXCITING DEVELOPMENTS 10 00:00:36,560 --> 00:00:40,720 AND BUY OL AND ENGINEERING WITH 11 00:00:40,720 --> 00:00:45,640 MEDIC 12 00:00:45,640 --> 00:00:45,920 MEDICINE. 13 00:00:45,920 --> 00:00:46,840 INTENT IS ACQUAINTING EVERYONE 14 00:00:46,840 --> 00:00:49,040 WITH DEVELOPMENTS IN A MANNER 15 00:00:49,040 --> 00:00:51,240 THAT ARE NOT INTENSIVE AND ARE 16 00:00:51,240 --> 00:00:53,680 NOT RESEARCH SEMINARS. 17 00:00:53,680 --> 00:00:58,080 BUT, THE GOAL IS TO EXCITE 18 00:00:58,080 --> 00:00:59,480 INDIVIDUALS INTO THE 19 00:00:59,480 --> 00:01:01,400 OPPORTUNITIES PROVIDED AND 20 00:01:01,400 --> 00:01:05,120 PARTICULARLY BASED UPON THESE 21 00:01:05,120 --> 00:01:07,480 EXTRAORDINARY DEVELOPMENTS AND 22 00:01:07,480 --> 00:01:10,560 SOME PROGRAMS HAVE BEEN TO BUILD 23 00:01:10,560 --> 00:01:12,720 BRIDGES BETWEEN MEDICINE AND 24 00:01:12,720 --> 00:01:14,920 PATIENTS AND BIOLOGY AND 25 00:01:14,920 --> 00:01:17,520 ENGINEERING AND WE HAVE ALSO 26 00:01:17,520 --> 00:01:19,320 CONSIDERED BRIDGES INTO SPACE 27 00:01:19,320 --> 00:01:21,720 AND INTO THE MICRO BIOLOGICAL 28 00:01:21,720 --> 00:01:25,320 WORLD AT THE BOTTOM OF THE SEA 29 00:01:25,320 --> 00:01:26,880 AND ORIGIN OF LIFE AND WIDE 30 00:01:26,880 --> 00:01:31,000 VARIETY OF TOPICS AND TODAY'S 31 00:01:31,000 --> 00:01:34,800 TOPIC IS ONE THAT REPRESENTS AN 32 00:01:34,800 --> 00:01:37,720 INCREASING AREA OF INTEREST FOR 33 00:01:37,720 --> 00:01:40,440 THE PUBLIC IN GENERAL. 34 00:01:40,440 --> 00:01:46,360 AND FOR SCIENCE AND MEDICINE IN 35 00:01:46,360 --> 00:01:47,520 PARTICULAR. 36 00:01:47,520 --> 00:01:51,200 SO, AS I HAVE SAID, THE PURPOSE 37 00:01:51,200 --> 00:01:53,680 OF THIS COURSE IS REPRESENTED BY 38 00:01:53,680 --> 00:01:56,320 THE LOGO. 39 00:01:56,320 --> 00:01:59,120 IT IS THE BROOKLYN BRIDGE. ONCE 40 00:01:59,120 --> 00:02:01,200 YOU BUILD A BRIDGE, THINGS ARE 41 00:02:01,200 --> 00:02:02,960 NEVER THE SAME ON EITHER SIDE. 42 00:02:02,960 --> 00:02:06,000 WE ARE LIKE TWO INDIVIDUALS THAT 43 00:02:06,000 --> 00:02:08,880 ARE ON THE CAT WALK THAT ARE 44 00:02:08,880 --> 00:02:12,720 REPRESENTING OUR SPEAKERS WHO 45 00:02:12,720 --> 00:02:14,720 ARE SEEKING TO TEACH US ABOUT 46 00:02:14,720 --> 00:02:17,000 THE BRIDGE THAT IS EXISTING 47 00:02:17,000 --> 00:02:20,480 BETWEEN PSYCHEDELIC SUBSTANCES 48 00:02:20,480 --> 00:02:24,600 AND NEUROSCIENCE AND MEDICINE 49 00:02:24,600 --> 00:02:25,960 AND DISEASE. 50 00:02:25,960 --> 00:02:29,360 BIGGER PURPOSES OF THE COURSE IS 51 00:02:29,360 --> 00:02:31,080 TO CONVERT SILOS OF INFORMATION 52 00:02:31,080 --> 00:02:35,560 THAT ARE INDICATED IN THE LOWER 53 00:02:35,560 --> 00:02:37,920 RIGHT INTO WHAT BRIDGE TO 54 00:02:37,920 --> 00:02:43,560 COMMUNICATE. THE NEXT SLIDE, 55 00:02:43,560 --> 00:02:45,080 PLE 56 00:02:45,080 --> 00:02:46,400 PLEASE. 57 00:02:46,400 --> 00:02:50,320 CME CREDIT PHONE NUMBER TO TEXT 58 00:02:50,320 --> 00:02:59,600 IS 45389 AND PHONE NUMBER IS 59 00:02:59,600 --> 00:03:01,880 443-541-5052. DR. OLSON HAS A 60 00:03:01,880 --> 00:03:02,680 DISCLOSURE STATEMENT THAT 61 00:03:02,680 --> 00:03:04,880 APPEARS AT THE BOTTOM OF THE 62 00:03:04,880 --> 00:03:05,280 SLIDE. 63 00:03:05,280 --> 00:03:09,040 NEXT SLIDE, PLEASE. 64 00:03:09,040 --> 00:03:12,960 SO, PSYCHEDELICS, WHAT IS IN THE 65 00:03:12,960 --> 00:03:13,760 WORD? 66 00:03:13,760 --> 00:03:17,760 IF WE GO BACK IN HISTORY, THERE 67 00:03:17,760 --> 00:03:20,400 ARE MANY LITERARY DESCRIPTIONS 68 00:03:20,400 --> 00:03:23,120 OF MYSTICAL EXPERIENCES AND 69 00:03:23,120 --> 00:03:25,600 RELIGIOUS EXPERIENCES ASSOCIATED 70 00:03:25,600 --> 00:03:28,560 WITH THE INGESTION OF MUSHROOMS 71 00:03:28,560 --> 00:03:34,200 AND OTHER BIOLOGICALLY DERIVED 72 00:03:34,200 --> 00:03:34,680 COMPOUNDS. 73 00:03:34,680 --> 00:03:37,760 THIS WAS THE STATE FOR MANY, 74 00:03:37,760 --> 00:03:38,480 MANY YEARS. 75 00:03:38,480 --> 00:03:43,240 IN FACT, IN TODAY'S WORLD, THE 76 00:03:43,240 --> 00:03:45,840 POPULARITY AND PUBLIC AWARENESS 77 00:03:45,840 --> 00:03:50,200 HAS GREATLY EXCEEDED THE 78 00:03:50,200 --> 00:03:51,440 DEVELOPMENT OF FUNDAMENTAL 79 00:03:51,440 --> 00:03:53,200 UNDERSTANDING AS TO MECHANISMS. 80 00:03:53,200 --> 00:03:56,080 WE CAN ASK WHAT IS THE NEURAL 81 00:03:56,080 --> 00:04:00,560 BASIS OF THE DIFFERENT TYPES OF 82 00:04:00,560 --> 00:04:01,000 PSYCHEDELICS AND OF 83 00:04:01,000 --> 00:04:03,160 HALLUCINA 84 00:04:03,160 --> 00:04:04,000 HALLUCINATIONS. 85 00:04:04,000 --> 00:04:10,120 DO THEY HAVE A THERAPEUTIC 86 00:04:10,120 --> 00:04:13,160 POTENTIAL AND IS THAT POTENTIAL 87 00:04:13,160 --> 00:04:14,800 REALISTIC REALITY FOR 88 00:04:14,800 --> 00:04:15,160 PSYCHEDELICS? 89 00:04:15,160 --> 00:04:17,760 HOW DOES ONE STUDY THIS WHETHER 90 00:04:17,760 --> 00:04:20,680 IT BE HALLUCINATIONS OR 91 00:04:20,680 --> 00:04:23,480 PSYCHEDELIC AFFECTS IN NON-HUMAN 92 00:04:23,480 --> 00:04:24,480 SPECIES? 93 00:04:24,480 --> 00:04:28,480 I GUESS THE BIG QUESTION IS CAN 94 00:04:28,480 --> 00:04:29,680 NEUROPLASTIC EFFECTS OF 95 00:04:29,680 --> 00:04:31,560 PSYCHEDELICS IT THAT WE WILL 96 00:04:31,560 --> 00:04:35,080 HEAR ABOUT TODAY OPEN WINDOWS 97 00:04:35,080 --> 00:04:39,120 FOR THERAPEUTICS AND BASIC 98 00:04:39,120 --> 00:04:40,200 NEUROBIOLOGY AND PERHAPS A 99 00:04:40,200 --> 00:04:41,600 BETTER UNDERSTANDING OF 100 00:04:41,600 --> 00:04:44,280 EVOLUTION AND AGING AND 101 00:04:44,280 --> 00:04:44,760 NEURODEGENERATION. 102 00:04:44,760 --> 00:04:47,880 ARE WE CONFRONTING A BRAVE NEW 103 00:04:47,880 --> 00:04:48,640 WORLD? 104 00:04:48,640 --> 00:04:53,080 WELL, THERE IS A DANG THAT IS 105 00:04:53,080 --> 00:04:56,680 LURKING IN THIS PROCESS. 106 00:04:56,680 --> 00:05:03,120 AND THAT IS DUE TO SOCIAL MEDIA 107 00:05:03,120 --> 00:05:06,120 AND BOOKS AND LOTS OF PUBLICLY 108 00:05:06,120 --> 00:05:08,040 AVAILABLE MAGAZINES AND SO 109 00:05:08,040 --> 00:05:08,360 FORTH. 110 00:05:08,360 --> 00:05:15,120 THEY HAVE MADE PUBLIC AWARENESS 111 00:05:15,120 --> 00:05:17,800 OF PSYCHEDELICS FAR IN ADVANCE 112 00:05:17,800 --> 00:05:21,880 OF THE RAPIDLY CATCHING UP 113 00:05:21,880 --> 00:05:24,320 UNDERSTANDING OF BASIC 114 00:05:24,320 --> 00:05:24,640 MECHANISMS. 115 00:05:24,640 --> 00:05:26,880 THIS PUBLIC AWARENESS AND USE 116 00:05:26,880 --> 00:05:30,080 HAS GREATLY PROCEEDED SCIENTIFIC 117 00:05:30,080 --> 00:05:30,320 STUDY. 118 00:05:30,320 --> 00:05:33,760 SO, TODAY, WE ARE VERY FORTUNATE 119 00:05:33,760 --> 00:05:37,320 TO HAVE TWO LEADERS IN THE 120 00:05:37,320 --> 00:05:40,520 SCIENTIFIC ASPECT OF 121 00:05:40,520 --> 00:05:40,840 PSYCHEDELICS. 122 00:05:40,840 --> 00:05:42,440 THEY WILL DISCUSS THESE 123 00:05:42,440 --> 00:05:45,120 QUESTIONS AND THE STATUS OF 124 00:05:45,120 --> 00:05:48,400 THEIR RESEARCH AND INTERESTS. 125 00:05:48,400 --> 00:05:51,440 NEXT SLIDE, PLEASE. 126 00:05:51,440 --> 00:05:53,840 SO, THE FIRST SPEAKER IS FRED 127 00:05:53,840 --> 00:05:57,680 BARRETT WHO IS A COGNITIVE 128 00:05:57,680 --> 00:05:59,560 NEUROSCIENTIST WHO HAD 129 00:05:59,560 --> 00:06:02,680 UNDERGRADUATE DEGREE AT TEMPLE 130 00:06:02,680 --> 00:06:04,320 UNIVERSITY IN MUSIC THAT WILL 131 00:06:04,320 --> 00:06:06,280 APPEAR IN SOME DISCUSSIONS. 132 00:06:06,280 --> 00:06:09,120 AND RECEIVED HIS PHD AT THE 133 00:06:09,120 --> 00:06:11,880 UNIVERSITY OF CALIFORNIA, DAVIS 134 00:06:11,880 --> 00:06:15,160 AND DID FURTHER TRAINING AT 135 00:06:15,160 --> 00:06:18,440 JOHNS HOPKINS AND BEHAVIORAL 136 00:06:18,440 --> 00:06:19,680 PHARMACOLOGY AND FRED IS 137 00:06:19,680 --> 00:06:23,600 ASSOCIATE PROFESSOR OF 138 00:06:23,600 --> 00:06:25,440 PSYCHIATRY AND BEHAVIORAL 139 00:06:25,440 --> 00:06:28,840 SCIENCES AT JOHNS HOPKINS CENTER 140 00:06:28,840 --> 00:06:30,480 FOR PSYCHEDELIC CONSCIOUSNESS 141 00:06:30,480 --> 00:06:32,880 AND RESEARCH AND RESEARCH 142 00:06:32,880 --> 00:06:34,480 CONCERNING NEURAL BASIS OF 143 00:06:34,480 --> 00:06:39,560 EMOTION AND ALTERED CONNESS THAT 144 00:06:39,560 --> 00:06:45,920 IS RELATIVE TO MUSIC AND 145 00:06:45,920 --> 00:06:47,560 FORMCOLOGICAL INFORMATION AND 146 00:06:47,560 --> 00:06:49,120 COMPUTERIZED TESTING AND BRAIN 147 00:06:49,120 --> 00:06:53,200 IMAGING AND FOR YEARS 148 00:06:53,200 --> 00:06:57,160 COLLABORATED WITH ROLAND 149 00:06:57,160 --> 00:07:01,440 GRIFFITH FOUNDER FOR PSYCHEDELIC 150 00:07:01,440 --> 00:07:04,360 CONSCIOUSNESS AT HOPKINS. 151 00:07:04,360 --> 00:07:06,960 SECOND SPEAKER, NEXT SLIDE, 152 00:07:06,960 --> 00:07:09,480 PLEASE. IS DAVID OLSON WHO 153 00:07:09,480 --> 00:07:11,280 GRADUATED FROM UNION COLLEGE AND 154 00:07:11,280 --> 00:07:14,240 RECEIVED HIS PHD IN NEUROBIOLOGY 155 00:07:14,240 --> 00:07:16,760 AND CHEMISTRY AT STANFORD 156 00:07:16,760 --> 00:07:18,880 UNIVERSITY AND DID A POST 157 00:07:18,880 --> 00:07:21,040 DOCTORAL FELLOWSHIP AT BROAD 158 00:07:21,040 --> 00:07:23,120 INSTITUTE AT MIT IN CAMBRIDGE 159 00:07:23,120 --> 00:07:27,240 AND IS ASSOCIATE PROFESSOR OF 160 00:07:27,240 --> 00:07:30,000 CHEMISTRY, BIOCHEMISTRY AND 161 00:07:30,000 --> 00:07:32,000 MOLECULAR MEDICINE AND DIRECTOR 162 00:07:32,000 --> 00:07:34,720 OF INSTITUTE FOR PSYCHEDELICS 163 00:07:34,720 --> 00:07:36,560 AND NEUROTHERAPEUTICS AT 164 00:07:36,560 --> 00:07:42,240 UNIVERSITY OF CALIFORNIA, DAVIS. 165 00:07:42,240 --> 00:07:45,360 DAVID'S RESEARCH IS VERY 166 00:07:45,360 --> 00:07:45,720 REDUCTIONIST. 167 00:07:45,720 --> 00:07:48,320 HE IS CONCERNED WITH REGULATION 168 00:07:48,320 --> 00:07:51,480 OF NEURAL PLASTICITY AND 169 00:07:51,480 --> 00:07:53,880 LEARNING AND MEMORY AND AS 170 00:07:53,880 --> 00:07:56,040 PRODUCED BY SMALL MOLECULES SOME 171 00:07:56,040 --> 00:07:59,520 OF WHICH ARE ANALOGUES AND 172 00:07:59,520 --> 00:08:02,240 DERIVATIVES OF PSYCHEDELIC 173 00:08:02,240 --> 00:08:04,240 COMPOUNDS EXISTING IN NATURE AND 174 00:08:04,240 --> 00:08:07,760 LAB USES A VARIETY OF TECHNIQUES 175 00:08:07,760 --> 00:08:10,240 FROM CHEMICAL BUY OJ TO 176 00:08:10,240 --> 00:08:12,560 SYNTHETIC CHEMISTRY AND 177 00:08:12,560 --> 00:08:15,200 MOLECULAR NEURAL BUY OL AND 178 00:08:15,200 --> 00:08:17,320 BEHAVIORAL NEURAL FARM COLAND WE 179 00:08:17,320 --> 00:08:19,560 WELCOME BOTH OF YOU AND 180 00:08:19,560 --> 00:08:21,200 APPRECIATE YOUR VERY MUCH 181 00:08:21,200 --> 00:08:23,200 SPENDING THIS TIME WITH US AND 182 00:08:23,200 --> 00:08:26,760 PERHAPS, FRED, IF YOU WOULD, 183 00:08:26,760 --> 00:08:27,600 PLEASE BEGIN. 184 00:08:27,600 --> 00:08:28,640 >>THANK YOU VERY MUCH, DR. 185 00:08:28,640 --> 00:08:29,240 ARIAS FOR YOUR GENTLE AND 186 00:08:29,240 --> 00:08:31,560 WONDERFUL INTRODUCTION. 187 00:08:31,560 --> 00:08:34,040 TODAY WE WILL TALK ABOUT 188 00:08:34,040 --> 00:08:36,000 DEMYSTIFYING MUSHROOMS. IT IS 189 00:08:36,000 --> 00:08:38,400 AN HONOR TO BE HERE TO SHARE A 190 00:08:38,400 --> 00:08:41,760 SMALL SLICE OF THE FIELDS AND 191 00:08:41,760 --> 00:08:44,920 GROWING FIELD WITH YOU ALL. 192 00:08:44,920 --> 00:08:47,600 I SHOULD DISCLOSE I'M A 193 00:08:47,600 --> 00:08:51,040 SCIENTIFIC ADVISOR FOR MIND LABS 194 00:08:51,040 --> 00:08:52,760 AND CONSULTED WITH 195 00:08:52,760 --> 00:08:54,000 PHARMACEUTICALS AND LIFE 196 00:08:54,000 --> 00:08:55,280 SCIENCES AND NOTHING IN MY 197 00:08:55,280 --> 00:08:56,200 PRESENTATION WILL INVOLVE 198 00:08:56,200 --> 00:08:57,960 ANYTHING THAT I HAVE CONSULTED 199 00:08:57,960 --> 00:08:58,960 WITH THEM FOR. 200 00:08:58,960 --> 00:09:01,160 I WOULD LIKE TO START WITH A 201 00:09:01,160 --> 00:09:05,240 QUESTION. WHAT ARE PSYCHEDELIC 202 00:09:05,240 --> 00:09:06,520 DRUGS? 203 00:09:06,520 --> 00:09:08,320 LOOKING IN DICTIONARY YOU WILL 204 00:09:08,320 --> 00:09:09,760 FIND A DEFINITION INCLUDING 205 00:09:09,760 --> 00:09:13,000 PHRASES AND IDEA SUCH AS SENSORY 206 00:09:13,000 --> 00:09:14,720 PERCEPTION AND SENSORY 207 00:09:14,720 --> 00:09:20,280 DISTORTION AND HALLUCINATIONS -- 208 00:09:20,280 --> 00:09:23,920 AND THOSE THAT EXPERIENCE THESE 209 00:09:23,920 --> 00:09:25,680 DRUGS IT IS NOT NECESSARILY THE 210 00:09:25,680 --> 00:09:27,920 CASE IN ANY OF THESE THINGS THAT 211 00:09:27,920 --> 00:09:29,840 DOESN'T REALLY KIND OF DO 212 00:09:29,840 --> 00:09:31,480 JUSTICE TO WORD PSYCHEDELIC 213 00:09:31,480 --> 00:09:33,440 ITSELF AS IT IS ORIGINALLY 214 00:09:33,440 --> 00:09:35,640 INTENDED AND PSYCHEDELIC IS 215 00:09:35,640 --> 00:09:39,880 COINED BY HUMPHREY OS-MONDAY A 216 00:09:39,880 --> 00:09:42,680 BRITISH SCIENTIST EX PATRIOT IN 217 00:09:42,680 --> 00:09:47,800 CANADA AND FIRST INDIVIDUAL TO 218 00:09:47,800 --> 00:09:50,440 ADMINISTER PSYCHEDELIC AND HE 219 00:09:50,440 --> 00:09:52,000 TOOK THEM AND OTHER COMPOUNDS 220 00:09:52,000 --> 00:09:54,120 BECAUSE HE WANTED TO UNDERSTAND 221 00:09:54,120 --> 00:09:55,480 HOW COMPOUNDS WORKED AND WHAT 222 00:09:55,480 --> 00:09:57,560 THEY DID AND THOUGHT BY DOING SO 223 00:09:57,560 --> 00:09:59,480 HE MIGHT BETTER UNDERSTAND HOW 224 00:09:59,480 --> 00:10:00,760 THESE COMPOUNDS COULD BE 225 00:10:00,760 --> 00:10:05,240 THERAPEUTIC IF AT ALL. HE WENT 226 00:10:05,240 --> 00:10:06,960 ON TO ADMINISTER LSD TO 227 00:10:06,960 --> 00:10:08,760 THOUSANDS OF PATIENTS IN HIS 228 00:10:08,760 --> 00:10:10,960 CLINIC AT THE TIME FOR WHAT WAS 229 00:10:10,960 --> 00:10:12,520 CALLED ALCOHOLISM AND CLAIMED 230 00:10:12,520 --> 00:10:15,320 THAT OVER 40% OF HIS PATIENTS 231 00:10:15,320 --> 00:10:18,040 ACROSS THE YEARS REMAINED 232 00:10:18,040 --> 00:10:20,120 ABSTINENT FOR AT LEAST A YEAR 233 00:10:20,120 --> 00:10:21,800 AFTER TREATMENT WITH LSD THAT IS 234 00:10:21,800 --> 00:10:24,120 A REMARKABLE OUTCOME FOR THAT 235 00:10:24,120 --> 00:10:26,720 TIME AND WOULD STILL BE A 236 00:10:26,720 --> 00:10:27,320 REMARKABLE OUTCOME TODAY AND 237 00:10:27,320 --> 00:10:33,000 GAVE LSD TO -- RATHER MESCALIN 238 00:10:33,000 --> 00:10:35,800 TO ALBUS HUXLEY WHO IS FAMOUS 239 00:10:35,800 --> 00:10:38,080 AUTHOR PENNING DOORS TO 240 00:10:38,080 --> 00:10:39,480 PERCEPTION THAT IS CLASSIC TEXT 241 00:10:39,480 --> 00:10:41,960 IN MIND OF PHILOSOPHY IN MIND AS 242 00:10:41,960 --> 00:10:46,560 IT RELATES TO PSYCHEDELICS. 243 00:10:46,560 --> 00:10:49,480 HUMPHREY OS-MONDAY THOUGHT THAT 244 00:10:49,480 --> 00:10:51,480 COMPOUNDS MANIFESTED SOME SENSE 245 00:10:51,480 --> 00:10:53,280 OF MIND THAT INDIVIDUAL WASN'T 246 00:10:53,280 --> 00:10:54,720 AWARE OF OR DIDN'T HAVE ACCESS 247 00:10:54,720 --> 00:10:57,400 TO COURSE OF NORMAL WAKING 248 00:10:57,400 --> 00:11:00,160 CONSCIOUSNESS AND COINED PSYCHE 249 00:11:00,160 --> 00:11:03,640 AND DELOS AND PSYCHEDELICS 250 00:11:03,640 --> 00:11:06,480 MANIFESTED ASPECTS IN MIND AND 251 00:11:06,480 --> 00:11:07,720 MEDICINE THAT IS MIND 252 00:11:07,720 --> 00:11:09,000 MANIFESTING PROPERTY THAT IS 253 00:11:09,000 --> 00:11:10,840 ESSENTIAL TO THERAPEUTIC 254 00:11:10,840 --> 00:11:13,720 EFFICACY OR POTENTIAL OF 255 00:11:13,720 --> 00:11:15,680 PSYCHEDELIC DRUGS AND TAKEN AT 256 00:11:15,680 --> 00:11:18,080 BROADEST DEFINITION OF SOMETHING 257 00:11:18,080 --> 00:11:20,520 MANIFESTING MIND OF COFFEE I'M 258 00:11:20,520 --> 00:11:22,160 DRINKING THAT IS MIND 259 00:11:22,160 --> 00:11:24,840 MANIFESTING AND IN A SENSE 260 00:11:24,840 --> 00:11:27,080 HUMPHREY OSMOND DIDN'T MEAN THAT 261 00:11:27,080 --> 00:11:28,960 AND THERE IS A WIDE RANGE OF 262 00:11:28,960 --> 00:11:30,000 COMPOUNDS BY SOME AT LEAST ARE 263 00:11:30,000 --> 00:11:34,040 CALL OR CLAIMED TO BE 264 00:11:34,040 --> 00:11:41,680 PSYCHEDELIC INCLUDING NOT ONLY 265 00:11:41,680 --> 00:11:46,600 PSILOCYBINO OR MESCALINE OR 266 00:11:46,600 --> 00:11:49,720 SYNTHETIC DRUGS LIKE WILL. SD 267 00:11:49,720 --> 00:11:56,440 AND MORE EXOTIC COMPOUNDS LIKE 268 00:11:56,440 --> 00:12:00,720 SALVINORIN AND MDMA AND THC IS 269 00:12:00,720 --> 00:12:02,360 CALLED PSYCHEDELIC BY SOME AND 270 00:12:02,360 --> 00:12:06,040 COMPOUNDS SPAN A WIDE AND 271 00:12:06,040 --> 00:12:09,120 DIVERSE RANGE OF FARM COLONL CAL 272 00:12:09,120 --> 00:12:11,880 CLASSES WITH VERY DISPARATE 273 00:12:11,880 --> 00:12:14,080 MOLECULAR TARGETS IN THE BRAIN 274 00:12:14,080 --> 00:12:15,280 AND LIABILITY USE CASES AND 275 00:12:15,280 --> 00:12:17,520 OTHER THINGS POINTING THIS OUT 276 00:12:17,520 --> 00:12:19,840 THAT NOT EVERYTHING IS THE SAME 277 00:12:19,840 --> 00:12:22,120 AND THESE ARE NOT OR ARE VERY 278 00:12:22,120 --> 00:12:23,360 DIFFERENT DRUGS AND WANT TO 279 00:12:23,360 --> 00:12:25,640 BRING YOUR ATTENTION TO THAT AND 280 00:12:25,640 --> 00:12:26,760 TALKING ABOUT PSYCHEDELIC DRUGS 281 00:12:26,760 --> 00:12:29,720 I'M TALKING ABOUT CLASSIC 282 00:12:29,720 --> 00:12:31,280 PSYCHEDELICS THAT I WILL SHARE 283 00:12:31,280 --> 00:12:34,360 IN A FORM OR ANOTHER PROPERTY OF 284 00:12:34,360 --> 00:12:37,640 BEING AGONIST OR PARTIAL AGONIST 285 00:12:37,640 --> 00:12:41,680 OF CERTIFY TONIM A RECEPTOR IN 286 00:12:41,680 --> 00:12:44,280 THE BRAIN MODULAR SYMPTOM IN 287 00:12:44,280 --> 00:12:49,760 BRAIN AND WE WILL FOCUS ON SILO 288 00:12:49,760 --> 00:12:53,520 KRIEB BIN FOR REST OF MY TALK 289 00:12:53,520 --> 00:13:04,040 WITH MENTIONS TO LSD -- PLANT 290 00:13:11,400 --> 00:13:12,160 SOURCES AND OTHERWISE USED FOR 291 00:13:12,160 --> 00:13:13,240 RELIGIOUS AND SPIRITUAL PURPOSES 292 00:13:13,240 --> 00:13:15,360 IF NOT OTHER PURPOSES AND 293 00:13:15,360 --> 00:13:18,040 SPECULATION OF CEREMONIAL USE OF 294 00:13:18,040 --> 00:13:19,800 SIMILAR PSYCHOACTIVE COMPOUNDS 295 00:13:19,800 --> 00:13:20,960 FOR THOUSANDS OF YEARS AND 296 00:13:20,960 --> 00:13:22,680 EVIDENCE IS REALLY CALLED INTO 297 00:13:22,680 --> 00:13:25,000 QUESTION WHAT YOU SEE ON THE 298 00:13:25,000 --> 00:13:28,560 RIGHT IS A PHOTO OF A CAVE 299 00:13:28,560 --> 00:13:32,320 DRAWING FOUND IN ALGERIA THAT 300 00:13:32,320 --> 00:13:37,400 APPEARS TO BE SHAWMAN KOVRED IN 301 00:13:37,400 --> 00:13:40,040 MUSHROOMS AND EVIDENCE IN CAVE 302 00:13:40,040 --> 00:13:42,560 DRAWN MANY THOUSANDS OF YEARS 303 00:13:42,560 --> 00:13:43,760 OLD AND OTHER ARCHAEOLOGICAL 304 00:13:43,760 --> 00:13:47,920 FINDS THAT IS NOTABLE THAT 305 00:13:47,920 --> 00:13:51,160 MUSHROOMS OF [INDISCERNIBLE] 306 00:13:51,160 --> 00:13:55,640 GENERALUS AND MUSHROOMS IN IT 307 00:13:55,640 --> 00:13:57,720 AND RELATED -- THEY ARE FOUND ON 308 00:13:57,720 --> 00:14:02,400 ALL CONTINENTS AND CEREMONIALLY 309 00:14:02,400 --> 00:14:04,440 SOOILO KRIEB BIN CONTAINING 310 00:14:04,440 --> 00:14:10,040 MUSHROOMS HAVE CONTRACTED MORE 311 00:14:10,040 --> 00:14:13,400 CONCRETELY IN 15TH CENTURY BY 312 00:14:13,400 --> 00:14:24,680 INDIGENOUS PEOPLE IPEOPLE IN ME 313 00:14:29,120 --> 00:14:30,080 LSD ITSELF IS FIRST SYNTHESIZED 314 00:14:30,080 --> 00:14:32,560 BY ALBERT HOFFMAN IN 1938 AND 315 00:14:32,560 --> 00:14:38,520 NOT UNTIL 1943 THAT HE 316 00:14:38,520 --> 00:14:40,680 SERENDIPITOUSLY OR ACCIDENTALLY 317 00:14:40,680 --> 00:14:43,880 DISCOVERED EFFECTS OF LSD BY 318 00:14:43,880 --> 00:14:45,240 ACCIDENTALLY DOSING HIMSELF AS 319 00:14:45,240 --> 00:14:49,920 STORY GOES AND NOT LONG AFTER 320 00:14:49,920 --> 00:14:52,960 THAT LABORATORIES THAT ALBERT 321 00:14:52,960 --> 00:14:56,240 HOFFMAN WORKED BEGAN TO MAKE LSD 322 00:14:56,240 --> 00:14:58,280 AND CLINICS AROUND THE WORLD AND 323 00:14:58,280 --> 00:15:02,000 50S AND INTO THE 60S SAW A GREAT 324 00:15:02,000 --> 00:15:04,640 PROLIFERATION OF LSD AND SOME 325 00:15:04,640 --> 00:15:06,720 RELATED COMPOUNDS THAT ARE IN A 326 00:15:06,720 --> 00:15:09,720 VARIETY OF CLINICAL SETTINGS AND 327 00:15:09,720 --> 00:15:13,200 RESEARCH SETTINGS AND CLAN 328 00:15:13,200 --> 00:15:14,120 DEFENDANTINED USE BY 329 00:15:14,120 --> 00:15:16,960 INTELLIGENCE AGENCIES AND 1957 A 330 00:15:16,960 --> 00:15:22,920 RETIRED BANKER AND AMATEUR MICRO 331 00:15:22,920 --> 00:15:24,440 ANTHROPOLOGIST GOREDON WENT TO 332 00:15:24,440 --> 00:15:28,400 SEARCH FOR WHAT IS THE MAGIC 333 00:15:28,400 --> 00:15:33,480 MUSHROOM AND FOUND MARY SABINA A 334 00:15:33,480 --> 00:15:35,560 MUSHROOM IN WA HACKA AND BROUGHT 335 00:15:35,560 --> 00:15:37,000 THAT INFORMATION BACK TO THE 336 00:15:37,000 --> 00:15:39,040 WESTERN WORLD AND EXPERIENCE IS 337 00:15:39,040 --> 00:15:42,040 PUBLISHED IN LIFE MAGAZINE IN 338 00:15:42,040 --> 00:15:44,160 1957 AND MAY HAVE BEEN ONE OF 339 00:15:44,160 --> 00:15:46,200 THE FIRST TIME POINTS THAT 340 00:15:46,200 --> 00:15:48,640 PSYCHEDELICS ARE BROUGHT TO 341 00:15:48,640 --> 00:15:49,320 WESTERN CONSCIOUSNESS WRIT LARGE 342 00:15:49,320 --> 00:15:52,400 AND TURNS OUT TENS OF THOUSANDS 343 00:15:52,400 --> 00:15:54,320 OF RESEARCH SUBJECTS ARE 344 00:15:54,320 --> 00:15:57,440 ADMINISTERED PSYCHEDELICS IN LSD 345 00:15:57,440 --> 00:16:00,520 IN 1950S AND CONTROLLED 346 00:16:00,520 --> 00:16:06,080 SUBSTANCES ACT OF 1971 AND 347 00:16:06,080 --> 00:16:07,360 PRECLINICAL RESEARCH ON 348 00:16:07,360 --> 00:16:09,480 SEROTONIN 2A RECEPTORS AND 349 00:16:09,480 --> 00:16:12,560 PSYCHEDELIC DRUGS AND NUMBER OF 350 00:16:12,560 --> 00:16:14,040 PRECLINICAL RESEARCHERS 351 00:16:14,040 --> 00:16:18,040 CONTINUING PROGRAMS OF RESEARCH 352 00:16:18,040 --> 00:16:20,880 STUDYING CONTINUED EFFECTS OF 353 00:16:20,880 --> 00:16:22,520 PSYCHEDELICS ON THE BRAIN SUCH 354 00:16:22,520 --> 00:16:25,560 AS MIKE AND A NUMBER OF OTHER 355 00:16:25,560 --> 00:16:26,400 FOLKS. 356 00:16:26,400 --> 00:16:31,480 THERE WAS A STUDY IN 1994 BY 357 00:16:31,480 --> 00:16:33,360 RICK STATSMAN AT UNIVERSITY OF 358 00:16:33,360 --> 00:16:38,640 MEXICO STUDYING EFFECTS OF DMT 359 00:16:38,640 --> 00:16:42,080 DIMETHIL TRIPTO MEAN THAT IS A 360 00:16:42,080 --> 00:16:43,560 COMPOUND WITH -- EFFECTS OF 361 00:16:43,560 --> 00:16:45,560 THOSE THAT ARE HEAVY PSYCHEDELIC 362 00:16:45,560 --> 00:16:48,920 USERS AND A FEW STUDIES 363 00:16:48,920 --> 00:16:49,800 INVESTIGATED PSYCHEDELIC MODELS 364 00:16:49,800 --> 00:16:53,640 OF PSYCHOSIS IN EUROPE AND 365 00:16:53,640 --> 00:16:56,040 MOSTLY BY FRANZ AND BY 366 00:16:56,040 --> 00:16:56,720 [INDISCERNIBLE] AND WASN'T UNTIL 367 00:16:56,720 --> 00:16:59,560 THIS STUDY WAS PUBLISHED IN 2006 368 00:16:59,560 --> 00:17:04,080 BY MY MENTOR ROLAND GRIFFITHS 369 00:17:04,080 --> 00:17:07,760 THAT THIS AREA TOOK FLIGHT AGAIN 370 00:17:07,760 --> 00:17:11,040 AND IS A STUDY IN A NUMBER OF 371 00:17:11,040 --> 00:17:14,880 OTHERWISE HEALTHY AND 372 00:17:14,880 --> 00:17:18,080 FUNCTIONING WELL EDUCATED AND 373 00:17:18,080 --> 00:17:22,800 HIGH CS INDIVIDUALS WITH SILO 374 00:17:22,800 --> 00:17:25,360 KRIEBIN ADMINISTRATED IN THE 375 00:17:25,360 --> 00:17:26,840 REPORT AND FOLLOW UP STUDIES ARE 376 00:17:26,840 --> 00:17:29,400 NOT ONLY EXPERIENCES THAT ARE 377 00:17:29,400 --> 00:17:30,680 WELL TOLERATED BY PARTICIPANTS 378 00:17:30,680 --> 00:17:32,360 AND OTHERWISE KIND OF A 379 00:17:32,360 --> 00:17:34,480 COMPLETELY MEDICALLY MANAGEABLE 380 00:17:34,480 --> 00:17:36,960 THAT WAS PSYCHOLOGICALLY 381 00:17:36,960 --> 00:17:38,440 MANAGEABLE AND THESE EXPERIENCES 382 00:17:38,440 --> 00:17:41,280 LED TO ENDURING IMPROVEMENTS 383 00:17:41,280 --> 00:17:44,960 THAT ARE IN WELLBEING IN THESE 384 00:17:44,960 --> 00:17:47,080 INDIVIDU 385 00:17:47,080 --> 00:17:47,440 INDIVIDUALS. 386 00:17:47,440 --> 00:17:48,720 I WANT TO TAKE A MINUTE TO POINT 387 00:17:48,720 --> 00:17:52,520 OUT THAT COMPOUNDS ARE 388 00:17:52,520 --> 00:17:54,120 ABSOLUTELY NOT WITHOUT RISK. 389 00:17:54,120 --> 00:17:59,160 THEIR RISK PROFILE NEEDS SPECIAL 390 00:17:59,160 --> 00:18:00,680 ATTENTION AND SCHEDULING 391 00:18:00,680 --> 00:18:02,800 COMPOUNDS THAT ARE AS FAR AS DEA 392 00:18:02,800 --> 00:18:04,960 IS CONCERNED THAT MEANS THEY 393 00:18:04,960 --> 00:18:07,200 HAVE NO KNOWN MEDICAL VALUE AND 394 00:18:07,200 --> 00:18:09,600 ARE HIGHLY DANGEROUS AND/OR HAVE 395 00:18:09,600 --> 00:18:11,840 GREAT RISK OF USE LIABILITY AND 396 00:18:11,840 --> 00:18:13,320 COMPOUNDS HAVE VERY LITTLE 397 00:18:13,320 --> 00:18:16,080 SIMILARITY TO TYPICAL DRUGS AND 398 00:18:16,080 --> 00:18:19,480 ABUSE ON MANY ANIMAL ASSAYS OF 399 00:18:19,480 --> 00:18:21,080 ABUSE LIABILITY AND THESE DRUGS 400 00:18:21,080 --> 00:18:23,280 BY AND LARGE DON'T REALLY PUSH 401 00:18:23,280 --> 00:18:28,560 THE NEEDLE AND DON'T TYPICALLY 402 00:18:28,560 --> 00:18:32,960 ENGENDER A CRAVING OR WITHDRAWAL 403 00:18:32,960 --> 00:18:35,520 SYMPTOM TYPICAL TO DRUG ABUSE 404 00:18:35,520 --> 00:18:37,800 AND THEY ARE POWERFUL DRUGS WITH 405 00:18:37,800 --> 00:18:39,800 SPECIFIC AND KNOWN RISKS AND ARE 406 00:18:39,800 --> 00:18:43,360 EXPECTED TO RELIABLY AND 407 00:18:43,360 --> 00:18:45,240 DOSE-DEPENDENTLY INCREASE HEART 408 00:18:45,240 --> 00:18:46,520 RATE AND BLOOD PRESSURE 409 00:18:46,520 --> 00:18:47,560 PRESENTING A PARTICULAR RISK FOR 410 00:18:47,560 --> 00:18:50,000 PEOPLE WITH A PERSON OR FAMILY 411 00:18:50,000 --> 00:18:54,640 HISTORY OF PSYCHOSIS AND IN 412 00:18:54,640 --> 00:18:59,920 UNCONTROLLED SETTINGS THESE CAN 413 00:18:59,920 --> 00:19:02,160 BE RISKY DRUGS TO ENCOUNTER AND 414 00:19:02,160 --> 00:19:03,800 CONDUCTED A STUDY OF PEOPLE WHO 415 00:19:03,800 --> 00:19:07,360 REPORTED HAVING HAD A BAD TRIP 416 00:19:07,360 --> 00:19:10,040 OR CHALLENGING EXPERIENCE WITH 417 00:19:10,040 --> 00:19:13,480 SPECIFICALLY SILO KRIEBIN THAT 418 00:19:13,480 --> 00:19:14,400 CONTAINED MUSHROOMS DON'T KNOW 419 00:19:14,400 --> 00:19:16,600 RATES OF BAD TRIPS IN THE WORLD 420 00:19:16,600 --> 00:19:18,240 AND POPULATION FROM THIS STUDY 421 00:19:18,240 --> 00:19:20,280 AND KNOW THAT THOSE REPORTING 422 00:19:20,280 --> 00:19:22,800 HAVING A BAD TRIP THAT 11% PUT 423 00:19:22,800 --> 00:19:24,760 THEMSELVES AT RISK OF PHYSICAL 424 00:19:24,760 --> 00:19:28,040 HARM OVER 7% SAID THEY SOUGHT 425 00:19:28,040 --> 00:19:30,080 TREATMENT FOR ENDURING 426 00:19:30,080 --> 00:19:30,680 PSYCHOLOGICAL SYMPTOMS THAT 427 00:19:30,680 --> 00:19:32,360 DEVELOP AS A WAY TO ATTRIBUTE TO 428 00:19:32,360 --> 00:19:36,080 A BAD TRIP AND NEARLY 3% SOUGHT 429 00:19:36,080 --> 00:19:37,600 AND RECEIVED MEDICAL HELP AND 430 00:19:37,600 --> 00:19:38,960 GOING TO EMERGENCY DEPARTMENT TO 431 00:19:38,960 --> 00:19:43,240 COPE WITH ACUTE EFFECTS OF SILO 432 00:19:43,240 --> 00:19:46,040 KRIEBIN MUSHROOMS AND ARE REAL 433 00:19:46,040 --> 00:19:49,400 RISKS THAT PEOPLE CAN INCREDIBLY 434 00:19:49,400 --> 00:19:52,480 PSYCHOLOGICALLY VULNERABLE 435 00:19:52,480 --> 00:19:53,040 EXPERIENCING DRUGS WITHOUT 436 00:19:53,040 --> 00:19:55,040 PROPER SUPERVISION CAN DO THINGS 437 00:19:55,040 --> 00:19:58,080 TO PUT OTHERS AT RISK OR HARM 438 00:19:58,080 --> 00:20:01,320 AND ARE REASONS THAT WE HAVE 439 00:20:01,320 --> 00:20:03,320 DEVELOPED AND MAINTAINED BEST 440 00:20:03,320 --> 00:20:05,560 PRACTICES FOR ADMINISTRATION OF 441 00:20:05,560 --> 00:20:09,880 COMPOUNDS AND WE ESSENTIALLY ARE 442 00:20:09,880 --> 00:20:14,360 CAREFUL TO SCREEN OUT 443 00:20:14,360 --> 00:20:17,200 INDIVIDUALS WITH CARDIOVASCULAR 444 00:20:17,200 --> 00:20:19,200 RISK WHO WANT TO SCREEN OUT 445 00:20:19,200 --> 00:20:22,960 CLINICAL TRIALS FOR RISKS OF 446 00:20:22,960 --> 00:20:27,320 PSYCHOSIS AND SOME MEDICATIONS 447 00:20:27,320 --> 00:20:28,400 SPECIFICALLY FOR SILO KRIEBIN 448 00:20:28,400 --> 00:20:30,080 AND NOT NECESSARILY A MEDICAL 449 00:20:30,080 --> 00:20:32,400 RISK AND INTERACTING WITH 450 00:20:32,400 --> 00:20:43,840 COMPOUNDS TO MODULATETO MODULAT 451 00:20:48,600 --> 00:20:49,080 AFTER CAREFULLY SCREENING 452 00:20:49,080 --> 00:20:49,640 INDIVIDUALS THEY GO THROUGH 453 00:20:49,640 --> 00:20:50,200 ANOTHER ROUND OF CAREFUL 454 00:20:50,200 --> 00:20:51,600 PREPARATION WITH TYPICALLY ABOUT 455 00:20:51,600 --> 00:20:54,600 6 TO 8 HOURS OF MEETINGS WITH 456 00:20:54,600 --> 00:20:59,040 TWO TRAINED THERAPISTS OR 457 00:20:59,040 --> 00:21:01,760 FACILITATORS WHO ARE TRAINED TO 458 00:21:01,760 --> 00:21:03,640 HELP PEOPLE WITH EXPERIENCES AND 459 00:21:03,640 --> 00:21:05,720 MONITOR PROVIDING CARE FOR 460 00:21:05,720 --> 00:21:07,440 EXPERIENCES AND DURING 461 00:21:07,440 --> 00:21:08,760 PREPARATION PERIOD BIG GOAL OF 462 00:21:08,760 --> 00:21:11,160 PREPARATION IS TO ESSENTIALLY 463 00:21:11,160 --> 00:21:13,080 BUILD TRUST AND REPOIRE BETWEEN 464 00:21:13,080 --> 00:21:17,520 THE STUDY TEAM AND THOSE 465 00:21:17,520 --> 00:21:18,120 PARTICULAR FACILITATORS AND 466 00:21:18,120 --> 00:21:20,680 PARTICIPANT AND IS THOUGHT THAT 467 00:21:20,680 --> 00:21:22,720 TRUST AND REPOIRE THAT IS 468 00:21:22,720 --> 00:21:24,000 DEVELOPED BEFORE DRUG 469 00:21:24,000 --> 00:21:25,600 ADMINISTRATION GOES A LONG WAY 470 00:21:25,600 --> 00:21:27,400 TO HELPING PEOPLE FEEL SAFE AND 471 00:21:27,400 --> 00:21:29,520 COMFORTABLE AND SUPPORTED DURING 472 00:21:29,520 --> 00:21:31,400 EXPERIENCES TO NAVIGATE THEM IF 473 00:21:31,400 --> 00:21:33,560 THEY BECOME CHALLENGING AND IF 474 00:21:33,560 --> 00:21:37,520 STUDY IS BEING CONDUCTED FOR 475 00:21:37,520 --> 00:21:39,600 THERAPEUTIC PURPOSE THIS IS A 476 00:21:39,600 --> 00:21:41,280 TIME THAT UNSTRUCTURED 477 00:21:41,280 --> 00:21:44,000 [INDISCERNIBLE] IS DELIVERED 478 00:21:44,000 --> 00:21:46,720 TYPICALLY AND MOVING TO DRUG 479 00:21:46,720 --> 00:21:47,320 ADMINISTRATION SETTING THAT 480 00:21:47,320 --> 00:21:50,040 LASTS 6 TO 8 HOURS ASKING PEOPLE 481 00:21:50,040 --> 00:21:52,920 TO COME EVERY MORNING HAVING 482 00:21:52,920 --> 00:21:56,000 EATEN LOW FAT AND LOCALE ORREE 483 00:21:56,000 --> 00:21:57,640 BREAKFAST TESTING PARTICIPANTS 484 00:21:57,640 --> 00:21:59,800 TO MAKE SURE THEY DON'T HAVE 485 00:21:59,800 --> 00:22:01,760 MISUSED DRUGS RECENTLY AND FOR 486 00:22:01,760 --> 00:22:04,040 WOMEN WE MAKE SURE TO TEST FOR 487 00:22:04,040 --> 00:22:06,640 PREGNANCY AND AFTER TESTS ARE 488 00:22:06,640 --> 00:22:09,840 CLEARED WE ADMINISTER A CAPSULE 489 00:22:09,840 --> 00:22:13,200 WITH WATER AND ASK PARTICIPANT 490 00:22:13,200 --> 00:22:16,320 TO LIE DOWN ON A COMFORTABLE 491 00:22:16,320 --> 00:22:18,040 COUCH AND ENVIRONMENT WITH 492 00:22:18,040 --> 00:22:22,040 SHADES AND IPHONE WITH PROGRAM 493 00:22:22,040 --> 00:22:25,760 OF MOSTLY WESTERN ART AND TUCK 494 00:22:25,760 --> 00:22:28,080 THEM IN WITH A BLANKET AND 495 00:22:28,080 --> 00:22:29,080 TURNING ATTENTION INWARD AND 496 00:22:29,080 --> 00:22:30,240 BEING PRESENT FOR WHATEVER 497 00:22:30,240 --> 00:22:33,880 ARISES IN CONSCIOUSNESS THAT IS 498 00:22:33,880 --> 00:22:37,000 NOT A GUIDED MEDITATION OR 499 00:22:37,000 --> 00:22:39,240 IMAGERY SESSION OR SESSION WHERE 500 00:22:39,240 --> 00:22:40,280 ACTIVE PSYCHOTHERAPY OCCURS. 501 00:22:40,280 --> 00:22:42,600 IT IS A SESSION WHERE TWO 502 00:22:42,600 --> 00:22:44,920 FACILITATORS AND MONITORS ARE 503 00:22:44,920 --> 00:22:48,880 THERE TO PERIODICALLY MONITOR 504 00:22:48,880 --> 00:22:49,720 PARTICIPANTS HEARTRATE AND BLOOD 505 00:22:49,720 --> 00:22:51,840 PRESSURE AND VITAL SIGNS 506 00:22:51,840 --> 00:22:53,800 FIENTDING THEMSELVES IN 507 00:22:53,800 --> 00:22:54,600 STRESSFUL SITUATIONS WE TALK 508 00:22:54,600 --> 00:22:57,400 THEM THROUGH THAT AND AFTER THAT 509 00:22:57,400 --> 00:22:58,680 EXPERIENCE PARTICIPANTS WHEN 510 00:22:58,680 --> 00:22:59,960 CLARED FOR DISCHARGE WILL GO 511 00:22:59,960 --> 00:23:02,680 HOME AND COMPANY OF LOVED ONE OR 512 00:23:02,680 --> 00:23:04,160 TRUSTED FRIEND AND WILL COME 513 00:23:04,160 --> 00:23:07,000 BACK NEXT DAY TO SIT AND RECOUNT 514 00:23:07,000 --> 00:23:08,760 THEIR EXPERIENCES THEY REMEMBER 515 00:23:08,760 --> 00:23:10,920 IT WITH A STUDY TEAM AND FROM 516 00:23:10,920 --> 00:23:12,840 THAT POINT AFTER CARE 517 00:23:12,840 --> 00:23:14,400 INTEGRATION SESSIONS AND 518 00:23:14,400 --> 00:23:16,440 ESSENTIALLY MORE UNSTRUCTURED 519 00:23:16,440 --> 00:23:17,880 COUNSELING OCCUR FOR DAYS TO 520 00:23:17,880 --> 00:23:20,280 WEEKS AND SOMETIMES MONTHS FOR 521 00:23:20,280 --> 00:23:22,080 POPULATION AND IS PACKAGE WHAT 522 00:23:22,080 --> 00:23:24,480 WE MEAN WHEN WE SAY PSYCHEDELIC 523 00:23:24,480 --> 00:23:26,560 THERAPY OR PSYCHEDELIC ASSISTIVE 524 00:23:26,560 --> 00:23:28,440 THERAPY THAT IS CONTEXT WHICH 525 00:23:28,440 --> 00:23:29,640 EVERYTHING ELSE I WILL TALK 526 00:23:29,640 --> 00:23:31,360 ABOUT OCCURS. IT IS IMPORTANT 527 00:23:31,360 --> 00:23:35,760 TO NOTE THAT ONE OF THE MOST 528 00:23:35,760 --> 00:23:36,640 REMARKABLE EXPERIENCES DURING 529 00:23:36,640 --> 00:23:39,040 THE -- DURING THE EXPERIENCE OF 530 00:23:39,040 --> 00:23:41,520 A HIGH DOSE OF A PSYCHEDELIC 531 00:23:41,520 --> 00:23:45,720 DRUG OR THERAPEUTIC DOSE IS 532 00:23:45,720 --> 00:23:48,240 DIFFICULT TO CAPTURE AND 533 00:23:48,240 --> 00:23:50,040 DIFFICULT TO DESCRIBE. 534 00:23:50,040 --> 00:23:53,840 SOME HAVE CALLED EGO DISSOLUTION 535 00:23:53,840 --> 00:23:55,840 AND OTHERS BROADLY PEEKED 536 00:23:55,840 --> 00:23:56,480 EXPERIENCE AND OPERATIONALIZE 537 00:23:56,480 --> 00:23:58,720 THIS EXPERIENCE AS A MYSTICAL 538 00:23:58,720 --> 00:23:59,520 EXPERIENCE AND MYSTICAL 539 00:23:59,520 --> 00:24:01,400 EXPERIENCE I WILL BE FIRST TO 540 00:24:01,400 --> 00:24:04,120 ADMIT MIGHT BE A FAILURE IN 541 00:24:04,120 --> 00:24:05,360 MARKETING AND SOME THINK IS MIST 542 00:24:05,360 --> 00:24:07,800 THAT CAN'T BE CAPTURED OR 543 00:24:07,800 --> 00:24:09,360 GRABBED THAT IS UNDESCRIBABLE 544 00:24:09,360 --> 00:24:12,360 AND WE WILL GET TO IN A MINUTE 545 00:24:12,360 --> 00:24:14,560 AND OTHERS THINK IT HAS 546 00:24:14,560 --> 00:24:17,120 RELIGIOUS CONNOTATION AND IS IT 547 00:24:17,120 --> 00:24:19,440 MYSTICAL AND SOMETHING THAT ONLY 548 00:24:19,440 --> 00:24:22,520 A FEW CAN ATTAIN AND MYSTICAL 549 00:24:22,520 --> 00:24:24,080 EXPERIENCES MEAN IN 550 00:24:24,080 --> 00:24:26,640 OPERATIONALIZE THE FASHION ARE 551 00:24:26,640 --> 00:24:29,680 EXPERIENCES PUNCTUATED BY 552 00:24:29,680 --> 00:24:31,880 BREAKDOWN OF FELT BOUNDARY 553 00:24:31,880 --> 00:24:32,880 BETWEEN SELF AND OTHER PEOPLE 554 00:24:32,880 --> 00:24:36,040 EXPLAIN AS FEELING OF UNITY WITH 555 00:24:36,040 --> 00:24:37,680 SELF AND SURROUNDINGS AND PEOPLE 556 00:24:37,680 --> 00:24:39,840 IN ROOM AND WITH UNIVERSE AND 557 00:24:39,840 --> 00:24:42,040 FEELING ONE HAVING A BREAKDOWN 558 00:24:42,040 --> 00:24:43,400 OF BOUNDARY AND SELF AND OTHER 559 00:24:43,400 --> 00:24:45,400 AND IS THIS MYSTICAL EXPERIENCE 560 00:24:45,400 --> 00:24:47,360 THAT IS OPERATIONALIZED AND IS A 561 00:24:47,360 --> 00:24:50,600 FEELING OF UNITY AND 562 00:24:50,600 --> 00:24:51,720 TRANSCENDENCE OF TIME AND SPACE 563 00:24:51,720 --> 00:24:54,640 AND WHERE CONCEPTS OF IT BEGIN 564 00:24:54,640 --> 00:24:56,280 TO NO THE HAVE MEANING AFTER 565 00:24:56,280 --> 00:24:58,560 SOME PERIOD OF TIME AND DEEPLY 566 00:24:58,560 --> 00:25:00,680 POSITIVE MOOD AND LAST BUT NOT 567 00:25:00,680 --> 00:25:02,040 LEAST DISTINCT DIFFICULTY IN 568 00:25:02,040 --> 00:25:04,200 TRULY REFLECTING EXPERIENCE AND 569 00:25:04,200 --> 00:25:04,440 WORDS. 570 00:25:04,440 --> 00:25:08,400 WE ASK PEOPLE AT END OF EACH 571 00:25:08,400 --> 00:25:10,640 EXPERIENCE TO FILL OUT A 572 00:25:10,640 --> 00:25:12,360 QUESTIONNAIRE PROBING DIMENSIONS 573 00:25:12,360 --> 00:25:13,800 IN SYSTEMATIC FASHION THAT FROM 574 00:25:13,800 --> 00:25:15,520 THAT WE CAN DERIVE A SCALE SCORE 575 00:25:15,520 --> 00:25:18,040 AND PERCENTAGE OF TOTAL POSSIBLE 576 00:25:18,040 --> 00:25:24,840 SCORE OF MYSTICAL EXPERIENCE. 577 00:25:24,840 --> 00:25:27,520 WE HAVE A FIGURE THAT SUMMARIZES 578 00:25:27,520 --> 00:25:30,840 FINDINGS OF RELATIONSHIP BETWEEN 579 00:25:30,840 --> 00:25:34,040 DOSE OF PSILOCYBIN AND SCORES ON 580 00:25:34,040 --> 00:25:35,160 MYSTICAL EXPERIENCE 581 00:25:35,160 --> 00:25:37,400 QUESTIONNAIRE AND DOSE EFFECT 582 00:25:37,400 --> 00:25:40,200 STUDY OF 18 PARTICIPANTS AND 583 00:25:40,200 --> 00:25:42,960 SUMMARY ACROSS 30 MILLIGRAM 584 00:25:42,960 --> 00:25:44,400 ACROSS THREE STUDIES AND SEE 585 00:25:44,400 --> 00:25:46,840 MYSTICAL EXPERIENCE THAT IS DOSE 586 00:25:46,840 --> 00:25:49,360 DEPENDENT AND FOLLOWS ORDERLY 587 00:25:49,360 --> 00:25:52,200 FASHION IN THAT OF HIGHER DOSE 588 00:25:52,200 --> 00:25:55,440 OF SILO KRIEBIN LEADS TO GREATER 589 00:25:55,440 --> 00:25:58,160 CHANCE OF MYSTICAL EXPERIENCE 590 00:25:58,160 --> 00:25:59,680 AND STRONGER MYSTICAL EXPERIENCE 591 00:25:59,680 --> 00:26:03,560 AND MOST RELIABLY EVOKES 592 00:26:03,560 --> 00:26:05,080 MYSTICAL EXPERIENCE THAT USUALLY 593 00:26:05,080 --> 00:26:07,440 MINIMIZES LIKELIHOOD OF 594 00:26:07,440 --> 00:26:08,440 CHALLENGING EXPERIENCE OR 595 00:26:08,440 --> 00:26:09,680 NEGATIVE EFFECTIVE EXPERIENCES 596 00:26:09,680 --> 00:26:12,520 THAT TURNS OUT THAT MYSTICAL 597 00:26:12,520 --> 00:26:15,920 EXPERIENCES ARE NOT ONLY DOSE 598 00:26:15,920 --> 00:26:20,960 DEPENDENT BUT ALSO PREDICT RATED 599 00:26:20,960 --> 00:26:22,040 MEANINGFULNESS AND SPIRITUAL 600 00:26:22,040 --> 00:26:23,160 EXPERIENCE OF EXPERIENCE THAT 601 00:26:23,160 --> 00:26:25,280 PEOPLE HAD AND REMARKABLE THINGS 602 00:26:25,280 --> 00:26:29,400 THAT CAME OUT OF ROLAND'S FIRST 603 00:26:29,400 --> 00:26:32,440 PAPER OF PSILOCYBIN IN 2006 IS 604 00:26:32,440 --> 00:26:37,240 THAT INDIVIDUALS IN STUDY WERE 605 00:26:37,240 --> 00:26:40,160 ENDORSING EXPERIENCES THEY HAD 606 00:26:40,160 --> 00:26:43,440 WITH SILO KRIEBIN AMONG TOP 5 607 00:26:43,440 --> 00:26:47,520 THAT ARE MEANINGFUL SPIRITUAL 608 00:26:47,520 --> 00:26:49,080 SIGNIFICANTS OF THEIR LIES THAT 609 00:26:49,080 --> 00:26:51,120 IS REMARKABLE YOU MIGHT IMAGINE 610 00:26:51,120 --> 00:26:54,040 SOMEONE SAYING I PASSED BAR AND 611 00:26:54,040 --> 00:26:57,200 GOT APPOINTED AS A FEDERAL JUDGE 612 00:26:57,200 --> 00:26:59,800 OR WHOEVER AND I BECAME A DOCTOR 613 00:26:59,800 --> 00:27:02,520 AND I'M THE CHIEF OF MEDICINE AT 614 00:27:02,520 --> 00:27:04,680 SOME ILUFT TREE OWE US 615 00:27:04,680 --> 00:27:07,440 UNIVERSITY AND I HAD AN 616 00:27:07,440 --> 00:27:09,680 EXPERIENCE ON A COUCH IN EAST 617 00:27:09,680 --> 00:27:11,080 BALTIMORE. THAT IS -- THOSE ARE 618 00:27:11,080 --> 00:27:16,720 -- THAT IS UP THERE AMONG TOP 5 619 00:27:16,720 --> 00:27:18,400 MOST SINGLE MEANINGFUL 620 00:27:18,400 --> 00:27:20,960 EXPERIENCE OF MY LIFE AND THOSE 621 00:27:20,960 --> 00:27:23,120 REMARKABLE EFFECTS SEEMED TO 622 00:27:23,120 --> 00:27:25,160 LEAD TO OTHER REMARKABLE EFFECTS 623 00:27:25,160 --> 00:27:27,640 AND WHAT WE FOUND WAS -- WHAT 624 00:27:27,640 --> 00:27:29,440 ROLAND FOUND WAS IN THE VERY 625 00:27:29,440 --> 00:27:31,600 FIRST SERIES OF STUDIES IS THAT 626 00:27:31,600 --> 00:27:34,000 THESE EFFECTS PERSIST WITH THE 627 00:27:34,000 --> 00:27:36,360 ATTRIBUTION OF THAT EXPERIENCE 628 00:27:36,360 --> 00:27:38,440 PERSISTENT FOR SOME PEOPLE AT 629 00:27:38,440 --> 00:27:40,280 LEAST 14 MONTHS AFTER THE 630 00:27:40,280 --> 00:27:41,520 EXPERIENCE AND NOT ONLY THOSE I 631 00:27:41,520 --> 00:27:43,160 SAY WHAT DO YOU THINK ONCE YOU 632 00:27:43,160 --> 00:27:45,480 GET BACK TO REAL LIFE GETTING 633 00:27:45,480 --> 00:27:47,160 CAUGHT IN TRAFFIC PAYING YOUR 634 00:27:47,160 --> 00:27:48,960 TAXES WHAT DO YOU THINK 635 00:27:48,960 --> 00:27:51,000 HAPPENED? THESE ATTRIBUTIONS 636 00:27:51,000 --> 00:27:53,680 PERSIST AND PEOPLE ENDORSE AN 637 00:27:53,680 --> 00:27:55,880 INCREASE IN WELL-BEING AND LIFE 638 00:27:55,880 --> 00:27:57,040 SATISFACTION AND LESS ANXIETY 639 00:27:57,040 --> 00:27:59,200 ABOUT THE FUTURE AND ABOUT THE 640 00:27:59,200 --> 00:28:01,600 PRESENT AND PROSOCIAL ATTITUDES 641 00:28:01,600 --> 00:28:04,000 AND THESE ENDORSEMENTS ARE NOT 642 00:28:04,000 --> 00:28:06,280 ONLY MADE BY PARTICIPANTS BUT BY 643 00:28:06,280 --> 00:28:07,800 BLINDED INDIVIDUALS IN THE 644 00:28:07,800 --> 00:28:09,800 ENVIRONMENT THAT ARE NOT PART OF 645 00:28:09,800 --> 00:28:13,720 THE STUDY BUT WERE PROBED WEEKS 646 00:28:13,720 --> 00:28:15,960 TO MONTHS OVER A YEAR LATER AND 647 00:28:15,960 --> 00:28:18,280 IN THIS EXPERIENCE SALLY WAS 648 00:28:18,280 --> 00:28:20,880 MORE PROSOCIAL AND SALLY HAD 649 00:28:20,880 --> 00:28:22,880 ANXIETY THAT WAS ESSENTIALLY 650 00:28:22,880 --> 00:28:25,640 CONFIRMED AND VALIDATED BY 651 00:28:25,640 --> 00:28:27,400 COMMUNITY COHORTS AND ANOTHER 652 00:28:27,400 --> 00:28:30,040 REMARKABLE EFFECT OF THESE 653 00:28:30,040 --> 00:28:33,360 COMPOUNDS IS POTENTIAL FOR 654 00:28:33,360 --> 00:28:34,640 THERAPEUTIC EFFECTS IN VAR EYETY 655 00:28:34,640 --> 00:28:36,640 OF CLINICAL POPULATIONS AND ONE 656 00:28:36,640 --> 00:28:39,280 OF THE FIRST CLINICAL STUDIES 657 00:28:39,280 --> 00:28:42,040 PUBLISHED IN MODERN ERA AND ONE 658 00:28:42,040 --> 00:28:44,800 FIRST REALLY RIGOROUS RANDOMIZE 659 00:28:44,800 --> 00:28:49,560 THE CONTROL LEVELS WAS IN LAB IN 660 00:28:49,560 --> 00:28:52,200 HOPKINS AND WE HAD PATIENTS WITH 661 00:28:52,200 --> 00:28:53,880 LATE STAGE CANCER DIAGNOSIS AND 662 00:28:53,880 --> 00:28:56,480 IF YOU EVER HAD A LOVED ONE OR 663 00:28:56,480 --> 00:28:58,840 KNOWN SOMEONE WHO HAS HAD TO 664 00:28:58,840 --> 00:29:01,080 GRAPPLE WITH LATE STAGE CANCER 665 00:29:01,080 --> 00:29:02,480 DIAGNOSIS AND EXISTENTIAL CRISIS 666 00:29:02,480 --> 00:29:04,720 THAT COMPANY COULD BE OF THE 667 00:29:04,720 --> 00:29:07,560 MOST CHALLENGING ASPECTS OF 668 00:29:07,560 --> 00:29:09,240 DIAGNOSIS TO DEAL WITH AND TREAT 669 00:29:09,240 --> 00:29:11,880 ASIDE FROM ACTUAL CANCER AND IN 670 00:29:11,880 --> 00:29:13,600 STUDY PATIENTS WERE RANDOMIZED 671 00:29:13,600 --> 00:29:17,600 TO RECEIVE A TRIVIAL DOSE OF 672 00:29:17,600 --> 00:29:19,920 PSILOCYBIN FIRST OR HIGH DOSE OF 673 00:29:19,920 --> 00:29:21,440 IT FIRST AND SECOND TREATMENT 674 00:29:21,440 --> 00:29:22,880 TIME POINT EVERY WAS CROSSED OWE 675 00:29:22,880 --> 00:29:24,240 EVERY TO TREATMENT THEY DIDN'T 676 00:29:24,240 --> 00:29:27,600 RECEIVE ON FIRST DOSE AND SEE 677 00:29:27,600 --> 00:29:32,000 AFTER THE FIRST SESSION THAT A 678 00:29:32,000 --> 00:29:32,520 REMARKABLE CLINICALLY 679 00:29:32,520 --> 00:29:34,000 SIGNIFICANT RESPONSE IN THOSE 680 00:29:34,000 --> 00:29:38,040 PATIENTS CLINICALLY SIGNIFICANT 681 00:29:38,040 --> 00:29:38,840 RESPONSE REDUCTION IN SEVERITY 682 00:29:38,840 --> 00:29:40,680 OF 50% MORE OF BASELINE AND 683 00:29:40,680 --> 00:29:42,520 INDIVIDUALS IN THAT STUDY 684 00:29:42,520 --> 00:29:43,800 SHOWING CLINICAL RESPONSE AND 685 00:29:43,800 --> 00:29:45,760 60% OF INDIVIDUALS AFTER VERY 686 00:29:45,760 --> 00:29:49,200 FIRST HIGH DOSE OF PSILOCYBIN 687 00:29:49,200 --> 00:29:51,320 THAT WERE IN REMISSION FROM 688 00:29:51,320 --> 00:29:53,840 DEPRESSION AFTER DOSE OF SILO 689 00:29:53,840 --> 00:29:55,960 KRIEBIN AND FINDINGS REMAINED AT 690 00:29:55,960 --> 00:29:57,880 LEAST 6 MONTHS AFTER TREATMENT 691 00:29:57,880 --> 00:30:00,680 AND WAS A STUDY CONDUCTED IN 692 00:30:00,680 --> 00:30:03,160 PATIENTS WITH LATE-STAGE CANCER 693 00:30:03,160 --> 00:30:05,360 DIAGNOSIS AND CONDUCTED FIRST 694 00:30:05,360 --> 00:30:07,120 RIGOROUS CONTROL TRIAL WITH 695 00:30:07,120 --> 00:30:09,880 PATIENTS WITH MAJOR DEPRESSIVE 696 00:30:09,880 --> 00:30:11,200 DISORDER TREATED WITH SILO 697 00:30:11,200 --> 00:30:13,320 KRIEBIN AND FOUND NOT ONLY A 698 00:30:13,320 --> 00:30:14,920 SIMILAR LEVEL OR SOMEWHAT 699 00:30:14,920 --> 00:30:16,760 SIMILAR LEVEL OF EFFICACY AND 700 00:30:16,760 --> 00:30:18,640 OVER 50% OF PEOPLE IN THAT STUDY 701 00:30:18,640 --> 00:30:21,280 FOR MAJOR DEPRESSIVE DISORDER 702 00:30:21,280 --> 00:30:23,560 WERE IN REMISSION AT LEAST A 703 00:30:23,560 --> 00:30:25,480 YEAR AFTER SILO KRIEBIN 704 00:30:25,480 --> 00:30:27,240 TREATMENT AND 70% OF INDIVIDUALS 705 00:30:27,240 --> 00:30:30,040 TREATED FOR MAJOR DEPRESSIVE 706 00:30:30,040 --> 00:30:31,800 DISORDER SHOWED CLINICALLY 707 00:30:31,800 --> 00:30:32,480 SIGNIFICANT RESPONSE AND GRAPH 708 00:30:32,480 --> 00:30:36,400 TO RIGHT SHOWS BASELINE 709 00:30:36,400 --> 00:30:38,480 PRE-TREATMENT GRID MD SCORES OR 710 00:30:38,480 --> 00:30:41,120 BLINDED CLINICIAN RATED HAM 711 00:30:41,120 --> 00:30:43,120 ILLTON DEPRESSION RATING SCALE 712 00:30:43,120 --> 00:30:45,840 SCORES AND ABOVE 8 TA INIS 713 00:30:45,840 --> 00:30:47,960 MODERATELY TO SEVERELY DEPRESSED 714 00:30:47,960 --> 00:30:50,040 AND BELOW 8 IS CONSIDERED IN 715 00:30:50,040 --> 00:30:51,720 REMISSION AND FOO IND THAT AT 716 00:30:51,720 --> 00:30:54,040 LEAST ONE WEEK BUT LASTING FOR 717 00:30:54,040 --> 00:30:56,560 AT LEAST 12 MONTHS AFTER 718 00:30:56,560 --> 00:30:58,960 TREATMENT PATIENTS IN STUDY SHOW 719 00:30:58,960 --> 00:31:01,600 REMARKABLE AND DURING DURABLE 720 00:31:01,600 --> 00:31:03,280 RESPONSE, THERAPEUTIC RESPONSE 721 00:31:03,280 --> 00:31:06,040 FOLLOWED UP BY A STUDY AND 722 00:31:06,040 --> 00:31:08,280 COLLEAGUES AT IMPERIAL COLLEGE 723 00:31:08,280 --> 00:31:11,080 IN LONDON WITH HEAD TO HEAD 724 00:31:11,080 --> 00:31:12,640 COMPARISON COMPARED TO 6 WEEKS 725 00:31:12,640 --> 00:31:14,920 OF STANDARD OF CARE FIRST LINE 726 00:31:14,920 --> 00:31:17,200 FOR TREATMENT OF DEPRESSION OF 727 00:31:17,200 --> 00:31:20,160 SSRI AS TELEPRAM AND THEY 728 00:31:20,160 --> 00:31:22,040 DEMONSTRATED NOT ONLY WHAT I 729 00:31:22,040 --> 00:31:24,360 WOULD INTERPRET AS 730 00:31:24,360 --> 00:31:28,280 NONINFERIORITY FINDING IN STUDY 731 00:31:28,280 --> 00:31:32,440 OF PSILOCYBIN BEING NOT ONLY 732 00:31:32,440 --> 00:31:33,760 INFERIOR 42 DAYS AFTER TREATMENT 733 00:31:33,760 --> 00:31:35,800 AND IS RATINGS ON QUICK 734 00:31:35,800 --> 00:31:39,120 INVENTORY OF DEPRESSIVE SYMPTOMS 735 00:31:39,120 --> 00:31:41,000 SELF RATED DEPRESSION RATING 736 00:31:41,000 --> 00:31:44,520 SCALE IN THIS STUDY EVERYBODY 737 00:31:44,520 --> 00:31:50,080 RECEIVED 42 DAYS OF DAILY PILL. 738 00:31:50,080 --> 00:31:52,720 EVERYBODY RECEIVED AN 739 00:31:52,720 --> 00:31:54,480 EXPERIMENTAL DRUG ADMINISTRATION 740 00:31:54,480 --> 00:31:56,400 SESSION IN PSYCHOACTIVE THERAPY 741 00:31:56,400 --> 00:31:59,080 AND HALF PARTICIPANTS WERE 742 00:31:59,080 --> 00:32:01,480 RANDOMIZED TO RECEIVE SILO 743 00:32:01,480 --> 00:32:03,200 KRIEBIN AND OTHER HALF OF THE 744 00:32:03,200 --> 00:32:05,640 INDIVIDUALS IN THE STUDY WERE 745 00:32:05,640 --> 00:32:07,840 RANDOMIZED TO RECEIVE PLACEBO 746 00:32:07,840 --> 00:32:10,560 DURING EXPERIMENTAL DRUG 747 00:32:10,560 --> 00:32:12,040 ADMINISTRATIONS AND TALI PRAM 748 00:32:12,040 --> 00:32:15,880 DAILY FOR 42 DAYS AND ON THIS 749 00:32:15,880 --> 00:32:17,760 QUICK INVENTORY OF DEPRESSIVE 750 00:32:17,760 --> 00:32:20,000 SYMPTOMS WAS PRE-REGISTERED 751 00:32:20,000 --> 00:32:21,640 PRIMARY OUTCOME AND IN THAT 752 00:32:21,640 --> 00:32:22,800 OUTCOME THERE IS NO SIGNIFICANT 753 00:32:22,800 --> 00:32:30,080 DITCHES AT 42 DAYS BETWEEN 754 00:32:30,080 --> 00:32:33,800 PSILOCYBIN YUP AND MEASURES 755 00:32:33,800 --> 00:32:39,200 EQUAL AND FAVORABLE ABOVE SILO 756 00:32:39,200 --> 00:32:39,600 KRI 757 00:32:39,600 --> 00:32:44,120 KRIEBIN AVOIDANCE AND HEADONIA 758 00:32:44,120 --> 00:32:45,680 FLOURISHING AND ANXIETY WELL 759 00:32:45,680 --> 00:32:47,200 BEING ARE REMARKABLE EFFECTS. 760 00:32:47,200 --> 00:32:51,080 ANOTHER STUDY TO NOTE THAT 761 00:32:51,080 --> 00:32:53,520 RECENTLY CAME OUT WAS 762 00:32:53,520 --> 00:32:55,040 ESSENTIALLY RESULTS OF 763 00:32:55,040 --> 00:32:57,680 MULTINATIONAL PHASE 2B 764 00:32:57,680 --> 00:33:01,160 REGISTRATION TRIAL IN WHICH OVER 765 00:33:01,160 --> 00:33:04,680 75 PEOPLE WERE RANDOMIZED INTO 766 00:33:04,680 --> 00:33:07,720 EACH GROUP AND ONE MILLIDOSE OF 767 00:33:07,720 --> 00:33:10,800 -- 10 MILLIGRAM DOSE OR 25 768 00:33:10,800 --> 00:33:13,120 MILLIGRAM DOSE AND WE HAVE ON 769 00:33:13,120 --> 00:33:14,120 LEFT SIDE SQUARES AND MEAN 770 00:33:14,120 --> 00:33:17,680 CHANGE IN SCORES ON THE 771 00:33:17,680 --> 00:33:19,720 MONTGOMERY A** BERGER DEPRESSION 772 00:33:19,720 --> 00:33:21,480 RATING SCALE AND WHAT WE 773 00:33:21,480 --> 00:33:23,560 ESSENTIALLY SEE IS A RAPID 774 00:33:23,560 --> 00:33:24,880 REDUCTION IN RESPONSE THAT 775 00:33:24,880 --> 00:33:29,000 SOMEWHAT NORMALIZES AT SLIGHTLY 776 00:33:29,000 --> 00:33:31,400 HIGHER LEVELS OF DEPRESSION AND 777 00:33:31,400 --> 00:33:34,080 SEVERITY FROM DAY TO WEEK 12 AND 778 00:33:34,080 --> 00:33:36,880 SEE AT WEEK 12 A SUBSTANTIAL 779 00:33:36,880 --> 00:33:40,800 REDUCTION IN DEPRESSION FOR 25 780 00:33:40,800 --> 00:33:44,640 MILLIGRAM SILO KRIEB BIN GROUP 781 00:33:44,640 --> 00:33:52,240 AND TREATMENT RESISTANT 782 00:33:52,240 --> 00:33:53,640 DEPRESSION THAT ARE DIFFICULT TO 783 00:33:53,640 --> 00:33:57,720 REACH WITH ANY OUTCOME AND ANY 784 00:33:57,720 --> 00:34:00,360 INTERVENTION A FACT THAT THEY 785 00:34:00,360 --> 00:34:01,520 SHOWED A 12 WEEK DURABLE 786 00:34:01,520 --> 00:34:04,640 RESPONSE IN THIS POPULATION THAT 787 00:34:04,640 --> 00:34:08,120 WAS REMARKABLE. 788 00:34:08,120 --> 00:34:11,600 I HAVE SPOKEN ONLY ABOUT MOOD 789 00:34:11,600 --> 00:34:13,520 DISORDERS AND SUBSTANCE USE 790 00:34:13,520 --> 00:34:16,000 DISORDERS AND TREATING THOUSANDS 791 00:34:16,000 --> 00:34:19,160 OF PATIENTS FOR ALCOHOL USE 792 00:34:19,160 --> 00:34:21,560 DISORDER WITH LSD AND WAS A 793 00:34:21,560 --> 00:34:24,760 PAPER PUBLISHED ABOUT I 2012 AND 794 00:34:24,760 --> 00:34:25,920 SCOUR PREVIOUS LITERATURE AND 795 00:34:25,920 --> 00:34:29,280 WERE HUNDREDS OF THOUSANDS OF 796 00:34:29,280 --> 00:34:32,120 STUDIES PUBLISHED WITH A FORM OF 797 00:34:32,120 --> 00:34:36,120 PSYCHEDELIC IN 50S AND 60S AND 798 00:34:36,120 --> 00:34:38,880 VAST MANL ORTD WOULDN'T MEET 799 00:34:38,880 --> 00:34:44,120 MODERN CRITERIA KREBS AND 800 00:34:44,120 --> 00:34:45,040 JOHANNSON IDENTIFIED 6 STUDIES 801 00:34:45,040 --> 00:34:51,240 OUT OF TIME PERIOD THEY HAD 802 00:34:51,240 --> 00:34:53,840 DEFENSIBLE RIGOR AND WHICH LSD 803 00:34:53,840 --> 00:34:57,600 WAS COMPARED WITH TREATMENT OF 804 00:34:57,600 --> 00:34:58,520 PATIENTS WITH ALSO USE DISORDER 805 00:34:58,520 --> 00:35:01,280 AND FINDINGS WITH OVERALL 806 00:35:01,280 --> 00:35:03,320 FAVORABLE EFFECT OF LSD OVER 807 00:35:03,320 --> 00:35:04,840 VARIETY OF CONTROLS SOME OF 808 00:35:04,840 --> 00:35:08,760 WHICH ARE PLACEBO AND SOME ARE 809 00:35:08,760 --> 00:35:12,920 ACTIVE COMPARATIVE DRUGS THAT 810 00:35:12,920 --> 00:35:14,440 ARE PSYCHOACTIVE BUT ARE NOT 811 00:35:14,440 --> 00:35:17,720 PSYCHEDELIC AND SPURRED INTEREST 812 00:35:17,720 --> 00:35:26,680 AND WAS A SIMILAR IMPRESSIVE 813 00:35:26,680 --> 00:35:30,760 STUDY IN THE 70S WITH TREAT 814 00:35:30,760 --> 00:35:36,480 TREATINGENTS PATIENTS WITH -- 815 00:35:36,480 --> 00:35:38,080 2014 PUBLISHED OPEN LABEL PILOT 816 00:35:38,080 --> 00:35:40,280 STUDY THAT IS DEMONSTRATING THAT 817 00:35:40,280 --> 00:35:43,720 AFTER 2 TO 3 ADMINISTRATIONS OF 818 00:35:43,720 --> 00:35:45,760 PSILOCYBIN IMBEDDED WITH COURSE 819 00:35:45,760 --> 00:35:47,560 OF COGNITIVE BEHAVIORAL THERAPY 820 00:35:47,560 --> 00:35:50,160 WITH SMOKING CESSATION THAT OVER 821 00:35:50,160 --> 00:35:53,640 80% OF INDIVIDUALS IN TRIAL WERE 822 00:35:53,640 --> 00:35:55,960 BIOLOGICALLY VERIFIED ABSTINNANT 823 00:35:55,960 --> 00:35:58,360 NICOTINE FOR 6 MONTHS AND LONG 824 00:35:58,360 --> 00:36:00,560 TERM FOLLOW UP AND FOUND ONE 825 00:36:00,560 --> 00:36:02,280 MORE INDIVIDUAL LAPSED OAF A 826 00:36:02,280 --> 00:36:04,520 YEAR AND A HALF AFTERWARDS THAT 827 00:36:04,520 --> 00:36:07,400 ARE REMARKABLE EFFECTS WITH 828 00:36:07,400 --> 00:36:08,160 POTENTIALLY COMPARED TO GOLD 829 00:36:08,160 --> 00:36:09,880 STANDARD THAT COULD BE 830 00:36:09,880 --> 00:36:11,720 CONSIDERED [INDISCERNIBLE] AND 6 831 00:36:11,720 --> 00:36:14,080 MONTHS POST TREATMENT YOU SP 832 00:36:14,080 --> 00:36:16,640 EXPECT 30 TO 40% EFFICACY AFTER 833 00:36:16,640 --> 00:36:18,560 TREATMENT AND DR. JOHNSON AND 834 00:36:18,560 --> 00:36:20,960 DR. GARCIA REMOVED FOLLOWING UP 835 00:36:20,960 --> 00:36:22,960 WITH RANDOMIZED CONTROL TRIAL 836 00:36:22,960 --> 00:36:25,920 NOT YET PUBLISHED AND STAY TUNED 837 00:36:25,920 --> 00:36:28,000 AND ABOUT SOMEWHAT THE SAME TIME 838 00:36:28,000 --> 00:36:31,560 A COLLEAGUE AT NEW YORK 839 00:36:31,560 --> 00:36:32,760 UNIVERSITY MICHAEL PUBLISHED 840 00:36:32,760 --> 00:36:35,480 OPEN LABEL CLINICAL TRIAL IN 841 00:36:35,480 --> 00:36:36,720 PATIENTS WITH ALCOHOL USE 842 00:36:36,720 --> 00:36:39,160 DISORDER AND FOLLOWED UP WITH 843 00:36:39,160 --> 00:36:42,040 RANDOMIZE THE CONTROL TRIAL AND 844 00:36:42,040 --> 00:36:44,800 FOLLOWING UP WITH EFFECTS OF 845 00:36:44,800 --> 00:36:46,080 [INDISCERNIBLE] ACTIVE 846 00:36:46,080 --> 00:36:49,840 CONCOMPOUND AND SHOWED SIMILAR 847 00:36:49,840 --> 00:36:50,800 REMARKABLE REDUCTION AND 848 00:36:50,800 --> 00:36:52,800 VARIABLES RELATED TO ALCOHOL USE 849 00:36:52,800 --> 00:36:55,520 DISORDER AND PLOTTED REDUCTIONS 850 00:36:55,520 --> 00:36:57,080 AND DRINKS PER DAY THROUGH 851 00:36:57,080 --> 00:36:59,440 SCREENING ALL THE WAY THROUGH 36 852 00:36:59,440 --> 00:37:01,600 WEEKS PUSH TREATMENT AND WHERE 853 00:37:01,600 --> 00:37:06,080 ARROWS ARE ARE PSILOCYBIN 854 00:37:06,080 --> 00:37:07,960 ADMINISTRATION DAYS AND SAW 855 00:37:07,960 --> 00:37:09,440 REMARKABLE AND DURABLE REDUCTION 856 00:37:09,440 --> 00:37:11,800 IN DRINKS PER DAY AND SAW 857 00:37:11,800 --> 00:37:13,240 SIMILAR EFFECTS IN HEAVY 858 00:37:13,240 --> 00:37:16,840 DRINKING DAYS AND PERCENT 859 00:37:16,840 --> 00:37:18,080 DRINKING DAYS. 860 00:37:18,080 --> 00:37:22,120 I WANT TO REMIND YOU OF THAT 861 00:37:22,120 --> 00:37:24,320 MYSTICAL EXPERIENCE AND QUESTION 862 00:37:24,320 --> 00:37:26,440 COMING INTO THERAPEUTIC EFFECTS 863 00:37:26,440 --> 00:37:29,040 IS, WELL, OKAY. INTERESTING AND 864 00:37:29,040 --> 00:37:31,840 PUZZLING HOW ONE SINGLE 865 00:37:31,840 --> 00:37:33,640 INTERVENTION WOULD LEAD A PERSON 866 00:37:33,640 --> 00:37:36,360 HAVING TREATMENT RESISTANT 867 00:37:36,360 --> 00:37:38,400 DEPRESSION TO HAVE A DURABLE 868 00:37:38,400 --> 00:37:41,120 SPONLSZ OR PATIENT WITH MAJOR 869 00:37:41,120 --> 00:37:44,440 DEPRESSIVE DISORDER AND SMOKING 870 00:37:44,440 --> 00:37:48,440 A PACK OF 10 -- WHEN COMPARING 871 00:37:48,440 --> 00:37:50,000 MEASURES OF THERAPEUTIC EFFICACY 872 00:37:50,000 --> 00:37:52,080 TO MEASURES OF MYSTICAL 873 00:37:52,080 --> 00:37:55,160 EXPERIENCE WE SEE A RELIABLE 874 00:37:55,160 --> 00:37:56,880 RELATIONSHIP HERE. 875 00:37:56,880 --> 00:37:59,320 THESE ARE GRAPHS FROM THE 876 00:37:59,320 --> 00:38:02,440 INITIAL STUDY IN CANCER PATIENTS 877 00:38:02,440 --> 00:38:06,080 PUBLISHED BY LAB IN 2016 AND WE 878 00:38:06,080 --> 00:38:07,560 SHOW A SIGNIFICANT CORRELATION 879 00:38:07,560 --> 00:38:09,720 IN STRENGTH OF MYSTICAL 880 00:38:09,720 --> 00:38:11,480 EXPERIENCE WITH REDUCTION IN 881 00:38:11,480 --> 00:38:12,840 DEPRESSION AND REDUCTION IN 882 00:38:12,840 --> 00:38:15,000 ANXIETY AND SIMILAR STUDY 883 00:38:15,000 --> 00:38:18,760 PUBLISHED ABOUT THE SAME TIME BY 884 00:38:18,760 --> 00:38:22,080 STEVEN ROSS AT NYU SHOWING 885 00:38:22,080 --> 00:38:24,000 SIMILAR EFFECTS AND ALSO SHOWING 886 00:38:24,000 --> 00:38:26,080 A VERY STRONG CORRELATION 887 00:38:26,080 --> 00:38:28,040 BETWEEN STRENGTH OF MYSTICAL 888 00:38:28,040 --> 00:38:31,560 EXPERIENCE CHANGE IN CRAVING AND 889 00:38:31,560 --> 00:38:33,160 EXPERIENCES OF PERSONAL 890 00:38:33,160 --> 00:38:35,560 MEANINGFULNESS PREDICTED BY 891 00:38:35,560 --> 00:38:37,680 MYSTICAL EXPERIENCES STRONGLY 892 00:38:37,680 --> 00:38:39,200 PREDICTING CHANGE AND CONFIDENCE 893 00:38:39,200 --> 00:38:41,360 TO ABSTAIN TO SMOKE AND BELIEVED 894 00:38:41,360 --> 00:38:43,600 IN MYSTICAL EXPERIENCE MAY BE A 895 00:38:43,600 --> 00:38:45,600 CATALYST IN SOME WAY FOR 896 00:38:45,600 --> 00:38:47,720 REMARKABLE CHANGES IN CLINICAL 897 00:38:47,720 --> 00:38:50,240 STATUS WE ARE OBSERVING IN 898 00:38:50,240 --> 00:38:53,840 STUDIES AND THERE IS A GROWING 899 00:38:53,840 --> 00:38:55,680 LITERATURE AROUND WHAT IS 900 00:38:55,680 --> 00:38:57,040 OCCURRING IN THE BRAIN. 901 00:38:57,040 --> 00:38:59,960 QUESTION OF DEEP INTEREST TO 902 00:38:59,960 --> 00:39:02,480 MIND IS WHILE THESE REMARKABLE 903 00:39:02,480 --> 00:39:03,280 EXPERIENCES ARE OCCURRING AND 904 00:39:03,280 --> 00:39:05,400 THEN FOR DAYS AND WEEKS AND 905 00:39:05,400 --> 00:39:15,960 MONTHS AND YEARS AFTERWARDS WHEN 906 00:39:18,160 --> 00:39:20,040 EXPERIENCE SUBSIDED AND FIRST TO 907 00:39:20,040 --> 00:39:26,080 BE PUBLISHED WITH PSILOCYBIN 908 00:39:26,080 --> 00:39:28,840 MAGNETIC RESONANCE TECHNIQUES IN 909 00:39:28,840 --> 00:39:31,840 2012 DEMONSTRATING REMARKABLE 910 00:39:31,840 --> 00:39:33,920 REDUCTION IN OXYGENATION LEVEL 911 00:39:33,920 --> 00:39:35,640 OF [INDISCERNIBLE] AND PROXY AT 912 00:39:35,640 --> 00:39:38,080 SOME LEVEL FOROVERALL BRAIN 913 00:39:38,080 --> 00:39:40,000 FUNCTION AND ACTIVITY WITHIN 914 00:39:40,000 --> 00:39:42,880 DISCRETE BRAIN AREAS AND SAW 915 00:39:42,880 --> 00:39:46,040 REDUCTION IN BALD SIGNALS AS 916 00:39:46,040 --> 00:39:48,600 WELL AS CEREBRAL BLOOD FLOW 917 00:39:48,600 --> 00:39:51,800 MOSTLY RESTRICT TODAY DEFAULT 918 00:39:51,800 --> 00:39:54,760 MODE NETWORK AND MEDIAL TEMPORAL 919 00:39:54,760 --> 00:39:58,000 LOBE AND BASAL GANGLIA REGIONS 920 00:39:58,000 --> 00:40:00,120 INVOLVED IN REWARD RESPONSIVITY 921 00:40:00,120 --> 00:40:02,920 AND MANY FOLLOW UP ANALYSIS OF 922 00:40:02,920 --> 00:40:05,000 DATA SETS AND MANY ON RIGHT THAT 923 00:40:05,000 --> 00:40:08,640 IS A PRETTY WELL-KNOWN FIGURE IN 924 00:40:08,640 --> 00:40:11,480 PSYCHEDELIC TALKS THAT ON THE 925 00:40:11,480 --> 00:40:14,080 LEFT IS A DEPICTION OF 926 00:40:14,080 --> 00:40:15,640 MATHEMATICAL MODELING OF NETWORK 927 00:40:15,640 --> 00:40:18,720 STATE SPACE IN THE BRAIN DURING 928 00:40:18,720 --> 00:40:21,400 NON-DRUG RESTING STATE SCAN AND 929 00:40:21,400 --> 00:40:23,320 TO RIGHT YOU SEE SAME 930 00:40:23,320 --> 00:40:24,960 MATHEMATICAL MODEL APPLIED TO 931 00:40:24,960 --> 00:40:28,160 BRAIN ACTIVITY DURING 932 00:40:28,160 --> 00:40:29,080 PSYCHEDELIC EXPERIENCES 933 00:40:29,080 --> 00:40:32,720 SPECIFICALLY WITH SILO KRIEBIN 934 00:40:32,720 --> 00:40:33,800 AND SEE EMERGENCE OF CONNECTIONS 935 00:40:33,800 --> 00:40:36,800 AND NETWORKS AND EXPANSION OF 936 00:40:36,800 --> 00:40:38,520 NETWORKS STATE SPACE THAT IS 937 00:40:38,520 --> 00:40:39,920 WELL BEYOND THAT WHICH IS 938 00:40:39,920 --> 00:40:45,000 OBSERVED DURING A NORMAL WAKING 939 00:40:45,000 --> 00:40:55,240 CONSCIOUS 940 00:40:58,880 --> 00:40:59,200 CONSCIOUSNESS. 941 00:40:59,200 --> 00:40:59,840 IN THIS MODEL THEY PROPOSED THAT 942 00:40:59,840 --> 00:41:00,320 UNDER A NORMAL WAKING 943 00:41:00,320 --> 00:41:01,320 CONSCIOUSNESS WHEN WE RECEIVE 944 00:41:01,320 --> 00:41:03,640 SENSORY INPUT THAT SENSE YRY 945 00:41:03,640 --> 00:41:06,080 INPUT IS INTERPRETED HEAVILY AND 946 00:41:06,080 --> 00:41:10,080 HIGHLY WEIGHTED BASED ON TOP 947 00:41:10,080 --> 00:41:12,000 PREDICTIONS THAT YOU CAN 948 00:41:12,000 --> 00:41:13,000 CONSIDER BAYESIAN PRIORS ABOUT 949 00:41:13,000 --> 00:41:15,720 THE WORLD AND HAVE MODELS HOW 950 00:41:15,720 --> 00:41:17,200 THE WORLD SHOULD WORK AND APPLY 951 00:41:17,200 --> 00:41:19,040 THEM IN UNDERSTANDING TO INPUTS 952 00:41:19,040 --> 00:41:20,920 WE RECEIVE ON A REGULAR BASIS 953 00:41:20,920 --> 00:41:24,000 AND IN MODELS PSYCHEDELICS 954 00:41:24,000 --> 00:41:26,080 ESSENTIALLY FLATTEN ENERGY 955 00:41:26,080 --> 00:41:28,360 LANDSCAPE OF PREDICTIONS AND 956 00:41:28,360 --> 00:41:29,880 MODELS THAT YOU CAN IMAGINE A 957 00:41:29,880 --> 00:41:32,560 REDUCTION IN WEIGHT OF PRIORS OR 958 00:41:32,560 --> 00:41:34,320 REDUCTION IN WEIGHT OF MODELS 959 00:41:34,320 --> 00:41:36,400 HELPING YOU TO INTERPRET THE 960 00:41:36,400 --> 00:41:40,720 WORLD AND THEN ALLOWS FOR 961 00:41:40,720 --> 00:41:41,320 DIFFERENT PREDICTIONS AND 962 00:41:41,320 --> 00:41:43,080 PREDICTION ERRORS TO PUSH AROUND 963 00:41:43,080 --> 00:41:45,720 AND BEGIN TO MODULATE YOUR BRAIN 964 00:41:45,720 --> 00:41:49,800 STATE GOING FORWARD AND 965 00:41:49,800 --> 00:41:50,760 PSYCHOLOGICAL STATE GOING 966 00:41:50,760 --> 00:41:52,920 FORWARD AND THIS IS ONE MODEL OF 967 00:41:52,920 --> 00:41:55,960 HOW PSYCHEDELICS MAY BE ALTERING 968 00:41:55,960 --> 00:41:58,120 BRAIN FUNCTION ACUTELY DURING 969 00:41:58,120 --> 00:42:01,440 EXPERIENCES AND ANOTHER MODEL 970 00:42:01,440 --> 00:42:12,000 THAT COMES OUT OF A VAST AMOUNT 971 00:42:13,680 --> 00:42:16,280 OF WORK ON PSYCHOSIS AND 972 00:42:16,280 --> 00:42:17,520 [INDISCERNIBLE] FOCUSES IN ON A 973 00:42:17,520 --> 00:42:21,120 KIND OF RECURRENT CIRCUIT 974 00:42:21,120 --> 00:42:26,600 BETWEEN THALAMIC NUCLEI AND 975 00:42:26,600 --> 00:42:30,080 CORTICAL SITES AND WITHIN THIS 976 00:42:30,080 --> 00:42:32,400 CIRCUIT IT IS KNOWN AND EXPECTED 977 00:42:32,400 --> 00:42:34,760 THAT PREFRONTAL BRAIN REGIONS 978 00:42:34,760 --> 00:42:36,920 WILL EXERT TOP-DOWN INFLUENCE 979 00:42:36,920 --> 00:42:40,920 OVER THALAMUS THAT WILL EXERT 980 00:42:40,920 --> 00:42:44,040 SIL AMIC NUCLEI AND CONTROL OVER 981 00:42:44,040 --> 00:42:46,560 AMOUNT OF SENSORY INFORMATION 982 00:42:46,560 --> 00:42:48,880 PASSING FROM THALAMUS TO HIGHER 983 00:42:48,880 --> 00:42:50,680 AREAS FOR PERCEPTION AND 984 00:42:50,680 --> 00:42:52,960 COGNITION TO OCCUR AND TURNS OUT 985 00:42:52,960 --> 00:42:54,840 THROUGHOUT THIS CIRCUIT AND 986 00:42:54,840 --> 00:42:59,680 SOMEWHAT RECURRENT AND 987 00:42:59,680 --> 00:43:01,160 SELF-REGULATING CIRCUIT MANY 988 00:43:01,160 --> 00:43:03,120 SEROTONIN RECEPTORS AND 989 00:43:03,120 --> 00:43:06,040 PSYCHEDELIC DRUGS AND IDEA IN 990 00:43:06,040 --> 00:43:07,320 PLAIN LANGUAGE GOES WHEN YOU 991 00:43:07,320 --> 00:43:09,760 HAVE A PSYCHEDELIC EXPERIENCE 992 00:43:09,760 --> 00:43:12,040 DRUGS ARE DISRUPTING THE CIRCUIT 993 00:43:12,040 --> 00:43:14,040 LEADING TO OVERFLOW OF SENSORY 994 00:43:14,040 --> 00:43:15,440 INFORMATION MAKING IT TO CORTEX 995 00:43:15,440 --> 00:43:19,520 THAT LEADS TO FURTHER BREAK DOWN 996 00:43:19,520 --> 00:43:20,760 CIRCUIT LEADING TO SENSORY 997 00:43:20,760 --> 00:43:22,920 INFORMATION LEADING TO CORTEX 998 00:43:22,920 --> 00:43:24,080 AND THEN EVERYTHING PROCEEDS 999 00:43:24,080 --> 00:43:27,600 FROM THAT AND FROM THAT STATE. 1000 00:43:27,600 --> 00:43:30,320 THIS IS HEAVILY RELIANT ON WORK 1001 00:43:30,320 --> 00:43:32,280 FROM MARK AND [INDISCERNIBLE] 1002 00:43:32,280 --> 00:43:34,000 WHO APPLIED THIS MODEL THAT HAS 1003 00:43:34,000 --> 00:43:37,400 BEEN DEVELOPED IN STUDY OF 1004 00:43:37,400 --> 00:43:39,040 PSYCHOSIS TO UNDERSTANDING OF 1005 00:43:39,040 --> 00:43:41,280 PSYCHEDELIC EXPERIENCES. 1006 00:43:41,280 --> 00:43:43,560 AND THESE -- THESE MODELS TO 1007 00:43:43,560 --> 00:43:46,040 THIS POINT, THEY EXPLAIN WHAT IS 1008 00:43:46,040 --> 00:43:47,680 OCCURRING CUTELY DURING 1009 00:43:47,680 --> 00:43:49,440 PSYCHEDELIC EXPERIENCES THAT 1010 00:43:49,440 --> 00:43:54,960 DON'T GO FAR IN EXPLAINING WHAT 1011 00:43:54,960 --> 00:43:57,280 HAPPENS AND CHANGES AFTER THE 1012 00:43:57,280 --> 00:43:59,640 FACT AND MODELS PREDICTING BRAIN 1013 00:43:59,640 --> 00:44:01,160 [INDISCERNIBLE] AND WHAT HAPPENS 1014 00:44:01,160 --> 00:44:03,520 NEXT AND WORKING ON DATA AND 1015 00:44:03,520 --> 00:44:05,520 [INDISCERNIBLE] SUGGESTS 1016 00:44:05,520 --> 00:44:06,760 PSYCHOLOGICAL FLEXIBILITY 1017 00:44:06,760 --> 00:44:08,840 COGNITIVE FLEXIBILITY AND NEURAL 1018 00:44:08,840 --> 00:44:11,760 FLEXIBILITY ALTERED IN ENDURING 1019 00:44:11,760 --> 00:44:14,000 FASHION AFTER PSYCHEDELIC 1020 00:44:14,000 --> 00:44:15,000 EXPERIENCES THAT IS IMPORTANT 1021 00:44:15,000 --> 00:44:19,080 BECAUSE COGNITIVE EXPERIENCES 1022 00:44:19,080 --> 00:44:21,440 ARE TARGETS IMPAIRED IN MOOD AND 1023 00:44:21,440 --> 00:44:24,440 SUBSTANCE USE DISORDERS AND IN 1024 00:44:24,440 --> 00:44:26,480 OTHER DISORDERS POSSIBLY THAT IS 1025 00:44:26,480 --> 00:44:29,040 PICTURE OF ALLAN DAVIS FIRST 1026 00:44:29,040 --> 00:44:31,680 AUTHOR IN PUBLICATION AND LEAD 1027 00:44:31,680 --> 00:44:34,280 AUTHOR POST DOCTORAL FELLOW 1028 00:44:34,280 --> 00:44:37,320 GOING ON TO LEAD RESEARCH CENTER 1029 00:44:37,320 --> 00:44:39,240 AT OHIO UNIVERSITY AND SURVEY 1030 00:44:39,240 --> 00:44:41,320 AND INDIVIDUALS IN WORLD THAT 1031 00:44:41,320 --> 00:44:43,400 CLAIM TO RECOVER FROM DEPRESSION 1032 00:44:43,400 --> 00:44:45,880 AFTER TAKING MUSHROOMS AND ASKED 1033 00:44:45,880 --> 00:44:47,640 HIM TO COMPLETE QUESTIONNAIRES 1034 00:44:47,640 --> 00:44:50,360 AND OF COURSE CAVEATS ABOUND AND 1035 00:44:50,360 --> 00:44:53,920 SURVEY SAMPLE AND ALMOST 1036 00:44:53,920 --> 00:44:55,720 CERTAINLY RESPONSE AND 1037 00:44:55,720 --> 00:44:57,480 SELECTIVITY BIAS AND 1038 00:44:57,480 --> 00:44:59,600 RECOLLECTION AND POSITIVITY BIAS 1039 00:44:59,600 --> 00:45:01,760 AND OF DATA WE COLLECTED WE 1040 00:45:01,760 --> 00:45:03,240 FOUND THAT THERE WASN'T 1041 00:45:03,240 --> 00:45:05,720 NECESSARILY ACCUSE MYSTICAL 1042 00:45:05,720 --> 00:45:07,800 EXPERIENCES PREDICTING 1043 00:45:07,800 --> 00:45:09,040 INCREASING IN DEPRESSION THAT 1044 00:45:09,040 --> 00:45:11,360 PERSON EXPERIENCED AFTER 1045 00:45:11,360 --> 00:45:13,000 PSYCHEDELIC EVENT AND RATHER 1046 00:45:13,000 --> 00:45:16,240 MYSTICAL EXPERIENCES STRONGLY 1047 00:45:16,240 --> 00:45:17,600 PREDICTED OCCURRENCE OF ACUTE 1048 00:45:17,600 --> 00:45:20,200 PSYCH LONL INSIGHTS PEOPLE 1049 00:45:20,200 --> 00:45:21,560 GAINING INSIGHTS TO THEMSELVES 1050 00:45:21,560 --> 00:45:22,880 MRAPSD IN WORLD AND 1051 00:45:22,880 --> 00:45:24,760 RELATIONSHIPS DURING EXPERIENCES 1052 00:45:24,760 --> 00:45:28,800 THAT THEN PREDICT INCREASES IN 1053 00:45:28,800 --> 00:45:29,840 PSYCHOLOGICAL FLEXIBILITY THAT 1054 00:45:29,840 --> 00:45:32,320 SEEM TO FINALLY PREDICT 1055 00:45:32,320 --> 00:45:36,680 DECREASES IN DEPRESSION AND 1056 00:45:36,680 --> 00:45:37,480 ANXIETY CENTERING FLEXIBILITY 1057 00:45:37,480 --> 00:45:41,520 AND INCREASED CAPACITY FOR 1058 00:45:41,520 --> 00:45:43,960 FLEXIBILITY AS POTENTIAL 1059 00:45:43,960 --> 00:45:45,120 THERAPEUTIC TARGET OF 1060 00:45:45,120 --> 00:45:47,520 PSYCHEDELIC DRUGS AND UNDER 1061 00:45:47,520 --> 00:45:48,600 SURVEY BRINGING UNDER TIGHT 1062 00:45:48,600 --> 00:45:51,040 EXPERIENCE AND CONTROL AND STUDY 1063 00:45:51,040 --> 00:45:54,600 OF PATIENTS WITH MAJOR 1064 00:45:54,600 --> 00:45:56,120 DEPRESSIVE DISORDER WE ASK 1065 00:45:56,120 --> 00:45:56,600 PATIENTS TO COMPLETE 1066 00:45:56,600 --> 00:45:58,000 [INDISCERNIBLE] AND THIS IS A 1067 00:45:58,000 --> 00:45:59,640 DEPICTION OF THE TASK WE USE AND 1068 00:45:59,640 --> 00:46:04,040 IS ADAPTATION OF WISCONSIN 1069 00:46:04,040 --> 00:46:04,640 [INDISCERNIBLE] CALLED PEN 1070 00:46:04,640 --> 00:46:05,320 CONDITIONAL EXCLUSION TASK AND 1071 00:46:05,320 --> 00:46:08,480 IN TASK YOU ARE TOLD TO CLICK ON 1072 00:46:08,480 --> 00:46:09,880 OBJECT THAT DOESN'T BELONG AND 1073 00:46:09,880 --> 00:46:12,640 YOU SEE OH, WELL. WHAT IS THE 1074 00:46:12,640 --> 00:46:13,120 RULE? 1075 00:46:13,120 --> 00:46:15,720 IS SQUARE AN OBJECT THAT DOESN'T 1076 00:46:15,720 --> 00:46:17,200 BELONG AND IT IS DIFFERENT THAN 1077 00:46:17,200 --> 00:46:19,240 OBJECT IN THE STARS AND BOLD 1078 00:46:19,240 --> 00:46:21,440 STAR THAT STNT BELONG IN LINE 1079 00:46:21,440 --> 00:46:23,720 WITH WEIGHT FROM FIGURES AND 1080 00:46:23,720 --> 00:46:26,600 FIRST FIGURE SMALL STAR BECAUSE 1081 00:46:26,600 --> 00:46:28,360 SMALLER THAN OTHER THREE FIGURE 1082 00:46:28,360 --> 00:46:30,840 ERRS AND PERSON COMPLETING TASK 1083 00:46:30,840 --> 00:46:32,680 HAS TO CLICK THROUGH AFTER EACH 1084 00:46:32,680 --> 00:46:34,240 CLICK ON OBJECT TO SELECT AND 1085 00:46:34,240 --> 00:46:38,440 THIS IS ONE I THINK DOESN'T 1086 00:46:38,440 --> 00:46:40,400 BELONG GIVEN FEEDBACK IT HAS 1087 00:46:40,400 --> 00:46:43,680 INCORRECT AND ALONG WAY YOU 1088 00:46:43,680 --> 00:46:45,080 LEARN RULE AND CHUG ALONG 1089 00:46:45,080 --> 00:46:46,520 PLAYING WITH RULE AND TOLD 1090 00:46:46,520 --> 00:46:48,040 CHANGES AND START TO BE TOLD 1091 00:46:48,040 --> 00:46:51,320 THAT RESPONSE IS INCORRECT AND 1092 00:46:51,320 --> 00:46:52,920 YOU HAVE TO SWITCH SEARCH AND 1093 00:46:52,920 --> 00:46:54,480 EXPLORE AND FIND NEW RULE AND 1094 00:46:54,480 --> 00:46:56,360 BEGIN TO RESPOND TO THAT RULE 1095 00:46:56,360 --> 00:46:58,960 AND CHUG ALONG FOR A WHILE UNTIL 1096 00:46:58,960 --> 00:47:00,800 THAT RULE CHANGES AND FIX YOUR 1097 00:47:00,800 --> 00:47:03,000 RESPONDING AND DEGREE TO WHICH 1098 00:47:03,000 --> 00:47:04,960 YOU PERCEIVERATE ON PREVIOUS 1099 00:47:04,960 --> 00:47:08,240 RULE AFTER RULE HAS CHANGED IS A 1100 00:47:08,240 --> 00:47:12,640 MEASURE OF COGNITIVE 1101 00:47:12,640 --> 00:47:14,880 INFLEXIBILITY AND REDUCTION IN 1102 00:47:14,880 --> 00:47:19,560 PERSEVERATIVE RORS IS INCREASE 1103 00:47:19,560 --> 00:47:26,080 IN COGNITIVE FLEXIBILITY AND -- 1104 00:47:26,080 --> 00:47:28,360 RERECEIVE REDUCTION IN 1105 00:47:28,360 --> 00:47:31,000 BEHAVIORAL CONTROL HERE AND 1106 00:47:31,000 --> 00:47:33,200 ALONG THAT SAME STUDY WE ALSO 1107 00:47:33,200 --> 00:47:34,680 HAD PEOPLE SCANNED WITH 1108 00:47:34,680 --> 00:47:37,240 FUNCTIONAL MRI BEFORE AND AFTER 1109 00:47:37,240 --> 00:47:39,000 THEIR TREATMENT AND SAW INCREASE 1110 00:47:39,000 --> 00:47:41,480 IN DYNAMIC FUNCTIONAL 1111 00:47:41,480 --> 00:47:42,840 CONNECTIVITY AND VARIANCE, 1112 00:47:42,840 --> 00:47:44,920 MOMENT TO MOMENT VARIANCE IN 1113 00:47:44,920 --> 00:47:45,800 CONNECTIVITY AND COMMUNICATION, 1114 00:47:45,800 --> 00:47:49,680 IF YOU WILL, OF POSTERIOR 1115 00:47:49,680 --> 00:47:52,640 SINGLET AND ANTERIOR SINGLET 1116 00:47:52,640 --> 00:47:54,080 INVOLVED HEAVILY IN PROCESS OF 1117 00:47:54,080 --> 00:47:56,360 EXECUTIVE AND COGNITIVE CONTROL 1118 00:47:56,360 --> 00:47:57,720 AND FLEXIBILITY AND SEEING 1119 00:47:57,720 --> 00:48:01,680 INCREASE IN DYNAMIC CONNECTIVITY 1120 00:48:01,680 --> 00:48:05,640 AND NEURAL FLEXIBILITY OF BRAIN 1121 00:48:05,640 --> 00:48:08,200 REGION THAT PREDICTED CHANGE AND 1122 00:48:08,200 --> 00:48:09,080 DEPRESSION A MONTH AFTER 1123 00:48:09,080 --> 00:48:10,480 TREATMENT AND SEEING EVIDENCE 1124 00:48:10,480 --> 00:48:12,600 FOR PSYCHOLOGICAL AND COGNITIVE 1125 00:48:12,600 --> 00:48:15,640 AND NEURAL FLEXIBILITY INCREASES 1126 00:48:15,640 --> 00:48:17,720 PREDICTIVE OF THERAPEUTIC 1127 00:48:17,720 --> 00:48:19,720 OUTCOMES THAT COULD BE AN 1128 00:48:19,720 --> 00:48:21,560 EXPLANATION OF WHY PSYCHEDELICS 1129 00:48:21,560 --> 00:48:24,480 MAY BE THERAPEUTICALLY EFFECTIVE 1130 00:48:24,480 --> 00:48:26,640 IN MOOD AND SUBSTANCE USE 1131 00:48:26,640 --> 00:48:29,520 DISORDERS THAT IN ITSELF MIGHT 1132 00:48:29,520 --> 00:48:32,160 BE REMARKABLE DON'T THINK OF 1133 00:48:32,160 --> 00:48:35,440 MOOD DISORDERS TO BE FOR THERAPY 1134 00:48:35,440 --> 00:48:37,400 FOR TOBACCO USE DISORDERS TO BE 1135 00:48:37,400 --> 00:48:38,600 FIRST LINE OF THERAPY FOR 1136 00:48:38,600 --> 00:48:39,640 ALCOHOL USE DISORDER AND SO ON 1137 00:48:39,640 --> 00:48:42,360 AND SO FORTH. 1138 00:48:42,360 --> 00:48:46,040 IF WE CAN DETERMINE THESE TYPES 1139 00:48:46,040 --> 00:48:50,000 OF POTENTIAL TRANSDIAGNOSTIC 1140 00:48:50,000 --> 00:48:51,040 THERAPEUTICS FOR PSYCHEDELIC 1141 00:48:51,040 --> 00:48:53,080 DRUGS WE WILL HAVE GONE A LONG 1142 00:48:53,080 --> 00:48:55,960 WAY TO UNDERSTAND BETTER HOW TO 1143 00:48:55,960 --> 00:48:57,720 OPTIMIZE DELIVERY OF THERAPIES 1144 00:48:57,720 --> 00:48:59,280 AND WE HAVE ONE OTHER HYPOTHESIS 1145 00:48:59,280 --> 00:49:01,920 HERE WE ARE WORKING ON THAT IS 1146 00:49:01,920 --> 00:49:03,800 PSYCHEDELICS CHANGING BALANCE OF 1147 00:49:03,800 --> 00:49:04,680 COGNITIVE FLEXIBILITY AND 1148 00:49:04,680 --> 00:49:07,720 STABILITY LEADING TO LONG-TERM 1149 00:49:07,720 --> 00:49:10,440 EFFECTS THAT THIS IS MY POST 1150 00:49:10,440 --> 00:49:11,600 DOCTORAL FELLOW AND 1151 00:49:11,600 --> 00:49:12,480 [INDISCERNIBLE] IS LEADING THE 1152 00:49:12,480 --> 00:49:14,840 CHARGE ON THIS AND ACKNOWLEDGING 1153 00:49:14,840 --> 00:49:17,800 POST DOCTORAL FELLOW WHO LED 1154 00:49:17,800 --> 00:49:19,920 CHARGES ON BRAIN ANALYSIS AND 1155 00:49:19,920 --> 00:49:22,040 WANT TO GIVE A NOD AND HANDOFF 1156 00:49:22,040 --> 00:49:25,600 TO DAVID OLSON'S WORK AND 1157 00:49:25,600 --> 00:49:28,040 DAVID'S WORK IS REMARKABLE 1158 00:49:28,040 --> 00:49:30,160 LEADING WAY DEMONSTRATING 1159 00:49:30,160 --> 00:49:32,680 POTENTIAL FOR MOLECULAR NEURONAL 1160 00:49:32,680 --> 00:49:35,640 BASIS FOR EFFECTS I DESCRIBED 1161 00:49:35,640 --> 00:49:39,040 AND POSSIBLE THAT NEURAL 1162 00:49:39,040 --> 00:49:40,240 PSYCHOLOGICAL FLEXIBILITY ARE 1163 00:49:40,240 --> 00:49:42,560 UNDERLAYED BY INCREASE OF SPINE 1164 00:49:42,560 --> 00:49:44,360 DENSITY AND SNAPPO GENESIS THAT 1165 00:49:44,360 --> 00:49:47,160 MAY BE POSSIBLE AFTER THE 1166 00:49:47,160 --> 00:49:49,440 ADMINISTRATION OF VARIETY OF 1167 00:49:49,440 --> 00:49:50,800 PSYCHEDELIC COMPOUNDS AND THINK 1168 00:49:50,800 --> 00:49:54,960 THAT I SHOULD NOW PAUSE TO 1169 00:49:54,960 --> 00:49:56,400 ACKNOWLEDGE THE VERY LARGE AND 1170 00:49:56,400 --> 00:49:58,840 DIVERSE TEAM OF PROFESSIONALS AT 1171 00:49:58,840 --> 00:50:00,680 MANY LEVELS OF ACADEMIC CAREER 1172 00:50:00,680 --> 00:50:02,840 AND WITH WHOM I HAVE HAD THE 1173 00:50:02,840 --> 00:50:07,120 PRIVILEGE TO WORK AT JOHNS 1174 00:50:07,120 --> 00:50:07,960 HOPKINS UNIVERSITY FOR CENTER 1175 00:50:07,960 --> 00:50:10,240 FOR PSYCHEDELIC RESEARCH AND OF 1176 00:50:10,240 --> 00:50:12,520 WHICH NONE WILL HAVE SHOWED YOU 1177 00:50:12,520 --> 00:50:13,560 AND HAVE OCCURRED AND WANT TO 1178 00:50:13,560 --> 00:50:15,560 ALSO THANK YOU FOR YOUR TIME AND 1179 00:50:15,560 --> 00:50:17,960 ATTENTION. NOW, I WILL 1180 00:50:17,960 --> 00:50:19,080 OFFICIALLY HAND OFF THE MIC TO 1181 00:50:19,080 --> 00:50:21,000 DR. OLSON. 1182 00:50:21,000 --> 00:50:24,480 >>THANK YOU VERY MUCH, FRED, 1183 00:50:24,480 --> 00:50:26,280 FOR AN EXCITING PANORAMIC VIEW 1184 00:50:26,280 --> 00:50:29,240 OF THIS FIELD AND TURNING TO 1185 00:50:29,240 --> 00:50:31,200 DAVID OLSON WHO WILL DISCUSS 1186 00:50:31,200 --> 00:50:33,240 PSYCHEDELICS AND RELATED 1187 00:50:33,240 --> 00:50:36,680 PLASTICITY PROMOTING 1188 00:50:36,680 --> 00:50:37,360 NEUROTHERAPEUTICS. DAVID? 1189 00:50:37,360 --> 00:50:38,840 >>CAN EVERYONE SEE SLIDES AND 1190 00:50:38,840 --> 00:50:40,840 HEAR ME? 1191 00:50:40,840 --> 00:50:48,760 >>GREAT. FANTATASTIC 1192 00:50:48,760 --> 00:50:51,560 FRED AND NOW TALKING ABOUT HOW 1193 00:50:51,560 --> 00:50:53,080 DRUGS MIGHT IMPACT THE BRAIN AND 1194 00:50:53,080 --> 00:50:58,880 BEFORE I GET INTO THIS I HAVE TO 1195 00:50:58,880 --> 00:51:17,920 TELL NEW ADIDITION TO -- DELLIX 1196 00:51:17,920 --> 00:51:18,400 LICENSES TECHNOLOGY FROM UC 1197 00:51:18,400 --> 00:51:19,720 DAVIS AND HOPE YOU COME AWAY 1198 00:51:19,720 --> 00:51:24,360 WITH A BETTER UNDERSTANDING OF 1199 00:51:24,360 --> 00:51:25,720 -- AND HOPE YOU GAIN KNOWLEDGE 1200 00:51:25,720 --> 00:51:31,200 ABOUT MECHANISMS BY WHICH 1201 00:51:31,200 --> 00:51:33,640 PSYCHEDELICS CAN PRO NONOTE 1202 00:51:33,640 --> 00:51:36,080 STRUCTURAL NEUROPLASTICITY AND 1203 00:51:36,080 --> 00:51:39,400 TALK ABOUT THE POSSIBILITY OF 1204 00:51:39,400 --> 00:51:42,080 SEPARATING HALLUCINOGENIC 1205 00:51:42,080 --> 00:51:46,320 EFFECTS ON NEUROPLASTICITY AND 1206 00:51:46,320 --> 00:51:51,200 LONG TERM BENEFICIAL EFFECTS AND 1207 00:51:51,200 --> 00:51:52,960 OUR GROUP IS FINDING TREATMENTS 1208 00:51:52,960 --> 00:51:55,160 IN STRESS RELATED 1209 00:51:55,160 --> 00:51:57,360 NEUROPSYCHIATRIC DISEASES THAT 1210 00:51:57,360 --> 00:51:57,880 ARE CONDITIONS THAT ARE 1211 00:51:57,880 --> 00:52:02,760 PRECIPITATED OR EXACERBATED BY 1212 00:52:02,760 --> 00:52:04,120 CHRONIC STRESS LIKE DEPRESSION 1213 00:52:04,120 --> 00:52:07,240 AND POST-TRAUMATIC STRESS 1214 00:52:07,240 --> 00:52:09,040 DISORDER AND SUBSTANCE USE 1215 00:52:09,040 --> 00:52:10,920 DISORDER AND HALLMARK OF 1216 00:52:10,920 --> 00:52:11,760 ILLNESSES ARE PHYSICAL CHANGES 1217 00:52:11,760 --> 00:52:14,160 IN STRUCTURE OF THE BRAIN AND 1218 00:52:14,160 --> 00:52:16,560 PARTICULARLY AT TROE FEEING OF 1219 00:52:16,560 --> 00:52:18,920 NEURONS IN PART OF THE BRAIN 1220 00:52:18,920 --> 00:52:20,840 THAT IS PREFRONTAL CORTEX 1221 00:52:20,840 --> 00:52:23,360 SITTING HERE AND PFC IS CRITICAL 1222 00:52:23,360 --> 00:52:26,160 BRAIN REGION THAT GOES TO 1223 00:52:26,160 --> 00:52:28,960 SUBCORTICAL REGIONS DOING THINGS 1224 00:52:28,960 --> 00:52:30,360 LIKE CONTROLLING MOOD AND 1225 00:52:30,360 --> 00:52:31,760 MOTIVATION AND FEAR AND REWARD 1226 00:52:31,760 --> 00:52:35,040 THAT IS PERHAPS UNSURPRISING 1227 00:52:35,040 --> 00:52:37,440 THAT STRESS INDUCED CHANGES IN 1228 00:52:37,440 --> 00:52:39,200 STRUCTURE OF BRAIN REGION LEADS 1229 00:52:39,200 --> 00:52:42,360 TO SYMPTOMS OF MANY OF THE 1230 00:52:42,360 --> 00:52:44,160 NEUROPSYCHIATRIC CONDITIONS. 1231 00:52:44,160 --> 00:52:46,320 NOW, THE CURRENT THERAPEUTIC 1232 00:52:46,320 --> 00:52:48,200 APPROACH TO TREAT ILLNESSES HAVE 1233 00:52:48,200 --> 00:52:51,160 RELIED ON TRYING TO RECTIFY 1234 00:52:51,160 --> 00:52:53,400 SO-CALLED CHEMICAL IMBALANCES IN 1235 00:52:53,400 --> 00:52:56,040 THE BRAIN THROUGH USE OF THINGS 1236 00:52:56,040 --> 00:52:59,360 LIKE SELECTIVE SEROTONIN 1237 00:52:59,360 --> 00:53:01,400 REUPTAKE INHIBITORS AND HAVE 1238 00:53:01,400 --> 00:53:02,760 LARGELY EFFECTIVE ANYONE KNOWING 1239 00:53:02,760 --> 00:53:05,640 ABOUT SSRIS KNOWS IT TAKES WEEKS 1240 00:53:05,640 --> 00:53:08,560 TO MONTHS FOR THAT TYPE OF 1241 00:53:08,560 --> 00:53:10,480 MEDICINE TO DEMONSTRATE CLINICAL 1242 00:53:10,480 --> 00:53:13,480 EFFICACY AND 1/3 OF ALL PATIENTS 1243 00:53:13,480 --> 00:53:15,400 WILL NEVER RESPOND TO MORE 1244 00:53:15,400 --> 00:53:17,280 TRADITIONAL ANTIDEPRESSANT 1245 00:53:17,280 --> 00:53:19,120 TREATMENTS AND OUR GROUP IS 1246 00:53:19,120 --> 00:53:20,840 INTERESTED REALLY IN TRYING TO 1247 00:53:20,840 --> 00:53:22,280 PUSH FORWARD A NEW APPROACH AND 1248 00:53:22,280 --> 00:53:24,920 ONE THAT INVOLVES USE OF SMALL 1249 00:53:24,920 --> 00:53:27,040 MOLECULE DRUGS TO SELECTIVELY 1250 00:53:27,040 --> 00:53:28,640 MODULATE SPECIFIC CIRCUITS IN 1251 00:53:28,640 --> 00:53:30,920 THE BRAIN TO PRODUCE 1252 00:53:30,920 --> 00:53:35,520 LONG-LASTING CHANGES IN 1253 00:53:35,520 --> 00:53:37,200 BEHAVIOR. WE REASON ONE BEST 1254 00:53:37,200 --> 00:53:40,480 WAY TO IMPACT NEURAL CIRCUIT IS 1255 00:53:40,480 --> 00:53:42,080 PHYSICALLY CHANGING STRUCTURE OF 1256 00:53:42,080 --> 00:53:43,360 NEURONS WITHIN CIRCUIT AND 1257 00:53:43,360 --> 00:53:45,560 PURPOSES OF TODAY'S TALK I WILL 1258 00:53:45,560 --> 00:53:49,160 FOCUS ON THESE LAYER 5 PARAMETAL 1259 00:53:49,160 --> 00:53:52,680 NEURONS OF CORTEX THAT TEND TO 1260 00:53:52,680 --> 00:53:54,880 ATROPHY IN RESPONSE TO CHRONIC 1261 00:53:54,880 --> 00:53:55,080 STRESS. 1262 00:53:55,080 --> 00:53:59,000 WE STARTED STUDYING A CLASS OF 1263 00:53:59,000 --> 00:54:02,480 COMPOUNDS CALLED PSYCHOMRAFTI 1264 00:54:02,480 --> 00:54:04,640 GENERALS THAT ARE STIMULI 1265 00:54:04,640 --> 00:54:06,360 INDUCING STRUCTURAL FUNCTIONAL 1266 00:54:06,360 --> 00:54:08,240 NEURAL PLASTICITY AND YOU WILL 1267 00:54:08,240 --> 00:54:10,000 SEE COMPOUNDS PROMOTE GROWTH OF 1268 00:54:10,000 --> 00:54:12,520 NEW DENDRITES AND IF YOU ZOOM IN 1269 00:54:12,520 --> 00:54:14,760 ON ONE OF THE DENDRITES YOU WILL 1270 00:54:14,760 --> 00:54:17,280 SEE GROWTH OF THE LITTLE TINY 1271 00:54:17,280 --> 00:54:18,960 NUMBERS CALLED DENDRITIC SPINES 1272 00:54:18,960 --> 00:54:21,960 THAT ARE SITES OF EXCITATORY 1273 00:54:21,960 --> 00:54:24,280 SYNAPSES IN THE BRAIN AND 1274 00:54:24,280 --> 00:54:27,080 CHANGES IN NEURONAL STRUCTURE 1275 00:54:27,080 --> 00:54:28,480 OFTEN MANIFEST AS FUNCTIONAL 1276 00:54:28,480 --> 00:54:30,200 CHANGES YOU CAN MEASURE WITH 1277 00:54:30,200 --> 00:54:33,840 TRADITIONAL TECHNIQUES LIKE 1278 00:54:33,840 --> 00:54:34,760 ELECTROPHYSIOLOGY. 1279 00:54:34,760 --> 00:54:37,520 NOW, ONE OF THE BEST KNOWN 1280 00:54:37,520 --> 00:54:39,360 PSYCHOMRAFTI GENERALS IS 1281 00:54:39,360 --> 00:54:42,280 MOLECULE KETAMINE THAT IS 1282 00:54:42,280 --> 00:54:43,960 DISASSOCIATIVE ANESTHETIC THAT 1283 00:54:43,960 --> 00:54:46,000 IS IN MEDICINE FOR MANY YEARS 1284 00:54:46,000 --> 00:54:48,320 AND IS KNOWN AS SPECIAL K ON 1285 00:54:48,320 --> 00:54:51,000 STREET WHEN IT IS ABUSED AND 1286 00:54:51,000 --> 00:54:55,840 MORE RECENTLY FDA HAS APPROVED 1287 00:54:55,840 --> 00:54:58,480 KETAMINE FOR TREATMENT RESISTANT 1288 00:54:58,480 --> 00:55:03,360 DEPRESSION AND BELIEVE THAT 1289 00:55:03,360 --> 00:55:05,040 KETAMINE'S ANTIDEPRESSIVE 1290 00:55:05,040 --> 00:55:06,720 EFFECTS STEM FROM NEURAL 1291 00:55:06,720 --> 00:55:08,240 PLASSISTY AND SHOWING NEURONS 1292 00:55:08,240 --> 00:55:10,320 THAT ARE CULTURED IN A DISH AND 1293 00:55:10,320 --> 00:55:13,480 ON LEFT NEURONS ARE TREATED WITH 1294 00:55:13,480 --> 00:55:14,840 VEHICLE CONTROL AND ON RIGHT 1295 00:55:14,840 --> 00:55:16,480 NEURONS ARE TREATED WITH 1296 00:55:16,480 --> 00:55:19,080 KETAMINE THAT KETAMINE TREATED 1297 00:55:19,080 --> 00:55:21,520 NEURONS HAVE MORE DENDRITIC 1298 00:55:21,520 --> 00:55:23,600 BRANCHES IF YOU LOOK BELOW GREEN 1299 00:55:23,600 --> 00:55:26,080 DOTS ARE REPRESENTING SYNAPSES 1300 00:55:26,080 --> 00:55:28,600 AND KETAMINE PROMOTES GROWTH OF 1301 00:55:28,600 --> 00:55:33,920 NEURITES AND NEUR EATO GENESIS 1302 00:55:33,920 --> 00:55:36,880 AND PROMOTES NEUROGENESIS OR SIN 1303 00:55:36,880 --> 00:55:40,400 APTO GENESIS AND SHOWING IN VIVO 1304 00:55:40,400 --> 00:55:41,400 DATA FROM LATE [INDISCERNIBLE] 1305 00:55:41,400 --> 00:55:43,720 AND THEY REALLY DEMONSTRATED 1306 00:55:43,720 --> 00:55:46,760 THAT CHRONIC STRESS COULD LEAD 1307 00:55:46,760 --> 00:55:49,760 TO CORTICAL ATROPHY IN LOSS OF 1308 00:55:49,760 --> 00:55:51,360 DENDRITIC SPINES I TOLD YOU 1309 00:55:51,360 --> 00:55:53,360 ABOUT BEFORE AND LOSS OF 1310 00:55:53,360 --> 00:55:56,960 DENDRITIC SPINES MANIFEST AS 1311 00:55:56,960 --> 00:55:58,840 SYNAPTIC DEFICITS YOU CAN 1312 00:55:58,840 --> 00:56:01,240 MANIFEST WITH ELECTROPHYSIOLOGY 1313 00:56:01,240 --> 00:56:03,400 AND WHAT IS REMARKABLE ABOUT 1314 00:56:03,400 --> 00:56:05,080 KETAMINE IS SINGLE 1315 00:56:05,080 --> 00:56:06,200 ADMINISTRATION OF THE DRUG 1316 00:56:06,200 --> 00:56:08,720 RAPIDLY IN 24 HOURS CAN REGROW 1317 00:56:08,720 --> 00:56:12,120 LOST DENDRITIC SPINES 1318 00:56:12,120 --> 00:56:13,520 REESTABLISHING SYNAPTIC 1319 00:56:13,520 --> 00:56:15,520 CONNECTIVITY IN THE CORTEX AND 1320 00:56:15,520 --> 00:56:17,040 KETAMINE IS A REALLY INTERESTING 1321 00:56:17,040 --> 00:56:20,480 DRUG THAT IS PUSHING 1322 00:56:20,480 --> 00:56:21,560 NEUROPSYCHIATRY IN NEW 1323 00:56:21,560 --> 00:56:24,360 DIRECTIONS AND IN DIRECTION 1324 00:56:24,360 --> 00:56:27,400 TOWARDS HEALING DANL NEURAL 1325 00:56:27,400 --> 00:56:31,080 BRAIN CIRCUITRY SIMPLY THAN 1326 00:56:31,080 --> 00:56:32,360 TREATING SYMPTOMS AND KETAMINE 1327 00:56:32,360 --> 00:56:36,000 IS A DRUG AND MMDA RECEPTOR 1328 00:56:36,000 --> 00:56:37,360 FOUND BROADLY ACROSS ENTIRE 1329 00:56:37,360 --> 00:56:38,360 BRAIN AND GETTING INTO THE FIELD 1330 00:56:38,360 --> 00:56:40,200 WE ARE REALLY INTERESTED IN 1331 00:56:40,200 --> 00:56:42,480 TRYING TO FIND MOLECULES THAT 1332 00:56:42,480 --> 00:56:47,520 MIGHT HAVE MORE CIRCUIT-LEVEL 1333 00:56:47,520 --> 00:56:50,560 SEA ACTIVITY CONTROLLING WHERE 1334 00:56:50,560 --> 00:56:51,360 NEURAL PLASTICITY HAPPENS IN THE 1335 00:56:51,360 --> 00:56:53,520 BRAIN AND REMEMBER THAT NEURAL 1336 00:56:53,520 --> 00:56:55,200 PLASTICITY EVERYWHERE IS NOT A 1337 00:56:55,200 --> 00:56:58,120 GOOD THING PROMOTING NEURAL 1338 00:56:58,120 --> 00:56:59,800 PLASTICITY IN ADDICTION 1339 00:56:59,800 --> 00:57:02,440 CIRCUITRY ADDICTIVE COMPOUNDS 1340 00:57:02,440 --> 00:57:06,080 LIKE COCAINE DO AND PROMOTING 1341 00:57:06,080 --> 00:57:07,760 NEURAL PLASTICITY PAIN SENSING 1342 00:57:07,760 --> 00:57:09,960 NEURONS IN PERATIVERY CAN LEAD 1343 00:57:09,960 --> 00:57:12,280 TO CHRONIC PAIN AND WE THINK 1344 00:57:12,280 --> 00:57:17,960 DEEPLY ABOUT GENETICS OF BRAIN 1345 00:57:17,960 --> 00:57:19,800 TRYING TO FIND A TARGET 1346 00:57:19,800 --> 00:57:22,120 SELECTIVELY EXPRESSED IN NEURONS 1347 00:57:22,120 --> 00:57:27,160 IN CORTEX THAT ATROPHY IN 1348 00:57:27,160 --> 00:57:29,520 NEUROPSYCHIATRIC DISEASES LIKE 1349 00:57:29,520 --> 00:57:39,400 DEPRESSION STUDYING SEROTONIN 1350 00:57:39,400 --> 00:57:39,680 A 1351 00:57:39,680 --> 00:57:40,360 AND 5-HT2A RECEPTORS AND VERY 1352 00:57:40,360 --> 00:57:42,360 HIGH EXPRESSION IN THE ANTERIOR 1353 00:57:42,360 --> 00:57:44,240 PARTS OF THE BRAIN AND LESS 1354 00:57:44,240 --> 00:57:46,160 EXPRESSION MOVING TOWARDS BACK 1355 00:57:46,160 --> 00:57:47,480 OF THE BRAIN AND VERY LITTLE 1356 00:57:47,480 --> 00:57:50,320 EXPRESSION IN STRUCTURES LIKE 1357 00:57:50,320 --> 00:57:51,560 HIPPOCAMPUS AND STRIATUM AND IF 1358 00:57:51,560 --> 00:57:57,240 YOU ARE THINKING OF TRYING TO 1359 00:57:57,240 --> 00:58:00,360 MODULATE SEROTONIN 2A RECEPTOR 1360 00:58:00,360 --> 00:58:02,560 CLASSIC MOLECULES ARE 1361 00:58:02,560 --> 00:58:06,800 PSYCHEDELICS MOLECULES LIKE LSD 1362 00:58:06,800 --> 00:58:10,640 AND SILO SIL COMING FROM 1363 00:58:10,640 --> 00:58:12,400 MUSHROOMS AND FIRST EXPERIMENT 1364 00:58:12,400 --> 00:58:14,840 WE DID IS TOOK NEURONS TREATING 1365 00:58:14,840 --> 00:58:16,440 THEM WITH PSYCHEDELIC COMPOUNDS 1366 00:58:16,440 --> 00:58:18,400 YOU SEE COMPARED TO NEURONS 1367 00:58:18,400 --> 00:58:20,680 TREATED WITH VEHICLE CONTROL 1368 00:58:20,680 --> 00:58:21,920 NEURONS TREATED WITH 1369 00:58:21,920 --> 00:58:24,360 PSYCHEDELICS DMT AND LSD THAT 1370 00:58:24,360 --> 00:58:27,960 HAVE SUBSTANTIALLY MORE COMPLEX 1371 00:58:27,960 --> 00:58:31,680 DENDRITIC HARBORS AND DOG SUPER 1372 00:58:31,680 --> 00:58:34,040 RESOLUTION MICROSCOPY ZOOMING IN 1373 00:58:34,040 --> 00:58:36,000 ON DENDRITES YOU SEE GROWTH OF 1374 00:58:36,000 --> 00:58:41,200 DENDRITIC SPINES AND 1375 00:58:41,200 --> 00:58:42,400 FILLOPODIA-LIKE STRUCTURES AND 1376 00:58:42,400 --> 00:58:45,120 TO DEMONSTRATE THIS IN VIVO WE 1377 00:58:45,120 --> 00:58:47,480 RELIED ON A VERY FAST ACTING 1378 00:58:47,480 --> 00:58:52,160 RAPIDLY CLEARED PSYCHEDELIC DIE 1379 00:58:52,160 --> 00:58:54,040 MENLIL TRIPTO MEAN AND HALF LIFE 1380 00:58:54,040 --> 00:58:56,520 ERODANT IS ABOUT 10 MINUTES AND 1381 00:58:56,520 --> 00:58:58,240 FOR THIS EXPERIMENT WE GAVE 1382 00:58:58,240 --> 00:58:59,880 SYSTEMIC ADMINISTRATION OF DMT 1383 00:58:59,880 --> 00:59:01,880 AND WAITED 24 HOURS AND TIME 1384 00:59:01,880 --> 00:59:03,360 PERIOD WHEN ALL OF THE DRUG IS 1385 00:59:03,360 --> 00:59:07,360 CLEARED FROM THE BODY AND WE 1386 00:59:07,360 --> 00:59:08,440 SACRIFICED ANIMAL AND TOOK 1387 00:59:08,440 --> 00:59:11,360 TISSUE LOOKING AT NEURONAL 1388 00:59:11,360 --> 00:59:14,320 STRUCTURE VIA GOLGI STAINING AND 1389 00:59:14,320 --> 00:59:15,920 ELECTROPHYSIOLOGY AND LOOKING AT 1390 00:59:15,920 --> 00:59:18,400 STRUCTURE OF THE CORTEX AND WE 1391 00:59:18,400 --> 00:59:22,200 SEE A LARGE INCREASE IN 1392 00:59:22,200 --> 00:59:23,120 DENDRITIC SPINE DENSITY THAT 1393 00:59:23,120 --> 00:59:24,960 STRUCTURAL CHANGES ARE 1394 00:59:24,960 --> 00:59:25,680 ACCOMPANIED BY FUNCTIONAL 1395 00:59:25,680 --> 00:59:29,200 CHANGES AND SEE INCREASE IN BOTH 1396 00:59:29,200 --> 00:59:31,560 AMMRITTUDE AND FREQUENCY OF 1397 00:59:31,560 --> 00:59:34,040 SPONTANEOUS EXCITATORY 1398 00:59:34,040 --> 00:59:34,680 POSTSYNAPTIC CURRENTS AND NOW 1399 00:59:34,680 --> 00:59:37,320 SINCE WE PUBLISHED THIS STUDY 1400 00:59:37,320 --> 00:59:42,360 WAY BACK IN 2018, IT HAS BEEN 1401 00:59:42,360 --> 00:59:44,160 REPLICATED AND EXTENDED BY A 1402 00:59:44,160 --> 00:59:45,760 NUMBER OF GROUPS AND WANT TO 1403 00:59:45,760 --> 00:59:46,800 HIGHLIGHT ONE GROUP IN 1404 00:59:46,800 --> 00:59:51,400 PARTICULAR AND WORK FROM ALEX 1405 00:59:51,400 --> 00:59:54,760 QUAN'S GROUP WHO WAS AT YALE AND 1406 00:59:54,760 --> 00:59:56,840 MOVED TO CORNELL AND ALEX WAS 1407 00:59:56,840 --> 00:59:58,600 INTERESTED IN SEEING HOW LONG 1408 00:59:58,600 --> 01:00:00,360 EFFECT ON STRUCTURAL 1409 01:00:00,360 --> 01:00:02,360 NEUROPLASTICITY LASTS AND TOLD 1410 01:00:02,360 --> 01:00:04,880 YOU EARLIER THAT EFFECTS OF 1411 01:00:04,880 --> 01:00:07,120 THERAPEUTICS OF PSYCHEDELICS ARE 1412 01:00:07,120 --> 01:00:09,920 ENDURING AND COUPLE OF DOSES 1413 01:00:09,920 --> 01:00:11,480 WITH THERAPEUTICS LASTING WEEKS 1414 01:00:11,480 --> 01:00:14,480 TO MONTHS AND ALEX FOUND SINGLE 1415 01:00:14,480 --> 01:00:17,640 DOSE OF SILO KRIEBIN TO RODENTS 1416 01:00:17,640 --> 01:00:20,640 IN MALE AND FEMALE RODENTS LED 1417 01:00:20,640 --> 01:00:23,400 TO INCREASE IN CORTEX LASTING 1418 01:00:23,400 --> 01:00:25,000 FOR AT LEAST A MONTH THAT IS 1419 01:00:25,000 --> 01:00:26,480 QUITE REMARKABLE. 1420 01:00:26,480 --> 01:00:28,720 NOW, IN ADDITION TO THEIR 1421 01:00:28,720 --> 01:00:30,360 ENDURING EFFECTS AND SOMETHING 1422 01:00:30,360 --> 01:00:32,480 ELSE IS UNIQUE ABOUT 1423 01:00:32,480 --> 01:00:33,560 PSYCHEDELICS AND IT IS THAT THEY 1424 01:00:33,560 --> 01:00:39,200 HAVE A PANACEA-LIKE PROPERTY AND 1425 01:00:39,200 --> 01:00:40,800 TEND TO WORK ACROSS INDICATIONS 1426 01:00:40,800 --> 01:00:43,120 AND EMPHASIZING THAT DRUGS ARE 1427 01:00:43,120 --> 01:00:46,400 NOT PANACEAS AND ONE HYPOTHESIS 1428 01:00:46,400 --> 01:00:48,240 FOR WHY THEY SEEM TO HAVE 1429 01:00:48,240 --> 01:00:50,360 EFFICACY FOR DISORDERS LIKE 1430 01:00:50,360 --> 01:00:51,760 DEPRESSION AND SUBSTANCE USE 1431 01:00:51,760 --> 01:00:54,400 DISORDERS AND POST-TRAUMATIC 1432 01:00:54,400 --> 01:00:55,920 STRESS DISORDER IS THEY ARE 1433 01:00:55,920 --> 01:00:57,680 TARGETING A CRITICAL HUB IN THE 1434 01:00:57,680 --> 01:01:00,720 BRAIN OF PREFRONTAL CORTEX AND 1435 01:01:00,720 --> 01:01:04,960 KNOW FROM OPTOAND KINETIC 1436 01:01:04,960 --> 01:01:05,480 REVOLUTIONS THAT ARE 1437 01:01:05,480 --> 01:01:07,240 CIRCUMSTANCE CUTS ORIGINATING 1438 01:01:07,240 --> 01:01:09,800 FROM PREFRONTAL CORTEX DOG 1439 01:01:09,800 --> 01:01:11,400 THINGS LIKE REGULATING DRUG 1440 01:01:11,400 --> 01:01:14,240 SEEKING BEHAVIOR AND CONTROLLING 1441 01:01:14,240 --> 01:01:16,120 EXPRESSION OF FEAR AND ENHANCED 1442 01:01:16,120 --> 01:01:18,240 MOTIVATION FOR INSTANCE AND I 1443 01:01:18,240 --> 01:01:20,800 WILL SUMMARIZE LOTS OF WORK 1444 01:01:20,800 --> 01:01:29,000 QUICKLY AND WILL SAY IN GENERAL 1445 01:01:29,000 --> 01:01:33,800 PSYCHOMRAFTO GINS WILL HAVE LONG 1446 01:01:33,800 --> 01:01:35,360 LASTING BEHAVIORAL EFFECTS SUCH 1447 01:01:35,360 --> 01:01:37,440 AS ENHANCEMENT OF FEAR EXTENSION 1448 01:01:37,440 --> 01:01:39,400 LEARNING RELEVANT TO TREATMENT 1449 01:01:39,400 --> 01:01:42,360 OF POST-TRAUMATIC STRESS 1450 01:01:42,360 --> 01:01:48,520 DISORDER OR ANTIDEPRESSANT-LIKE 1451 01:01:48,520 --> 01:01:50,560 [INDISCERNIBLE] AND 1452 01:01:50,560 --> 01:01:54,360 ANTIDEPRESSANTS THAT PROMOTE A 1453 01:01:54,360 --> 01:02:00,200 SWIMMING BEHAVIOR IN THIS TEST 1454 01:02:00,200 --> 01:02:03,040 OUR GROUP WAS INTERESTED IN -- 1455 01:02:03,040 --> 01:02:06,080 PROMOTING NEUROPLASTICITY AND 1456 01:02:06,080 --> 01:02:07,400 PRODUCE THERAPEUTIC EFFECTS AND 1457 01:02:07,400 --> 01:02:12,040 START BY DOING SELECTIVE 1458 01:02:12,040 --> 01:02:13,720 PHARMACOLOGY AND THIS IS MEASURE 1459 01:02:13,720 --> 01:02:15,680 OF STRUCTURAL NEUROPLASTICITY 1460 01:02:15,680 --> 01:02:18,360 AND SEE FROM PSYCHEDELICS FROM 1461 01:02:18,360 --> 01:02:19,760 THREE DISTINCT CHEMICAL 1462 01:02:19,760 --> 01:02:23,000 SCAFFOLDS LIKE LSD AND TRIPTO 1463 01:02:23,000 --> 01:02:24,760 MEANS AND AMPHETAMINES ARE GOOD 1464 01:02:24,760 --> 01:02:28,480 AT PROMOTING GROWTH OF COURTI CO 1465 01:02:28,480 --> 01:02:33,480 NEURONS USING ANTAGONIST OF 1466 01:02:33,480 --> 01:02:36,360 5HT2A RECEPTORS HAVE BLOCKS WE 1467 01:02:36,360 --> 01:02:38,200 CHOSE THIS BECAUSE THERE IS LOTS 1468 01:02:38,200 --> 01:02:40,960 OF LITERATURE SHOWING THIS 1469 01:02:40,960 --> 01:02:44,040 MEDIATES HAG USE KNOW GENIC 1470 01:02:44,040 --> 01:02:46,760 EFFECTS OF PSYCHEDELICS AND 1471 01:02:46,760 --> 01:02:49,480 LOOKED AT A COUPLE DOWNSTREAM 1472 01:02:49,480 --> 01:02:52,520 KINASES KNOWN TO BE INVOLVED IN 1473 01:02:52,520 --> 01:02:55,360 KETAMINE NEUROINDEESED PLASSISTY 1474 01:02:55,360 --> 01:02:58,160 AND HIGH AFFINITY RECEPTOR FOR 1475 01:02:58,160 --> 01:03:02,400 BRAIN [INDISCERNIBLE] AND 1476 01:03:02,400 --> 01:03:05,600 ANOTHER IS MTOR THAT IS 1477 01:03:05,600 --> 01:03:09,400 PRODUCTION FOR PROTEINS 1478 01:03:09,400 --> 01:03:12,400 NECESSARY FOR PLASTICITY AND 1479 01:03:12,400 --> 01:03:15,040 STRUCTURAL PROTEINS -- ION 1480 01:03:15,040 --> 01:03:17,000 CHANNELS ALLOWING THEM TO CHANGE 1481 01:03:17,000 --> 01:03:18,080 SYNAPTIC [INDISCERNIBLE] AND 1482 01:03:18,080 --> 01:03:22,000 BLOCKING MTOR OR TRACK B YOU 1483 01:03:22,000 --> 01:03:24,360 BLOCK PSYCHEDELIC INDUCED 1484 01:03:24,360 --> 01:03:25,480 NEUROPLASTICITY AND IN THIS 1485 01:03:25,480 --> 01:03:30,360 STAGE ANTAGONIST USING TO BLOCK 1486 01:03:30,360 --> 01:03:32,560 5HT2A RECEPTOR IS NOT A PERFECT 1487 01:03:32,560 --> 01:03:34,680 DRUG TO BE REALLY CERTAIN THAT 1488 01:03:34,680 --> 01:03:37,040 2A RECEPTOR IS MEDIATING EFFECTS 1489 01:03:37,040 --> 01:03:40,080 TO RELY ON GENETIC KNOCKOUTS AND 1490 01:03:40,080 --> 01:03:43,160 HERE WE ARE GIVING PSYCHEDELIC 1491 01:03:43,160 --> 01:03:46,240 DRUG 5 METH OXY [INDISCERNIBLE] 1492 01:03:46,240 --> 01:03:48,800 TO WILD TYPE ANIMALS AND 1493 01:03:48,800 --> 01:03:51,360 INCREASE IN DENDRITIC INCREASE 1494 01:03:51,360 --> 01:03:57,160 IN CORTEX AND THIS IS COMPLETELY 1495 01:03:57,160 --> 01:04:02,360 GONE IN 5-HT2A -- PRODUCING LONG 1496 01:04:02,360 --> 01:04:04,000 LASTING CHANGES IN FUNCTIONAL 1497 01:04:04,000 --> 01:04:06,360 PLASTICITY AND AGAIN EFFECTS ARE 1498 01:04:06,360 --> 01:04:11,360 COMPLETELY GONE 5HT2A KNOCKOUT 1499 01:04:11,360 --> 01:04:13,960 ANIMALS IN TERMS OF BEHAVIORAL 1500 01:04:13,960 --> 01:04:15,960 EFFECTS WE RELIED ON VERSION OF 1501 01:04:15,960 --> 01:04:18,640 SWIM TEST THAT IS A LITTLE MORE 1502 01:04:18,640 --> 01:04:23,360 CHALLENGING AND TRADITIONAL 1503 01:04:23,360 --> 01:04:24,400 ANTIDEPRESSANT DON'T TYPICALLY 1504 01:04:24,400 --> 01:04:28,920 WORK IN AND NEUROMRAFTINS LIKE 1505 01:04:28,920 --> 01:04:31,360 KETAMINE GO IN AND RUN A SWIM 1506 01:04:31,360 --> 01:04:33,320 TEST DAY 1 PROVIDING A LITTLE 1507 01:04:33,320 --> 01:04:35,280 STRESS TO ANIMALS MAKING SURE 1508 01:04:35,280 --> 01:04:37,920 ALSO THAT ALL GROUPS HAVE EQUAL 1509 01:04:37,920 --> 01:04:39,640 RESPONSES AND WE THEN GIVE A 1510 01:04:39,640 --> 01:04:44,560 SINGLE DOSE OF 5MEODMT AND DO A 1511 01:04:44,560 --> 01:04:47,400 BEHAVIORAL MEASURE TO MAKE SURE 1512 01:04:47,400 --> 01:04:49,000 THAT ANIMALS GOT APPROPRIATE 1513 01:04:49,000 --> 01:04:51,760 DOSE AND 24 HOURS LATER AFTER 1514 01:04:51,760 --> 01:04:54,040 DRUG IS CLEARED FROM SYSTEM WE 1515 01:04:54,040 --> 01:04:56,240 LOOK FOR ANTIDEPRESSANT EFFECTS 1516 01:04:56,240 --> 01:05:00,120 AND SEE 5MDOT ON ITS OWN YOU CAN 1517 01:05:00,120 --> 01:05:02,680 SEE A ROBUST ANTIDEPRESSANT 1518 01:05:02,680 --> 01:05:05,000 RESPONSE AND IF YOU PRETREAT 1519 01:05:05,000 --> 01:05:09,320 ANIMALS WITH ANTAGONIST OF 1520 01:05:09,320 --> 01:05:11,720 5HT2AR RECEPTOR YOU SEE THIS IS 1521 01:05:11,720 --> 01:05:13,800 COMPLETELY BLOCKED AND IN 1522 01:05:13,800 --> 01:05:15,360 ADDITION LOOKING TO SWIM TEST 1523 01:05:15,360 --> 01:05:17,680 YOU LOOK AT MEASURE OF 1524 01:05:17,680 --> 01:05:19,800 ANADON'TIA AND ANIMALS LIKE 1525 01:05:19,800 --> 01:05:22,000 MYSELF WILL PREFER A SUGARLY 1526 01:05:22,000 --> 01:05:24,040 DRINK OVER PLAIN OLD WATER AND 1527 01:05:24,040 --> 01:05:26,240 GIVE OPTION OF DRINKING A BOTTLE 1528 01:05:26,240 --> 01:05:29,480 OF WATER THAT CONTAINS SUCROSE 1529 01:05:29,480 --> 01:05:32,400 THEY WILL PREFER SUCROSE AND 1530 01:05:32,400 --> 01:05:33,320 MEASURE THIS IN SUCROSE 1531 01:05:33,320 --> 01:05:35,360 PREFERENCE TEST AND HERE WE ARE 1532 01:05:35,360 --> 01:05:38,680 SHOWING AT BASELINE WILD TYPE 1533 01:05:38,680 --> 01:05:43,320 AND 5HT2A KNOCKOUT ANIMALS HAVE 1534 01:05:43,320 --> 01:05:45,920 ROBUST PRECHS FOR SOLUTION AND 1535 01:05:45,920 --> 01:05:48,360 PRODUCE THIS LIKE PHENOTYPE 1536 01:05:48,360 --> 01:05:51,480 DOING ANIMALS CHRONIC COURTI CO 1537 01:05:51,480 --> 01:05:53,040 STEROID AND CHRONIC STRESS 1538 01:05:53,040 --> 01:05:55,400 HORMONE AND AFTER 10 DAYS OF 1539 01:05:55,400 --> 01:05:59,320 THAT RUNNING ANOTHER SUCROSE 1540 01:05:59,320 --> 01:06:00,640 PREFERENCE TEST AND SEE WILD 1541 01:06:00,640 --> 01:06:02,720 TYPE AND KNOCKOUT HAVE REDUCTION 1542 01:06:02,720 --> 01:06:04,440 IN PREVENS FOR SUCROSE SUGGEST 1543 01:06:04,440 --> 01:06:08,000 THEY HAVE ANHEADONIA AND SINGLE 1544 01:06:08,000 --> 01:06:09,480 ADMINISTRATION OF SIGNO SIEL 1545 01:06:09,480 --> 01:06:12,360 ABIN COME BACK 24 HOURS LATER 1546 01:06:12,360 --> 01:06:14,720 AND DO ANOTHER TEST YOU SEE IT 1547 01:06:14,720 --> 01:06:17,040 IN WILD TYPE ANIMALS RESCUES 1548 01:06:17,040 --> 01:06:19,680 DEFICIT AND DOES NOTHING IN 1549 01:06:19,680 --> 01:06:21,680 5HT2A KNOCKOUT ANIMALS THAT 1550 01:06:21,680 --> 01:06:24,880 SUGGESTED TO US THAT 5H2TA 1551 01:06:24,880 --> 01:06:27,400 RECEPTOR IS CRITICAL FOR 1552 01:06:27,400 --> 01:06:29,440 PSYCHEDELIC INDUCED STRUCTURAL 1553 01:06:29,440 --> 01:06:30,840 NEUROPLASTICITY IN THE CORTEX 1554 01:06:30,840 --> 01:06:35,000 AND IS RESPONSIBLE FOR SOME 1555 01:06:35,000 --> 01:06:36,240 ANTIDEPRESSANT-LIKE BEHAVIORAL 1556 01:06:36,240 --> 01:06:38,240 EFFECTS AND NOW AT THIS POINT WE 1557 01:06:38,240 --> 01:06:40,400 HAVE ONE RESULT THAT REALLY LEFT 1558 01:06:40,400 --> 01:06:41,720 US SCRATCHING OUR HEAD THAT WAS 1559 01:06:41,720 --> 01:06:44,480 FACT THAT THIS MOLECULE HERE ON 1560 01:06:44,480 --> 01:06:51,360 THE LEFT SEROTONIN COULD NOT 1561 01:06:51,360 --> 01:06:53,520 PRODUCE PSYCHEDELICLIKE EFFECTS 1562 01:06:53,520 --> 01:06:56,360 ON STRUCTURAL NEURAL PLASTICITY 1563 01:06:56,360 --> 01:06:58,760 AND BOTHERED US SPENDING LAST 1564 01:06:58,760 --> 01:07:01,800 FEW SLIDES SAYING THAT SEROTONIN 1565 01:07:01,800 --> 01:07:04,200 RECEPTOR IS CRITICAL FOR 1566 01:07:04,200 --> 01:07:05,880 PSYCHEDELIC BASED 1567 01:07:05,880 --> 01:07:07,080 NEUROPLASTICITY AND DIDN'T 1568 01:07:07,080 --> 01:07:08,040 UNDERSTAND IT UNTIL WE SAW A 1569 01:07:08,040 --> 01:07:09,840 STRUCTURE OF ACTIVITY 1570 01:07:09,840 --> 01:07:11,160 RELATIONSHIP STUDY AND FOUND 1571 01:07:11,160 --> 01:07:14,880 THAT IF WE STARTED TO METHYLATE 1572 01:07:14,880 --> 01:07:16,280 SEROTONIN TO PRODUCE COMPOUNDS 1573 01:07:16,280 --> 01:07:18,040 LIKE THIS OR PSYCHEDELIC 1574 01:07:18,040 --> 01:07:19,920 COMPOUNDS LIKE ONES ON RIGHT WE 1575 01:07:19,920 --> 01:07:22,840 SAW INCREASE IN THEIR ABILITY TO 1576 01:07:22,840 --> 01:07:27,120 PROMOTE GROWTH OF CORTICAL 1577 01:07:27,120 --> 01:07:31,680 NEURONS THAT LED US TO 1578 01:07:31,680 --> 01:07:34,680 HYPOTHESIS THAT SEROTONIN NOT 1579 01:07:34,680 --> 01:07:36,520 THAT IT CAN'T ACTIVATE TARGET WE 1580 01:07:36,520 --> 01:07:39,160 KNOW IT CAN. MAYBE IT CAN'T 1581 01:07:39,160 --> 01:07:41,280 ACTUALLY ACCESS THE TARGET AND 1582 01:07:41,280 --> 01:07:43,520 MAYBE TARGET OF G PROTEIN 1583 01:07:43,520 --> 01:07:46,480 COUPLED RECEPTOR NOT FOUND ON 1584 01:07:46,480 --> 01:07:49,040 CELL SURFACE LIKE MOST GCPCRS IS 1585 01:07:49,040 --> 01:07:51,360 ON INSIDE OF THE CELL AND THAT 1586 01:07:51,360 --> 01:07:55,360 VERY POLAR MOLECULES LIKE 1587 01:07:55,360 --> 01:07:57,560 SEROTONIN CAN'T SIMPLY CROSS 1588 01:07:57,560 --> 01:07:59,520 MEMBRANES TO ACCESS THAT TARGET 1589 01:07:59,520 --> 01:08:02,400 AND WE TRY TO CORRELATE EFFICACY 1590 01:08:02,400 --> 01:08:06,240 IN NEURAL PLASTICITY ASSAYS TO 1591 01:08:06,240 --> 01:08:08,800 ACTIVATION OF 5HT2A RECEPTOR AND 1592 01:08:08,800 --> 01:08:12,400 SAW NO CORRELATION AND IN FACT 1593 01:08:12,400 --> 01:08:14,720 WE IS A YOU A SLIGHT 1594 01:08:14,720 --> 01:08:16,880 ANTI-CELATION AND THEN WHEN WE 1595 01:08:16,880 --> 01:08:19,280 JUST TRIED TO CORRELATE LIPO 1596 01:08:19,280 --> 01:08:21,840 PHALLUSTY OF THE DRUG AND HOW 1597 01:08:21,840 --> 01:08:23,800 GREASY IT IS WE SAW A NICE 1598 01:08:23,800 --> 01:08:26,560 CORRELATION AND VERY POLAR DRUGS 1599 01:08:26,560 --> 01:08:29,320 THAT CAN'T CROSS CELL MEMBRANES 1600 01:08:29,320 --> 01:08:33,440 LIKE SEROTONIN ARE NOT GOOD AT 1601 01:08:33,440 --> 01:08:36,360 PROMOTING COURTI CO GROWTH AND 1602 01:08:36,360 --> 01:08:39,720 THESE ARE VERY GOOD AT PROMOTING 1603 01:08:39,720 --> 01:08:41,200 CORTICAL NEURON GROWTH AND NEXT 1604 01:08:41,200 --> 01:08:43,880 WE WANTED LOOK AND SEE WHERE 1605 01:08:43,880 --> 01:08:45,200 RECEPTORS ARE LOCALIZED AND FOR 1606 01:08:45,200 --> 01:08:50,640 THESE STUDIES WE EXPRESSED 2 1607 01:08:50,640 --> 01:08:57,320 DIFFERENT GCPRS IN AN EXCEL LINE 1608 01:08:57,320 --> 01:09:01,920 AND CONTROL SHOWING CFP GOES 1609 01:09:01,920 --> 01:09:03,120 EVERYWHERE IN THE CELL AND THEY 1610 01:09:03,120 --> 01:09:07,360 ARE PRIMARILY LOCALIZED TO THE 1611 01:09:07,360 --> 01:09:12,360 CELL MEMBRANE AND WHITE LINES 1612 01:09:12,360 --> 01:09:15,400 HERE ARE A MARKER FOR PLASMA 1613 01:09:15,400 --> 01:09:17,360 MEMBRANE AND WHAT YOU WOULD 1614 01:09:17,360 --> 01:09:20,920 EXPECT FOR GCPR AND LOOKING IN 1615 01:09:20,920 --> 01:09:23,920 NEURONS WE SEE SOMETHING 1616 01:09:23,920 --> 01:09:25,680 DIFFERENT AND -- THIS IS 1617 01:09:25,680 --> 01:09:29,160 PRIMARILY LOCALIZED INSIDE OF 1618 01:09:29,160 --> 01:09:30,880 THE CEMAND THIS IS STILL VISIBLE 1619 01:09:30,880 --> 01:09:33,200 ON THE CELL SURFACE AND WE WERE 1620 01:09:33,200 --> 01:09:34,400 NOT THE FIRST TO DISCOVER THIS 1621 01:09:34,400 --> 01:09:37,200 AND MANY OTHER GROUPS HAVE FOUND 1622 01:09:37,200 --> 01:09:40,360 THAT IN CORTICAL NEURONS 1623 01:09:40,360 --> 01:09:42,000 SEROTONIN A RECEPTORS SEEMS TO 1624 01:09:42,000 --> 01:09:44,520 LIVE ON INSIDE OF THE CELL AND 1625 01:09:44,520 --> 01:09:46,000 NO ONE UNDERSTOOD WHAT 1626 01:09:46,000 --> 01:09:49,400 FUNCTIONAL RELEVANCE OF THIS 1627 01:09:49,400 --> 01:09:53,040 LOCALIZATION WAS. 1628 01:09:53,040 --> 01:09:57,480 SO, AT THIS POINT WE -- WE 1629 01:09:57,480 --> 01:09:59,600 ASSUMED THAT IF SEROTONIN COULD 1630 01:09:59,600 --> 01:10:01,440 ACCESS TARGET ON INSIDE OF THE 1631 01:10:01,440 --> 01:10:05,280 CELL, IT SHOULD BE ABLE TO 1632 01:10:05,280 --> 01:10:07,520 PROMOTE PSYCHEDELICLIKE EFFECTS 1633 01:10:07,520 --> 01:10:09,120 ON NEURAL PLASTICITY AND TO GET 1634 01:10:09,120 --> 01:10:12,760 IT ON INSIDE OF THE CELL WE -- A 1635 01:10:12,760 --> 01:10:15,960 SPARSELY TRANCE FEKTED AND A 1636 01:10:15,960 --> 01:10:17,680 TRANSPORTER FOR SEROTONIN THAT 1637 01:10:17,680 --> 01:10:20,040 IS A SEROTONIN TRANSPORTER THAT 1638 01:10:20,040 --> 01:10:22,760 IS A COUPLE NEURONS IN SAME DISH 1639 01:10:22,760 --> 01:10:26,160 SIDE BY SIDE AND ONE NEURON HAS 1640 01:10:26,160 --> 01:10:28,600 A TRANSPORTER TO IMPORT 1641 01:10:28,600 --> 01:10:30,800 SEROTONIN AND OTHER NEURON LACKS 1642 01:10:30,800 --> 01:10:32,240 TRANSPORTER AND CANNOT AND ON 1643 01:10:32,240 --> 01:10:35,080 RIGHT SIDE HERE NEURON ON RIGHT 1644 01:10:35,080 --> 01:10:38,200 HAS TRANSPORTER AND ONE ON LEFT 1645 01:10:38,200 --> 01:10:42,320 DOES NOT WE FIND COMPARING 1646 01:10:42,320 --> 01:10:43,840 GENOTYPES VEHICLE DOES NOTHING 1647 01:10:43,840 --> 01:10:46,840 AND COMPOUND THAT CAN CROSS 1648 01:10:46,840 --> 01:10:48,840 MEMBRANE PROMOTES CORTICAL 1649 01:10:48,840 --> 01:10:51,160 NEURON GROWTH IN BOTH GENOTYPES 1650 01:10:51,160 --> 01:10:56,080 AND SEROTONIN CAN ONLY PROMOTE 1651 01:10:56,080 --> 01:10:57,720 NEURON GROWTH IN NEURONS THAT 1652 01:10:57,720 --> 01:11:01,680 CAN IMPORT MONOAMEAN. 1653 01:11:01,680 --> 01:11:04,520 WE SAW SOMETHING SIMILAR LOOKING 1654 01:11:04,520 --> 01:11:07,360 AT DENDRITIC SPINE DENSITY AND 1655 01:11:07,360 --> 01:11:10,680 DMT PROMOTES GROWTH IN BOTH 1656 01:11:10,680 --> 01:11:12,160 GENOTYPES AND SEROTONIN PROMOTES 1657 01:11:12,160 --> 01:11:15,680 GROWTH IN NEURONS IMPORTING 1658 01:11:15,680 --> 01:11:16,520 SEROTONIN. 1659 01:11:16,520 --> 01:11:18,960 NOW, TO DEMONSTRATE THIS IN 1660 01:11:18,960 --> 01:11:23,360 VIVO, WE RELIED ON EXPRESSING 1661 01:11:23,360 --> 01:11:25,960 SEROTONIN TRANSPORTER IN 1662 01:11:25,960 --> 01:11:27,960 PREFRONTAL CORTEX USING VIRUS 1663 01:11:27,960 --> 01:11:30,400 AND THREE WEEKS TO ALLOW 1664 01:11:30,400 --> 01:11:31,760 EXPRESSION OF TRANSPORTER AND 1665 01:11:31,760 --> 01:11:33,640 GAVE A DOSE OF THIS COMPOUND 1666 01:11:33,640 --> 01:11:37,640 HERE CALLED PARACOLORA 1667 01:11:37,640 --> 01:11:39,360 AMPHETAMINE THAT CAUSES RELEASE 1668 01:11:39,360 --> 01:11:42,360 OF SEROTONIN AND COMING BACK 24 1669 01:11:42,360 --> 01:11:45,480 HOURS LATER AND MEASURE SPINE 1670 01:11:45,480 --> 01:11:49,960 DENSITY WE FIND THAT NEURONS 1671 01:11:49,960 --> 01:11:52,760 WITH TRANSPORTER FOR SEROTONIN 1672 01:11:52,760 --> 01:11:55,280 WE SEE GROWTH EFFECTS AND 1673 01:11:55,280 --> 01:11:56,760 NEURONS LACKING TRANSPORTER WE 1674 01:11:56,760 --> 01:11:59,720 SEE NO EFFECT OF RELEASED 1675 01:11:59,720 --> 01:12:02,280 SEROTONIN AND IF STRUCTURAL 1676 01:12:02,280 --> 01:12:04,200 PLASTICITY IS IMPORTANT FOR 1677 01:12:04,200 --> 01:12:06,360 BEHAVIORAL EFFECT WE SEE 1678 01:12:06,360 --> 01:12:07,240 ANTIDEPRESSANT RESPONSE AS WELL 1679 01:12:07,240 --> 01:12:09,000 AND RAN A SIMILAR TYPE OF 1680 01:12:09,000 --> 01:12:11,360 EXPERIENCE FOR THIS ONE AFTER WE 1681 01:12:11,360 --> 01:12:14,080 EXPRESSED TRANSPORTER AND DO 1682 01:12:14,080 --> 01:12:16,280 NOVELTY INDUCE THE LOCOMOTION 1683 01:12:16,280 --> 01:12:17,280 ASSAY TO SHOW NO DIFFERENCE 1684 01:12:17,280 --> 01:12:19,080 BETWEEN TWO GENOTYPES AND THERE 1685 01:12:19,080 --> 01:12:21,280 IS NOT AND RUN PRETEST FOR THIS 1686 01:12:21,280 --> 01:12:23,120 TEST AND AGAIN SHOWING NO 1687 01:12:23,120 --> 01:12:25,040 DIFFERENCE BETWEEN TWO GENOTYPES 1688 01:12:25,040 --> 01:12:27,880 AND GIVE A SINGLE ADMINISTRATION 1689 01:12:27,880 --> 01:12:30,360 OF SEROTONIN RELEASING COMPOUND 1690 01:12:30,360 --> 01:12:33,200 AND RELEASING ANTIDEPRESSANTS 24 1691 01:12:33,200 --> 01:12:35,360 HOURS LATER IN THE SWIM TEST AND 1692 01:12:35,360 --> 01:12:37,400 FIND THAT ONLY NEURONS AND IN 1693 01:12:37,400 --> 01:12:42,040 ANIMALS THAT HAVE NEURONS IN PFC 1694 01:12:42,040 --> 01:12:45,640 EXPRESSING TRANSPORTER, THOSE 1695 01:12:45,640 --> 01:12:48,000 ANIMALS EXHIBIT ANTIDEPRESSANT 1696 01:12:48,000 --> 01:12:51,360 EFFECTS IN PARACHLOROFEEN AND 1697 01:12:51,360 --> 01:12:58,120 OTHER ANIMALS DO NOT. 1698 01:12:58,120 --> 01:13:02,520 AT THIS POINT WE FEEL CONFIDENT 1699 01:13:02,520 --> 01:13:05,760 THAT 5H2A RECEPTOR IS 1700 01:13:05,760 --> 01:13:09,000 RESPONSIBLE FOR HALLUCINOGENIC 1701 01:13:09,000 --> 01:13:12,880 AND ELASTICITY PROMOTING 1702 01:13:12,880 --> 01:13:15,120 PSYCHEDELIC AS AND RECREPTOR IS 1703 01:13:15,120 --> 01:13:17,080 KNOWN TO EXHIBIT FUNCTIONAL 1704 01:13:17,080 --> 01:13:18,920 SELECTIVITY AND TWO AGONISTS 1705 01:13:18,920 --> 01:13:22,280 COMBINED TO ECREPTOR CAUSING TWO 1706 01:13:22,280 --> 01:13:24,800 DIFFERENT DOWNSTREAM PATHWAYS 1707 01:13:24,800 --> 01:13:29,760 AND NO KNOWN AGONISTS OF 52HC 1708 01:13:29,760 --> 01:13:31,680 RECEPTORS THAT ARE 1709 01:13:31,680 --> 01:13:32,360 NONHALLUCINOGENIC AND WANT TO 1710 01:13:32,360 --> 01:13:34,080 ASK QUESTION WHETHER ORE NOT IT 1711 01:13:34,080 --> 01:13:36,840 IS POSSIBLE TO SEPARATE 1712 01:13:36,840 --> 01:13:38,800 HALLUCINOGENIC EFFECTS FROM 1713 01:13:38,800 --> 01:13:42,000 EFFECTS OF NEUROPLASTICITY AND 1714 01:13:42,000 --> 01:13:43,480 BENEFICIAL BEHAVIORAL EFFECTS 1715 01:13:43,480 --> 01:13:46,280 AND I'M HOPEFUL FOR THE DAY WHEN 1716 01:13:46,280 --> 01:13:48,160 PSYCHEDELICS WILL RECEIVE FDA 1717 01:13:48,160 --> 01:13:49,280 APPROVAL FOR VARIOUS CONDITIONS 1718 01:13:49,280 --> 01:13:52,000 AND THINK IT IS IMPORTANT TO 1719 01:13:52,000 --> 01:13:53,200 REALIZE THAT IN ORDER FOR DRUGS 1720 01:13:53,200 --> 01:13:55,440 TO BE SAFELY ADMINSTERED THEY 1721 01:13:55,440 --> 01:13:57,440 HAVE TO BE GIVEN UNDER CARE OF 1722 01:13:57,440 --> 01:14:00,360 HEALTH CARE PROFESSIONALS THAT 1723 01:14:00,360 --> 01:14:02,800 DRASTICALLY INCREASE COSTS AND 1724 01:14:02,800 --> 01:14:04,320 COMPLEXITY OF TREATMENT AND WHEN 1725 01:14:04,320 --> 01:14:07,000 YOU CONSIDER FACT THAT 1 IN 5 1726 01:14:07,000 --> 01:14:10,640 PEOPLE WILL SUFFER FROM 1727 01:14:10,640 --> 01:14:11,200 NEUROPSYCHIATRIC DISORDER 1728 01:14:11,200 --> 01:14:14,040 SOMETIME IN THEIR LIFETIME YOU 1729 01:14:14,040 --> 01:14:16,040 REALIZE THAT PSYCHEDELIC 1730 01:14:16,040 --> 01:14:17,880 PSYCHOTHERAPY AND MIGHT HELP 1731 01:14:17,880 --> 01:14:21,560 SOME PATIENTS AND HOPEFUL IT 1732 01:14:21,560 --> 01:14:23,360 WILL IT WON'T ADDRESS MASSIVE 1733 01:14:23,360 --> 01:14:24,440 ISSUES WE HAVE WITH MENTAL 1734 01:14:24,440 --> 01:14:30,360 HEALTH CARE WE HAVE TODAY BY 1735 01:14:30,360 --> 01:14:32,720 PRODUCING NONHALLUCINOGENIC 1736 01:14:32,720 --> 01:14:35,240 VARIANTS WE ARE HOPING TO REACH 1737 01:14:35,240 --> 01:14:37,920 A LARGER PATIENT POPULATION AND 1738 01:14:37,920 --> 01:14:45,240 TO DEVELOP NONHALLUCINOGENIC 1739 01:14:45,240 --> 01:14:47,880 PSYCHOMRAFTO GENERALS -- WE TURN 1740 01:14:47,880 --> 01:14:50,600 TO RODENT BEHAVIOR ON LEFT 1741 01:14:50,600 --> 01:14:52,080 CALLED THIS HEAD-TWITCH RESPONSE 1742 01:14:52,080 --> 01:14:54,680 ASSAY. IT IS A RAPID ROTATIONAL 1743 01:14:54,680 --> 01:14:57,960 MOVEMENT OF THE HEAD 1744 01:14:57,960 --> 01:14:59,760 CHARACTERISTIC OF PSYCHOCONTINUE 1745 01:14:59,760 --> 01:15:01,560 URGIC PSYCHEDELICS AND BEAUTIFUL 1746 01:15:01,560 --> 01:15:07,360 WORK FROM CO-WORKERS HAS SHOWN 1747 01:15:07,360 --> 01:15:09,400 ACROSS 30 STRUCTURALLY 1748 01:15:09,400 --> 01:15:10,720 PSYCHEDELIC COMPOUNDS THERE IS 1749 01:15:10,720 --> 01:15:13,560 CORRELATION BETWEEN POTENCY 1750 01:15:13,560 --> 01:15:17,160 TOWARDS RESPONSE ASSAY AND NOW 1751 01:15:17,160 --> 01:15:19,320 THIS RESPONSE IS HIGHLY 1752 01:15:19,320 --> 01:15:21,520 PREDICTIVE NOT AMENABLE TO DRUG 1753 01:15:21,520 --> 01:15:25,200 DISCOVERY BECAUSE IT IS NOT HIGH 1754 01:15:25,200 --> 01:15:27,040 THROUGH PUT ENOUGH AND TACKLING 1755 01:15:27,040 --> 01:15:30,360 THIS PROBLEM DEVELOPING IN VITRO 1756 01:15:30,360 --> 01:15:33,480 ASSAY FOR HALLUCINOGENIC 1757 01:15:33,480 --> 01:15:36,120 POTENTIAL WE DID SOMETHING 1758 01:15:36,120 --> 01:15:38,880 SIMPLE. WE LOPPED OFF 1759 01:15:38,880 --> 01:15:43,120 INTRACELLULAR LOOP OF GCPR AND 1760 01:15:43,120 --> 01:15:46,680 FUSE THE ON GREEN FLUORESCENT 1761 01:15:46,680 --> 01:15:48,440 PROTEIN THESE WORK CUT IN BETA 1762 01:15:48,440 --> 01:15:51,360 BARREL THAT IS OPEN AND ALLOWS 1763 01:15:51,360 --> 01:15:56,400 WATER TO GET IN QUENCHING FOR 1764 01:15:56,400 --> 01:15:58,720 ESSENCE OF FLOR OE FLOR AND WHEN 1765 01:15:58,720 --> 01:16:02,000 LYINGAND BINDS TO RECEPTOR 1766 01:16:02,000 --> 01:16:04,120 CONFIRMATIONAL CHANGE CLOSING 1767 01:16:04,120 --> 01:16:05,840 BETA BARREL PROTECTING IT 1768 01:16:05,840 --> 01:16:07,760 ALLOWING IT TO TURN ON AND 1769 01:16:07,760 --> 01:16:09,880 TREATING WITH AGONIST LIKE CER 1770 01:16:09,880 --> 01:16:15,360 TONIN YOU SEE A NICE 1771 01:16:15,360 --> 01:16:16,400 CONCENTRATION DEPENDENCE 1772 01:16:16,400 --> 01:16:18,760 INCREASE IN -- YOU SEE NO CHANGE 1773 01:16:18,760 --> 01:16:23,200 OR SLIGHT DECREASE IN 1774 01:16:23,200 --> 01:16:24,680 FLUORESCENCE INTENSITY AND GOT 1775 01:16:24,680 --> 01:16:26,840 EXCITED WHEN FINDING THIS 1776 01:16:26,840 --> 01:16:30,400 BIOASSAY CORRELATED WITH HUMAN 1777 01:16:30,400 --> 01:16:32,560 HALLUCINOGENIC POTENCY AND 1778 01:16:32,560 --> 01:16:34,000 CALLED THIS BIOCENSOR 1779 01:16:34,000 --> 01:16:35,160 [INDISCERNIBLE] AND I WAS MOST 1780 01:16:35,160 --> 01:16:40,920 EXCITED WHEN SEEING THESE DATA 1781 01:16:40,920 --> 01:16:42,960 WE SAW CYCLIC DIFFERENTIATED 1782 01:16:42,960 --> 01:16:46,800 BETWEEN TWO CLOSELY RELATED 1783 01:16:46,800 --> 01:16:48,960 STRUCTURAL ANALOG AND COMPOUNDS 1784 01:16:48,960 --> 01:16:55,000 LSD AND IN PURPLE SHOWING 1785 01:16:55,000 --> 01:16:55,640 NONHALLUCINOGENIC COMPOUNDS 1786 01:16:55,640 --> 01:16:58,160 [INDISCERNIBLE] AND 6MDMT AND 1787 01:16:58,160 --> 01:17:00,400 YOU FLIP THIS AND INSERT THAT 1788 01:17:00,400 --> 01:17:04,840 NITROGEN AND 6MDOMT COMPARED TO 1789 01:17:04,840 --> 01:17:07,160 5MEO YOU MOVE THIS ONE CARBON 1790 01:17:07,160 --> 01:17:10,600 OVER AND THAT IS IT AND 1791 01:17:10,600 --> 01:17:11,360 HALLUCINOGENIC COMPOUNDS TURN 1792 01:17:11,360 --> 01:17:14,600 THIS OVER NICELY AND 1793 01:17:14,600 --> 01:17:15,200 NONHALLUCINOGENIC COMPOUNDS 1794 01:17:15,200 --> 01:17:17,560 DON'T AND MIGHT ASK YOURSELF IF 1795 01:17:17,560 --> 01:17:18,400 THESE COMPOUNDS SIMPLY DON'T 1796 01:17:18,400 --> 01:17:20,360 BIND TO CENSOR AND WE CAN 1797 01:17:20,360 --> 01:17:22,600 ADDRESS THAT QUESTION RUNNING 1798 01:17:22,600 --> 01:17:24,280 ASSAY IN ANTAGONIST MODE AND CAN 1799 01:17:24,280 --> 01:17:26,840 GIVE A BIT OF AGONIST TO TURN ON 1800 01:17:26,840 --> 01:17:29,320 CENSOR AND TIGHT TRAIT IN 1801 01:17:29,320 --> 01:17:33,040 INCREASING QUANTITIES OF 1802 01:17:33,040 --> 01:17:35,400 NONHALLUCINOGENIC LYINGAND AND 1803 01:17:35,400 --> 01:17:40,720 WATCH FLUORESCENCE INCREASE ON 1804 01:17:40,720 --> 01:17:43,480 THE RIGHT AND COMPOUNDS ON 1805 01:17:43,480 --> 01:17:46,320 AGONIST MODE ON X AXIS AND 1806 01:17:46,320 --> 01:17:48,880 ANTAGONIST MODE ON Y AXIS AND 1807 01:17:48,880 --> 01:17:50,200 POINTING EYE TO BLACK DOT THERE 1808 01:17:50,200 --> 01:17:55,360 THAT IS VEHICLE CONTROL AND 1809 01:17:55,360 --> 01:17:58,400 COMPOUNDS INCREASING CYCLIC 1810 01:17:58,400 --> 01:17:59,360 FLUORESCENCE FROM ONE STANDARD 1811 01:17:59,360 --> 01:18:01,480 DEVIATION FROM THE VEHICLE THESE 1812 01:18:01,480 --> 01:18:04,640 ARE COMPOUNDS IN RED AND KNOWN 1813 01:18:04,640 --> 01:18:06,040 HALLUCINOGENIC COMPOUNDS THAT -- 1814 01:18:06,040 --> 01:18:07,240 MORE THAN ONE STANDARD DEVIATION 1815 01:18:07,240 --> 01:18:09,360 FROM THE VEHICLE CONTROL ARE 1816 01:18:09,360 --> 01:18:13,000 MOLECULES IN BLUE HERE AND ARE 1817 01:18:13,000 --> 01:18:16,400 NONHALLUCINOGENIC LIGANDS OF 1818 01:18:16,400 --> 01:18:19,240 52HC RECEPTOR AND COMBINING 1819 01:18:19,240 --> 01:18:22,280 ANTAGONIST MODE DATA PRODUCING 1820 01:18:22,280 --> 01:18:26,400 LYING YAPD SCORES HERE ON LEFT 1821 01:18:26,400 --> 01:18:29,520 AND COMPOUNDS WITH BLACK 1822 01:18:29,520 --> 01:18:32,040 LYINGAND SCORE ARE MOLECULES 1823 01:18:32,040 --> 01:18:33,360 CLUSTERING AROUND CONTROL NOT 1824 01:18:33,360 --> 01:18:36,120 PREDICTED TO BIOCENSOR AND 1825 01:18:36,120 --> 01:18:38,440 COMPOUNDS IN BLUE ARE LIGANDS 1826 01:18:38,440 --> 01:18:40,560 PREDICTED TO BE 1827 01:18:40,560 --> 01:18:41,640 NONHALLUCINOGENIC YOU SEE 1828 01:18:41,640 --> 01:18:42,800 INTERESTING COMPOUNDS IN HERE 1829 01:18:42,800 --> 01:18:44,960 AND YOU SEE CLASSIC ANTAGONISTS 1830 01:18:44,960 --> 01:18:47,760 LIKE MDL AND [INDISCERNIBLE] AND 1831 01:18:47,760 --> 01:18:52,240 YOU SEE ANTIPSYCHOTICS LIKE HALO 1832 01:18:52,240 --> 01:18:54,280 PERIDOLL AND SEE AGONISTS LIKE 1833 01:18:54,280 --> 01:18:56,000 LISTERIDE AND WILL TELL YOU 1834 01:18:56,000 --> 01:18:57,560 ABOUT INTERESTING COMPOUNDS NOW 1835 01:18:57,560 --> 01:19:00,120 AND STARTING WITH THIS ONE 5 1836 01:19:00,120 --> 01:19:02,360 BROMO-DMT AND WE ARE INTERESTED 1837 01:19:02,360 --> 01:19:05,120 IN THIS BECAUSE WE MADE FIVE 1838 01:19:05,120 --> 01:19:07,360 HALO GENERATED SERIES GOING FROM 1839 01:19:07,360 --> 01:19:09,080 FLOR OE TO CHLORO TO BROEM OE 1840 01:19:09,080 --> 01:19:12,360 AND DIFFERENCE HERE IS YOU ARE 1841 01:19:12,360 --> 01:19:14,840 INCREASING VANEDER WALL RADII OF 1842 01:19:14,840 --> 01:19:18,400 THAT ATOM AND PREDICTING 1843 01:19:18,400 --> 01:19:19,400 FLUOROAND CHLOROCOMPOUND SHOULD 1844 01:19:19,400 --> 01:19:22,040 BE HALLUCINOGENIC AND THIS 1845 01:19:22,040 --> 01:19:23,840 SHOULD BE NONHALLUCINOGENIC AND 1846 01:19:23,840 --> 01:19:27,360 SAW TO RESPONSE OF ASSAY AND 1847 01:19:27,360 --> 01:19:30,360 THIS TWITCHES AT ALL DOSES AND 1848 01:19:30,360 --> 01:19:32,080 NICE DEPENDENT INCREASE AND THIS 1849 01:19:32,080 --> 01:19:35,280 COMPOUND DID NOT PRODUCE HEAD 1850 01:19:35,280 --> 01:19:37,280 TWITCHES AT ANY DOSE. WE USE 1851 01:19:37,280 --> 01:19:39,640 THE PSYCH LIED TO IDENTIFY A 1852 01:19:39,640 --> 01:19:44,280 BUNCH OF NONHALLUCINOGENIC 1853 01:19:44,280 --> 01:19:48,400 MRAFTO JENS AND WILL TURN YOU TO 1854 01:19:48,400 --> 01:19:56,560 ONE CALLED -- WE SAW NO HEAD 1855 01:19:56,560 --> 01:20:00,680 TWITCHES UP TO MASSIVE 100 MEG 1856 01:20:00,680 --> 01:20:03,280 DOSE AND THIS DOSE OF AAZ IS 1857 01:20:03,280 --> 01:20:09,120 AROUND 10MIGS PER KEG AND IS 1858 01:20:09,120 --> 01:20:12,120 REMASHABLE IT PRODUCED 1859 01:20:12,120 --> 01:20:14,960 PSYCHOGENIC EFFECTS STRUCTURE OF 1860 01:20:14,960 --> 01:20:15,880 NEUROPLASTICITY AND PRODUCES 1861 01:20:15,880 --> 01:20:19,360 RAPID AND ENDURING EFFECTS ON 1862 01:20:19,360 --> 01:20:21,640 BEHAVIORS RELEVANT TO DEPRESSION 1863 01:20:21,640 --> 01:20:23,800 AND VERSION OF FOUR SWIM TESTS 1864 01:20:23,800 --> 01:20:25,760 SHOWING AFTER 30 MINUTES 1865 01:20:25,760 --> 01:20:29,240 KETAMINE AND AAZ PRODUCE RAPID 1866 01:20:29,240 --> 01:20:31,120 RESPONSE THAT EFFECT IS MAINTAIN 1867 01:20:31,120 --> 01:20:32,920 THE FOR A WEEK FOR BOTH OF THESE 1868 01:20:32,920 --> 01:20:35,360 COMPOUNDS AND LOOKING AT THAT 1869 01:20:35,360 --> 01:20:37,520 MEASURE OF ANODON'TIA WE TALKED 1870 01:20:37,520 --> 01:20:39,360 ABOUT EARLIER AND SUCROSE 1871 01:20:39,360 --> 01:20:41,200 PREFERENCE WE ARE USING A 1872 01:20:41,200 --> 01:20:44,000 GENETIC MODEL OF DEPRESSION 1873 01:20:44,000 --> 01:20:47,080 FOLLOWED BY BILL WECHLEL'S GROUP 1874 01:20:47,080 --> 01:20:49,800 AT DUKE AND WE KNOW IN HUMANS IF 1875 01:20:49,800 --> 01:20:53,440 YOU INHIBIT THIS YOU CAN INDUCE 1876 01:20:53,440 --> 01:20:55,160 PHENOTYPES AND THESE ANIMALS 1877 01:20:55,160 --> 01:20:57,160 HAVE BASE LINE DEPRESSIVE 1878 01:20:57,160 --> 01:21:00,240 PHENOTYPES AND ONE IS ANODON'TIA 1879 01:21:00,240 --> 01:21:03,160 AND IN WHITE ARE WILD TYPE 1880 01:21:03,160 --> 01:21:04,880 ANIMALS WITH NICE SUCROSE 1881 01:21:04,880 --> 01:21:08,400 PREFERENCE AND THESE 1882 01:21:08,400 --> 01:21:09,560 HETEROZYGOTE ANIMALS DON'T AND 1883 01:21:09,560 --> 01:21:14,240 SINGLE DOSE OF AAZ CAN RESCUE 1884 01:21:14,240 --> 01:21:15,640 ANHEADONIA RESPONSE AND EFFECT 1885 01:21:15,640 --> 01:21:17,240 LASTS FOR AT LEAST TWO WEEKS 1886 01:21:17,240 --> 01:21:21,800 BEFORE THE GENOTYPES START TO 1887 01:21:21,800 --> 01:21:22,720 DIVERGE. 1888 01:21:22,720 --> 01:21:24,080 WE HAVE DONE IT A NUMBER OF 1889 01:21:24,080 --> 01:21:27,000 TIMES AND WANT TO TELL YOU ABOUT 1890 01:21:27,000 --> 01:21:29,000 ONE COMPOUND ABOUT 1891 01:21:29,000 --> 01:21:30,120 NONHALLUCINOGENIC 1892 01:21:30,120 --> 01:21:31,200 [INDISCERNIBLE] AND YOU CAN SEE 1893 01:21:31,200 --> 01:21:33,080 SMALL STRUCTURAL CHANGES 1894 01:21:33,080 --> 01:21:35,080 REQUIRED TO TWEAK A PSYCHEDELIC 1895 01:21:35,080 --> 01:21:37,560 COMPOUND TO MAKE IT A SAFER AND 1896 01:21:37,560 --> 01:21:40,640 MORE SCALEABLE ALTERNATIVE AND 1897 01:21:40,640 --> 01:21:44,680 THIS IS POTENT HALLUCINOGEN 1898 01:21:44,680 --> 01:21:46,040 PRODUCING ROBUST HEAD TWITCH 1899 01:21:46,040 --> 01:21:48,200 RESPONSE AND CONFIRMATION ALLEY 1900 01:21:48,200 --> 01:21:49,920 RESTRICTING THIS GROUP TO 1901 01:21:49,920 --> 01:21:52,560 PRODUCE THIS MOLECULE YOU SEE 1902 01:21:52,560 --> 01:21:54,160 YOU REDUCE HEAD TWITCH RESPONSE 1903 01:21:54,160 --> 01:21:55,240 AND MOVING THIS ONE POSITION 1904 01:21:55,240 --> 01:21:58,520 OVER HERE YOU HAVE COMPLETELY 1905 01:21:58,520 --> 01:22:00,000 ELIMINATED THE HEAD TWITCH 1906 01:22:00,000 --> 01:22:02,600 RESPONSE AND IMPORTANTLY TCHLTD 1907 01:22:02,600 --> 01:22:05,480 BG IS A POTENT PSYCHOMRAFTO 1908 01:22:05,480 --> 01:22:08,120 GENERAL AND FOR THIS STUDY WE 1909 01:22:08,120 --> 01:22:13,200 RELIED ONL MICE WITH NEURONS IN 1910 01:22:13,200 --> 01:22:15,360 CORTEX PLACED WITH PROTEINS TO 1911 01:22:15,360 --> 01:22:17,160 VISUALIZE DENDRITES AND ON FIRST 1912 01:22:17,160 --> 01:22:19,720 DAY WE CAN REMOVE A PART OF THE 1913 01:22:19,720 --> 01:22:22,520 SKULL AND PUT IN A GLASS WINDOW 1914 01:22:22,520 --> 01:22:25,160 AND USE A TWO PHOTON MICROSCOPE 1915 01:22:25,160 --> 01:22:28,000 TO PEER INSIDE OF THE BRAIN AND 1916 01:22:28,000 --> 01:22:31,840 COUNT DENDRITIC SPINES ON A 1917 01:22:31,840 --> 01:22:34,600 BRANCH GIVING DOSE OF TBG GIVING 1918 01:22:34,600 --> 01:22:36,480 24 HOURS GIVING SECTION OF 1919 01:22:36,480 --> 01:22:38,160 DENDRITE ALLOWING TO QUANTIFY 1920 01:22:38,160 --> 01:22:41,960 NUMBER OF SPINES FORMED LIKE 1921 01:22:41,960 --> 01:22:43,800 THIS ONE IN BLUE AND NUMBER OF 1922 01:22:43,800 --> 01:22:48,440 SPINES ELIMINATED IN RED AND TBG 1923 01:22:48,440 --> 01:22:50,000 DOESN'T IMPACT [INDISCERNIBLE] 1924 01:22:50,000 --> 01:22:52,160 AND DOES PROMOTE SPINE FORMATION 1925 01:22:52,160 --> 01:22:54,920 AND DOES SO IN COMPARABLE EXTENT 1926 01:22:54,920 --> 01:22:58,160 TO HALLUCINOGENIC DRUG DOI AND 1927 01:22:58,160 --> 01:23:01,760 IF OUR HYPOTHESIS IS CORRECT 1928 01:23:01,760 --> 01:23:02,920 THAT STRUCTURAL PLASTICITY IN 1929 01:23:02,920 --> 01:23:05,400 THE CORTEX IS CRITICAL FOR 1930 01:23:05,400 --> 01:23:08,040 THERAPEUTIC EFFECTS ACROSS 1931 01:23:08,040 --> 01:23:09,280 INDICATIONS WE EXPECT TO SEE 1932 01:23:09,280 --> 01:23:11,440 BROAD EFFECTS OF TBG AND WHAT WE 1933 01:23:11,440 --> 01:23:15,240 SEE AND ANTIDEPRESSANT EFFECTS 1934 01:23:15,240 --> 01:23:17,600 IN SWIM TEST AND ANTI-ADDICTIVE 1935 01:23:17,600 --> 01:23:20,000 EFFECTS IN ASSAY RELEVANT TO 1936 01:23:20,000 --> 01:23:22,000 ALCOHOL USE DISORDER AND SEE 1937 01:23:22,000 --> 01:23:25,880 EVERY ANIMAL IN STUDY REDUCED 1938 01:23:25,880 --> 01:23:29,320 ALCOHOL CONSUMPTION AFTER 1939 01:23:29,320 --> 01:23:31,320 ADMINISTRATION OF TBG AND 1940 01:23:31,320 --> 01:23:35,680 EFFECTS OF BEHAVIOR RELEVANT USE 1941 01:23:35,680 --> 01:23:38,160 DISORDER AND DOESN'T MATTER WHEN 1942 01:23:38,160 --> 01:23:41,360 WE ADMINISTER TBG DURING EARLY 1943 01:23:41,360 --> 01:23:44,360 STAGES OF WITHDRAWAL AND 1944 01:23:44,360 --> 01:23:45,920 IMMEDIATELY PRIOR TO 1945 01:23:45,920 --> 01:23:47,440 REINSTATEMENT AND TIME POINTS 1946 01:23:47,440 --> 01:23:51,360 THAT TBG HAD LONG LASTING 1947 01:23:51,360 --> 01:23:52,760 PROTECTIVE EFFECT ON HER WIN 1948 01:23:52,760 --> 01:23:54,920 SEEKING BEHAVIOR AND LAST TO 1949 01:23:54,920 --> 01:24:00,280 MENTION IS TBG HAS POTENTIAL TO 1950 01:24:00,280 --> 01:24:02,720 HEAL DAMAGED NEURAL CIRCUITS AND 1951 01:24:02,720 --> 01:24:06,360 SHOWING YOU HERE CALCIUM IMAGING 1952 01:24:06,360 --> 01:24:07,360 FROM SOMATOSENSORY 1953 01:24:07,360 --> 01:24:09,480 [INDISCERNIBLE] FROM MICE THAT 1954 01:24:09,480 --> 01:24:12,360 ARE TACTILE CREATURES THAT 1955 01:24:12,360 --> 01:24:14,200 ENVIRONMENT FROM WHIS KERS AND 1956 01:24:14,200 --> 01:24:15,720 YOU SEE A NICE COORDINATED 1957 01:24:15,720 --> 01:24:18,240 RESPONSE IN SOMATOSENSORY CORTEX 1958 01:24:18,240 --> 01:24:22,240 AND YOU WILL NOTICE 1959 01:24:22,240 --> 01:24:24,400 UNPREDICTABLE MIELTD STRESS 1960 01:24:24,400 --> 01:24:26,040 COMPLETELY DISRESULTS THIS 1961 01:24:26,040 --> 01:24:27,280 COORDINATED RESPONSE AND SINGLE 1962 01:24:27,280 --> 01:24:30,840 DOSE OF TBG CAN RESCUE 1963 01:24:30,840 --> 01:24:31,600 COORDINATOR RESPONSE EVEN AFTER 1964 01:24:31,600 --> 01:24:34,360 DRUG HAS BEEN CLEARED FROM THE 1965 01:24:34,360 --> 01:24:35,840 SYSTEM AND TO SUMMARIZE WHAT I 1966 01:24:35,840 --> 01:24:38,120 TRIED TO TELL YOU ABOUT TODAY IN 1967 01:24:38,120 --> 01:24:41,520 HEALTHY BRAIN AND CORTEX NEURONS 1968 01:24:41,520 --> 01:24:44,080 HAVE LOTS OF DENDRITIC BRANCHES 1969 01:24:44,080 --> 01:24:45,960 AND DENDRITIC SPINES HELPING 1970 01:24:45,960 --> 01:24:48,080 COMMUNICATE WITH NEIGHBORS AND 1971 01:24:48,080 --> 01:24:51,360 IN MANY BRAIN DISORDERS IT THAT 1972 01:24:51,360 --> 01:24:53,400 ARE INCLUDING NEUROSTRESS 1973 01:24:53,400 --> 01:24:55,360 DISORDERS LIKE DEPRESSION YOU 1974 01:24:55,360 --> 01:24:58,640 SEE PHYSICAL ATROPHYING LOSS OF 1975 01:24:58,640 --> 01:25:00,800 NEURONS AND DEN DRIDIC SPINES 1976 01:25:00,800 --> 01:25:04,200 AND MRAFTO JENS LIKE 1977 01:25:04,200 --> 01:25:06,240 PSYCHO-DELLICS AND 1978 01:25:06,240 --> 01:25:07,760 NONHALLUCINOGENIC VARIANCE ARE 1979 01:25:07,760 --> 01:25:10,960 GOOD AT PROMOTING GROWTH OF 1980 01:25:10,960 --> 01:25:12,560 CORTICAL NEURONS AND SUMMARIZING 1981 01:25:12,560 --> 01:25:16,680 I TOLD YOU TODAY THAT 1982 01:25:16,680 --> 01:25:19,920 PSYCHO-DELLICS -- ACTIVATION OF 1983 01:25:19,920 --> 01:25:22,400 INTRACELLULAR POPULATION OF 5H2A 1984 01:25:22,400 --> 01:25:24,400 RECEPTORS AND THAT IS A 1985 01:25:24,400 --> 01:25:27,360 BIOCENSOR THAT IS GOOD AT 1986 01:25:27,360 --> 01:25:28,800 PREDICTING HALLUCINOGENIC 1987 01:25:28,800 --> 01:25:33,960 [INDISCERNIBLE] IN VITRO THAT 1988 01:25:33,960 --> 01:25:35,360 ARE POTENTIALLY SAFER 1989 01:25:35,360 --> 01:25:38,560 PSYCHOMRAFTO JENS AND THANKING 1990 01:25:38,560 --> 01:25:39,360 FUNDING AGENCIES ON RIGHT AND 1991 01:25:39,360 --> 01:25:40,840 KEY COLLABORATORS IN PARTICULAR 1992 01:25:40,840 --> 01:25:42,520 AND WOULD LIKE TO THANK LYNNE 1993 01:25:42,520 --> 01:25:44,520 WHO WAS A REALLY GREAT 1994 01:25:44,520 --> 01:25:47,680 COLLABORATION WORKING WITH HER 1995 01:25:47,680 --> 01:25:51,040 GROUP ON DEVELOPMENT OF 1996 01:25:51,040 --> 01:25:53,080 [INDISCERNIBLE] AND THANKING 1997 01:25:53,080 --> 01:25:54,000 INCREDIBLE STUDENTS WORKING WITH 1998 01:25:54,000 --> 01:25:56,640 TODAY AND HARD WORKING BUNCH AND 1999 01:25:56,640 --> 01:25:58,000 PASSIONATE ABOUT SCIENCE AND 2000 01:25:58,000 --> 01:26:00,200 WHAT THEY DO AND INCREDIBLY 2001 01:26:00,200 --> 01:26:01,960 CREATIVE AND HIGHLIGHTING NAMES 2002 01:26:01,960 --> 01:26:04,120 AND A FEW STUDENTS WHOSE WORK I 2003 01:26:04,120 --> 01:26:07,200 TALKED ABOUT TODAY AND THANKS 2004 01:26:07,200 --> 01:26:09,080 FOR YOUR ATTENTION. 2005 01:26:09,080 --> 01:26:11,160 >>I WANT TO THANK BOTH OF YOU 2006 01:26:11,160 --> 01:26:15,360 FOR THESE EXTRAORDINARY AND 2007 01:26:15,360 --> 01:26:21,680 EXCITING PRESENTATIONS. 2008 01:26:21,680 --> 01:26:23,840 WE HAVE A SLEW OF QUESTIONS I 2009 01:26:23,840 --> 01:26:25,000 WILL TRY TO DIRECT AND STARTING 2010 01:26:25,000 --> 01:26:28,720 AT THE BEGINNING ANY WANT TO 2011 01:26:28,720 --> 01:26:31,720 COMMENT WHAT FUNCTION OF 2012 01:26:31,720 --> 01:26:42,280 PSYCHOBIOME IN THE MUSHROOM IS? 2013 01:26:43,480 --> 01:26:45,760 >>WHAT IS FUNCTION OF 2014 01:26:45,760 --> 01:26:47,360 PSILOCYBIN IN THE MUSHROOM? WE 2015 01:26:47,360 --> 01:26:49,680 DON'T KNOW IN TERMS OF EVOLUTION 2016 01:26:49,680 --> 01:26:52,240 OF THE MUSHROOM, GREAT QUESTION 2017 01:26:52,240 --> 01:26:55,560 AND UNCLEAR WHETHER PSILOCYBIN 2018 01:26:55,560 --> 01:26:58,720 IS ADAPTABLE CHANGE IN MUSHROOMS 2019 01:26:58,720 --> 01:27:02,800 AND UNCLEAR WHETHER IT CONFERRED 2020 01:27:02,800 --> 01:27:03,560 EVOLUTIONARY ADVANTAGE IN 2021 01:27:03,560 --> 01:27:05,760 DEVELOPMENT AND EVOLUTION OF THE 2022 01:27:05,760 --> 01:27:08,080 MUSHROOMS AND SEE MUSHROOMS ARE 2023 01:27:08,080 --> 01:27:11,360 SLIGHTLY DIFFERENT THAN I DO 2024 01:27:11,360 --> 01:27:12,040 ANIMAL SPECIES. 2025 01:27:12,040 --> 01:27:14,800 IT SEEMS MUSHROOMS THEMSELVES 2026 01:27:14,800 --> 01:27:17,680 OUTSIDE OF PSYCHOACTIVE 2027 01:27:17,680 --> 01:27:19,080 MUSHROOMS ARE REMARKABLE FORMS 2028 01:27:19,080 --> 01:27:23,360 OF LIFE AND THEY ARE LITTLE 2029 01:27:23,360 --> 01:27:25,800 CHEMICAL FACTORIES AND THERE ARE 2030 01:27:25,800 --> 01:27:29,040 LOTS OF DIFFERENT SPECIES OF 2031 01:27:29,040 --> 01:27:31,000 MUSHROOMS WITH LOTS OF DIFFERENT 2032 01:27:31,000 --> 01:27:35,360 RELATIONSHIPS WITH PLANTS AND 2033 01:27:35,360 --> 01:27:37,440 MICROBUY OATA IN NATURAL 2034 01:27:37,440 --> 01:27:39,360 ENVIRONMENTS AND SOME MUSHROOMS 2035 01:27:39,360 --> 01:27:43,280 ARE SACK ROW PHILIC AND EXIST IN 2036 01:27:43,280 --> 01:27:44,640 SYMBIOTIC RELATIONSHIP WITH 2037 01:27:44,640 --> 01:27:46,520 DIFFERENT PLANTS AND 2038 01:27:46,520 --> 01:27:48,160 ENVIRONMENTS IN WHICH THEY 2039 01:27:48,160 --> 01:27:51,920 OPERATE AND SOME FORM TO KIND OF 2040 01:27:51,920 --> 01:27:53,560 RECYCLE CERTAIN TYPES OF 2041 01:27:53,560 --> 01:27:55,200 CHEMICALS AND COMPOUNDS IN THEIR 2042 01:27:55,200 --> 01:27:58,840 ENVIRONMENT AND OTHERS HELP AS 2043 01:27:58,840 --> 01:28:00,400 REALLY KIND OF DECOMPOSERS IN 2044 01:28:00,400 --> 01:28:03,360 THE FOREST AND THIS IS ME 2045 01:28:03,360 --> 01:28:05,160 DANCING AROUND THE ANSWER I 2046 01:28:05,160 --> 01:28:07,640 DON'T REALLY KNOW AND IS NOT 2047 01:28:07,640 --> 01:28:10,720 CLEAR THAT PSILOCYBIN HAS TO 2048 01:28:10,720 --> 01:28:12,680 NECESSARILY PROVIDE SOME KIND OF 2049 01:28:12,680 --> 01:28:13,960 EVOLUTIONARY ADVANTAGE TO THE 2050 01:28:13,960 --> 01:28:15,640 SPECIES THAT CARRY IT. IT COULD 2051 01:28:15,640 --> 01:28:17,720 BE ITS PRESENCE COULD BE A 2052 01:28:17,720 --> 01:28:19,360 BYPRODUCT OF ENVIRONMENT THEY 2053 01:28:19,360 --> 01:28:20,360 FIND THEMSELVES IN AND 2054 01:28:20,360 --> 01:28:21,680 PARTICULAR RELATIONSHIPS THEY 2055 01:28:21,680 --> 01:28:23,200 HAVE WITH OTHER PLANTS AND 2056 01:28:23,200 --> 01:28:27,920 THINGS IN THEIR ENVIRONMENT. 2057 01:28:27,920 --> 01:28:32,560 >>PARDON ME? 2058 01:28:32,560 --> 01:28:33,600 >> GO AHEAD. 2059 01:28:33,600 --> 01:28:37,160 >>FOLLOWING UP ON WHAT FRED WAS 2060 01:28:37,160 --> 01:28:39,360 SAYING AND SOMETHING THAT WILL 2061 01:28:39,360 --> 01:28:40,560 SURPRISE LISTENERS IS 2062 01:28:40,560 --> 01:28:42,400 PSYCHEDELICS ARE FOUND BROADLY 2063 01:28:42,400 --> 01:28:44,680 ACROSS SPECIES IN MANY, MANY 2064 01:28:44,680 --> 01:28:47,040 PLANTS AND ARE OF COURSE EVEN 2065 01:28:47,040 --> 01:28:49,600 PRODUCED BY ANIMALS LIKE HUMANS 2066 01:28:49,600 --> 01:28:53,200 AND LOTS OR MANY PEOPLE KNOW OF 2067 01:28:53,200 --> 01:28:53,880 PSYCHEDELIC MUSHROOMS FOUND IN 2068 01:28:53,880 --> 01:28:55,600 VERY COMMON PLANTS TOO AND YOU 2069 01:28:55,600 --> 01:28:58,240 CAN FIND PSYCHEDELICS IN 2070 01:28:58,240 --> 01:28:59,520 ORANGES, FOR INSTANCE. 2071 01:28:59,520 --> 01:29:04,520 >>JUST AN INCREDIBLY LOW 2072 01:29:04,520 --> 01:29:05,520 CONCENTRATIONS; RIGHT? 2073 01:29:05,520 --> 01:29:09,880 >>CORRECT. 2074 01:29:09,880 --> 01:29:12,160 >>DESERVING TO KEEP PREDATORS 2075 01:29:12,160 --> 01:29:14,280 AWAY AND ALL RIGHT A VERY 2076 01:29:14,280 --> 01:29:17,280 IMPORTANT QUESTION THAT POPPED 2077 01:29:17,280 --> 01:29:20,600 UP. 2078 01:29:20,600 --> 01:29:22,640 INITIAL RESPONSE TO A 2079 01:29:22,640 --> 01:29:23,240 PSYCHEDELIC COMPOUND IS 2080 01:29:23,240 --> 01:29:24,640 SOMETHING THAT OCCURS WITHIN A 2081 01:29:24,640 --> 01:29:27,240 MATTER OF MINUTES THROUGH A VERY 2082 01:29:27,240 --> 01:29:29,080 SHORT PERIOD OF TIME. 2083 01:29:29,080 --> 01:29:33,440 AND THEN WE HAVE THESE PROLONGED 2084 01:29:33,440 --> 01:29:38,560 EFFECTS AS MANIFESTED AND 2085 01:29:38,560 --> 01:29:44,640 EXPERIMENTALLY AND CLINICALLY. 2086 01:29:44,640 --> 01:29:46,520 ARE THEY BY THE SAME AND IN 2087 01:29:46,520 --> 01:29:49,200 THINKING BY THE SAME MECHANISM? 2088 01:29:49,200 --> 01:29:50,800 IMPLICATION THAT YOU COULD 2089 01:29:50,800 --> 01:29:53,880 DEVELOP A COMPOUND THAT IS 2090 01:29:53,880 --> 01:29:55,360 NONHALLUCINOGENIC BUT HAS 2091 01:29:55,360 --> 01:29:56,760 THERAPEUTIC IMPLICATIONS THAT 2092 01:29:56,760 --> 01:29:59,720 SORT OF IMPLIES THAT THE -- THEY 2093 01:29:59,720 --> 01:30:02,160 MAY BE DIFFERENT. I DON'T KNOW. 2094 01:30:02,160 --> 01:30:04,240 WHAT ARE YOUR -- THIS HAS POPPED 2095 01:30:04,240 --> 01:30:05,280 UP IN SEVERAL QUESTIONS. 2096 01:30:05,280 --> 01:30:07,760 >>YOU KNOW, IT IS A REALLY 2097 01:30:07,760 --> 01:30:08,920 INTERESTING QUESTION. I THINK 2098 01:30:08,920 --> 01:30:11,920 THAT IT REALLY SPEAKS TO THE 2099 01:30:11,920 --> 01:30:15,160 COMPLEXITY OF G PROTEIN COUPLED 2100 01:30:15,160 --> 01:30:16,160 RECEPTOR BIOLOGY THAT ARE 2101 01:30:16,160 --> 01:30:18,360 INCREDIBLE MACHINES AND AS I 2102 01:30:18,360 --> 01:30:21,200 MENTIONED IN THE TALK, THEY 2103 01:30:21,200 --> 01:30:22,640 EXHIBIT FUNCTIONAL SELECTIVITY 2104 01:30:22,640 --> 01:30:26,800 AND TWO COMPOUNDS BINDED TO 2105 01:30:26,800 --> 01:30:27,400 RECEPTOR GETTING DIFFERENT 2106 01:30:27,400 --> 01:30:28,320 DOWNSTREAM EFFECTS AND WHY THAT 2107 01:30:28,320 --> 01:30:31,360 IS THE CASE IS VARIETY OF 2108 01:30:31,360 --> 01:30:32,840 DIFFERENT HYPOTHESES AND ONE 2109 01:30:32,840 --> 01:30:35,160 HYPOTHESIS IS RELATED TO 2110 01:30:35,160 --> 01:30:37,320 EFFECTORS AND THINGS G PROTEIN 2111 01:30:37,320 --> 01:30:41,880 ECREPTOR COUPLES TO IS COUPLED 2112 01:30:41,880 --> 01:30:45,200 TO BIAS AGNIX AND FUNCTIONAL 2113 01:30:45,200 --> 01:30:46,200 SELECTIVITY CALLED LOCATION BIAS 2114 01:30:46,200 --> 01:30:50,680 AND LOCATION OF RECEPTOR 2115 01:30:50,680 --> 01:30:52,600 DICTATES DOWNSTREAM FUNCTION AND 2116 01:30:52,600 --> 01:30:53,400 ANOTHER HYPOTHESIS COULD BE 2117 01:30:53,400 --> 01:30:56,360 NEURAL CIRCUITS IT THAT 2118 01:30:56,360 --> 01:30:57,400 DIFFERENT POPULATIONS THAT THEY 2119 01:30:57,400 --> 01:30:58,600 EXIST IN MIGHT PLAY DIFFERENT 2120 01:30:58,600 --> 01:31:02,640 ROLES AND FINALLY YOU HAVE TO 2121 01:31:02,640 --> 01:31:03,240 CONSIDER POLYPHARMACOLOGY AND 2122 01:31:03,240 --> 01:31:06,040 COULD BE DRUGS ARE ACTIVATING 2123 01:31:06,040 --> 01:31:10,800 OTHER ADDITIONAL RECEPTORS THAT 2124 01:31:10,800 --> 01:31:11,480 MODULATE THERAPEUTIC RESPONSE. 2125 01:31:11,480 --> 01:31:13,080 I THINK THIS IS A LONG WAY OF 2126 01:31:13,080 --> 01:31:15,360 SAYING IT THAT I THINK THAT THE 2127 01:31:15,360 --> 01:31:17,320 FIELD DOESN'T KNOW EXACTLY WHY 2128 01:31:17,320 --> 01:31:19,920 THIS IS POSSIBLE JUST YET AND 2129 01:31:19,920 --> 01:31:22,680 PHENOMENON SEEMS TO BE REAL AND 2130 01:31:22,680 --> 01:31:24,760 SOME COMPOUNDS AND 2131 01:31:24,760 --> 01:31:26,120 NONHALLUCINOGENIC AGONISTS ARE 2132 01:31:26,120 --> 01:31:29,200 TESTED IN PEOPLE AND KNOWN TO BE 2133 01:31:29,200 --> 01:31:30,800 DEFINITIVELY NONHALLUCINOGENIC 2134 01:31:30,800 --> 01:31:33,600 AND SOME USED AS THERAPEUTICS 2135 01:31:33,600 --> 01:31:36,040 FOR INSTANCE LIKE PARKINSON'S 2136 01:31:36,040 --> 01:31:37,160 DISEASE OR SOMETHING LIKE THIS 2137 01:31:37,160 --> 01:31:41,600 AND WHY YOU CAN CREATE 2138 01:31:41,600 --> 01:31:44,320 NONHALLUCINOGENIC AGONIST IS A 2139 01:31:44,320 --> 01:31:45,880 MYSTERY TO THE FIELD STILL. 2140 01:31:45,880 --> 01:31:49,640 >>RELATED TO THAT IS MORE 2141 01:31:49,640 --> 01:31:56,000 MOLECULAR NATURE OF THE 2142 01:31:56,000 --> 01:32:00,360 RESPONSE. FOR EXAMPLE 2143 01:32:00,360 --> 01:32:02,320 EXTRAORDINARY EFFECTS OF 2144 01:32:02,320 --> 01:32:03,600 NEURONAL PLASTICITY AND SPINES 2145 01:32:03,600 --> 01:32:07,560 AND EXTENSIONS AND ARE THESE 2146 01:32:07,560 --> 01:32:12,240 BASICALLY DUE TO TRANSCRIPTIONAL 2147 01:32:12,240 --> 01:32:16,680 EFFECTS OR TRANSLATIONAL? 2148 01:32:16,680 --> 01:32:18,960 DO WE HAVE AN UNDERSTANDING OF 2149 01:32:18,960 --> 01:32:19,320 THAT? 2150 01:32:19,320 --> 01:32:24,520 >>YEAH. I DID MY POST DOCTORAL 2151 01:32:24,520 --> 01:32:32,960 WORK AND GENE EXPRESSION THAT 2152 01:32:32,960 --> 01:32:35,080 MUST LEAD TO LONG LASTING 2153 01:32:35,080 --> 01:32:39,040 CHANGES AND TO BE HONEST WE 2154 01:32:39,040 --> 01:32:43,240 HAVEN'T SEEN MANY ROBUST CHANGES 2155 01:32:43,240 --> 01:32:44,600 IN GENE EXPRESSION OF 2156 01:32:44,600 --> 01:32:46,800 PSYCHEDELIC AND PEOPLE HAVE 2157 01:32:46,800 --> 01:32:49,520 LOOKED ACROSS THE BRAIN AND DONE 2158 01:32:49,520 --> 01:32:50,080 TRANSCRIPTOMICS YOU SEE 2159 01:32:50,080 --> 01:32:52,240 IMMEDIATE CHANGES IN EARLY GENES 2160 01:32:52,240 --> 01:32:55,000 BUT NOT MASSIVE CHANGESES IN 2161 01:32:55,000 --> 01:32:56,280 GENE EXPRESSION AND SOME 2162 01:32:56,280 --> 01:32:58,600 INDICATIONS MAY BE EPIGENETICS 2163 01:32:58,600 --> 01:33:01,000 THAT ARE CHANGE THE AND MAYBE IF 2164 01:33:01,000 --> 01:33:02,920 YOU CAN FOCUS ON VERY SPECIFIC 2165 01:33:02,920 --> 01:33:06,680 CELL POPULATIONS YOU MIGHT SEE 2166 01:33:06,680 --> 01:33:07,360 TRANSCRIPTIONAL CHANGES THAT 2167 01:33:07,360 --> 01:33:09,320 STILL IS WORK THAT IS ONGOING 2168 01:33:09,320 --> 01:33:11,200 AND CURRENTLY HYPOTHESIS IS THAT 2169 01:33:11,200 --> 01:33:17,400 THIS LARGELY RELIES ON 2170 01:33:17,400 --> 01:33:17,720 TRANSLATION. 2171 01:33:17,720 --> 01:33:22,560 WHAT IS KNOWN IS IF YOU ACTIVATE 2172 01:33:22,560 --> 01:33:26,280 M4 PATHWAY AND START PRODUCING 2173 01:33:26,280 --> 01:33:29,440 PROTEINS FOR NEUROPLASTICITY IT 2174 01:33:29,440 --> 01:33:33,320 IS FEEDBACK LOOP AND WILL 2175 01:33:33,320 --> 01:33:39,760 PRODUCE BRAIN DERIVED -- YOU CAN 2176 01:33:39,760 --> 01:33:42,640 GET A LONG LASTING EFFECT ON 2177 01:33:42,640 --> 01:33:43,800 NEURONAL GROWTH THAT IS 2178 01:33:43,800 --> 01:33:47,480 STIMULATING IN A SHORT PERIOD OF 2179 01:33:47,480 --> 01:33:47,680 TIME. 2180 01:33:47,680 --> 01:33:51,720 >>IN ELAITION TO INCREASED 2181 01:33:51,720 --> 01:33:53,880 SPINES AND AXONAL GROWTH IS THAT 2182 01:33:53,880 --> 01:33:56,800 NEW PROTEIN SYNTHESIS OR RE -- 2183 01:33:56,800 --> 01:34:00,080 IN SOME WAY ASSEMBLY AND 2184 01:34:00,080 --> 01:34:03,320 ORGANIZATION OF BUILDING BLOCKS 2185 01:34:03,320 --> 01:34:06,200 THAT ARE ALREADY THERE? 2186 01:34:06,200 --> 01:34:09,600 >>WE BELIEVE A LARGE PART OF IT 2187 01:34:09,600 --> 01:34:15,680 IS NEW PROTEIN SYNTHESIS. 2188 01:34:15,680 --> 01:34:20,080 >>THAT CAN OCCUR IN -- IN 2189 01:34:20,080 --> 01:34:22,240 MATTER OF MINUTES WITH 2190 01:34:22,240 --> 01:34:23,400 ADMINISTRATION OF PSYCHEDELIC? 2191 01:34:23,400 --> 01:34:25,840 >>NO. WE KNOW TIME COURSE FOR 2192 01:34:25,840 --> 01:34:28,480 WHICH THIS HAPPENS AND LOTS OF 2193 01:34:28,480 --> 01:34:32,880 WORK DONE IN VIVO WITH KETAMINE 2194 01:34:32,880 --> 01:34:36,720 AND SILO KRIEBIN AND OUR GROUP 2195 01:34:36,720 --> 01:34:40,160 HAS DONE WORK IN VITRO AND WE 2196 01:34:40,160 --> 01:34:42,360 FOUND THAT SPINES TEND TO GROW 2197 01:34:42,360 --> 01:34:49,240 OVER COURSE OF ABOUT 24 HOURS. 2198 01:34:49,240 --> 01:34:50,800 YOU DON'T SEE SPINE GROWTH UNTIL 2199 01:34:50,800 --> 01:34:57,240 6 TO 24 HOURS AND THEY REACH 2200 01:34:57,240 --> 01:34:58,800 MAXIMUM AND PERSIST OVER A 2201 01:34:58,800 --> 01:35:00,680 PERIOD OF TIME. YOU CAN PULSE 2202 01:35:00,680 --> 01:35:03,120 FOR DIFFERENT AMOUNTS OF TIME 2203 01:35:03,120 --> 01:35:06,320 AND GET STRUCTURAL PLASTICITY 2204 01:35:06,320 --> 01:35:11,360 EFFECTS AND FOR INSTANCE YOU CAN 2205 01:35:11,360 --> 01:35:15,040 PUT DRUGS ON CORTICAL NEURONS 2206 01:35:15,040 --> 01:35:17,960 AND YOU CAN PUT THEM ON NEURONS 2207 01:35:17,960 --> 01:35:20,360 FOR 15 MINUTES TAKE DRUG AWAY 2208 01:35:20,360 --> 01:35:22,280 AND WAIT THREE DAYS AND COMING 2209 01:35:22,280 --> 01:35:24,000 BACK THREE DAYS LATER THEY WILL 2210 01:35:24,000 --> 01:35:25,600 HAVE GROWN BUT DON'T GROW IN 2211 01:35:25,600 --> 01:35:30,640 FIRST 15 MINUTES BUT TAKE A FEW 2212 01:35:30,640 --> 01:35:37,280 DAYS TO GROW FRIEND IN VARIOUS 2213 01:35:37,280 --> 01:35:40,600 STUDIES YOU AND OTHERS PERFORM 2214 01:35:40,600 --> 01:35:46,000 AND MENTIONED TODAY ROLONGED 2215 01:35:46,000 --> 01:35:48,360 CLINICAL EFFECTS OF DOSES OF 2216 01:35:48,360 --> 01:35:51,360 PSYCHEDELICS AND PATIENTS 2217 01:35:51,360 --> 01:35:54,520 RECEIVED PSYCHOTHERAPY AND MAYBE 2218 01:35:54,520 --> 01:35:59,280 YOU WILL COMMENT ABOUT MUSIC. 2219 01:35:59,280 --> 01:36:03,120 WHAT ROLE DOES THAT SUPPORTIVE 2220 01:36:03,120 --> 01:36:09,880 THERAPY HAVE. 2221 01:36:09,880 --> 01:36:13,480 IS PSYCHEDELIC MAKING PEOPLE 2222 01:36:13,480 --> 01:36:15,320 RESPONSIVE TO TRADITIONAL WAYS 2223 01:36:15,320 --> 01:36:18,040 OF TREATMENT? WHAT IS 2224 01:36:18,040 --> 01:36:19,240 RELATIONSHIP BETWEEN THEM? 2225 01:36:19,240 --> 01:36:21,280 >>MOST HONEST ANSWER IS WE 2226 01:36:21,280 --> 01:36:24,120 DON'T KNOW REALLY. THE MORE 2227 01:36:24,120 --> 01:36:25,080 INFORMED CLINICALLY INFORMED 2228 01:36:25,080 --> 01:36:27,800 ANSWER IS THAT WE DO BELIEVE 2229 01:36:27,800 --> 01:36:31,680 THAT PSYCHOTHERAPEUTIC ASPECT OF 2230 01:36:31,680 --> 01:36:34,120 PSYCHEDELIC THERAPY IS A REAL 2231 01:36:34,120 --> 01:36:36,640 AND ACTIVE INGREDIENT YOU MIGHT 2232 01:36:36,640 --> 01:36:38,360 RECALL BACK IN SLIDES AND SLIDE 2233 01:36:38,360 --> 01:36:41,240 I SHOWED FROM FIRST CLINICAL 2234 01:36:41,240 --> 01:36:43,160 STUDY IN CANCER PATIENTS THAT 2235 01:36:43,160 --> 01:36:45,840 PEOPLE WERE RANDOMIZED TO 2236 01:36:45,840 --> 01:36:49,800 RECEIVE A VERY HIGH DOSE OF 2237 01:36:49,800 --> 01:36:53,400 PSILOCYBIN FIRST OR TRIVIAL DOSE 2238 01:36:53,400 --> 01:36:57,320 OF PSILOCYBIN FIRST. 2239 01:36:57,320 --> 01:36:59,360 PREPARATION AND MONITORING 2240 01:36:59,360 --> 01:37:01,160 INTEGRATION AND AFTER CARE AND 2241 01:37:01,160 --> 01:37:03,760 WHILE THOSE WHO RECEIVED HIGH 2242 01:37:03,760 --> 01:37:08,520 DOSE OF PSILOCYBIN FIRST SHOWED 2243 01:37:08,520 --> 01:37:11,240 EMARKETABLE REDUCTION IN -- 2244 01:37:11,240 --> 01:37:14,440 THOSE SHOWING PSILOCYBIN SHOWED 2245 01:37:14,440 --> 01:37:17,480 HALF EFFECT SIZE THAT IS 2246 01:37:17,480 --> 01:37:18,640 REMARKABLE EFFECTS PERFECT 2247 01:37:18,640 --> 01:37:20,880 EXAMPLE OF EFFECT OF FARM COLONL 2248 01:37:20,880 --> 01:37:23,720 CAL PACKAGING AROUND IT AND TO 2249 01:37:23,720 --> 01:37:30,360 CONSIDER IS IN STUDY THAT 2250 01:37:30,360 --> 01:37:31,800 [INDISCERNIBLE] HARRIS CONDUCTED 2251 01:37:31,800 --> 01:37:34,800 WILL YOU SEE FIGURE AND PANEL 2252 01:37:34,800 --> 01:37:37,320 FOR THOSE GETTING TELO PRAM WAS 2253 01:37:37,320 --> 01:37:39,000 COUPLED TO PATH OF THOSE 2254 01:37:39,000 --> 01:37:40,960 RECEIVING PSILOCYBIN AND 2255 01:37:40,960 --> 01:37:45,040 SEVERITY 7 DAYS AFTER INITIATION 2256 01:37:45,040 --> 01:37:47,880 OF THERAPY THAT IS NOT WHAT YOU 2257 01:37:47,880 --> 01:37:49,920 EXPECT AND PATIENT RECEIVING 2258 01:37:49,920 --> 01:37:51,760 THIS AND TAKES LONGER FOR 2259 01:37:51,760 --> 01:37:53,360 EFFECTS TO KICK IN THAT MIGHT BE 2260 01:37:53,360 --> 01:37:55,600 EXAMPLE OF EFFECT OF ALL OTHER 2261 01:37:55,600 --> 01:37:59,320 STUFF AND PSYCHOTHERAPY AROUND 2262 01:37:59,320 --> 01:38:01,400 IT TWO OTHER WAYS TO THINK ABOUT 2263 01:38:01,400 --> 01:38:03,480 THIS WITH YOU. ONE, LOTS OF 2264 01:38:03,480 --> 01:38:07,160 PEOPLE TOOK LSD IN 50S AND 60S 2265 01:38:07,160 --> 01:38:09,080 AND DIDN'T BECOME DEPRESSED AND 2266 01:38:09,080 --> 01:38:10,640 STOP SMOKING OR DRINKING AND 2267 01:38:10,640 --> 01:38:14,040 DOING OTHER THINGS AND BELIEVE 2268 01:38:14,040 --> 01:38:16,840 THAT CONTEXT AND FRAMING AROUND 2269 01:38:16,840 --> 01:38:17,640 EXPERIENCES HAVE HUGE EFFECT AND 2270 01:38:17,640 --> 01:38:20,480 LAST WAY TO THINK ABOUT THIS IS 2271 01:38:20,480 --> 01:38:22,280 BECAUSE IF YOU TAKE BROAD 2272 01:38:22,280 --> 01:38:24,400 EXAMPLE OR SENSE OR HEURISTIC 2273 01:38:24,400 --> 01:38:27,280 KNOWLEDGE THAT MAYBE DRUGS ARE 2274 01:38:27,280 --> 01:38:30,360 SOMEHOW LEANING TO 2275 01:38:30,360 --> 01:38:31,760 NEUROPLASTICITY AND I DON'T 2276 01:38:31,760 --> 01:38:33,080 THINK WE SHOULD EXPECT THE BRAIN 2277 01:38:33,080 --> 01:38:35,560 TO NATURALLY EVOLVE TO A MORE 2278 01:38:35,560 --> 01:38:36,800 ADAPTIVE STATE BECAUSE WE MADE 2279 01:38:36,800 --> 01:38:39,960 IT MORE PLASTIC AND THINK THAT 2280 01:38:39,960 --> 01:38:42,240 WE HAVE TO IF WE MAKE BRAIN 2281 01:38:42,240 --> 01:38:45,640 PLASTIC WE DO SOMETHING WITH 2282 01:38:45,640 --> 01:38:47,360 PLASTICITY AND THE PREPARATION 2283 01:38:47,360 --> 01:38:49,440 AND MONITORING AND AFTER CARE WE 2284 01:38:49,440 --> 01:38:53,520 PROVIDE PROVIDES A REAL MOLD 2285 01:38:53,520 --> 01:38:56,160 WITHIN WHICH YOU CAN PUT PLASTIC 2286 01:38:56,160 --> 01:38:59,200 BRAIN TO HELP IT INTO A MORE 2287 01:38:59,200 --> 01:39:00,760 ADAPTIVE STATE AFTERWARDS. 2288 01:39:00,760 --> 01:39:03,360 >>WE HAVE SEVERAL QUESTIONS TO 2289 01:39:03,360 --> 01:39:06,400 THE RELATIONSHIP BETWEEN SLEEP 2290 01:39:06,400 --> 01:39:08,840 AND RESPONSE TO A PSYCHEDELIC. 2291 01:39:08,840 --> 01:39:10,440 HAVE THERE BEEN ANY STUDIES 2292 01:39:10,440 --> 01:39:13,280 WHERE PSYCHEDELICS HAVE BEEN 2293 01:39:13,280 --> 01:39:16,560 ADMINISTERED TO SLEEPING 2294 01:39:16,560 --> 01:39:20,160 PATIENTS? 2295 01:39:20,160 --> 01:39:22,320 >>NOT THAT I'M AWARE OF AND A 2296 01:39:22,320 --> 01:39:24,760 NUMBER OF FOLKS TALKED ABOUT 2297 01:39:24,760 --> 01:39:27,800 CONDUCTING STUDIES AND PATIENTS 2298 01:39:27,800 --> 01:39:30,200 THAT ARE ENASSISTHETIZE THE AND 2299 01:39:30,200 --> 01:39:33,440 [INDISCERNIBLE] AT UNIVERSITY OF 2300 01:39:33,440 --> 01:39:36,360 WISCONSIN MADISON AND BORIS HYPE 2301 01:39:36,360 --> 01:39:39,320 AT STANFORD AND NOT SURE IF THEY 2302 01:39:39,320 --> 01:39:41,080 CONDUCTED STUDIES OR PUBLISHED 2303 01:39:41,080 --> 01:39:43,280 IT YOU ARE IN GEOGRAPHY. WHAT 2304 01:39:43,280 --> 01:39:44,360 IS UP? 2305 01:39:44,360 --> 01:39:47,320 >>WE ARE COLLABORATING ON THAT 2306 01:39:47,320 --> 01:39:48,880 AND NOT READY FOR STUDY YET. WE 2307 01:39:48,880 --> 01:39:51,200 ARE STILL WORKING ON IT AND NO 2308 01:39:51,200 --> 01:39:53,360 ONE HAS GIVEN A PSYCHEDELIC TO 2309 01:39:53,360 --> 01:39:55,040 SOMEONE WHILE THEY ARE SLEEPING 2310 01:39:55,040 --> 01:39:56,600 BUT BELIEVE THAT PSYCHEDELICS 2311 01:39:56,600 --> 01:39:59,360 HAVE BEEN ADMINSTERED BEFORE 2312 01:39:59,360 --> 01:40:02,760 SOMEONE GOES TO SLEEP AND ARE 2313 01:40:02,760 --> 01:40:03,360 EFFECTS. 2314 01:40:03,360 --> 01:40:04,760 FOR INSTANCE THERE IS SOME 2315 01:40:04,760 --> 01:40:07,360 SUPPRESSION THAT IS A GOOD 2316 01:40:07,360 --> 01:40:10,880 HALLMARK ACTUALLY OF MANY 2317 01:40:10,880 --> 01:40:16,600 ANTIDEPRESSANT COMPOUNDS THAT 2318 01:40:16,600 --> 01:40:17,640 SUPPRESS ANTIDEPRESSION. 2319 01:40:17,640 --> 01:40:18,560 >>WHAT DO YOU THINK. 2320 01:40:18,560 --> 01:40:20,560 >>HE GAVE DURING SLEEP I DON'T 2321 01:40:20,560 --> 01:40:22,800 KNOW WAS SUBJECT OF ONE OF MY 2322 01:40:22,800 --> 01:40:24,720 PROPOSALS GOING TO UC DAVIS BUT 2323 01:40:24,720 --> 01:40:28,600 NEVER HAD A CHANCE TO TRY IT. 2324 01:40:28,600 --> 01:40:30,040 FRED, HAVE ANY THOUGHTS? 2325 01:40:30,040 --> 01:40:32,040 >>I THINK IT IS POSSIBLE YOU 2326 01:40:32,040 --> 01:40:36,240 MAY GET MUCH MORE VIVID DREAM 2327 01:40:36,240 --> 01:40:37,440 STATES AND PEOPLE LIKE TO 2328 01:40:37,440 --> 01:40:41,120 COMPARE PSYCHEDELIC STATES TO 2329 01:40:41,120 --> 01:40:43,960 DREAMLIKE STATES THAT OFFER REM 2330 01:40:43,960 --> 01:40:44,320 SUPPRESSION. 2331 01:40:44,320 --> 01:40:46,920 >>I SUSPECT WHAT MIGHT HAPPEN 2332 01:40:46,920 --> 01:40:48,760 IS PATIENTS MIGHT WAKE UP. 2333 01:40:48,760 --> 01:40:49,360 >>POSSIBLE. 2334 01:40:49,360 --> 01:40:53,040 >>I CAN SAY IT IS UNLIKELY FOR 2335 01:40:53,040 --> 01:40:55,360 PATIENTS TO FALL ASLEEP UNDER 2336 01:40:55,360 --> 01:40:58,400 EFFECTS OF HIGH DOSE OF SOOILO 2337 01:40:58,400 --> 01:40:59,360 KRIEBIN. 2338 01:40:59,360 --> 01:41:05,440 >>THERE IS EVIDENCE PLAYING A 2339 01:41:05,440 --> 01:41:07,440 ROLE IN WAKING CONSCIOUSNESS. 2340 01:41:07,440 --> 01:41:08,560 YOU KNOW? 2341 01:41:08,560 --> 01:41:11,840 >>SLEEP BY WHATEVER ITS 2342 01:41:11,840 --> 01:41:14,280 MECHANISM IS MAY ACTUALLY HAVE A 2343 01:41:14,280 --> 01:41:17,680 PROFOUND EFFECT ON THE 2344 01:41:17,680 --> 01:41:21,760 PSYCHEDELIC COMPOUND. MAYBE 2345 01:41:21,760 --> 01:41:23,560 DELAY ACTION. 2346 01:41:23,560 --> 01:41:27,160 >>THERE HAS BEEN A HYPOTHESIS 2347 01:41:27,160 --> 01:41:29,600 FOR A LONG TIME DREAMING STATES 2348 01:41:29,600 --> 01:41:32,400 MIGHT BE IN RELEASE OF 2349 01:41:32,400 --> 01:41:35,400 PSYCHEDELICS IN A WAY, SHAPE OR 2350 01:41:35,400 --> 01:41:36,440 FORM THAT HAS NEVER BEEN 2351 01:41:36,440 --> 01:41:38,520 RIGOROUSLY TESTED IN LARGE PART 2352 01:41:38,520 --> 01:41:40,560 BECAUSE IT IS EXTREMELY HARD TO 2353 01:41:40,560 --> 01:41:45,400 MEASURE MOLECULES WITH TEMPORAL 2354 01:41:45,400 --> 01:41:47,920 PRECISION THAT IS REQUIRED AND 2355 01:41:47,920 --> 01:41:49,480 WITH SENSITIVITY BECAUSE THEY 2356 01:41:49,480 --> 01:41:52,920 ARE PRODUCED IN LOW QUANTITIES. 2357 01:41:52,920 --> 01:41:56,000 >>COULD WE IMAGINE A HEALTHY 2358 01:41:56,000 --> 01:41:59,360 DOSE OF ANOTHER 2A AGONIST 2359 01:41:59,360 --> 01:42:01,880 BEFORE SLEEP IN A FEW WEEKS FOR 2360 01:42:01,880 --> 01:42:03,440 PEOPLE TO SEE IF THEY DREAM? 2361 01:42:03,440 --> 01:42:07,200 >>INTERESTING QUESTION. 2362 01:42:07,200 --> 01:42:13,160 ARE THERE PEOPLE WHO CAN TAKE 5 2363 01:42:13,160 --> 01:42:16,680 OR 10 MILLIGRAM DOSE AND 2364 01:42:16,680 --> 01:42:18,280 ACTUALLY HAVE NO PSYCHIC 2365 01:42:18,280 --> 01:42:18,760 EXPERIENCE? 2366 01:42:18,760 --> 01:42:22,160 IS THERE SOME SORT OF 2367 01:42:22,160 --> 01:42:22,720 PSYCHOLOGICAL RESIDUAL OR 2368 01:42:22,720 --> 01:42:24,040 WHATEVER IT IS? 2369 01:42:24,040 --> 01:42:27,120 DO THESE PEOPLE EXIST? 2370 01:42:27,120 --> 01:42:31,360 >>I THINK THOSE WHO FORM 2371 01:42:31,360 --> 01:42:32,400 PSYCHOLOGICAL RESISTANCE TO 2372 01:42:32,400 --> 01:42:35,480 EFFECTS HAVE BAD TRIPS BECAUSE 2373 01:42:35,480 --> 01:42:40,440 THEY TRY TO CONTROL EXPERIENCE 2374 01:42:40,440 --> 01:42:42,440 AND EFFECT. I HAVE HAD ONE 2375 01:42:42,440 --> 01:42:50,200 PARTICIPANT IN A STUDY WHERE IT 2376 01:42:50,200 --> 01:42:55,280 WAS OPEN DOSE AND HIGH DOSE OF 2377 01:42:55,280 --> 01:42:56,720 PSILOCYBIN AND EFFECTS AND VERY 2378 01:42:56,720 --> 01:42:59,240 FEW AND FAR BETWEEN AND DON'T 2379 01:42:59,240 --> 01:43:01,280 BELIEVE ARE WELL CHARACTERIZE AT 2380 01:43:01,280 --> 01:43:03,920 ALL HARD TO FIND CAN'T PREDICT 2381 01:43:03,920 --> 01:43:06,640 IT YET BUT BELIEVE THAT PEOPLE 2382 01:43:06,640 --> 01:43:06,920 EXIST. 2383 01:43:06,920 --> 01:43:07,360 >>YEAH. 2384 01:43:07,360 --> 01:43:10,720 >>INTERESTING TO KNOW IF SUCH 2385 01:43:10,720 --> 01:43:14,400 INDIVIDUALS HAVE EMILORATION OF 2386 01:43:14,400 --> 01:43:14,960 CLINICAL PHENOTYPE. 2387 01:43:14,960 --> 01:43:18,440 >>THIS IS ANECDOTAL AND GOT AN 2388 01:43:18,440 --> 01:43:22,360 E-MAIL ONCE FROM A PERSON WHO 2389 01:43:22,360 --> 01:43:27,160 CLAIMS THAT HE AND HIS DAUGHTERS 2390 01:43:27,160 --> 01:43:30,480 HAVE TAKE N EXTREMELY HIGH DOSE 2391 01:43:30,480 --> 01:43:33,080 OF PSYCHEDELICS NEVER 2392 01:43:33,080 --> 01:43:36,960 EXPERIENCED HALLUCINOGENIC 2393 01:43:36,960 --> 01:43:39,440 EFFECTS BUT HAVE HIGHLY 2394 01:43:39,440 --> 01:43:41,000 ANTIDEPRESSANT EFFECTS AND 2395 01:43:41,000 --> 01:43:42,400 WANTED GENOTYPE THEM AND SEE 2396 01:43:42,400 --> 01:43:44,600 WHAT IT WAS ABOUT THEIR 2397 01:43:44,600 --> 01:43:47,040 RECEPTORS THAT HAS TO DO WITH 2398 01:43:47,040 --> 01:43:47,920 RECEPTOR DENSITY IN BRAINS AND 2399 01:43:47,920 --> 01:43:53,200 MAYBE HAVING TO DO WITH SMALL 2400 01:43:53,200 --> 01:43:54,480 SINGLE NUCLEOTIDE POLYMORPH ISMS 2401 01:43:54,480 --> 01:43:56,880 AND KNOWN THAT GENETIC 2402 01:43:56,880 --> 01:44:00,000 MODIFICATIONS TO RECEPTOR COULD 2403 01:44:00,000 --> 01:44:01,560 IMPACT RESPONSE AND FRED SAID 2404 01:44:01,560 --> 01:44:03,360 THEY ARE NOT WELL CHARACTERIZED 2405 01:44:03,360 --> 01:44:05,000 IF OUT THERE WANTING TO 2406 01:44:05,000 --> 01:44:06,120 VOLUNTEER FOR STUDIES LET US 2407 01:44:06,120 --> 01:44:11,360 KNOW. REALLY INTERESTING 2408 01:44:11,360 --> 01:44:17,280 QUESTION PLANS TO TAKE 2409 01:44:17,280 --> 01:44:20,520 INDIVIDUALS WITH LOW EXPRESSION 2410 01:44:20,520 --> 01:44:24,800 OF PSYCHEDELIC EFFECT AND SOME 2411 01:44:24,800 --> 01:44:26,640 WITH HIGH EXPRESSION OF TOX TIS 2412 01:44:26,640 --> 01:44:30,280 AND DO ACTUALLY GENE SEQUENCING 2413 01:44:30,280 --> 01:44:30,960 ON PEOPLE OR. 2414 01:44:30,960 --> 01:44:32,400 >>I THINK FINDING PEOPLE HAS 2415 01:44:32,400 --> 01:44:33,920 BEEN HARD AND WE DON'T HAVE 2416 01:44:33,920 --> 01:44:36,240 ENOUGH OF THEM TO BE ABLE TO YOU 2417 01:44:36,240 --> 01:44:40,840 KNOW HAVE THINGS THAT WOULD BE 2418 01:44:40,840 --> 01:44:43,280 STATISTICALLY SIGNIFICANT. 2419 01:44:43,280 --> 01:44:43,560 >>YEAH. 2420 01:44:43,560 --> 01:44:47,960 >>SO, NEXT QUESTION, IS THERE A 2421 01:44:47,960 --> 01:44:50,920 RELATIONSHIP BETWEEN NATURE AND 2422 01:44:50,920 --> 01:44:52,600 MAGNITUDE OF PSYCHEDELIC 2423 01:44:52,600 --> 01:44:54,560 EXPERIENCE AND CLINICAL EFFECT? 2424 01:44:54,560 --> 01:44:58,440 >>THERE HAVE BB A NUMBER OF 2425 01:44:58,440 --> 01:45:00,920 STUDIES AND ANALYSIS CONDUCTED 2426 01:45:00,920 --> 01:45:02,920 ACROSS NUMBER OF SITES AND 2427 01:45:02,920 --> 01:45:05,880 INSTITUTIONS SUGGESTING IN FACT, 2428 01:45:05,880 --> 01:45:08,080 YES. EXACT NATURE OF 2429 01:45:08,080 --> 01:45:10,920 RELATIONSHIP IS SOMETHING THAT 2430 01:45:10,920 --> 01:45:14,400 IS VERY AMENABLE TO DEEPER 2431 01:45:14,400 --> 01:45:16,560 INVESTIGATION AND INTERROGATION 2432 01:45:16,560 --> 01:45:19,440 AND AT MOMENT SEEMS TO BE CASE 2433 01:45:19,440 --> 01:45:23,400 AND SOME CAVEATS HERE COULD BE 2434 01:45:23,400 --> 01:45:25,440 EVERYBODY READ MICHAEL COLLIN'S 2435 01:45:25,440 --> 01:45:27,120 BOOK AND EVERYBODY THINKS THEY 2436 01:45:27,120 --> 01:45:29,320 SHOULD HAVE A BIGAMIST CAL 2437 01:45:29,320 --> 01:45:30,840 EXPERIENCE THAT WILL HEAL THEM 2438 01:45:30,840 --> 01:45:32,480 AND FIGHTING AGAINST EXPECTANCY 2439 01:45:32,480 --> 01:45:37,560 OF SORTS OF TYPES AND MANNER AND 2440 01:45:37,560 --> 01:45:40,080 ONE DATA POINT IS IN CONTRAST IS 2441 01:45:40,080 --> 01:45:43,520 THAT YOU CAN -- WE ASK PEOPLE 2442 01:45:43,520 --> 01:45:46,320 OFTEN TO RATE OVERALL STRENGTH 2443 01:45:46,320 --> 01:45:48,400 OF DRUG EFFECT ON SCALE AND HAVE 2444 01:45:48,400 --> 01:45:53,480 DIFFERENT RATING SCALES TO TRY 2445 01:45:53,480 --> 01:45:55,400 TO INTERROGATE ASPECTS OF 2446 01:45:55,400 --> 01:45:57,000 SUBJECTIVE EXPERIENCE THAT IS 2447 01:45:57,000 --> 01:45:59,280 NOT OVERALL STRENGTH OF DRUG 2448 01:45:59,280 --> 01:46:01,160 EFFECT AND NOT GOOD OR BAD DRUG 2449 01:46:01,160 --> 01:46:04,240 EFFECTS NECESSARILY AND SEEMS TO 2450 01:46:04,240 --> 01:46:09,120 BE MORE SPECIFICALLY PECULIAR 2451 01:46:09,120 --> 01:46:12,160 ASPECTS EXPERIENCING MYSTICAL 2452 01:46:12,160 --> 01:46:14,360 EXPERIENCE AND CORRELATED TO 2453 01:46:14,360 --> 01:46:15,280 THERAPEUTIC OUTCOMES AND MAY BE 2454 01:46:15,280 --> 01:46:18,320 IT IS NOT JUST A MYSTICAL 2455 01:46:18,320 --> 01:46:20,720 EXPERIENCE THAT IS PREDICTIVE OF 2456 01:46:20,720 --> 01:46:22,320 PSYCH LONL INSIGHT THAT PEOPLE 2457 01:46:22,320 --> 01:46:24,400 GAIN DURING EXPERIENCES THAT 2458 01:46:24,400 --> 01:46:26,320 LEAD TO THERAPEUTIC OUTCOME AND 2459 01:46:26,320 --> 01:46:29,400 AGAIN ARE EARLY STAGE STUDIES 2460 01:46:29,400 --> 01:46:32,000 STILL. LOTS OF EFFECTS HAVE TO 2461 01:46:32,000 --> 01:46:35,840 BE FULLY REPLICATED ACROSS ALL 2462 01:46:35,840 --> 01:46:36,080 SITES. 2463 01:46:36,080 --> 01:46:38,120 >>ANOTHER INTERESTING QUESTION, 2464 01:46:38,120 --> 01:46:43,000 YOU FOCUS ON SEROTONIN RECEPTOR 2465 01:46:43,000 --> 01:46:48,440 BASED ON ELEGANT WORK YOU HAVE 2466 01:46:48,440 --> 01:46:52,680 DONE AND IS THERE A ROLE OF 2467 01:46:52,680 --> 01:46:59,360 OTHER CENTRAL NERVOUS SYSTEM 2468 01:46:59,360 --> 01:47:01,160 RECEPTORS THAT DO THEY 2469 01:47:01,160 --> 01:47:01,800 PARTICIPATE? 2470 01:47:01,800 --> 01:47:04,120 IS THERE ANY EVIDENCE OF THERE 2471 01:47:04,120 --> 01:47:07,360 BEING INTRINSICALLY INVOLVED OR 2472 01:47:07,360 --> 01:47:07,720 SECONDARILY? 2473 01:47:07,720 --> 01:47:09,560 WHAT IS STATUS OF THAT? 2474 01:47:09,560 --> 01:47:10,680 WHAT -- 2475 01:47:10,680 --> 01:47:13,040 >>I WOULD SAY IT DEPENDS ON 2476 01:47:13,040 --> 01:47:15,200 DRUG. YOU KNOW, PSYCHEDELICS 2477 01:47:15,200 --> 01:47:17,160 AND CLASSIC PSYCHEDELICS THAT 2478 01:47:17,160 --> 01:47:21,320 FRED MENTIONED ARE 5HT2A 2479 01:47:21,320 --> 01:47:23,640 AGONISTS THAT HAVE UNIQUE 2480 01:47:23,640 --> 01:47:28,720 POLYPHARMACOLOGY PROFILE AND 2481 01:47:28,720 --> 01:47:29,680 AMPHETAMINE PROFILES ARE 2482 01:47:29,680 --> 01:47:34,080 SELECTED FOR 2HC AND 2P AND 2483 01:47:34,080 --> 01:47:37,400 TRIPTO MEANS ARE LESS SELECTIVE 2484 01:47:37,400 --> 01:47:39,880 HITTING SEROTONIN RECEPTORS AND 2485 01:47:39,880 --> 01:47:40,640 [INDISCERNIBLE] ARE LESS THAN 2486 01:47:40,640 --> 01:47:45,000 THAT HITTING DOPAMINE RECEPTORS 2487 01:47:45,000 --> 01:47:46,200 AND [INDISCERNIBLE] RECEPTORS 2488 01:47:46,200 --> 01:47:48,680 AND YOU CAN DO A TEST IN RODENTS 2489 01:47:48,680 --> 01:47:51,360 WHERE BASICALLY YOU TRAIN THEM 2490 01:47:51,360 --> 01:47:55,840 TO PRESS A LEVER WHEN YOU GIVE 2491 01:47:55,840 --> 01:47:57,480 THEM A PSYCHEDELIC DRUG. YOU 2492 01:47:57,480 --> 01:48:05,560 CAN USE IT TO TEASE OUT 2493 01:48:05,560 --> 01:48:07,360 MECHANISM WITH SUBJECTIVE 2494 01:48:07,360 --> 01:48:10,760 EXPERIENCE AND LSD AND DOPAMINE 2495 01:48:10,760 --> 01:48:12,880 EARTHIC SYSTEM THAT SEEMS TO BE 2496 01:48:12,880 --> 01:48:15,200 IMPORTANT FOR THAT PARTICULAR 2497 01:48:15,200 --> 01:48:18,440 EXPERIENCE OF THOSE ANIMALS THAT 2498 01:48:18,440 --> 01:48:22,480 ARE ADMINISTERED LSD. 2499 01:48:22,480 --> 01:48:25,480 >>FRED, THERE IS A QUESTION 2500 01:48:25,480 --> 01:48:26,880 ABOUT I MENTIONED IN 2501 01:48:26,880 --> 01:48:28,320 INTRODUCTION THE WORD MUSIC. 2502 01:48:28,320 --> 01:48:30,120 YOU DIDN'T COMMENT ABOUT IT. 2503 01:48:30,120 --> 01:48:33,240 DO YOU -- SOMEONE ASKED WHAT IS 2504 01:48:33,240 --> 01:48:36,120 RELATIONSHIP THAT IS BETWEEN 2505 01:48:36,120 --> 01:48:38,960 MUSIC AND PSYCHEDELIC EFFECTS 2506 01:48:38,960 --> 01:48:39,600 AND TREATMENT? 2507 01:48:39,600 --> 01:48:42,360 >>I'M SORRY FOR NOT PICKING UP 2508 01:48:42,360 --> 01:48:44,200 ON THAT. I KNOW I HEARD YOU SAY 2509 01:48:44,200 --> 01:48:46,040 THAT. I CAN SPEAK FOR ANOTHER 2510 01:48:46,040 --> 01:48:48,440 HOUR AND A HALF ABOUT 2511 01:48:48,440 --> 01:48:50,400 RELATIONSHIP BETWEEN MUSIC AND 2512 01:48:50,400 --> 01:48:53,360 PSYCHEDELICS AND DIDN'T WANT TO 2513 01:48:53,360 --> 01:48:53,920 BEHAVIOR THE POINT. 2514 01:48:53,920 --> 01:48:55,920 >>YOU CAN TALK AS LONG AS YOU 2515 01:48:55,920 --> 01:48:58,640 WANT. WE CAN GO HOME IN 10 2516 01:48:58,640 --> 01:48:58,880 MINUTES. 2517 01:48:58,880 --> 01:49:00,440 >>OKAY. I WILL TRY TO SEE WHAT 2518 01:49:00,440 --> 01:49:06,320 I CAN DO WITH THIS. 2519 01:49:06,320 --> 01:49:08,560 SO SOME OF EARLIER STUDIES WITH 2520 01:49:08,560 --> 01:49:10,880 LSD IN CLINIC AND RESEARCH LAB 2521 01:49:10,880 --> 01:49:12,840 WERE SET BY A NUMBER OF PROBLEMS 2522 01:49:12,840 --> 01:49:14,600 MOSTLY DOO YOU TO IGNORANCE 2523 01:49:14,600 --> 01:49:17,680 ABOUT SUBJECTIVE EFFECTS OF 2524 01:49:17,680 --> 01:49:19,080 DRUGS AND SOME ADMINISTRATIONS 2525 01:49:19,080 --> 01:49:22,000 OF LSD THAT OCCURRED EARLY ON IN 2526 01:49:22,000 --> 01:49:26,040 HISTORY OF USE OF COMPOUNDS IN 2527 01:49:26,040 --> 01:49:28,480 CLINIC AND LAB. THEY OCCURRED 2528 01:49:28,480 --> 01:49:30,360 WITHOUT MUCH PSYCHOLOGICAL 2529 01:49:30,360 --> 01:49:35,120 SUPPORT IF AT ALL AND STORIES 2530 01:49:35,120 --> 01:49:37,480 BEING STRAPPED TO GURNEY 2531 01:49:37,480 --> 01:49:41,520 SUBJECTED WITH LSD WITHOUT PRIOR 2532 01:49:41,520 --> 01:49:44,040 PREPLATION THAT LEFT HOURS ON 2533 01:49:44,040 --> 01:49:46,200 ENDS AND NOT ENDING WELL AND 2534 01:49:46,200 --> 01:49:48,240 THROUGH RECEIVED KNOWLEDGE FROM 2535 01:49:48,240 --> 01:49:50,640 INDIGENOUS PRACTICE OR 2536 01:49:50,640 --> 01:49:53,200 EXPERIMENTATION AND NATURAL 2537 01:49:53,200 --> 01:49:56,560 EVOLUTION OF THIS EXPERIENCE 2538 01:49:56,560 --> 01:49:58,600 PEOPLE REALIZED CREATING 2539 01:49:58,600 --> 01:49:59,240 COMFORTABLE ENVIRONMENT THIS 2540 01:49:59,240 --> 01:50:01,280 COULD BE BETTER RECEIVED THAN 2541 01:50:01,280 --> 01:50:03,640 CHAOTIC OR UNCONTROLLED OR 2542 01:50:03,640 --> 01:50:07,800 UNCOMFORTABLE ENVIRONMENT AND IS 2543 01:50:07,800 --> 01:50:09,880 ACTUALLY A CIRCUIT LEVEL 2544 01:50:09,880 --> 01:50:11,160 NEUROSCIENCE HERE TO BE EXPLORED 2545 01:50:11,160 --> 01:50:14,520 AND 2A RECEPTORS EXPRESSED ALONG 2546 01:50:14,520 --> 01:50:16,960 AUDITORY PATHWAY NOT ON COCHLEAR 2547 01:50:16,960 --> 01:50:21,160 NERVE BUT IN GENETIC NUCLEI AND 2548 01:50:21,160 --> 01:50:24,080 IN BRAINSTEM NUCLEI THAT LEAD TO 2549 01:50:24,080 --> 01:50:26,200 PRIMARY AUDITORY CORTEX AND ARE 2550 01:50:26,200 --> 01:50:29,040 EARLIER ANIMAL STUDIES THAT ARE 2551 01:50:29,040 --> 01:50:32,320 DEMONSTRATING ACTIVATION OF 2552 01:50:32,320 --> 01:50:35,040 SEROTONIN 2A RECEPTOR CHANGING 2553 01:50:35,040 --> 01:50:36,200 FIELDS OF CERTAIN AUDITORY 2554 01:50:36,200 --> 01:50:39,920 NEURONS IN THIS PATHWAY AND ALSO 2555 01:50:39,920 --> 01:50:42,960 YOU KNOW RESPONSE PROFILES AND 2556 01:50:42,960 --> 01:50:44,520 FREQUENCY RESPONSE PROFILES FOR 2557 01:50:44,520 --> 01:50:48,120 NEURONS AND IS A BASIC AUDITORY 2558 01:50:48,120 --> 01:50:50,760 NEUROSCIENCE PLAYING IN 2559 01:50:50,760 --> 01:50:53,160 PSYCHEDELIC EXPERIENCES THAT 2560 01:50:53,160 --> 01:50:54,400 CHANGES FUNDAMENTAL WAY THAT YOU 2561 01:50:54,400 --> 01:50:57,600 HEAR SOUND AND IN PARTICULAR 2562 01:50:57,600 --> 01:50:57,840 MUSIC. 2563 01:50:57,840 --> 01:51:01,320 THERE ARE LOTS OF STUDIES THAT 2564 01:51:01,320 --> 01:51:04,400 COULD BE DONE TO TRY TO 2565 01:51:04,400 --> 01:51:07,000 DETERMINE BASIC AUDITORY 2566 01:51:07,000 --> 01:51:08,480 NEUROSCIENCE THAT HAVE BY AND 2567 01:51:08,480 --> 01:51:10,200 LARGE NOT BEEN DONE AND PEOPLE 2568 01:51:10,200 --> 01:51:13,880 COME ING OUT OF EXPERIENCES AND 2569 01:51:13,880 --> 01:51:16,360 ALONG WAY WHEN FOLKS REALIZE 2570 01:51:16,360 --> 01:51:18,440 TUNING SETTING OR CONTEXT OF 2571 01:51:18,440 --> 01:51:20,200 ENVIRONMENT OF EXPERIENCE THAT 2572 01:51:20,200 --> 01:51:22,240 CAN HELP PROVIDE STABLE PLATFORM 2573 01:51:22,240 --> 01:51:23,800 FOR PEOPLE TO HAVE EXPERIENCES 2574 01:51:23,800 --> 01:51:26,320 THAT IS MUCH MORE COMFORTABLE 2575 01:51:26,320 --> 01:51:28,280 ENVIRONMENT AND PEOPLE REALLY 2576 01:51:28,280 --> 01:51:31,400 PLAYED WITH MUSIC AND BEGAN TO 2577 01:51:31,400 --> 01:51:34,120 FIND THAT PSYCHEDELICS CAN 2578 01:51:34,120 --> 01:51:36,360 REALLY, REALLY DEEPEN AND CHANGE 2579 01:51:36,360 --> 01:51:40,520 HOW YOU EXPERIENCE MUSIC PEOPLE 2580 01:51:40,520 --> 01:51:45,920 COMING OUT OF HYDROPSILOCYBIN 2581 01:51:45,920 --> 01:51:47,400 MUSICIANS SAID THEY BECAME AND 2582 01:51:47,400 --> 01:51:50,280 WERE INSEPARABLE FROM THE MUSIC 2583 01:51:50,280 --> 01:51:52,520 AND THEY FELT EVERY NOTE PLAYED 2584 01:51:52,520 --> 01:51:55,760 AND CLAIMING RADICAL THINGS SUCH 2585 01:51:55,760 --> 01:51:59,600 AS I UNDERSTOOD WHAT THE 2586 01:51:59,600 --> 01:52:01,960 COMPOSER MEANT WHEN THEY TRIED 2587 01:52:01,960 --> 01:52:03,520 TO EXPRESS AND COMPOSE THIS 2588 01:52:03,520 --> 01:52:05,800 PIECE AND THAT IS UNVERIFIABLE 2589 01:52:05,800 --> 01:52:07,960 AND BEST LEFT TO SPECULATION BUT 2590 01:52:07,960 --> 01:52:11,240 SEEMS TO ME INCONTROVERTIBLE 2591 01:52:11,240 --> 01:52:14,600 THAT PSYCHEDELICS REALLY OPEN A 2592 01:52:14,600 --> 01:52:18,080 PERSON UP IN A PROFOUND WAY TO 2593 01:52:18,080 --> 01:52:22,720 DEEPLY IMMERSING THEMSELVES AND 2594 01:52:22,720 --> 01:52:24,960 BECOMING ABSORBED IN AESTHETIC 2595 01:52:24,960 --> 01:52:27,320 EXPERIENCES THAT HAVE BEEN 2596 01:52:27,320 --> 01:52:28,560 ATTEMPTS TO UNDERSTANDING THIS. 2597 01:52:28,560 --> 01:52:30,400 IN FACT INTERESTING STORY TO 2598 01:52:30,400 --> 01:52:33,120 TELL ABOUT A WOMAN NAMED HELEN 2599 01:52:33,120 --> 01:52:35,320 BONNIE WHO WAS A PSYCHIATRIC 2600 01:52:35,320 --> 01:52:38,960 NURSE AT MARYLAND PSYCHIATRIC 2601 01:52:38,960 --> 01:52:40,320 INSTITUTE IN SPRING GROVE 2602 01:52:40,320 --> 01:52:42,480 RESEARCH CENTER IN MARYLAND WHO 2603 01:52:42,480 --> 01:52:47,520 WAS A PRIMARY PSYCHIATRIC NURSE 2604 01:52:47,520 --> 01:52:50,160 INVOLVED IN [INDISCERNIBLE] 2605 01:52:50,160 --> 01:52:57,520 THERE AND CONCERT VIOLINIST AND 2606 01:52:57,520 --> 01:53:00,640 MUSICAL PROFILE AND BACK IN DAY 2607 01:53:00,640 --> 01:53:05,640 PEOPLE WOULD -- SIT WITH BOX OF 2608 01:53:05,640 --> 01:53:07,520 VINYL AND THEY ARE 2609 01:53:07,520 --> 01:53:09,120 GETTINGAGETATED AND I WILL PUT 2610 01:53:09,120 --> 01:53:11,240 ON SOMETHING CALM AND THEY ARE 2611 01:53:11,240 --> 01:53:13,160 GETTING TOO CALM I WILL PUT 2612 01:53:13,160 --> 01:53:14,840 SOMETHING ON TO STIR THE POT AND 2613 01:53:14,840 --> 01:53:17,520 GET THEM ENGAGED PSYCHOLOGICALLY 2614 01:53:17,520 --> 01:53:22,400 AND HELEN CAME UP WITH A METHOD 2615 01:53:22,400 --> 01:53:25,760 GUIDED MUSIC DIFFERENT PHASES OF 2616 01:53:25,760 --> 01:53:28,520 PSYCHEDELIC EXPERIENCE AND 2617 01:53:28,520 --> 01:53:30,440 CONTROLLED SUBSTANCE ACT WAS 2618 01:53:30,440 --> 01:53:34,800 PASSED AND THIS WENT AWAY DIDN'T 2619 01:53:34,800 --> 01:53:38,960 STOP BEING A MUSIC FILE -- 2620 01:53:38,960 --> 01:53:40,040 GUIDED IMAGERY WITH WITH NEW 2621 01:53:40,040 --> 01:53:42,280 MUSIC THAT EXISTS OUTSIDE OF 2622 01:53:42,280 --> 01:53:44,400 PSYCHEDELICS AND TO SAY THERE IS 2623 01:53:44,400 --> 01:53:54,920 A WHOLE WORLD HERE TO EXPLORE -- 2624 01:53:56,400 --> 01:53:58,680 >>AND YES. WE ARE SLOWLY 2625 01:53:58,680 --> 01:54:00,440 RUNNING OUT OF TIME. HERE WE 2626 01:54:00,440 --> 01:54:03,240 WANT TO END WITH TWO REALLY 2627 01:54:03,240 --> 01:54:04,600 CRITICAL QUESTIONS. 2628 01:54:04,600 --> 01:54:07,520 ONE, IS THE FREQUENT OR 2629 01:54:07,520 --> 01:54:13,280 LONG-TERM USE OF PSYCHEDELICS 2630 01:54:13,280 --> 01:54:13,520 SAFE? 2631 01:54:13,520 --> 01:54:19,400 >>DEPENDS. DEPENDS. 2632 01:54:19,400 --> 01:54:21,360 PSYCHEDELICS ARE MEDICALLY SAFE 2633 01:54:21,360 --> 01:54:23,400 FOR THE RIGHT PROPERLY SCREENED 2634 01:54:23,400 --> 01:54:25,040 INDIVIDUALS WHEN ADMINISTERED IN 2635 01:54:25,040 --> 01:54:27,520 A CONTROLLED ENVIRONMENT THAT WE 2636 01:54:27,520 --> 01:54:29,080 DON'T HAVE A LOT OF INFORMATION 2637 01:54:29,080 --> 01:54:31,360 ABOUT CHRONIC USE OF 2638 01:54:31,360 --> 01:54:32,680 PSYCHEDELICS AND CONCERN ABOUT 2639 01:54:32,680 --> 01:54:35,720 MICRO DOSING MOVEMENT IS DUE TO 2640 01:54:35,720 --> 01:54:39,320 POTENTIAL BINDING OF VARIOUS 2641 01:54:39,320 --> 01:54:41,360 PSYCHEDELIC DRUGS TO SEROTONIN 2642 01:54:41,360 --> 01:54:44,760 2B RECEPTORS EXPRESSED ON WALLS 2643 01:54:44,760 --> 01:54:47,840 OF THE HEART AND CHRONIC 2644 01:54:47,840 --> 01:54:49,760 ADMINISTRATION DRUG AND DISEASE 2645 01:54:49,760 --> 01:54:53,320 AND CARDIO MYOPATHY THAT IS 2646 01:54:53,320 --> 01:54:55,040 HYPOTHETICAL RISK NOT BORED OUT 2647 01:54:55,040 --> 01:54:57,520 BY EVIDENCE BUT A CONCERN. 2648 01:54:57,520 --> 01:55:01,560 >>OKAY. AND ANOTHER CRITICAL 2649 01:55:01,560 --> 01:55:05,240 QUESTION, GIVEN HUGE PUBLIC HYPE 2650 01:55:05,240 --> 01:55:07,760 ABOUT PSYCHEDELICS, HOW DOES 2651 01:55:07,760 --> 01:55:11,280 THAT INFLUENCE SELECTION OF 2652 01:55:11,280 --> 01:55:14,680 PATIENTS FOR YOUR STUDY? 2653 01:55:14,680 --> 01:55:17,000 CAN YOU HAVE A REAL CONTROL IF 2654 01:55:17,000 --> 01:55:20,480 THE EXPERIENCE IS REQUIRED FOR 2655 01:55:20,480 --> 01:55:22,640 LONG TERM EFFECTS? IS THAT A 2656 01:55:22,640 --> 01:55:25,320 PRACTICAL PROBLEM IN TRYING TO 2657 01:55:25,320 --> 01:55:28,120 DO CLINICAL STUDIES THAT HAVE 2658 01:55:28,120 --> 01:55:30,240 PEOPLE THAT ALREADY HAVE 2659 01:55:30,240 --> 01:55:32,080 ANTICIPATION AND ALL KINDS OF 2660 01:55:32,080 --> 01:55:35,040 INFORMATION THAT I SUSPECT IS 2661 01:55:35,040 --> 01:55:37,200 VERY MISLEADING. 2662 01:55:37,200 --> 01:55:38,640 SO, MAYBE A BRIEF FINAL COMMENT 2663 01:55:38,640 --> 01:55:40,560 ABOUT THAT, DAVID. 2664 01:55:40,560 --> 01:55:42,480 WHAT IS YOUR VIEW? 2665 01:55:42,480 --> 01:55:44,000 >>I THINK THAT FRED PROBABLY 2666 01:55:44,000 --> 01:55:45,520 WOULD BE A BETTER PERSON TO 2667 01:55:45,520 --> 01:55:46,640 ANSWER THIS QUESTION. 2668 01:55:46,640 --> 01:55:50,840 I WILL SAY THAT, YOU KNOW, 2669 01:55:50,840 --> 01:55:52,360 EXPECTATIONS ARE A HUGE ISSUE 2670 01:55:52,360 --> 01:55:55,720 FOR CLINICAL TRIALS. 2671 01:55:55,720 --> 01:55:58,480 IN DESIGNING PLACEBO CONTROLLED 2672 01:55:58,480 --> 01:56:02,440 CLINICAL TRIALS IS INCREDIBLY 2673 01:56:02,440 --> 01:56:03,240 CHALLENGING AND MAYBE IMPOSSIBLE 2674 01:56:03,240 --> 01:56:05,440 IN SOME WAYS AND WAYS TO GET 2675 01:56:05,440 --> 01:56:08,400 EFFICACY WITHOUT DOING STANDARD 2676 01:56:08,400 --> 01:56:10,480 PLACEBO CLINICAL TRIAL AND FDA 2677 01:56:10,480 --> 01:56:13,200 PUSHED FOR DOSE RESPONSE STUDIES 2678 01:56:13,200 --> 01:56:14,960 SEEING NICE DOSE ESCALATION, YOU 2679 01:56:14,960 --> 01:56:16,920 KNOW, YOU CAN FILL IN FOR THE 2680 01:56:16,920 --> 01:56:19,160 DRUG THAT IS EFFICACIOUS. FRED, 2681 01:56:19,160 --> 01:56:21,040 WANTING TO PICK UP ON THIS? 2682 01:56:21,040 --> 01:56:22,720 >>YEAH. JUST TO SAY THAT THE 2683 01:56:22,720 --> 01:56:26,560 QUESTION OF HOW DO YOU BLIND A 2684 01:56:26,560 --> 01:56:28,840 MYSTICAL EXPERIENCE. IS IT A 2685 01:56:28,840 --> 01:56:31,400 PERTINENT ONE OR STRUGGLE FOR 2686 01:56:31,400 --> 01:56:32,880 FIELD AND VERY IMPERFECT ACT OF 2687 01:56:32,880 --> 01:56:34,560 CONTROL CONDITIONS THAT HAVE 2688 01:56:34,560 --> 01:56:38,320 BEEN ATTEMPTED LIKE NIEOCENE AND 2689 01:56:38,320 --> 01:56:41,400 METHO FEN ADATE AND SOMETHING 2690 01:56:41,400 --> 01:56:43,440 THAT THE FIELD CONTINUES TO 2691 01:56:43,440 --> 01:56:45,720 STRUGGLE WITH FOR SURE. 2692 01:56:45,720 --> 01:56:50,320 >>SO, IS IT A CONTROLLED 2693 01:56:50,320 --> 01:56:50,600 SUBSTANCE? 2694 01:56:50,600 --> 01:56:51,040 >>YES. 2695 01:56:51,040 --> 01:56:52,400 >>YES, IT IS. 2696 01:56:52,400 --> 01:56:54,120 >>IN SAME WAY AS PEOPLE THAT 2697 01:56:54,120 --> 01:57:01,800 ARE GROWING MARIJUANA PLANTS 2698 01:57:01,800 --> 01:57:03,600 THEY CAN GET THEIR OWN 2699 01:57:03,600 --> 01:57:05,400 MUSHROOMS. IS THAT A PRACTICAL 2700 01:57:05,400 --> 01:57:07,880 ISSUE YOU THINK FROM PRACTICAL 2701 01:57:07,880 --> 01:57:09,920 HEALTH STANDPOINT OR SHOULDN'T 2702 01:57:09,920 --> 01:57:13,040 WE BE CONCERNED ABOUT THAT? 2703 01:57:13,040 --> 01:57:15,120 >>MY CONCERN LIKE FRED 2704 01:57:15,120 --> 01:57:16,120 MENTIONED WHEN COMPOUNDS ARE 2705 01:57:16,120 --> 01:57:18,320 GIVEN IN A SAFE ENVIRONMENT AND 2706 01:57:18,320 --> 01:57:20,120 SUPPORTIVE ENVIRONMENT THEY 2707 01:57:20,120 --> 01:57:22,560 COULD BE ADMINISTERED AND BE 2708 01:57:22,560 --> 01:57:24,680 SAFE AND INCREDIBLY HELPFUL FOR 2709 01:57:24,680 --> 01:57:27,360 PATIENTS WHEN ADMINISTERED IN 2710 01:57:27,360 --> 01:57:28,600 UNCONTROLLED ENVIRONMENTS THOUGH 2711 01:57:28,600 --> 01:57:30,720 THERE ARE GREATER RISKS OF 2712 01:57:30,720 --> 01:57:32,560 COURSE AND DECRIMINALIZATION 2713 01:57:32,560 --> 01:57:34,720 EFFORTS AND GREATER ACCESS TO 2714 01:57:34,720 --> 01:57:36,400 MOLECULES IN GENERAL PUBLIC WE 2715 01:57:36,400 --> 01:57:39,200 HAVE TO BE CONCERNED ABOUT THOSE 2716 01:57:39,200 --> 01:57:43,480 TYPES OF ADVERSE EVENTS. 2717 01:57:43,480 --> 01:57:47,280 >>GOOD. WELL, LISTEN, ON 2718 01:57:47,280 --> 01:57:50,480 BEHALF OF THE HUNDREDS OR MAYBE 2719 01:57:50,480 --> 01:57:51,840 THOUSANDS OF PEOPLE AROUND THE 2720 01:57:51,840 --> 01:57:54,400 WORLD, I FORGOT TO MENTION THAT 2721 01:57:54,400 --> 01:57:57,360 FOLKS IN 38 DIFFERENT COUNTRIES 2722 01:57:57,360 --> 01:57:58,800 NOW DOWNLOAD THESE PROGRAMS 2723 01:57:58,800 --> 01:58:01,200 EITHER LIKE NOW OR FROM THE 2724 01:58:01,200 --> 01:58:01,960 VIDEO ARCHIVE. 2725 01:58:01,960 --> 01:58:06,160 ON BEHALF OF EVERYBODY, WE WANT 2726 01:58:06,160 --> 01:58:08,560 TO REALLY THANK YOU FOR VERY 2727 01:58:08,560 --> 01:58:10,760 EXCITING AND INSIGHTFUL 2728 01:58:10,760 --> 01:58:13,800 PRESENTATIONS OF THE STATE OF 2729 01:58:13,800 --> 01:58:14,920 THE SITUATION. 2730 01:58:14,920 --> 01:58:17,560 IT IS OBVIOUSLY EVOLVING AND WE 2731 01:58:17,560 --> 01:58:20,600 WILL HEAR MUCH, MUCH MORE ABOUT 2732 01:58:20,600 --> 01:58:21,400 IT. 2733 01:58:21,400 --> 01:58:25,480 BOTH FROM A CLINICAL 2734 01:58:25,480 --> 01:58:26,360 INVESTIGATIVE STANDPOINT AND 2735 01:58:26,360 --> 01:58:31,000 ALSO BRIDGING THE THEME OF THE 2736 01:58:31,000 --> 01:58:32,520 COURSE TO A REDUCTION 2737 01:58:32,520 --> 01:58:34,600 UNDERSTANDING OF WHAT IS GOING 2738 01:58:34,600 --> 01:58:35,360 ON. 2739 01:58:35,360 --> 01:58:38,000 SO, THANK YOU ALL VERY MUCH. 2740 01:58:38,000 --> 01:58:40,040 THERE ARE SOME ADDITIONAL 2741 01:58:40,040 --> 01:58:42,320 QUESTIONS THAT I WILL LOOK 2742 01:58:42,320 --> 01:58:43,000 THROUGH. 2743 01:58:43,000 --> 01:58:45,440 PERHAPS I CAN SEND THEM OFF TO 2744 01:58:45,440 --> 01:58:47,120 YOU IF YOU WISH TO ANSWER TO THE 2745 01:58:47,120 --> 01:58:49,200 INDIVIDUAL WHO PRESENTED THEM. 2746 01:58:49,200 --> 01:58:52,240 SO, THANK YOU ALL AGAIN. 2747 01:58:52,240 --> 01:58:54,480 WE APPRECIATE VERY MUCH YOUR 2748 01:58:54,480 --> 00:00:00,000 PARTICIPATING.