1 00:00:11,916 --> 00:00:12,884 GOOD MORNING, EVERYONE, AND 2 00:00:12,884 --> 00:00:16,721 WELCOME TO WHAT I THINK IS THE 3 00:00:16,721 --> 00:00:19,524 PENULTIMATE EVENT OF THIS YEAR'S 4 00:00:19,524 --> 00:00:22,660 RESEARCH FESTIVAL AND WHAT A 5 00:00:22,660 --> 00:00:23,828 FESTIVAL IT HAS BEEN. I THANK 6 00:00:23,828 --> 00:00:26,798 ALL OF YOU FOR BEING HERE AND I 7 00:00:26,798 --> 00:00:29,934 MUST THANK BEFORE I SAY ANYTHING 8 00:00:29,934 --> 00:00:34,372 ELSE THE CHEN FAMILY FOR BEING 9 00:00:34,372 --> 00:00:39,510 WITH US AND FOR DR. CHEN WHO I 10 00:00:39,510 --> 00:00:42,180 FEEL I KNOW PERSONALLY WHO I 11 00:00:42,180 --> 00:00:43,815 JUST MET BECAUSE HIS PHOTOGRAPH 12 00:00:43,815 --> 00:00:45,750 SITS VERY SQUARELY ABOVE MY DESK 13 00:00:45,750 --> 00:00:47,318 AND SO YOU HAVE BEEN WITHOUT 14 00:00:47,318 --> 00:00:49,620 KNOWING IT, DR. CHEN, YOU'VE 15 00:00:49,620 --> 00:00:50,655 BEEN WATCHING OVER ME FOR THE 16 00:00:50,655 --> 00:00:53,091 YEAR THAT I'VE BEEN THE DDIR SO 17 00:00:53,091 --> 00:00:57,729 I THANK YOU VERY, VERY MUCH FOR 18 00:00:57,729 --> 00:00:59,497 THAT. SO I WILL BEGIN BY 19 00:00:59,497 --> 00:01:00,998 TELLING YOU A LITTLE BIT ABOUT 20 00:01:00,998 --> 00:01:03,968 DR. CHEN. IT'S A LITTLE LIKE 21 00:01:03,968 --> 00:01:05,803 BRINGING COALS TO NEWCASTLE 22 00:01:05,803 --> 00:01:07,805 BECAUSE I SUSPECT MANY OF YOU IN 23 00:01:07,805 --> 00:01:08,806 THE AUDIENCE KNOW HIM MUCH 24 00:01:08,806 --> 00:01:11,809 BETTER THAN I. AND THEN I WILL 25 00:01:11,809 --> 00:01:14,178 INTRODUCE THIS MORNING'S 26 00:01:14,178 --> 00:01:16,147 SPEAKER. SO DR. CHEN RECEIVED 27 00:01:16,147 --> 00:01:18,883 HIS PH.D. IN PHARMACOLOGY FROM 28 00:01:18,883 --> 00:01:28,860 THE UNIVERSITY OF ROCHESTER. HE 29 00:01:28,860 --> 00:01:32,363 HAD A VERY DISTINGUISHED CAREER. 30 00:01:32,363 --> 00:01:34,799 HE WAS IN A PUBLICATION THAT 31 00:01:34,799 --> 00:01:37,068 DESCRIBED THE ANALYTICAL 32 00:01:37,068 --> 00:01:38,436 TECHNIQUE FOR DETERMINATION OF 33 00:01:38,436 --> 00:01:44,075 INCOVER -- INORGANIC PHOSPHATE. 34 00:01:44,075 --> 00:01:46,177 HE SERVED UNDER EIGHT DIRECTORS. 35 00:01:46,177 --> 00:01:52,850 YOU SHOULD GET AN AWARD FOR D 36 00:01:52,850 --> 00:01:54,886 DIP -- DIPLOMACY. THAT HAS TO 37 00:01:54,886 --> 00:01:56,354 BE UNIQUE. HE SERVED IN MANY 38 00:01:56,354 --> 00:01:59,690 ROLES AT THE NIH, HELD POSITIONS 39 00:01:59,690 --> 00:02:01,993 AT THE NATIONAL HEART INSTITUTE, 40 00:02:01,993 --> 00:02:04,061 THE DIVISION OF RESEARCH GRANTS. 41 00:02:04,061 --> 00:02:05,830 THE NATIONAL INSTITUTE OF 42 00:02:05,830 --> 00:02:06,464 GENERAL MEDICAL SCIENCES AND THE 43 00:02:06,464 --> 00:02:08,699 OFFICE OF THE DIRECTOR. THEY 44 00:02:08,699 --> 00:02:11,269 RANGED FROM BEING AN 45 00:02:11,269 --> 00:02:13,671 INVESTIGATOR TO BEING ASSOCIATE 46 00:02:13,671 --> 00:02:16,774 DIRECTOR FOR INTRAMURAL AFFAIRS 47 00:02:16,774 --> 00:02:18,876 AND ACTING DEPUTY DIRECTOR FOR 48 00:02:18,876 --> 00:02:22,847 SCIENCE FOR TWO YEARS. AS A 49 00:02:22,847 --> 00:02:24,415 SCIENCE ADMINISTRATOR, HE REALLY 50 00:02:24,415 --> 00:02:27,485 WAS KNOWN FOR HIS INNOVATION AND 51 00:02:27,485 --> 00:02:30,054 FOR HIS CREATIVITY. HIS ABILITY 52 00:02:30,054 --> 00:02:34,292 TO CREATIVELY SOLVE PROBLEMS AND 53 00:02:34,292 --> 00:02:35,593 ISSUES. HE CAME UP WITH NOVEL 54 00:02:35,593 --> 00:02:38,129 PAY AND PERSONNEL SYSTEMS FOR 55 00:02:38,129 --> 00:02:40,131 SCIENTIFIC RESEARCHERS. AND 56 00:02:40,131 --> 00:02:42,066 PROGRAMS FOR THE TRAINING OF 57 00:02:42,066 --> 00:02:48,639 FOREIGN SCIENTISTS. AT NIH. IN 58 00:02:48,639 --> 00:02:51,642 1986, DR. CHEN ESTABLISHED NIH'S 59 00:02:51,642 --> 00:02:53,845 FIRST OFFICE OF TECHNOLOGY 60 00:02:53,845 --> 00:02:56,948 TRANSFER. AND IT WAS THERE THAT 61 00:02:56,948 --> 00:03:00,685 HE IMPLEMENTED MANY, MANY 62 00:03:00,685 --> 00:03:03,221 INNOVATIVE SOLUTIONS TO THE 63 00:03:03,221 --> 00:03:06,757 INTERACTION BETWEEN NIH AS A 64 00:03:06,757 --> 00:03:09,160 GOVERNMENT AGENCY AND INDUSTRY 65 00:03:09,160 --> 00:03:12,630 OUTSIDE OF OUR FOUR WALLS. 66 00:03:12,630 --> 00:03:15,733 THINGS LIKE THE CRAY DA, THE 67 00:03:15,733 --> 00:03:18,102 COOPERATIVE RESEARCH AND 68 00:03:18,102 --> 00:03:19,403 DEVELOPMENT AGREEMENT REALLY HAD 69 00:03:19,403 --> 00:03:22,440 ITS ORIGINS WITH DR. CHEN AND I 70 00:03:22,440 --> 00:03:23,808 WOULD BET THAT MANY PEOPLE IN 71 00:03:23,808 --> 00:03:28,145 THE AUDIENCE HAVE TAKEN 72 00:03:28,145 --> 00:03:30,081 ADVANTAGE OF THIS SYNERGY 73 00:03:30,081 --> 00:03:35,920 BETWEEN NIH AND INDUSTRY. HE 74 00:03:35,920 --> 00:03:38,723 WAS KNOWN TO NIHERS FOR MANY, 75 00:03:38,723 --> 00:03:42,193 MANY GENERATIONS AS A TRUSTED 76 00:03:42,193 --> 00:03:46,531 AND COMPASSIONATE COUNSEL AND N 77 00:03:46,531 --> 00:03:48,499 VERY DIVERSE AREAS 78 00:03:48,499 --> 00:03:54,138 HE HAS EARNED THE RESPECT, THE 79 00:03:54,138 --> 00:03:56,407 AD ADMIRATION BOTH HERE AT NIH 80 00:03:56,407 --> 00:03:59,243 AND ACROSS THE UNITED STATES. 81 00:03:59,243 --> 00:04:04,482 SO A WORD ABOUT OUR SPEAKER 82 00:04:04,482 --> 00:04:07,952 TODAY. DR. CARLOS ZARATE IS NIH 83 00:04:07,952 --> 00:04:08,986 DISTINGUISHED INVESTIGATOR AND 84 00:04:08,986 --> 00:04:11,589 CHIEF OF THE SECTION ON 85 00:04:11,589 --> 00:04:14,358 NEUROBIOLOGY AND TREATMENT OF 86 00:04:14,358 --> 00:04:24,869 MOOD DISORDERS. WE'VE HAD 38 87 00:09:24,401 --> 00:09:25,069 PATENT APPLICATIONS WHICH 88 00:09:25,069 --> 00:09:27,705 RESULTED IN 19 PATENTS. I WILL 89 00:09:27,705 --> 00:09:30,875 FOCUS ONLY ON ONE WHICH IS THE 90 00:09:30,875 --> 00:09:35,379 STORY OF KETAMINE, HOW IT BECAME 91 00:09:35,379 --> 00:09:42,319 TO BE KNOWN AS SPRA VAT TO 92 00:09:42,319 --> 00:09:44,555 WHICH IS LICENSED IN 70 93 00:09:44,555 --> 00:09:46,257 COUNTRIES SO THIS IS AN OUTLINE 94 00:09:46,257 --> 00:09:48,058 OF TODAY'S TALK WHAT IS 95 00:09:48,058 --> 00:09:49,660 DEPRESSION? A BRIEF HISTORY OF 96 00:09:49,660 --> 00:09:52,329 PHARMACOLOGICAL TREATMENTS FOR 97 00:09:52,329 --> 00:09:52,963 DEPRESSION AND SUICIDE. NEXT 98 00:09:52,963 --> 00:09:54,865 GENERATION TREATMENTS FOR 99 00:09:54,865 --> 00:09:57,701 DEPRESSION AND SUICIDE WITH A 100 00:09:57,701 --> 00:09:59,937 FOCUS ON KETAMINE DEVELOPMENT 101 00:09:59,937 --> 00:10:02,940 AND IMPLEMENTATION. 102 00:10:02,940 --> 00:10:03,941 UNDERSTANDING KETAMINE'S 103 00:10:03,941 --> 00:10:06,410 MECHANISM OF ACTION AS A GATEWAY 104 00:10:06,410 --> 00:10:07,611 TO BETTER THERAPEUTICS IN THE 105 00:10:07,611 --> 00:10:12,049 FUTURE OF RAPID ACTING AND 106 00:10:12,049 --> 00:10:14,118 AGENTS FOR SUICIDE. SO WHAT IS 107 00:10:14,118 --> 00:10:18,722 DEPRESSION? WE COMMONLY SEE A 108 00:10:18,722 --> 00:10:19,623 CHECKLIST OF IF YOU HAVE THESE 109 00:10:19,623 --> 00:10:21,292 MANY SYMPTOMS YOU HAVE 110 00:10:21,292 --> 00:10:23,894 DEPRESSION AND HERE IT IS 111 00:10:23,894 --> 00:10:25,429 ILLUSTRATED IN THIS FIGURE IT 112 00:10:25,429 --> 00:10:30,868 EFFECTS ABOUT 4% OF THE POP 113 00:10:30,868 --> 00:10:33,070 HAITIAN -- POPULATION WHICH IS 114 00:10:33,070 --> 00:10:35,005 ABOUT 280 MILLION. IN A YEAR 115 00:10:35,005 --> 00:10:37,875 THERE'S 9,000 THAT COMMIT 116 00:10:37,875 --> 00:10:38,442 SUICIDE. 117 00:10:38,442 --> 00:10:39,677 THERE ARE VICTIMS REQUIRE AT 118 00:10:39,677 --> 00:10:41,979 LEAST ONE OF TWO SYMPTOMS. 119 00:10:41,979 --> 00:10:45,416 DEPRESSED MOOD OR APATHY AND 120 00:10:45,416 --> 00:10:46,283 LOST OF INTEREST WHAT WE REFER 121 00:10:46,283 --> 00:10:50,888 TO ANNA DONE YA AND FOUR OUT OF 122 00:10:50,888 --> 00:10:56,393 THESE FOLLOWING SYMPTOMS. 123 00:10:56,393 --> 00:11:02,900 CHANGES IN WEIGHT. PSYCHO MOTOR 124 00:11:02,900 --> 00:11:07,371 AGITATION, SAY KPSYCHO MOTOR 125 00:11:07,371 --> 00:11:10,407 RETARDATION, EXECUTIVE FUNCTION 126 00:11:10,407 --> 00:11:11,041 WHERE YOU HAVE PROBLEMS WITH 127 00:11:11,041 --> 00:11:12,910 MEMORY, ATTENTION, CONCENTRATION 128 00:11:12,910 --> 00:11:15,112 AND OF COURSE SUICIDAL IDEATION 129 00:11:15,112 --> 00:11:16,146 WHICH CAN UNFORTUNATELY RESULT 130 00:11:16,146 --> 00:11:17,848 IN SUICIDE. SO THIS IS KIND OF 131 00:11:17,848 --> 00:11:19,817 WHAT WE KNOW AND IF YOU START 132 00:11:19,817 --> 00:11:20,851 DOING THE MATH HERE YOU CAN FIND 133 00:11:20,851 --> 00:11:24,488 THAT THERE ARE HUNDREDS OF WAYS 134 00:11:24,488 --> 00:11:30,894 TO MAKE CRITERIA FOR MAJOR 135 00:11:30,894 --> 00:11:34,131 DEPRESSSIVE DISORDER. WE'RE 136 00:11:34,131 --> 00:11:37,067 TALKING ABOUT, THIS IS A 137 00:11:37,067 --> 00:11:38,736 HETEROGENOUS CONDITION. WE 138 00:11:38,736 --> 00:11:40,437 DON'T TALK ABOUT ONE DEPRESSION 139 00:11:40,437 --> 00:11:41,905 BUT HUNDREDS OF DEPRESSIONS AND 140 00:11:41,905 --> 00:11:45,309 WHAT NOW IS COMMONLY KNOWN AS 141 00:11:45,309 --> 00:11:47,978 THAT DEPRESSION HAS SOME CORE 142 00:11:47,978 --> 00:11:49,546 FEATURES. WHICH IS PROBLEMS NOT 143 00:11:49,546 --> 00:11:52,116 ONLY WITH MOOD BUT BEHAVIOR, 144 00:11:52,116 --> 00:11:53,617 CIRCADIAN RHYTHMS AND ACTIVITY 145 00:11:53,617 --> 00:11:54,685 LEVELS THAT RESULT IN 146 00:11:54,685 --> 00:11:55,686 SIGNIFICANT IMPAIRMENT AND 147 00:11:55,686 --> 00:11:57,521 FUNCTION AND THOSE ARE SOME KEY 148 00:11:57,521 --> 00:11:58,555 CONCEPTS THAT ARE BEING EXPLORED 149 00:11:58,555 --> 00:12:00,157 IN TODAY'S RESEARCH BUT RATHER 150 00:12:00,157 --> 00:12:01,759 THAN GOING THROUGH A CHECKLIST 151 00:12:01,759 --> 00:12:03,527 WE SHOULD HEAR IT FROM ONE OF 152 00:12:03,527 --> 00:12:05,462 OUR PATIENTS WHO I INTERVIEWED 153 00:12:05,462 --> 00:12:09,199 IF THIS WORKS, AT THE WHITE 154 00:12:09,199 --> 00:12:10,768 HOUSE MENTAL HEALTH EVENT LAST 155 00:12:10,768 --> 00:12:13,804 YEAR AND THIS WAS FROM THE 156 00:12:13,804 --> 00:12:15,873 OFFICE OF SCIENCE AND 157 00:12:15,873 --> 00:12:18,942 TECHNOLOGY. IN AS A FOCUS ON 158 00:12:18,942 --> 00:12:24,014 THE DISCOVERY AND THE RESEARCH 159 00:12:24,014 --> 00:12:26,350 THAT HAD BEEN KNOWN IN KETAMINE 160 00:12:26,350 --> 00:12:27,684 RESISTANT DEPRESSION. THIS IS 161 00:12:27,684 --> 00:12:29,153 MICHELE WHO HAS SUFFERED FROM 162 00:12:29,153 --> 00:12:29,820 LIFELONG DEPRESSION. 163 00:12:29,820 --> 00:12:32,956 >> WELL I GUESS JUST TO START 164 00:12:32,956 --> 00:12:36,226 OUT WHERE I HEADED WITH THIS 165 00:12:36,226 --> 00:12:38,629 DEPRESSION IS THAT MY OLDEST SON 166 00:12:38,629 --> 00:12:43,400 PASSED AWAY IN JULY OF 2020 AND 167 00:12:43,400 --> 00:12:44,802 OF COURSE I EXPERIENCED SHOCK 168 00:12:44,802 --> 00:12:45,969 AND INTENSE GRIEF AND THEN 169 00:12:45,969 --> 00:12:49,006 WITHIN A SHORT WHILE I WAS VERY 170 00:12:49,006 --> 00:12:51,708 DEPRESSED AND I JUST FELT 171 00:12:51,708 --> 00:12:54,344 EXTREMELY SAD AND WORTHLESS I 172 00:12:54,344 --> 00:12:58,382 DIDN'T HAVE ANY ENERGY. I FELT 173 00:12:58,382 --> 00:12:59,817 EXTREMELY HOPELESS AND JUST 174 00:12:59,817 --> 00:13:02,186 EMPTY AND I DIDN'T THINK I'D 175 00:13:02,186 --> 00:13:04,588 EVER FEEL OKAY AGAIN. I LOST 176 00:13:04,588 --> 00:13:06,090 INTEREST IN EVERYTHING. 177 00:13:06,090 --> 00:13:08,192 INCLUDING MY FAMILY, FRIENDS, 178 00:13:08,192 --> 00:13:09,660 AND HOBBIES AND, YOU KNOW, EVEN 179 00:13:09,660 --> 00:13:12,029 THE BLUE SKY AND THE SUN. YOU 180 00:13:12,029 --> 00:13:14,264 NAME IT, NOTHING WAS PLEASURABLE 181 00:13:14,264 --> 00:13:17,134 ANYMORE. I WAS HAVING A LOT OF 182 00:13:17,134 --> 00:13:18,535 DIFFICULTY SLEEPING. TROUBLE 183 00:13:18,535 --> 00:13:20,838 THINKING. AND REMEMBERING AND 184 00:13:20,838 --> 00:13:22,973 CONCENTRATING WHICH ALSO 185 00:13:22,973 --> 00:13:24,441 IMPACTED MY WORK. AND THEN IT 186 00:13:24,441 --> 00:13:28,045 GOT SO SEVERE I STARTED HAVING 187 00:13:28,045 --> 00:13:29,980 THOUGHTS OF SUICIDES. OR 188 00:13:29,980 --> 00:13:33,584 THOUGHTS OF SUICIDE AND SOME 189 00:13:33,584 --> 00:13:37,154 PLANS IN PLACE. 190 00:13:37,154 --> 00:13:38,021 >> CARLOS: THIS IS UNFORTUNATE 191 00:13:38,021 --> 00:13:41,158 BUT WHAT WE DEAL WITH ON A DAILY 192 00:13:41,158 --> 00:13:42,860 BASIS. AND WE CAN DO BETTER. 193 00:13:42,860 --> 00:13:46,763 SO LET ME GO TO THE NEXT TOPIC 194 00:13:46,763 --> 00:13:48,499 IS A BRIEF HISTORY OF THE 195 00:13:48,499 --> 00:13:51,802 PHARMACOLOGICAL TREATMENTS FOR 196 00:13:51,802 --> 00:13:54,404 DEPRESSION AND SUICIDE. SO WE 197 00:13:54,404 --> 00:13:56,507 HAVE OVER 36 DIFFERENT 198 00:13:56,507 --> 00:13:58,308 ANTIDEPRESSANTS. WHY DO WE NEED 199 00:13:58,308 --> 00:14:03,647 ANOTHER? AND LET SUMMARIZE THIS 200 00:14:03,647 --> 00:14:04,281 BRIEFLY. IT HAD A VERSE EFFECTS 201 00:14:04,281 --> 00:14:06,650 WE TALKED ABOUT MICHELE, OUR 202 00:14:06,650 --> 00:14:08,619 PATIENT, TALKED ABOUT SYMPTOMS 203 00:14:08,619 --> 00:14:10,888 BUT IT COMES DOWN TO THE 204 00:14:10,888 --> 00:14:14,358 DISRUPTION TO PERSONAL FAMILY 205 00:14:14,358 --> 00:14:17,928 AND SOCIETAL IMPAIRMENT AS WELL 206 00:14:17,928 --> 00:14:19,630 AND SO BEYOND THE SYMPTOMS YOU 207 00:14:19,630 --> 00:14:22,633 ALSO HAVE A RISK OF SUICIDAL 208 00:14:22,633 --> 00:14:23,834 BEHAVIOR AND ALTHOUGH WE HAVE 209 00:14:23,834 --> 00:14:26,870 THREE DOZEN ANTIDEPRESSANTS, 210 00:14:26,870 --> 00:14:28,005 THEY'RE ASSOCIATED WITH LOW 211 00:14:28,005 --> 00:14:30,307 REMISSION RATES. MEANING, 212 00:14:30,307 --> 00:14:32,976 SIGNIFICANT IMPROVEMENT, 30-40% 213 00:14:32,976 --> 00:14:37,781 HAVE TRD OR TREATMENT RESISTANT 214 00:14:37,781 --> 00:14:38,916 DEPRESSION MEANS YOU FILL 215 00:14:38,916 --> 00:14:39,583 MULTIPLE DIFFERENT TREATMENTS 216 00:14:39,583 --> 00:14:45,389 AND MICHELE HAS FILLED MANY T 217 00:14:45,389 --> 00:14:47,024 TYPES AND TALK THERAPIES AND THE 218 00:14:47,024 --> 00:14:49,326 NEXT IS THE LAG OF THERAPEUTIC 219 00:14:49,326 --> 00:14:50,861 DEPRESSION AND TARGET THE 220 00:14:50,861 --> 00:14:58,869 SUICIDAL THINKING. SO THIS 221 00:14:58,869 --> 00:15:01,738 FIGURE SHOWS THE MAJOR 222 00:15:01,738 --> 00:15:02,873 DEPRESSIVE EPISODE AND WHAT 223 00:15:02,873 --> 00:15:05,042 HAPPENS IS WHEN WE INITIATE 224 00:15:05,042 --> 00:15:10,814 TREATMENT WITH OUR CONVENTIONAL, 225 00:15:10,814 --> 00:15:14,518 OR TARGETING OF SEROTONIN YOU 226 00:15:14,518 --> 00:15:19,356 HAVE AN ANT ANTIDEPREZZIVE 227 00:15:19,356 --> 00:15:19,623 EFFECT. 228 00:15:19,623 --> 00:15:22,593 IT TAKES 14 WEEKS IF NOT LONGER 229 00:15:22,593 --> 00:15:24,228 AND REMEMBER, NOT EVERYONE GETS 230 00:15:24,228 --> 00:15:26,096 BETTER AND YOU ASK YOUR 231 00:15:26,096 --> 00:15:28,332 PATIENTS, HANG IN THERE, THINGS 232 00:15:28,332 --> 00:15:29,633 WILL GET BETTER. 233 00:15:29,633 --> 00:15:32,002 THEY HAVE A DISRUPTION IN THEIR 234 00:15:32,002 --> 00:15:33,770 SOCIAL LIFE AND ARE AT RISK FOR 235 00:15:33,770 --> 00:15:35,739 SUICIDE SO NEXT GENERATION 236 00:15:35,739 --> 00:15:36,340 TREATMENTS AND THIS IS NOW A 237 00:15:36,340 --> 00:15:39,109 REALITY HAVE AN ONSET WITHIN 238 00:15:39,109 --> 00:15:42,145 HOURS. OR A FEW DAYS AT MOST. 239 00:15:42,145 --> 00:15:44,014 AND THEY'RE MORE EFFECTIVE THAN 240 00:15:44,014 --> 00:15:46,817 THE PREVIOUS VERSION OF 241 00:15:46,817 --> 00:15:47,451 ANTIDEPRESSANTS AND THAT IS WHAT 242 00:15:47,451 --> 00:15:48,752 I'M GOING TO TALK ABOUT BUT 243 00:15:48,752 --> 00:15:50,053 FIRST WE NEED TO TALK ABOUT THE 244 00:15:50,053 --> 00:15:52,623 LONG AND WINDING JOURNEY OR ROAD 245 00:15:52,623 --> 00:15:53,957 TO IMPROVE THERAPEUTICS AND THIS 246 00:15:53,957 --> 00:15:58,862 IS WHERE THINGS STARTED. SO WE 247 00:15:58,862 --> 00:16:01,164 HAVE HERE THE BY SERENDIPITY 248 00:16:01,164 --> 00:16:04,468 DISCOVERY, I WON'T HAVE TIME TO 249 00:16:04,468 --> 00:16:09,039 GO INTO THAT BUT THE MONOAMINE 250 00:16:09,039 --> 00:16:10,774 SEROTONIN WERE FOUND TO HAVE 251 00:16:10,774 --> 00:16:12,276 THERAPEUTIC EFFECTS AND THIS WAS 252 00:16:12,276 --> 00:16:14,444 WONDERFUL NEWS. PEOPLE STARTED 253 00:16:14,444 --> 00:16:18,882 INVESTIGATING IT LATER ON THE 254 00:16:18,882 --> 00:16:22,586 ROLLOUT SIP GNATTIC AND PSYCHO 255 00:16:22,586 --> 00:16:24,655 TROPIC ACTIONS AND DISEASE WAS 256 00:16:24,655 --> 00:16:25,622 IDENTIFIED. 257 00:16:25,622 --> 00:16:31,528 AND IN 1987, AN SSRI FLUOXETINE, 258 00:16:31,528 --> 00:16:33,830 ALSO KNOWN AS PROZAC LED TO 259 00:16:33,830 --> 00:16:35,766 MILLIONS OF PEOPLE RECEIVING 260 00:16:35,766 --> 00:16:37,467 TREATMENT FOR DEPRESSION. AND 261 00:16:37,467 --> 00:16:42,739 THAT'S A GOOD THING. BUT WHAT 262 00:16:42,739 --> 00:16:45,242 HAPPENED WAS, AND THIS IS WHAT I 263 00:16:45,242 --> 00:16:47,811 REFER TO AS THE TITLE ME TOO 264 00:16:47,811 --> 00:16:49,313 DRUGS IS SEVERAL DIFFERENT 265 00:16:49,313 --> 00:16:53,317 CLASSES OF ANTIDEPRESSANTS EACH 266 00:16:53,317 --> 00:16:56,320 IN GENERAL WITH COMPARABLE 267 00:16:56,320 --> 00:16:57,087 EFFICACY TO THE PREVIOUS CLASS 268 00:16:57,087 --> 00:16:58,855 MAY BE BETTER TOLERATED IN TERMS 269 00:16:58,855 --> 00:17:00,524 OF SIDE EFFECTS BUT THEY WERE 270 00:17:00,524 --> 00:17:03,460 NOT BETTER THAN THE OLDER 271 00:17:03,460 --> 00:17:04,795 VERSIONS AND SO FOR LITERALLY 272 00:17:04,795 --> 00:17:06,530 SIX DECADES WE HAD WHAT WE CALL 273 00:17:06,530 --> 00:17:09,866 ME TOO DRUGS OR COPYCAT DRUGS. 274 00:17:09,866 --> 00:17:11,835 AND IT WASN'T THAT THE TRY WAS 275 00:17:11,835 --> 00:17:13,470 NOT -- THEY WERE TRYING REALLY 276 00:17:13,470 --> 00:17:15,305 HARD TO COME UP WITH NEW TARGETS 277 00:17:15,305 --> 00:17:18,842 BUT THEY DID NOT RESULT IN ANY 278 00:17:18,842 --> 00:17:21,511 NEW TREATMENT SO LET ME MOVE 279 00:17:21,511 --> 00:17:23,180 ONTO THE NEXT PART OF THE STORY 280 00:17:23,180 --> 00:17:25,015 WHICH IS NEXT GENERATION 281 00:17:25,015 --> 00:17:25,816 TREATMENTS FOR DEPRESSION AND 282 00:17:25,816 --> 00:17:28,352 SUICIDE WITH A FOCUS ON 283 00:17:28,352 --> 00:17:30,921 KETAMINE. NOW, HERE, THE STORY 284 00:17:30,921 --> 00:17:34,458 WAS THAT EVERYBODY WAS 285 00:17:34,458 --> 00:17:36,393 INTERESTED IN COMING UP WITH NEW 286 00:17:36,393 --> 00:17:38,862 VERSIONS AND IT STARTED BECOMING 287 00:17:38,862 --> 00:17:41,832 APPARENT. INDUSTRY STARTED 288 00:17:41,832 --> 00:17:44,901 LEAVING PSYCHIATRIC DRUG 289 00:17:44,901 --> 00:17:46,870 DEVELOPMENT AND THE TITLES OF 290 00:17:46,870 --> 00:17:49,539 THESE PIECES WERE -- IS PHARMA 291 00:17:49,539 --> 00:17:51,475 RUNNING OUT OF BRAINY IDEAS. 292 00:17:51,475 --> 00:17:52,876 YOU CAN SEE THE MEDICINE CAP 293 00:17:52,876 --> 00:17:54,778 NET. ONLY A FEW MEDICINES 294 00:17:54,778 --> 00:17:59,282 THERE. THE DRUG DEAD LOCK 295 00:17:59,282 --> 00:18:01,818 PHARMA COMPANIES QUITTING. 296 00:18:01,818 --> 00:18:03,754 AND THEY PREFERRED TO MOVE TO 297 00:18:03,754 --> 00:18:05,155 OTHER INFECTIOUS DISEASE WHICH 298 00:18:05,155 --> 00:18:07,924 WERE HIGHER PERCENTAGE RATES AND 299 00:18:07,924 --> 00:18:12,696 IN THE MARKET. THESE ARE THE 300 00:18:12,696 --> 00:18:14,197 CHALLENGES OF THE NEUROSCIENCE 301 00:18:14,197 --> 00:18:17,834 MARKET AND THIS IS A FUNNEL YOU 302 00:18:17,834 --> 00:18:19,736 PUT 10,000 MOLECULES, COMPOUNDS 303 00:18:19,736 --> 00:18:20,704 AND AT THE END IF YOU'RE 304 00:18:20,704 --> 00:18:22,572 FORTUNATE YOU COME OUT WITH ONE 305 00:18:22,572 --> 00:18:24,941 THE COST VARY FROM STUDY TO 306 00:18:24,941 --> 00:18:26,376 STUDY BUT IT'S QUITE 307 00:18:26,376 --> 00:18:27,644 SUBSTANTIAL. HERE YOU CAN SEE 308 00:18:27,644 --> 00:18:29,312 THE PRECLINICAL DEVELOPMENT. 309 00:18:29,312 --> 00:18:31,615 PHASE ONE STUDIES. PHASE TWO. 310 00:18:31,615 --> 00:18:34,584 AND WHEN YOU TRANSITION FROM ONE 311 00:18:34,584 --> 00:18:36,787 TO 2A TO A LITTLE BIT LATER WE 312 00:18:36,787 --> 00:18:38,889 REFER TO THIS AS THE VALLEY OF 313 00:18:38,889 --> 00:18:41,057 DEATH WHERE INDUSTRY GETS OUT OF 314 00:18:41,057 --> 00:18:45,362 BECAUSE IT'S TOO RISKY TO PURSUE 315 00:18:45,362 --> 00:18:48,598 AND THAT HAS BEEN A CONCERN. 316 00:18:48,598 --> 00:18:49,232 INTRAMURAL RESEARCH DOES FILL 317 00:18:49,232 --> 00:18:50,167 THAT VOID AND I WILL TALK ABOUT 318 00:18:50,167 --> 00:18:53,170 THAT IN A MINUTE BUT THIS IS THE 319 00:18:53,170 --> 00:18:54,571 CLINICAL APPROVAL SUCCESS RATE 320 00:18:54,571 --> 00:18:56,840 AND YOU CAN SEE THE INFECTIOUS 321 00:18:56,840 --> 00:18:58,408 DISEASE FROM ONCOLOGY WHERE YOU 322 00:18:58,408 --> 00:18:59,810 HAVE CLEAR TARGETS FOR 323 00:18:59,810 --> 00:19:00,944 PSYCHIATRY IT'S A BIT NEBULOUS 324 00:19:00,944 --> 00:19:05,816 WE RELY ON CRITERIA. AND SO WE 325 00:19:05,816 --> 00:19:08,952 HAVE THE LOWEST APPROVAL SUCCESS 326 00:19:08,952 --> 00:19:12,422 RATE IN CNS DISORDERS UNDER 8%. 327 00:19:12,422 --> 00:19:14,291 SO THIS IS WHY SOME OF THE 328 00:19:14,291 --> 00:19:15,158 REASONS THAT HAVE BEEN MENTIONED 329 00:19:15,158 --> 00:19:17,127 OR SUGGESTED WHY WE DON'T GET 330 00:19:17,127 --> 00:19:19,729 BETTER TREATMENTS FOR 331 00:19:19,729 --> 00:19:22,566 PSYCHIATRY. SHEER COMPLEXITY OF 332 00:19:22,566 --> 00:19:24,701 THE DISEASES, HIGHER -- BRAIN 333 00:19:24,701 --> 00:19:26,770 FUNCTION IS HARD OR VERY 334 00:19:26,770 --> 00:19:28,104 CHALLENGING TO MODEL CLINICALLY. 335 00:19:28,104 --> 00:19:29,806 WE TALKED ABOUT HETEROGENOUS 336 00:19:29,806 --> 00:19:30,774 CONDITIONS, HUNDREDS OF 337 00:19:30,774 --> 00:19:33,210 DEPRESSION AND SO IT'S HARD TO 338 00:19:33,210 --> 00:19:38,882 STRATIFY, COME UP WITH ENRICHED 339 00:19:38,882 --> 00:19:39,983 SUBGROUPS. ATTRITION IN LATER 340 00:19:39,983 --> 00:19:44,955 STATEMENTS -- STAGES OF THE 341 00:19:44,955 --> 00:19:47,224 DEVELOPMENT AND GENETICS AND 342 00:19:47,224 --> 00:19:48,825 PAYER PRESSURES AS WELL AND 343 00:19:48,825 --> 00:19:52,429 THESE ARE THE REASONS THAT THE 344 00:19:52,429 --> 00:19:53,630 INDUSTRY LEFT PSYCHIATRY. 345 00:19:53,630 --> 00:19:55,866 COMING UP WITH SOME TARGET, THIS 346 00:19:55,866 --> 00:19:59,536 WAS WORK IN AND A PAPER BY PHIL 347 00:19:59,536 --> 00:20:00,704 SKOAL NICK AND PLEASE REFER TO 348 00:20:00,704 --> 00:20:02,339 IT IF YOU HAVE TIME TO READ IT. 349 00:20:02,339 --> 00:20:05,809 THIS IS HOW WE COME UP WITH SOME 350 00:20:05,809 --> 00:20:07,844 NEW TARGETS. AN ESCAPABLE 351 00:20:07,844 --> 00:20:09,846 STRESS IS A PRECLINICAL TARGET 352 00:20:09,846 --> 00:20:11,281 THAT HAD BEEN EARLIER LINKED TO 353 00:20:11,281 --> 00:20:14,885 DEPRESSION. THAT MEANS I 354 00:20:14,885 --> 00:20:16,887 MENTIONED EARLIER SIR RAH TO 355 00:20:16,887 --> 00:20:18,488 ANYONE LINKED TO DEPRESSION. 356 00:20:18,488 --> 00:20:23,727 AND LATER ON IF YOU GIVE CHRONIC 357 00:20:23,727 --> 00:20:26,763 TREATMENT THAT AFFECTS SEROTONIN 358 00:20:26,763 --> 00:20:30,867 THEY HAVE ANTIDEPRESSANT LIKE 359 00:20:30,867 --> 00:20:32,002 PROPERTIES AND PRECLINICAL MODEL 360 00:20:32,002 --> 00:20:35,739 AND ALSO LATER ON DISCOVERY WAS 361 00:20:35,739 --> 00:20:41,144 IN THE STRESS LED TO LTP 362 00:20:41,144 --> 00:20:42,846 IMPAIRMENT AND THAT'S A MEASURE 363 00:20:42,846 --> 00:20:46,082 OF PLASTICITY AND THEN THE 364 00:20:46,082 --> 00:20:48,985 INVOLVEMENT OF RECEPTORS, 365 00:20:48,985 --> 00:20:51,888 KETAMINE, NNDA RECEPTORS WAS 366 00:20:51,888 --> 00:20:55,425 INVOLVED IN LONG-TERM PROTEN 367 00:20:55,425 --> 00:20:56,326 SHAGS AND WORK BY PHIL 368 00:20:56,326 --> 00:20:58,862 PSYCHOLOGICAL NICK IDENTIFIED 369 00:20:58,862 --> 00:21:00,630 THAT THEY HAVE ANTIDEPRESSANT 370 00:21:00,630 --> 00:21:02,132 LIKE PROPERTIES. 371 00:21:02,132 --> 00:21:02,966 FANTASTIC. BUT WHAT HAPPENED 372 00:21:02,966 --> 00:21:05,602 WAS NEARLY A DECADE WENT BY, NOT 373 00:21:05,602 --> 00:21:07,237 MUCH HAPPENED AND I'M GOING TO 374 00:21:07,237 --> 00:21:10,807 GET A LITTLE BIT BY AND HERE'S 375 00:21:10,807 --> 00:21:13,743 THE GROUP BY PHIL THAT LED TO 376 00:21:13,743 --> 00:21:16,079 THIS IMPORTANT BODY OF WORK 377 00:21:16,079 --> 00:21:17,247 HIGHLIGHTED IN THE GREEN. A 378 00:21:17,247 --> 00:21:19,382 DECADE PASSED BY WHERE INITIAL 379 00:21:19,382 --> 00:21:22,018 REPORT I WILL TALK ABOUT BY BOB 380 00:21:22,018 --> 00:21:26,856 BERMAN IN THE YEAR 2000 AND YOUR 381 00:21:26,856 --> 00:21:28,558 GROUP IN 2006 AND THAT WILL BE 382 00:21:28,558 --> 00:21:30,226 THE REST OF MY TALK. 383 00:21:30,226 --> 00:21:32,862 LET ME TALK ABOUT THE KETAMINE 384 00:21:32,862 --> 00:21:39,502 DRUG, AND IT'S USE. SO, CALVIN 385 00:21:39,502 --> 00:21:41,471 STEPHENS WAS -- SYNTHESIZED A 386 00:21:41,471 --> 00:21:44,507 BETTER VERSION OF PCP WHICH WAS 387 00:21:44,507 --> 00:21:47,811 KETAMINE, KETAMINE ALSO AFFECTS 388 00:21:47,811 --> 00:21:51,615 MNDA RECEPTORS. IT WAS BELIEVED 389 00:21:51,615 --> 00:21:55,318 THAT PCP WOULD BE AN EFFECTIVE 390 00:21:55,318 --> 00:21:56,953 ANESTHETIC AGENT BUT IT LASTED A 391 00:21:56,953 --> 00:22:00,457 LONG TIME. DAYS IF NOT LONGER 392 00:22:00,457 --> 00:22:05,829 AND SO SYNTHESIZE THAT AND 393 00:22:05,829 --> 00:22:07,897 SOMEONE WHO PASSED AWAY WAS 394 00:22:07,897 --> 00:22:09,065 INVOLVED IN THE CLINICAL 395 00:22:09,065 --> 00:22:11,835 DEVELOPMENT OF THIS AND IT WAS 396 00:22:11,835 --> 00:22:14,037 DESCRIBED AS A DISASSOCIATE 397 00:22:14,037 --> 00:22:15,905 ANESTHETIC WHICH MEANS YOUR MIND 398 00:22:15,905 --> 00:22:17,607 AND BODY ARE DISCONNECTED THERE 399 00:22:17,607 --> 00:22:19,209 ONE ANOTHER AND THE ADVANTAGE OF 400 00:22:19,209 --> 00:22:22,445 KETAMINE COMPARED TO OTHER 401 00:22:22,445 --> 00:22:25,582 AGENTS DID NOT CAUSE CNS 402 00:22:25,582 --> 00:22:28,218 DEPRESSION SO IN 1970 THE FDA 403 00:22:28,218 --> 00:22:30,220 APPROVES A KETAMINE AS AN 404 00:22:30,220 --> 00:22:33,256 ANESTHETIC AGENT AND IT BECAME 405 00:22:33,256 --> 00:22:36,393 KNOWN AS THE BUDDY DRUG IN THE 406 00:22:36,393 --> 00:22:37,494 VIETNAM WAR. WHY? BECAUSE IF 407 00:22:37,494 --> 00:22:38,862 YOU HAD A BUDDY NEXT TO YOU WHO 408 00:22:38,862 --> 00:22:41,231 HAD TO TREAT YOUR PAIN, YOUR 409 00:22:41,231 --> 00:22:42,432 INJURY, GIVE KETAMINE AND YOU 410 00:22:42,432 --> 00:22:44,834 WOULD NOT HAVE TO WORRY SO MUCH 411 00:22:44,834 --> 00:22:49,272 ABOUT CNS DEPRESSION COMPARED TO 412 00:22:49,272 --> 00:22:50,807 MORPHINE OR OTHER TYPES OF DRUGS 413 00:22:50,807 --> 00:22:53,443 AND SO THE ERA STARTED WHERE 414 00:22:53,443 --> 00:22:54,811 JOHN LILLY AND OTHERS, YOU 415 00:22:54,811 --> 00:22:57,080 PROBABLY KNOW ABOUT THAT, 416 00:22:57,080 --> 00:23:00,250 STARTED USING IT IN THE 417 00:23:00,250 --> 00:23:01,551 COMMUNITY TO EXPERIMENT IN IT 418 00:23:01,551 --> 00:23:02,886 AND ALSO A COMBINATION OF 419 00:23:02,886 --> 00:23:05,822 THERAPY AND IT'S SUMMARIZE THIS 420 00:23:05,822 --> 00:23:07,290 HAD THE KETAMINE PAPERS AND EVEN 421 00:23:07,290 --> 00:23:09,492 THERE'S PORTRAITS THAT DEPICT 422 00:23:09,492 --> 00:23:10,894 THIS TIME WHERE YOU CAN SEE 423 00:23:10,894 --> 00:23:13,463 HERE, THIS IS REFERRED BY -- 424 00:23:13,463 --> 00:23:17,801 THIS IS A PAINTING BY MARISSA 425 00:23:17,801 --> 00:23:20,070 BASSET AS THE KET XHEEN TIGER. 426 00:23:20,070 --> 00:23:21,571 YOU CAN SEE HERE THAT THIS IS 427 00:23:21,571 --> 00:23:25,241 THE UNIVERSE, THIS IS THE K 428 00:23:25,241 --> 00:23:26,776 HOLE, WHAT A CERTAIN EXPERIENCE 429 00:23:26,776 --> 00:23:28,445 EVERYTHING AROUND YOU IS YOU 430 00:23:28,445 --> 00:23:28,745 DON'T SEE. 431 00:23:28,745 --> 00:23:30,580 YOU JUST FOCUS ON THE TUNNEL. 432 00:23:30,580 --> 00:23:34,250 AND THIS IS YOUR BRAIN ON THE 433 00:23:34,250 --> 00:23:36,720 DRUG AND THE TWO HERE HAVE 434 00:23:36,720 --> 00:23:38,855 EFFECTS ON THE BRAIN AND ONE IS 435 00:23:38,855 --> 00:23:40,990 THE UNITY OF CONNECTION WITH THE 436 00:23:40,990 --> 00:23:42,926 UNIVERSE. AND THAT, YOU KNOW, 437 00:23:42,926 --> 00:23:46,062 BY DOSES, THE RIGHT DOSE OF 438 00:23:46,062 --> 00:23:48,932 KETAMINE YOU CAN CONTROL THE 439 00:23:48,932 --> 00:23:51,634 TIGER AND THAT WAS BELIEVED TO 440 00:23:51,634 --> 00:23:54,871 BE THE CASE. NOW LET'S LOOK AT 441 00:23:54,871 --> 00:23:56,606 THERE VERY GENERAL OVERVIEW OF 442 00:23:56,606 --> 00:23:58,108 THE RAPID ACTING -- THE 443 00:23:58,108 --> 00:24:01,277 DEVELOPMENT OF THE RAPID ACTING 444 00:24:01,277 --> 00:24:04,914 ANTIDEPRESSANT KETAMINE FOR 445 00:24:04,914 --> 00:24:05,815 SEVERE DEPRESSION AND IT WAS 446 00:24:05,815 --> 00:24:08,518 DESCRIBED THAT KETAMINE AND PCP 447 00:24:08,518 --> 00:24:12,155 WERE A RECEPTOR ANTAGONIST. AND 448 00:24:12,155 --> 00:24:13,790 THEN YALE HAD BEEN STUDYING 449 00:24:13,790 --> 00:24:16,392 KETAMINE FOR OVER A DECADE AS A 450 00:24:16,392 --> 00:24:18,528 MODEL FOR PSYCHOSIS AND FOR 451 00:24:18,528 --> 00:24:19,629 ADDICTION AND THEY WERE LOOKING 452 00:24:19,629 --> 00:24:21,264 AT COGNITION AND ALL OF A SUDDEN 453 00:24:21,264 --> 00:24:23,833 THEY FOUND IN SEVEN PATIENTS, 454 00:24:23,833 --> 00:24:25,668 STORY STARTED WITH SEVEN 455 00:24:25,668 --> 00:24:28,571 PATIENTS THAT THEY GOT BETTER IN 456 00:24:28,571 --> 00:24:32,442 A FEW HOURS. SO THAT IS RAPID 457 00:24:32,442 --> 00:24:34,344 AND PRESENT EFFECTS BUT THIS IS 458 00:24:34,344 --> 00:24:35,779 MAJOR DEPRESSION AND I'M GOING 459 00:24:35,779 --> 00:24:38,314 TO GET INTO THAT -- THE 460 00:24:38,314 --> 00:24:38,882 DIFFERENCE WITH TREATMENT 461 00:24:38,882 --> 00:24:40,984 RESISTANT DEPRESSION SO IN THE 462 00:24:40,984 --> 00:24:44,387 YEAR 2000 DENNIS AND -- WHO IS 463 00:24:44,387 --> 00:24:49,726 NOW DEAN OF DEANS AT MOUNT SINAI 464 00:24:49,726 --> 00:24:52,829 AND ANOTHER WHO WAS WITH THEM 465 00:24:52,829 --> 00:24:55,431 CREATED THE MOOD DISORDERS 466 00:24:55,431 --> 00:24:56,933 PROGRAM AND I WAS HIRED IN THE 467 00:24:56,933 --> 00:24:59,135 YEAR 2000 AND I CAME AS A STAFF 468 00:24:59,135 --> 00:25:00,503 CLINICIAN AND THEY SAID YOU HAVE 469 00:25:00,503 --> 00:25:01,938 A RESEARCH UNIT AND CAN DO WHAT 470 00:25:01,938 --> 00:25:04,207 YOU WANT AND TRY TO COME UP WITH 471 00:25:04,207 --> 00:25:06,776 BETTER TREATMENTS AND SO I WAS 472 00:25:06,776 --> 00:25:09,579 DELIGHTED TO LEAVE WHERE I WAS 473 00:25:09,579 --> 00:25:14,484 AND COME TO THE NIH AND THE 474 00:25:14,484 --> 00:25:15,485 WARREN MAGNUS SON CLINICAL 475 00:25:15,485 --> 00:25:17,120 CENTER. I'VE BEEN IN TWO 476 00:25:17,120 --> 00:25:17,554 CLINICAL CENTERS. 477 00:25:17,554 --> 00:25:18,855 WE'VE BEEN DOING THIS RESEARCH 478 00:25:18,855 --> 00:25:21,424 FOR CLOSE TO TWO DECADES WE 479 00:25:21,424 --> 00:25:23,626 SAID, LET'S DECIDE DO WE GO ON 480 00:25:23,626 --> 00:25:27,697 THE MONOALLERGIC PATHWAY LOOKING 481 00:25:27,697 --> 00:25:30,533 AT EPINEPHRINE OR DO WE GO IN A 482 00:25:30,533 --> 00:25:31,501 NEW DIRECTION. 483 00:25:31,501 --> 00:25:33,102 WE SAID LET'S GO IN A NEW 484 00:25:33,102 --> 00:25:34,904 DIRECTION AFTER THE PLASTICITY 485 00:25:34,904 --> 00:25:37,473 AND GLUTAMATE. THIS IS A 486 00:25:37,473 --> 00:25:40,510 PICTURE OF THE BAG, THE SALINE 487 00:25:40,510 --> 00:25:42,879 SOLUTION, WHY DO YOU PRESENT 488 00:25:42,879 --> 00:25:45,148 THIS AT A DISTINGUISHED LECTURE? 489 00:25:45,148 --> 00:25:47,750 IT'S THE FIRST BAG OF THE FIRST 490 00:25:47,750 --> 00:25:49,886 SUBJECT THAT WENT INTO KETAMINE 491 00:25:49,886 --> 00:25:53,289 SO YOU GIVE THE -- YOU PUT IT IN 492 00:25:53,289 --> 00:25:54,858 THERE AND THE SOLUTION AND WHAT 493 00:25:54,858 --> 00:25:57,861 HAPPENS IS THAT THE REST IS 494 00:25:57,861 --> 00:26:02,899 HISTORY. SO 2006, WE PUBLISHED 495 00:26:02,899 --> 00:26:04,167 THE FIRST PREPARE TREATMENT 496 00:26:04,167 --> 00:26:08,705 RESISTANT DEPRESSION WE KNFOCUS 497 00:26:08,705 --> 00:26:10,907 ON THIS, MAINLY FOR ETHICAL 498 00:26:10,907 --> 00:26:14,010 REASONS, AND THE OTHER BIG NEED 499 00:26:14,010 --> 00:26:14,510 FOR TREATMENT RESISTANT 500 00:26:14,510 --> 00:26:16,279 DEPRESSION TREATMENTS. AND THE 501 00:26:16,279 --> 00:26:18,781 OTHERS THAT THERE HAD BEEN MANY, 502 00:26:18,781 --> 00:26:20,984 MANY REPORTS OF RAPID ACTING 503 00:26:20,984 --> 00:26:22,185 AGENTS IN DEPRESSION. THE 504 00:26:22,185 --> 00:26:24,687 PROBLEM IS THAT THERE'S A HIGH 505 00:26:24,687 --> 00:26:26,789 PLACEBO EFFECT AND SO YOU HAVE 506 00:26:26,789 --> 00:26:28,591 TO SHOW THAT IT'S -- YOU'RE 507 00:26:28,591 --> 00:26:30,493 REALLY GETTING IT AT A LARGE 508 00:26:30,493 --> 00:26:31,794 EFFECT SIZE HERE. WE CONNECT 509 00:26:31,794 --> 00:26:34,864 THE RESEARCH ON THREE WEST IN 510 00:26:34,864 --> 00:26:38,868 THE OLDER BUILDING AND IN THE 511 00:26:38,868 --> 00:26:44,207 SOUTHEAST NORTH SIDE. AFTER 512 00:26:44,207 --> 00:26:45,775 THAT AND WE DID THREE 513 00:26:45,775 --> 00:26:48,411 INDEPENDENT CONTROLLED STUDIES 514 00:26:48,411 --> 00:26:49,712 HERE INTRAMURALLY AND THERE HAD 515 00:26:49,712 --> 00:26:53,516 BEEN UNTIL 2013 NO INDEPENDENT 516 00:26:53,516 --> 00:26:54,851 REPLICATION IN A CONTROL STUDY. 517 00:26:54,851 --> 00:26:56,853 CASE SERIES, YES BUT NOT CONTROL 518 00:26:56,853 --> 00:26:59,389 STUDY AND THAT WAS DONE -- AND A 519 00:26:59,389 --> 00:27:01,324 TWO SITE STUDY WHICH I WILL 520 00:27:01,324 --> 00:27:02,892 REVIEW BRIEFLY AND THEN OF 521 00:27:02,892 --> 00:27:05,128 COURSE IN 2019 YOU CAN SEE IT 522 00:27:05,128 --> 00:27:07,664 GOES FROM THE BAG, SALINE 523 00:27:07,664 --> 00:27:10,867 INFUSION TO INTRANASAL 524 00:27:10,867 --> 00:27:11,935 ADMINISTRATION. KNOWN AS BRO 525 00:27:11,935 --> 00:27:14,170 HAVE AED DO. SO WHAT ARE THE 526 00:27:14,170 --> 00:27:15,872 CHALLENGES IN THE BEGINNING OF 527 00:27:15,872 --> 00:27:16,873 STUDYING KETAMINE AND LET ME 528 00:27:16,873 --> 00:27:19,275 WALK YOU BACK IN THAT IN TIME 529 00:27:19,275 --> 00:27:20,777 BUT FIRST OF ALL YOU HAVE THIS 530 00:27:20,777 --> 00:27:22,879 CARTOON, KETAMINE BINDS TO THE 531 00:27:22,879 --> 00:27:26,683 PCP SITE, SORRY, HERE. WITHIN 532 00:27:26,683 --> 00:27:36,225 THE PROTEIN WHICH IS HARD TO SEE 533 00:27:36,225 --> 00:27:37,794 FROM HERE AT LEAST AND YOU HAVE 534 00:27:37,794 --> 00:27:40,229 IN RED OR ORANGE YOU HAVE S 535 00:27:40,229 --> 00:27:42,465 KETAMINE THAT BINDS WITHIN ITS 536 00:27:42,465 --> 00:27:47,470 POCKET. TO TWO AMINO ACIDS, ONE 537 00:27:47,470 --> 00:27:51,207 IS AT THE RECEPTOR WHICH IS 646 538 00:27:51,207 --> 00:27:58,014 AND AT THE GLYCINE SITE 616 IS 539 00:27:58,014 --> 00:27:58,548 THE OTHER AMINO ACID AND 540 00:27:58,548 --> 00:28:00,116 BELIEVED TO TRIGGER THE DOWN 541 00:28:00,116 --> 00:28:02,185 CASCADE EFFECTS OF KETAMINE. 542 00:28:02,185 --> 00:28:05,388 IT'S CLASSIFIED AS A 543 00:28:05,388 --> 00:28:06,456 DISSOCIATIVE ANESTHETIC, AHA 544 00:28:06,456 --> 00:28:14,764 LEWIS -- HALLUCINOGEN. AND TWO 545 00:28:14,764 --> 00:28:16,065 THINGS OF THE BIOAVAILABILITY 546 00:28:16,065 --> 00:28:21,237 ONE IS 100% IF YOU GIVE IT 547 00:28:21,237 --> 00:28:22,872 INTRAVENOUS AND INTRANASAL IT'S 548 00:28:22,872 --> 00:28:24,340 ABOUT HALF OF THAT. AND WE'LL 549 00:28:24,340 --> 00:28:26,542 COME MORE TO THEM LATER ON NOW 550 00:28:26,542 --> 00:28:29,812 THE INTERESTING PART IS HOW WE 551 00:28:29,812 --> 00:28:33,349 GOT THERE. SO RESEARCH, LET'S 552 00:28:33,349 --> 00:28:34,717 TALK ABOUT SOME OF THE HURDLES 553 00:28:34,717 --> 00:28:36,085 WHY DON'T WE PURSUE OTHER 554 00:28:36,085 --> 00:28:37,420 TARGETS BACK THEN BECAUSE THIS 555 00:28:37,420 --> 00:28:42,859 IS TOO COMPLEX, SEROTONIN, 556 00:28:42,859 --> 00:28:44,394 DOPAMINE, IT HAD BEEN ABANDONED 557 00:28:44,394 --> 00:28:46,129 RESEARCH. NOTHING WENT ON FOR A 558 00:28:46,129 --> 00:28:48,431 YEAR EVEN AFTER THE BERMAN 559 00:28:48,431 --> 00:28:49,098 STUDIED IT WAS FINISHED IN THE 560 00:28:49,098 --> 00:28:53,770 LATE 1990S, ALMOST A DECADE HAD 561 00:28:53,770 --> 00:28:56,039 GONE BY AND YOU WILL SEE WHY. 562 00:28:56,039 --> 00:28:58,141 THE CONCERN OF COURSE IS SAFETY, 563 00:28:58,141 --> 00:29:02,078 SAFETY, SAFETY WE WERE 564 00:29:02,078 --> 00:29:03,146 DEVELOPING A NEW PROGRAM AND THE 565 00:29:03,146 --> 00:29:06,049 LAST THING IS TO DEVELOP 566 00:29:06,049 --> 00:29:07,884 SOMETHING CONTROVERSIAL. WILL 567 00:29:07,884 --> 00:29:10,620 THIS JUST BE AN INTERESTING 568 00:29:10,620 --> 00:29:12,922 DISCOVERY OR IS THERE A REAL 569 00:29:12,922 --> 00:29:16,392 PATH TO THE CLINIC? THE NEXT 570 00:29:16,392 --> 00:29:19,295 CHALLENGE WOULD BE 571 00:29:19,295 --> 00:29:23,866 ADMINISTRATIVE. IT'S AN 572 00:29:23,866 --> 00:29:27,437 ANESTHETIC AGENT. AND YOU HAVE 573 00:29:27,437 --> 00:29:28,571 PATIENTS WHO ARE SEVERELY 574 00:29:28,571 --> 00:29:29,872 MENTALLY ILL AND SUFFER. THE 575 00:29:29,872 --> 00:29:33,609 TRAINING OF STAFF, WE ADMINISTER 576 00:29:33,609 --> 00:29:34,844 PSYCHOTHERAPY, TALK THERAPY AND 577 00:29:34,844 --> 00:29:35,878 MAYBE PILLS BUT WE DON'T GET 578 00:29:35,878 --> 00:29:39,782 MUCH INTO OTHER TYPES OF 579 00:29:39,782 --> 00:29:41,150 INTERVENTION UNTIL RECENTLY OF 580 00:29:41,150 --> 00:29:42,852 COURSE. THE LEGAL ASPECTS OF 581 00:29:42,852 --> 00:29:45,288 IT. FAILURE MODES, EFFECTS, 582 00:29:45,288 --> 00:29:46,789 ANALYSIS. THIS WAS PRIOR TO THE 583 00:29:46,789 --> 00:29:48,724 DEVELOPMENT OF THAT BUT IT'S A 584 00:29:48,724 --> 00:29:49,859 SYSTEM OF TRYING TO IDENTIFY 585 00:29:49,859 --> 00:29:51,727 WHERE THINGS COULD GO WRONG AND 586 00:29:51,727 --> 00:29:54,864 THERE'S SO MANY AREAS THAT COULD 587 00:29:54,864 --> 00:29:57,300 HAVE GONE WRONG. CULTURE. THE 588 00:29:57,300 --> 00:29:58,835 UNIT THAT I TOOK OVER WAS DOING 589 00:29:58,835 --> 00:30:02,338 A LOT OF PSYCHOTHERAPY BACK 590 00:30:02,338 --> 00:30:05,541 THEN. SOME MEDICATION 591 00:30:05,541 --> 00:30:07,210 CHALLENGES BUT NOTHING TO THIS 592 00:30:07,210 --> 00:30:08,344 DEGREE AND THEN OF COURSE 593 00:30:08,344 --> 00:30:09,679 THERE'S THE ETHICAL. OUR 594 00:30:09,679 --> 00:30:11,614 PATIENTS SUFFER ALREADY. YOU 595 00:30:11,614 --> 00:30:14,350 HEARD FROM MICHELE SO DO WE WANT 596 00:30:14,350 --> 00:30:18,855 TO GIVE OUR PATIENTS OR EVEN IN 597 00:30:18,855 --> 00:30:20,623 A TANGENT MANNER DISSOCIATIVE 598 00:30:20,623 --> 00:30:22,325 SIDE EFFECTS. THERE'S A RISK OF 599 00:30:22,325 --> 00:30:23,893 MISUSE OR ABUSE, RIGHT? AND WE 600 00:30:23,893 --> 00:30:28,030 WERE STUDYING UNMEDICATED 601 00:30:28,030 --> 00:30:28,764 SUBJECTS. THAT WAS THE PLAN 602 00:30:28,764 --> 00:30:30,333 BECAUSE WE WANTED TO UNDERSTAND 603 00:30:30,333 --> 00:30:32,235 BIOLOGY OF THE BRAIN AND 604 00:30:32,235 --> 00:30:34,670 MEDICATIONS AND PLACEBO 605 00:30:34,670 --> 00:30:38,074 COMPARISON. IT HAS BEEN VIEWED 606 00:30:38,074 --> 00:30:43,146 IN THE COMMUNITY THAT IT'S GOOD 607 00:30:43,146 --> 00:30:46,849 TO GIVE PLACEBO IF IT'S 608 00:30:46,849 --> 00:30:48,584 EFFECTIVE. BUT WHAT? THERE ARE 609 00:30:48,584 --> 00:30:51,254 FEW IF ANY. THE MAIN 610 00:30:51,254 --> 00:30:52,155 LIMITATIONS AND THAT LEADS TO 611 00:30:52,155 --> 00:30:53,890 ANOTHER DRUG WE'RE DEVELOPING IS 612 00:30:53,890 --> 00:30:56,325 IT'S AN ANESTHETIC, THE 613 00:30:56,325 --> 00:30:58,227 DISSOCIATIVE SIDE EFFECTS AND 614 00:30:58,227 --> 00:30:58,995 THE MISUSE POTENTIAL SO FOR 615 00:30:58,995 --> 00:31:02,899 ETHICAL REASONS IN OUR FIRST 616 00:31:02,899 --> 00:31:06,869 STUDY, WE STUDIED AN INDIVIDUAL 617 00:31:06,869 --> 00:31:10,873 WHO FAILED OVER SIX 618 00:31:10,873 --> 00:31:16,546 ANTIDEPRESSANTS AND 619 00:31:16,546 --> 00:31:17,713 ANTICONVULSIVE THERAPY AND MANY 620 00:31:17,713 --> 00:31:19,382 HAD PREVIOUS SUICIDE ATTEMPTS 621 00:31:19,382 --> 00:31:21,884 AND HERE IS QUESTION IS IF WE 622 00:31:21,884 --> 00:31:24,387 GIVE ONE DOSE WHICH TARGETS THE 623 00:31:24,387 --> 00:31:25,454 RECEPTOR WILL THAT BRING ABOUT 624 00:31:25,454 --> 00:31:28,324 THE EFFECTS. AND THE ANSWER WAS 625 00:31:28,324 --> 00:31:32,962 YES, BACK THEN. SO HERE IS THE 626 00:31:32,962 --> 00:31:36,399 DEPRESSION RATE OF SKILL ORANGE 627 00:31:36,399 --> 00:31:39,035 IS KETAMINE, THIS MEANS GREATER 628 00:31:39,035 --> 00:31:39,835 IMPROVEMENT. YOU CAN SEE 629 00:31:39,835 --> 00:31:40,803 SIGNIFICANCE AS EARLY AS A 630 00:31:40,803 --> 00:31:43,439 COUPLE OF HOURS WITH ONE 631 00:31:43,439 --> 00:31:45,508 ADMINISTRATION LASTING ONE WEEK 632 00:31:45,508 --> 00:31:50,213 WITH ONE INFUSION AN INDIVIDUAL 633 00:31:50,213 --> 00:31:52,315 WHO WERE RESISTANT IN TREATMENT 634 00:31:52,315 --> 00:31:54,850 FOR DEPRESSION. THE RESPONSE 635 00:31:54,850 --> 00:31:56,919 RATE MEANS YOU'RE 50% BETTER 636 00:31:56,919 --> 00:31:58,854 THAN WHEN YOU STARTED AND YOU 637 00:31:58,854 --> 00:32:02,258 GET 62-65%. THAT'S GOOD. BUT 638 00:32:02,258 --> 00:32:08,898 IT'S AT 8-10-12 WEEKS AND IN 639 00:32:08,898 --> 00:32:10,366 INDIVIDUALS WHO ARE NOT FOR 640 00:32:10,366 --> 00:32:11,334 TREATMENT RESISTANT FOR 641 00:32:11,334 --> 00:32:12,401 DEPRESSION. IN THE PATH YOU CAN 642 00:32:12,401 --> 00:32:17,473 SEE IT TAKES A LOCK TIME -- LONG 643 00:32:17,473 --> 00:32:17,673 TIME. 644 00:32:17,673 --> 00:32:18,874 AND YOU CAN SEE THERE'S SOME 645 00:32:18,874 --> 00:32:20,743 SUPERIOR WITHIN HOURS AND THAT 646 00:32:20,743 --> 00:32:24,580 WAS, WOW, ROBUST. AND 647 00:32:24,580 --> 00:32:26,315 RELATIVELY SUSTAINED 648 00:32:26,315 --> 00:32:27,283 ANTIDEPRESSANT EFFECT. SO WE 649 00:32:27,283 --> 00:32:29,885 WERE LIKE, VERY IMPRESSED EARLY 650 00:32:29,885 --> 00:32:32,021 ON BUT AGAIN THIS IS ONE STUDY. 651 00:32:32,021 --> 00:32:34,523 AND MICHELE DESCRIBES HER 652 00:32:34,523 --> 00:32:34,824 EXPERIENCE. 653 00:32:34,824 --> 00:32:37,026 >> SO IT WAS AMAZING, IT WAS 654 00:32:37,026 --> 00:32:39,829 LIKE, LIKE THE LIGHTS WERE 655 00:32:39,829 --> 00:32:41,330 TURNED ON AGAIN. AND WHAT I 656 00:32:41,330 --> 00:32:42,865 MEAN BY THAT IS, YOU KNOW, I 657 00:32:42,865 --> 00:32:45,668 COULD SEE COLORS AGAIN, THE SKY 658 00:32:45,668 --> 00:32:47,903 WAS BLUE AND THE GRASS WAS GREEN 659 00:32:47,903 --> 00:32:49,939 AND PEOPLE SEEMED ALIVE AGAIN 660 00:32:49,939 --> 00:32:52,842 AND I FELT ALIVE AGAIN. AND 661 00:32:52,842 --> 00:32:57,013 BEFORE THAT, IT WAS TOTALLY 662 00:32:57,013 --> 00:32:57,280 ABSENT. 663 00:32:57,280 --> 00:32:58,614 >> CARLOS: AND SO THAT WAS 664 00:32:58,614 --> 00:33:00,983 REALLY REWARDING TO SEE THAT IN 665 00:33:00,983 --> 00:33:03,753 OUR EARLIER PATIENTS AND STILL 666 00:33:03,753 --> 00:33:05,121 TO THIS DAY. NEVER GOES AWAY 667 00:33:05,121 --> 00:33:06,555 THAT FEELING. SO OBVIOUSLY THIS 668 00:33:06,555 --> 00:33:11,861 LED TO A LOT EARLY ON MEDIA 669 00:33:11,861 --> 00:33:17,900 EXPOSURE AND IN TIME, SCIENCE 670 00:33:17,900 --> 00:33:20,036 HAD BEEN DEEMED ONE OF THE MOST 671 00:33:20,036 --> 00:33:23,639 IMPORTANT DISCOVERIES IN 50 672 00:33:23,639 --> 00:33:25,074 YEARS. THERE HAD NOT BEEN MUCH 673 00:33:25,074 --> 00:33:26,409 ACCOMPLISHED IN THOSE DRUGS. WE 674 00:33:26,409 --> 00:33:27,877 SAID ALL THAT IS INTERESTING BUT 675 00:33:27,877 --> 00:33:29,879 HOW DO WE GET IT TO OUR PATIENTS 676 00:33:29,879 --> 00:33:31,747 AND THAT IS THE REAL CHALLENGE 677 00:33:31,747 --> 00:33:34,216 AND THE ANSWER, YOU KNOW, IS 678 00:33:34,216 --> 00:33:35,885 SUMMARIZED HERE BUT IT'S MUCH 679 00:33:35,885 --> 00:33:39,155 MORE THAN THIS BY DOING CLINICAL 680 00:33:39,155 --> 00:33:40,556 TRANSLATIONAL WORK STRENGTHENING 681 00:33:40,556 --> 00:33:42,525 OUR PARTNERSHIPS IN THE OFFICE 682 00:33:42,525 --> 00:33:43,659 OF TECHNOLOGY TRANSFER AND 683 00:33:43,659 --> 00:33:44,393 THAT'S BEEN IMPORTANT IN THE 684 00:33:44,393 --> 00:33:46,429 REST OF THE JOURNEY. SO WE 685 00:33:46,429 --> 00:33:48,864 CONTINUE TO TRY TO EXPLORE AND 686 00:33:48,864 --> 00:33:50,833 REPLICATE THE STUDIES BECAUSE 687 00:33:50,833 --> 00:33:56,105 FRANKLY VERY FEW BELIEVED THAT 688 00:33:56,105 --> 00:34:00,876 EARLY ON AND DEPUTY, CLINICAL 689 00:34:00,876 --> 00:34:05,314 DIRECTOR OF NIHHH DID THE FIRST 690 00:34:05,314 --> 00:34:08,150 STUDY SHOWING THE DEPRESSION 691 00:34:08,150 --> 00:34:10,553 SCORES, AND RED IS KETAMINE AND 692 00:34:10,553 --> 00:34:11,887 BIPOLAR DEPRESSION WITHIN 693 00:34:11,887 --> 00:34:13,422 MINUTES LASTING THE GOOD PART OF 694 00:34:13,422 --> 00:34:17,893 THE WE WEEK VERY SIMILAR TO THE 695 00:34:17,893 --> 00:34:18,361 OTHER STUDY. 696 00:34:18,361 --> 00:34:20,730 AND THE NEXT REPLICATION STUDY 697 00:34:20,730 --> 00:34:22,865 AS WELL. WE'RE UP TO THREE 698 00:34:22,865 --> 00:34:24,266 CONTROLLED STUDIES AND THEY LOOK 699 00:34:24,266 --> 00:34:25,468 VERY SIMILAR TO EACH OTHER 700 00:34:25,468 --> 00:34:27,169 SUGGESTS A TRUE BIOLOGIC EFFECT. 701 00:34:27,169 --> 00:34:29,672 WHAT THE TARGET IS REMAINS TO BE 702 00:34:29,672 --> 00:34:32,108 DETERMINED BUT THAT WAS 703 00:34:32,108 --> 00:34:33,309 INTRIGUING THAN THE YOUNG LAD 704 00:34:33,309 --> 00:34:35,311 WHO WAS A PREDOC AT THE TIME 705 00:34:35,311 --> 00:34:38,848 LOOKED AT ANNA DONE YA AS 706 00:34:38,848 --> 00:34:40,249 IDENTIFIED BY A LACK OF PLEASURE 707 00:34:40,249 --> 00:34:41,584 AND YOU HAVE LOSS OF PLEASURE 708 00:34:41,584 --> 00:34:46,188 THE HIGHER THE NUMBER AND IT 709 00:34:46,188 --> 00:34:48,891 IMPROVES AS YOU GO DOWN. IT 710 00:34:48,891 --> 00:34:50,860 STARTS IN TWO HOURS AND LASTS 711 00:34:50,860 --> 00:34:54,463 TWO WEEKS AND MORE IMPORTANT IS 712 00:34:54,463 --> 00:34:56,132 A RELATIONSHIP BETWEEN THE 713 00:34:56,132 --> 00:34:59,869 IMPROVEMENT AND CHANGES IN 714 00:34:59,869 --> 00:35:02,905 GLUCOSE METABOLISM WITH PET 715 00:35:02,905 --> 00:35:04,907 IMAGING IN THE STRAY TAMM 716 00:35:04,907 --> 00:35:06,876 SUGGEST THAT'S PART OF THE 717 00:35:06,876 --> 00:35:09,678 REWARD SUGGESTING HERE'S A PANEL 718 00:35:09,678 --> 00:35:11,881 AREA OR CIRCUIT OR REGION THAT 719 00:35:11,881 --> 00:35:13,749 MIGHT BE IMPLICATED IN THE 720 00:35:13,749 --> 00:35:16,819 PROPERTIES AND THEN IN 2013, 721 00:35:16,819 --> 00:35:23,959 MOVED FROM SALINE TO BEN SEW DYE 722 00:35:23,959 --> 00:35:34,503 DIAZ PEOPLE AND PRETTY SIMILAR 723 00:35:35,738 --> 00:35:37,406 ONSET AND OFFSET AND THERE'S 724 00:35:37,406 --> 00:35:38,641 SOMETHING THERE AND IT SEEMS TO 725 00:35:38,641 --> 00:35:41,110 BE PURSUED IN A MORE SYSTEMATIC 726 00:35:41,110 --> 00:35:44,180 FASHION. THE NEXT AREA, 727 00:35:44,180 --> 00:35:46,849 SUICIDE. WHERE THERE'S ALREADY 728 00:35:46,849 --> 00:35:52,655 48,000 SUICIDES PER YEAR, 12 729 00:35:52,655 --> 00:35:54,190 MILLION THINK OF SUICIDE. AND 730 00:35:54,190 --> 00:35:55,991 THERE'S A MILLION PER YEAR AND 731 00:35:55,991 --> 00:35:59,428 THAT'S ONE DEATH EVERY 11 732 00:35:59,428 --> 00:36:01,764 MINUTES. AND SO, IN EARLIER 733 00:36:01,764 --> 00:36:04,500 WORK, WE AND OTHERS IDENTIFIED 734 00:36:04,500 --> 00:36:06,869 KETAMINE AS HAVING EFFECTS ON 735 00:36:06,869 --> 00:36:09,672 SUICIDAL IDEATION, HIGHER NUMBER 736 00:36:09,672 --> 00:36:11,807 GREATER THOUGHTS OF SUICIDE AND 737 00:36:11,807 --> 00:36:14,210 RED IS THE HIGH RISK GROUP AND 738 00:36:14,210 --> 00:36:16,045 YOU BRING THEM DOWN IMPROVEMENT 739 00:36:16,045 --> 00:36:17,913 WITHIN 40 MINUTES AND WITH AN 740 00:36:17,913 --> 00:36:22,852 INFUSION LASTING ZEN SEVEN 741 00:36:22,852 --> 00:36:23,085 DAYS. 742 00:36:23,085 --> 00:36:24,820 WHICH GIVES YOU TIME TO TRANSFER 743 00:36:24,820 --> 00:36:26,155 PEOPLE BACK TO THEIR HOME OR GET 744 00:36:26,155 --> 00:36:28,424 TREATMENT WITH THEIR PROVIDERS 745 00:36:28,424 --> 00:36:32,394 IN THE COMMUNITY. AND SO, OTHER 746 00:36:32,394 --> 00:36:35,898 SIGHTS REPLICATED AND 747 00:36:35,898 --> 00:36:37,233 META-ANALYSIS THAT THE ONSET WAS 748 00:36:37,233 --> 00:36:38,868 IN AN HOUR OR A DAY LASTING ONE 749 00:36:38,868 --> 00:36:41,437 WEEK. SO REPLICATION, 750 00:36:41,437 --> 00:36:42,738 REPLICATION, IMPORTANCE OF DRUG 751 00:36:42,738 --> 00:36:44,640 DISCOVERY AND DEVELOPMENT. AND 752 00:36:44,640 --> 00:36:47,076 SO LET'S HEAR BACK FROM MICHELE 753 00:36:47,076 --> 00:36:48,978 AND HER EXPERIENCE MONTHS AFTER 754 00:36:48,978 --> 00:36:51,013 KETAMINE AND SPECIFICALLY THE 755 00:36:51,013 --> 00:36:51,213 FOCUS. 756 00:36:51,213 --> 00:36:52,982 >> THINGS ARE GOING REALLY WELL 757 00:36:52,982 --> 00:36:54,650 NOW, I'M FEELING SO MUCH BETTER 758 00:36:54,650 --> 00:36:58,320 AND I HAVE AN INTEREST IN THINGS 759 00:36:58,320 --> 00:37:05,294 AGAIN IN LIFE I'M BUSY PLANNING 760 00:37:05,294 --> 00:37:07,396 FOR MY FUTURE INSTEAD OF 761 00:37:07,396 --> 00:37:09,532 SUICIDE. I HAVEN'T HAD ANY 762 00:37:09,532 --> 00:37:11,901 SUICIDAL THOUGHTS SINCE 763 00:37:11,901 --> 00:37:12,835 COMPLETING THE STUDY. I 764 00:37:12,835 --> 00:37:13,669 PROBABLY WILL ALWAYS STRUGGLE 765 00:37:13,669 --> 00:37:16,939 WITH THE UPS AND DOWNS OF GRIEF 766 00:37:16,939 --> 00:37:18,874 BUT THAT I CAN GO THROUGH AND 767 00:37:18,874 --> 00:37:22,111 HANDLE THOSE WAVES IT'S JUST THE 768 00:37:22,111 --> 00:37:24,113 DEEPEST HELPLESS DARK DESPAIR OF 769 00:37:24,113 --> 00:37:25,748 DEPRESSION WHICH IS SO, SO 770 00:37:25,748 --> 00:37:27,349 DIFFICULT TO HANDLE. 771 00:37:27,349 --> 00:37:29,585 >> CARLOS: AND SO EFFICACY IS 772 00:37:29,585 --> 00:37:31,387 ESTABLISHED AND ONE GOES 773 00:37:31,387 --> 00:37:32,488 TOEFKTIVENESS. HOW DOES IT 774 00:37:32,488 --> 00:37:33,722 BEHAVE IN THE REAL WORLD. 775 00:37:33,722 --> 00:37:36,458 AND THE STUDY WAS RECENTLY 776 00:37:36,458 --> 00:37:37,860 PUBLISHED THE MOST EFFECTIVE 777 00:37:37,860 --> 00:37:39,929 TREATMENT IS ELECTROCONVULSIVE 778 00:37:39,929 --> 00:37:41,897 THERAPY AND HERE 400 ARE 779 00:37:41,897 --> 00:37:43,966 RANDOMIZED IN A NON INFERIOR 780 00:37:43,966 --> 00:37:45,434 DESIGN WHICH MEANS YOU SHOW 781 00:37:45,434 --> 00:37:47,903 YOU'RE AS GOOD AS THE BEST 782 00:37:47,903 --> 00:37:50,406 TREATMENT AVAILABLE. AND FOR 783 00:37:50,406 --> 00:37:53,909 DEPRESSION SCALES SHOW THAT 784 00:37:53,909 --> 00:37:57,079 KETAMINE INTRAVENOUSLY IS 785 00:37:57,079 --> 00:37:59,815 COMPARABLE TO TCT AND IN SIX 786 00:37:59,815 --> 00:38:02,885 MONTHS SHOW ITS NON INFERIOR SO 787 00:38:02,885 --> 00:38:06,622 IT SUGGESTS THIS IS ANOTHER 788 00:38:06,622 --> 00:38:07,456 PHARMACOLOGICAL OPTION FOR 789 00:38:07,456 --> 00:38:09,658 DEPRESSION IN THE COMMUNITY SO 790 00:38:09,658 --> 00:38:14,797 WITH THIS BODY OF WORK WE SAY, 791 00:38:14,797 --> 00:38:16,432 WOW, DO WE HAVE A PATH TO THE 792 00:38:16,432 --> 00:38:18,434 MARKET IN HERE IT'S A 793 00:38:18,434 --> 00:38:20,235 PARTNERSHIP BETWEEN ACADEMIA, 794 00:38:20,235 --> 00:38:21,136 GOVERNMENT INDUSTRY WITH SOME OF 795 00:38:21,136 --> 00:38:22,871 THE PEOPLE ALREADY MENTIONED. 796 00:38:22,871 --> 00:38:25,140 THAT WE GOT TOGETHER, AND WE 797 00:38:25,140 --> 00:38:28,777 SAY, LET'S TRY TO GET THIS TO 798 00:38:28,777 --> 00:38:31,780 THE MARKET. SO KEEP IN MIND NOW 799 00:38:31,780 --> 00:38:33,515 RECEIVING KETAMINE IS COMPOSED 800 00:38:33,515 --> 00:38:36,051 OF TWO ANTI HERS. R AND S SO 801 00:38:36,051 --> 00:38:39,822 WHICH ONE DO YOU CHOOSE? DO YOU 802 00:38:39,822 --> 00:38:41,657 DEVELOP R OR DO YOU DEVELOP S 803 00:38:41,657 --> 00:38:43,659 AND FOR A LONG STORY S WAS 804 00:38:43,659 --> 00:38:46,862 DECIDED BECAUSE IT WAS THE MOST 805 00:38:46,862 --> 00:38:48,097 POTENT RECEPTOR ANTAGONIST 806 00:38:48,097 --> 00:38:51,867 COMPARED TO R. AND SO GOING 807 00:38:51,867 --> 00:38:53,769 BACK TO OUR TRAINEES HAVE BEEN 808 00:38:53,769 --> 00:38:55,904 WONDERFUL AND SPEARHEADED MOST 809 00:38:55,904 --> 00:38:59,908 OF THIS WORK IS JAZZ WHO WAS A 810 00:38:59,908 --> 00:39:02,878 RESEARCH FELLOW AND WENT TO 811 00:39:02,878 --> 00:39:05,681 JANSON AND HELPED DEVELOP AND 812 00:39:05,681 --> 00:39:10,019 WAS A LARGE PART OF THESE 813 00:39:10,019 --> 00:39:11,887 STUDIES AND A LARGE PART WAS 814 00:39:11,887 --> 00:39:13,789 DOES KETAMINE HAVE THESE 815 00:39:13,789 --> 00:39:16,225 EFFECTS. OR DO YOU NEED A 816 00:39:16,225 --> 00:39:17,626 COMBINATION? YOU CAN SEE HERE 817 00:39:17,626 --> 00:39:21,130 TWO DOSES, .2 MILLIGRAMS, .4 818 00:39:21,130 --> 00:39:22,798 DECREASES THE DEPRESSION SCORES, 819 00:39:22,798 --> 00:39:24,266 STAY WELL FOR SEVEN DAYS SO 820 00:39:24,266 --> 00:39:25,567 PRETTY SIMILAR TO THE PREVIOUS 821 00:39:25,567 --> 00:39:26,869 STUDIES I MENTIONED THE NEXT 822 00:39:26,869 --> 00:39:29,204 QUESTION IS, OKAY, WE HAVE 823 00:39:29,204 --> 00:39:31,440 INTRAVENOUS KETAMINE BUT IT 824 00:39:31,440 --> 00:39:32,641 REQUIRES NURSING, 825 00:39:32,641 --> 00:39:34,643 ANESTHESIOLOGIST, THE 826 00:39:34,643 --> 00:39:38,647 MONITORING, IT'S NOT PRACTICAL 827 00:39:38,647 --> 00:39:39,114 FOR PSYCHIATRISTS OR 828 00:39:39,114 --> 00:39:41,417 NURSE-PRACTITIONERS IN THE 829 00:39:41,417 --> 00:39:43,619 COMMUNITY. THE FOCUS WAS TO 830 00:39:43,619 --> 00:39:45,721 COME UP WITH INTRANASAL. THE 831 00:39:45,721 --> 00:39:49,358 CHALLENGE IS 50% BIOAVAILABILITY 832 00:39:49,358 --> 00:39:53,128 BUT WITH MUCH WORK IT WAS 833 00:39:53,128 --> 00:39:55,664 APPROVED BY THE FOOD AND DRUG 834 00:39:55,664 --> 00:39:58,100 ADMINISTRATION FOR TWO 835 00:39:58,100 --> 00:39:59,935 INDICATIONS FOR ADULTS WITH 836 00:39:59,935 --> 00:40:01,336 MAJOR DEPRESSION WHO HAVE 837 00:40:01,336 --> 00:40:02,905 SUICIDAL IDEATION HERE IS THE 838 00:40:02,905 --> 00:40:04,873 DEVICE THAT WAS CREATED. THE 839 00:40:04,873 --> 00:40:11,013 TIP, YOU INSERT THE NOSE AREA, 840 00:40:11,013 --> 00:40:13,215 THEN YOU HAVE THE GREEN DOTS 841 00:40:13,215 --> 00:40:14,983 MEANS THAT THERE IS DRUG AND A 842 00:40:14,983 --> 00:40:18,654 28 MILLIGRAMS EACH AND SO ON AND 843 00:40:18,654 --> 00:40:22,357 SO FORTH. THIS IS HOW IT IS 844 00:40:22,357 --> 00:40:24,860 ADMINISTERED BUT HAS TO BE 845 00:40:24,860 --> 00:40:25,928 MONITORED BY SOMEONE WHO IS 846 00:40:25,928 --> 00:40:27,696 TRAINED. WE DO NOT GIVE IT TO 847 00:40:27,696 --> 00:40:29,465 THE COMMUNITY. THIS IS A 848 00:40:29,465 --> 00:40:31,600 RELAPSE STUDY. TIME TO RELAPSE 849 00:40:31,600 --> 00:40:33,869 WHERE YOU SEE HERE IF YOU -- SO, 850 00:40:33,869 --> 00:40:35,504 INDIVIDUALS WHO HAVE DEPRESSION 851 00:40:35,504 --> 00:40:37,773 ARE TREATED UNTIL THEY REMIT. 852 00:40:37,773 --> 00:40:40,242 AND THEN THEY ARE RANDOMIZED TO 853 00:40:40,242 --> 00:40:42,211 EITHER CONTINUE S KETAMINE OR 854 00:40:42,211 --> 00:40:45,481 COME OFF OF IT ON TOP OF A NEWLY 855 00:40:45,481 --> 00:40:46,882 STARTED ANTIDEPRESSANT AND YOU 856 00:40:46,882 --> 00:40:48,717 SEE HERE THE NUMBER OF RELAPSES 857 00:40:48,717 --> 00:40:49,918 IS ALMOST HALF OF THAT IF YOU 858 00:40:49,918 --> 00:40:53,922 COME OFF OF IT. AND THESE 859 00:40:53,922 --> 00:40:54,890 INDIVIDUALS ARE FOLLOWED FOR 860 00:40:54,890 --> 00:40:56,558 MANY WEEKS OUT SO THIS IS ONE OF 861 00:40:56,558 --> 00:40:59,128 THE PIVOTAL STUDIES THAT LED TO 862 00:40:59,128 --> 00:41:01,330 FDA APPROVAL NOW THE FUTURE 863 00:41:01,330 --> 00:41:03,665 RAPID ACTING ANTIDEPRESSANTS FOR 864 00:41:03,665 --> 00:41:06,068 DEPRESSION AND SUICIDE, WE AT 865 00:41:06,068 --> 00:41:07,970 THE INTRAMURAL PROGRAM 7 866 00:41:07,970 --> 00:41:10,873 SOUTHEAST HERE, DO A MULTISCALE 867 00:41:10,873 --> 00:41:12,641 APPROACH WHERE WE INTEGRATE A 868 00:41:12,641 --> 00:41:14,843 WIDE RANGE OF CLINICAL 869 00:41:14,843 --> 00:41:16,612 BEHAVIORAL OTHER TECHNOLOGIES 870 00:41:16,612 --> 00:41:18,647 AND HAVE STRONG BASIC SCIENCE 871 00:41:18,647 --> 00:41:19,715 COLLABORATION TO GET INFORMATION 872 00:41:19,715 --> 00:41:22,851 GOING FROM THE MECHANISM OF 873 00:41:22,851 --> 00:41:26,188 KETAMINE TAALL THE WAY TO BEHAVR 874 00:41:26,188 --> 00:41:29,258 GOING THROUGH CIRCUITS. AND WE 875 00:41:29,258 --> 00:41:31,627 HAVE LONG ENTER -- WE -- 876 00:41:31,627 --> 00:41:33,529 EXTRAMURAL COLLABORATORS THAT DO 877 00:41:33,529 --> 00:41:35,297 THIS ON THE PRECLINICAL SIDE TO 878 00:41:35,297 --> 00:41:38,367 GET A MECHANISM IN ON OUR SIDE. 879 00:41:38,367 --> 00:41:41,136 WE INTEGRATE LOOKING AT 880 00:41:41,136 --> 00:41:43,572 DIFFERENT TECHNOLOGIES, 881 00:41:43,572 --> 00:41:45,941 ELECTROPHYSIOLOGY, DIFFERENT 882 00:41:45,941 --> 00:41:49,178 TYPES OF IMAGE INSTRUCTIONAL AND 883 00:41:49,178 --> 00:41:51,013 FUNCTIONAL TO GET AT HOW 884 00:41:51,013 --> 00:41:52,881 KETAMINE MIGHT WORK SO THE STORY 885 00:41:52,881 --> 00:41:58,320 OF KETAMINE LED TO A SURGE IN 886 00:41:58,320 --> 00:42:01,456 FUNDING FOR CLINICAL STUDIES. 887 00:42:01,456 --> 00:42:04,459 SUB GENERAL PREFRONTAL CORTEX 888 00:42:04,459 --> 00:42:05,861 ABNORMALITIES HAVE BEEN REPORTED 889 00:42:05,861 --> 00:42:07,629 WHERE YOU SEE HERE INDIVIDUAL 890 00:42:07,629 --> 00:42:10,232 WITH MOOD DISORDERS BIPOLAR AND 891 00:42:10,232 --> 00:42:12,968 DEPRESSION HAVE REGIONAL 892 00:42:12,968 --> 00:42:14,837 REDUCTIONS IN GRAY MATTER AND 893 00:42:14,837 --> 00:42:18,207 YOU SEE HERE DECREASE GLUCOSE 894 00:42:18,207 --> 00:42:19,575 METABOLISM IN THE SAME REGION SO 895 00:42:19,575 --> 00:42:22,044 THIS WAS INTERESTING TO THE 896 00:42:22,044 --> 00:42:22,778 FIELD BECAUSE SUGGESTED THAT 897 00:42:22,778 --> 00:42:23,612 THERE ARE REDUCTION IN THE 898 00:42:23,612 --> 00:42:27,950 NUMBER, SIZE AND NEURONS AND 899 00:42:27,950 --> 00:42:29,151 SUGGESTED THAT THERE IS ANATOMY 900 00:42:29,151 --> 00:42:31,220 AND FUNCTION THAT IS DISTURBED 901 00:42:31,220 --> 00:42:33,789 HERE. SO THIS LED TO OTHER 902 00:42:33,789 --> 00:42:36,325 THEORIES SUCH AS DEPRESSION IS A 903 00:42:36,325 --> 00:42:38,827 DISORDER OF IMPAIRED RESILIENCE 904 00:42:38,827 --> 00:42:40,429 AND NEUROPLASTICITY AND THEN 905 00:42:40,429 --> 00:42:42,865 WORK BY THE LATE AND NOW 906 00:42:42,865 --> 00:42:45,767 DECEASED RON D. WHO CAME UP WITH 907 00:42:45,767 --> 00:42:47,903 A KETAMINE INCREASE IN SPINE, 908 00:42:47,903 --> 00:42:49,404 THESE ARE DENDRITES IN SPINES 909 00:42:49,404 --> 00:42:51,740 UNDER CONTROLLED CONDITIONS. 910 00:42:51,740 --> 00:42:53,408 AND THEN WHAT STRESS YOU CAN SEE 911 00:42:53,408 --> 00:42:59,915 REDUCTION IN NUMBER SIGNS IN 912 00:42:59,915 --> 00:43:00,582 SYNAPSES AND CIRCUITS AND THEN 913 00:43:00,582 --> 00:43:02,084 EVENTUALLY KETAMINE INCREASED IN 914 00:43:02,084 --> 00:43:05,921 THE SPINE. THIS WAS LIKE, WOW. 915 00:43:05,921 --> 00:43:10,259 WORK OUT OF A LAB SHOWED HERE 916 00:43:10,259 --> 00:43:16,765 THAT ACTUALLY IN RED IS STRESS. 917 00:43:16,765 --> 00:43:18,400 AND KETAMINE RESTORES THEM 918 00:43:18,400 --> 00:43:20,535 RATHER THAN PRODUCE NEW SPINES 919 00:43:20,535 --> 00:43:22,838 SO THIS MAY BE IMPORTANT MORE 920 00:43:22,838 --> 00:43:25,641 FOR THE SUSTAINED ANTIDEPRESSIVE 921 00:43:25,641 --> 00:43:26,842 EFFECTS OF KETAMINE HOW DO WE 922 00:43:26,842 --> 00:43:28,710 PUT THESE MECHANISMS TOGETHER? 923 00:43:28,710 --> 00:43:33,282 MOOD DISORDERS ARE DISORDERS OF 924 00:43:33,282 --> 00:43:34,850 PLASTICITY, EFFECTIVE SYNAPSES 925 00:43:34,850 --> 00:43:38,153 AND CIRCUITS. YOU CAN SEE HERE 926 00:43:38,153 --> 00:43:39,354 THE SPINES. THERE'S TWO 927 00:43:39,354 --> 00:43:41,924 THEORIES ON HOW KETAMINE MIGHT 928 00:43:41,924 --> 00:43:45,460 WORK. OR TWO SCHOOLS OF 929 00:43:45,460 --> 00:43:47,663 THOUGHT. KETAMINE BLOCKS THE 930 00:43:47,663 --> 00:43:49,831 RECEPTORS, INCREASES IN PROTEIN 931 00:43:49,831 --> 00:43:51,967 SYNTHESIS WHICH LEADS TO THE 932 00:43:51,967 --> 00:43:53,936 INCREASE IN SPINES, RESTORING 933 00:43:53,936 --> 00:43:55,971 SPINES IN CIRCUITS. THE OTHER 934 00:43:55,971 --> 00:43:57,639 THEORY THAT IS MORE INDIRECT, 935 00:43:57,639 --> 00:44:03,445 YOU BLOCK AN MDMA RECEPTORS, YOU 936 00:44:03,445 --> 00:44:05,047 DECREASE, GATHER EFFECTS THAT 937 00:44:05,047 --> 00:44:08,116 LEADS TO EXCITATION OF CELLS, 938 00:44:08,116 --> 00:44:10,152 EVOKED RELEASE OF GLUTAMATE 939 00:44:10,152 --> 00:44:11,920 ACTIVATES, THAT'S THE 940 00:44:11,920 --> 00:44:15,190 TRANSMITTER ACTIVATES RECEPTORS 941 00:44:15,190 --> 00:44:17,926 IN MACHINERY THAT LEADS TO 942 00:44:17,926 --> 00:44:20,462 PROTEIN SYNTHESIS, AND CIRCUITS. 943 00:44:20,462 --> 00:44:22,030 NOW THIS IS INTERESTING BUT WE 944 00:44:22,030 --> 00:44:26,034 SAID, WELL, IF YOU BLOCK 945 00:44:26,034 --> 00:44:28,337 RECEPTORS YOU HAVE WHAT, MAYBE 946 00:44:28,337 --> 00:44:29,604 ANESTHETIC EFFECTS AND REDUCED 947 00:44:29,604 --> 00:44:30,839 POTENTIAL SO WHY NOT PRODUCE 948 00:44:30,839 --> 00:44:34,009 THIS EVOKED RELEASE WITH ANOTHER 949 00:44:34,009 --> 00:44:35,377 MECHANISM AND SO WE HAVE THE SON 950 00:44:35,377 --> 00:44:38,647 OF KETAMINE WHICH IS HYDROXY NOR 951 00:44:38,647 --> 00:44:41,616 KETAMINE WHICH DOES NOT BLOCK 952 00:44:41,616 --> 00:44:44,086 BUT DOES PRODUCE THE EVOKED 953 00:44:44,086 --> 00:44:45,821 RELEASE OF GLUTAMATE AND 954 00:44:45,821 --> 00:44:46,822 ACTIVATES THIS MACHINERY 955 00:44:46,822 --> 00:44:49,157 NECESSARY FOR INCREASED SPINES 956 00:44:49,157 --> 00:44:54,396 RESTORING SYNAPSES IN THE 957 00:44:54,396 --> 00:44:54,830 CIRCUITS. 958 00:44:54,830 --> 00:44:56,698 I'M GOING TO SKIP THIS THIS THE 959 00:44:56,698 --> 00:44:59,301 INTEREST OF TIME. HERE WE SHOW 960 00:44:59,301 --> 00:45:02,070 THIS IS ANOTHER WAY OF 961 00:45:02,070 --> 00:45:05,807 MEASURING. THIS IS DEG 30-50 962 00:45:05,807 --> 00:45:09,378 HERTZ WHERE ONCE YOU ACTIVATE 963 00:45:09,378 --> 00:45:11,780 RECEPTORS, YOU PRODUCE INCREASES 964 00:45:11,780 --> 00:45:14,950 IN GAMMA POWER. IF YOU TREAT 965 00:45:14,950 --> 00:45:17,219 WITH AN AMP ANTAGONIST YOU BLOCK 966 00:45:17,219 --> 00:45:20,589 THE EFFECTS OF KETAMINE BUT YOU 967 00:45:20,589 --> 00:45:23,392 ALSO BLOCK GAMMA POWER AND THIS 968 00:45:23,392 --> 00:45:25,160 WAS OF INTEREST BECAUSE OF THE 969 00:45:25,160 --> 00:45:26,862 BIOMARKER WE CAN USE IN RODENTS 970 00:45:26,862 --> 00:45:29,064 AND IN HUMANS. IN HERE YOU SEE 971 00:45:29,064 --> 00:45:31,666 THAT WE SEE INCREASES IN GAMMA 972 00:45:31,666 --> 00:45:34,169 POWER WITH THE METABOLITE 973 00:45:34,169 --> 00:45:35,937 HYDROXY FAMILIAR KETAMINE THAT 974 00:45:35,937 --> 00:45:37,606 WE'RE INTERESTED IN. SO THIS IS 975 00:45:37,606 --> 00:45:39,808 ONE EXAMPLE OF THE STUDY THAT 976 00:45:39,808 --> 00:45:41,276 WE'RE DOING. I DON'T HAVE TIME 977 00:45:41,276 --> 00:45:42,878 TO GO INTO DETAIL HERE BUT THIS 978 00:45:42,878 --> 00:45:45,714 IS TO TRY TO GET AT MECHANISM WE 979 00:45:45,714 --> 00:45:49,785 DO PHARMACODYNAMIC IMAGING, 980 00:45:49,785 --> 00:45:52,854 STUDIES GETTING KETAMINE AND MRI 981 00:45:52,854 --> 00:45:55,590 AND EEG AND THEN HIGH OR LOW 982 00:45:55,590 --> 00:45:57,225 DOSE. WE OBTAIN MANY DIFFERENT 983 00:45:57,225 --> 00:45:59,861 PLEASURES. WE GET MRI AND THESE 984 00:45:59,861 --> 00:46:03,165 ARE WONDERFUL STAFF THAT DO ALL 985 00:46:03,165 --> 00:46:05,467 THE WORK AND ARE MENTIONED 986 00:46:05,467 --> 00:46:08,837 THERE. SO THE GROWING 987 00:46:08,837 --> 00:46:10,205 PHARMACOLOGICAL LANDSCAPE FOR 988 00:46:10,205 --> 00:46:10,872 NEXT GENERATION TREATMENT. THIS 989 00:46:10,872 --> 00:46:13,041 IS AN UGLY FIGURE FROM THE PAGE 990 00:46:13,041 --> 00:46:16,278 MAKER THAT I USED IN THIS PAPER 991 00:46:16,278 --> 00:46:18,880 BACK THEN AND WE HAD THE 992 00:46:18,880 --> 00:46:20,882 PRESYNAPTIC NEURON. WE HAD 993 00:46:20,882 --> 00:46:23,718 KETAMINE AS A POTENTIAL DRUG TO 994 00:46:23,718 --> 00:46:25,687 TEST. AND THIS IS FOR 995 00:46:25,687 --> 00:46:26,788 ALZHEIMER'S DISEASE WHICH WE 996 00:46:26,788 --> 00:46:28,356 DIDN'T FIND IN ANY PRESENT 997 00:46:28,356 --> 00:46:29,691 PROPERTIES AND SO AFTER TWENTY 998 00:46:29,691 --> 00:46:31,059 YEARS OF WORK HERE YOU CAN SEE 999 00:46:31,059 --> 00:46:35,530 HIGH THE FIGURE LOOKS MUCH 1000 00:46:35,530 --> 00:46:37,432 BETTER, YOU HAVE IN THIS COLOR 1001 00:46:37,432 --> 00:46:38,767 REDDISH PINK, YOU HAVE ALL THE 1002 00:46:38,767 --> 00:46:41,002 NEW DRUG TARGETS AND NEW DRUGS 1003 00:46:41,002 --> 00:46:42,871 SO IT'S QUITE INTERESTING. BUT 1004 00:46:42,871 --> 00:46:47,576 ONE OVER HERE IS THAT THE NMDA 1005 00:46:47,576 --> 00:46:49,978 RECEPTOR, MANY DRUG TARGETS HAVE 1006 00:46:49,978 --> 00:46:50,846 UNFORTUNATELY NOT PANNED OUT AND 1007 00:46:50,846 --> 00:46:53,181 MANY OF THE TRIALS WE DID AND 1008 00:46:53,181 --> 00:46:54,449 OTHERS. THERE'S A LONG STORY TO 1009 00:46:54,449 --> 00:46:55,617 THAT BUT WE WERE INTERESTED IN 1010 00:46:55,617 --> 00:46:59,788 THE METABOLITE OF KETAMINE WHICH 1011 00:46:59,788 --> 00:47:03,758 DOES NOT AFFECT AT THERAPEUTIC 1012 00:47:03,758 --> 00:47:05,527 RELEVANT CONCENTRATIONS OF THE 1013 00:47:05,527 --> 00:47:07,963 RECEPTOR AND SO VERY BRIEF 1014 00:47:07,963 --> 00:47:09,631 HISTORY OF HYDROXY NOR KEET 1015 00:47:09,631 --> 00:47:13,969 MEAN. SO HERE THE THE 1016 00:47:13,969 --> 00:47:15,237 METABOLISM GOES INTO NOR 1017 00:47:15,237 --> 00:47:17,973 KETAMINE AND TO A HYDROXY NOR 1018 00:47:17,973 --> 00:47:20,542 KETAMINE AND RS STAY WITHIN RS. 1019 00:47:20,542 --> 00:47:22,611 SO YOU START BY REVIEWING 1020 00:47:22,611 --> 00:47:23,345 ORIGINAL PAPERS. 1021 00:47:23,345 --> 00:47:24,446 READING WHAT'S THERE THIS THE 1022 00:47:24,446 --> 00:47:25,847 LITERATURE AND WE WERE, LIKE, 1023 00:47:25,847 --> 00:47:28,483 OH, THIS IS TERRIBLE. WE SAID, 1024 00:47:28,483 --> 00:47:32,854 LIKE, NOR KETAMINE IS THE ACTIVE 1025 00:47:32,854 --> 00:47:34,689 METABOLITE IN HYDROXY NOR 1026 00:47:34,689 --> 00:47:36,625 KETAMINES AND YOU SAY, OH, END 1027 00:47:36,625 --> 00:47:38,160 OF REVIEW BUT IT COMES TO 1028 00:47:38,160 --> 00:47:40,462 INACTIVE FOR WHAT? FOR 1029 00:47:40,462 --> 00:47:41,830 ANESTHESIA BUT NOT DEPRESSION SO 1030 00:47:41,830 --> 00:47:43,565 WE DECIDED TO PURSUE THAT. 1031 00:47:43,565 --> 00:47:46,268 AND IF YOU REMEMBER THIS FIGURE 1032 00:47:46,268 --> 00:47:49,337 HERE, YOU HAVE A RAPID ONSET OF 1033 00:47:49,337 --> 00:47:50,272 ANTIDEPRESSANT EFFECTS. THE 1034 00:47:50,272 --> 00:47:52,707 SIDE EFFECTS LAST VERY SHORTLY 1035 00:47:52,707 --> 00:47:53,975 THE HALF LIFE OF KETAMINE IS 1036 00:47:53,975 --> 00:47:56,511 ONLY A COUPLE OF HOURS AND SO 1037 00:47:56,511 --> 00:47:58,547 WHY IS THE EFFECT LASTING ONE TO 1038 00:47:58,547 --> 00:48:00,315 TWO WEEKS IN THAT'S UNHEARD OF. 1039 00:48:00,315 --> 00:48:01,316 USUALLY YOU HAVE A DRUG. YOU 1040 00:48:01,316 --> 00:48:02,784 HAVE AN EFFECT AND IT GOES AWAY 1041 00:48:02,784 --> 00:48:05,687 IN PSYCHIATRY AND WE WONDERED 1042 00:48:05,687 --> 00:48:07,422 MAYBE THERE'S METABOLITES. I 1043 00:48:07,422 --> 00:48:10,425 TOLD YOU A LITTLE BIT ABOUT THE 1044 00:48:10,425 --> 00:48:15,263 HISTORY AND THIS HAS WORKED WITH 1045 00:48:15,263 --> 00:48:18,166 IRVING AND WE THOUGHT MAYBE IT'S 1046 00:48:18,166 --> 00:48:21,002 A PRODRUG. THIS IS HARD TO 1047 00:48:21,002 --> 00:48:23,972 STUDY BECAUSE YOU GIVE KETAMINE 1048 00:48:23,972 --> 00:48:26,308 AND WITHIN MINUTES IN RATS AND 1049 00:48:26,308 --> 00:48:28,810 IN HUMANS YOU HAVE 24 1050 00:48:28,810 --> 00:48:29,878 METABOLITES SO HOW DO YOU KNOW 1051 00:48:29,878 --> 00:48:31,379 WHAT DOES WHAT? AND THIS IS THE 1052 00:48:31,379 --> 00:48:33,381 STORY. WE IDENTIFIED IN OUR 1053 00:48:33,381 --> 00:48:38,186 PATIENTS AND I BRIEFER LY BRIEY 1054 00:48:38,186 --> 00:48:41,990 SHOWED YOU THE CLINICAL DATA. 1055 00:48:41,990 --> 00:48:46,861 AND THERE'S THIS KETAMINE 1056 00:48:46,861 --> 00:48:47,495 METABOLITES. AND LONG PROCESS 1057 00:48:47,495 --> 00:48:51,299 WE IDENTIFIED 12R 6H IN K THAT 1058 00:48:51,299 --> 00:48:53,635 WE DECIDED TO MOVE FORWARD. SO 1059 00:48:53,635 --> 00:48:55,604 HERE THE STORY IS HIGH DO WE 1060 00:48:55,604 --> 00:48:57,772 SEPARATE THE WEED FROM THE CHAT 1061 00:48:57,772 --> 00:49:02,143 TO KNOW WHAT IS RELEVANT AND NOT 1062 00:49:02,143 --> 00:49:02,811 RELEVANT. 1063 00:49:02,811 --> 00:49:05,080 SO WE INJECT KETAMINE TO A 1064 00:49:05,080 --> 00:49:07,716 RODENT. WE GET 24 METABOLITES 1065 00:49:07,716 --> 00:49:11,987 AND WITHIN A VERY SHORT PERIOD 1066 00:49:11,987 --> 00:49:13,655 OF TIME, YOU CAN THEN DECIDE IS 1067 00:49:13,655 --> 00:49:16,524 IT RESPONSIBLE, THE SIDE 1068 00:49:16,524 --> 00:49:19,494 EFFECTS. HOW DO YOU DECREASE 1069 00:49:19,494 --> 00:49:22,264 METABOLISM? SO YOU STRENGTHEN 1070 00:49:22,264 --> 00:49:26,368 CARBON SIX. YOU DETERIORATE IT 1071 00:49:26,368 --> 00:49:29,304 AND YOU CAUSE D2 OR KETAMINE AND 1072 00:49:29,304 --> 00:49:31,806 YOU COME ONE A NEW COMPOUND THAT 1073 00:49:31,806 --> 00:49:34,876 IS PHARMACOLOGICALLY SIMILAR TO 1074 00:49:34,876 --> 00:49:38,079 GLYCEMIC KETAMINE BUT WHEN YOU 1075 00:49:38,079 --> 00:49:41,816 TEST IT AND YOU SHOW THAT THE 1076 00:49:41,816 --> 00:49:43,018 METABOLISM IS BLOCKED AND WHEN 1077 00:49:43,018 --> 00:49:45,020 YOU TEST IT IN RODENTS IT 1078 00:49:45,020 --> 00:49:46,888 DOESN'T HAVE SUSTAINED EFFECTS 1079 00:49:46,888 --> 00:49:47,989 BUT IT DOES HAVE THE ABUSE 1080 00:49:47,989 --> 00:49:49,991 POTENTIAL IN SIDE EFFECTS. 1081 00:49:49,991 --> 00:49:51,893 INTERESTING SO THEN WE TAKE OUR 1082 00:49:51,893 --> 00:49:55,563 DRUG TO OUR 6RHR AND WE INJECT 1083 00:49:55,563 --> 00:49:57,966 IT IN MICE AND YOU FIND IT DOES 1084 00:49:57,966 --> 00:50:02,937 HAVE RAPID EFFECTS BUT DOES 1085 00:50:02,937 --> 00:50:05,640 INDUCE ANESTHETIC EFFECTS. AND 1086 00:50:05,640 --> 00:50:07,175 ACTIVATES THE RECEPTOR AS I 1087 00:50:07,175 --> 00:50:09,244 MENTIONED IMPORTANT TO THE 1088 00:50:09,244 --> 00:50:12,013 CASCADES. AND IT INCREASES 1089 00:50:12,013 --> 00:50:15,350 GAMMA POWER. WHICH COULD BE AN 1090 00:50:15,350 --> 00:50:18,887 IMPORTANT BIOMARKER HERE IN THE 1091 00:50:18,887 --> 00:50:22,257 STUDY. HERE WE SHOW THAT HNK 1092 00:50:22,257 --> 00:50:25,160 INCREASES GAMMA POWER WE SHOW IT 1093 00:50:25,160 --> 00:50:27,195 HAPPENS IN HUMANS SO IT'S A 1094 00:50:27,195 --> 00:50:28,863 CROSS SPECIES BIOMARKER WE CAN 1095 00:50:28,863 --> 00:50:31,032 USE IN DRUG DISCOVERY AND 1096 00:50:31,032 --> 00:50:32,367 DEVELOPMENT SO VERY BRIEFLY THE 1097 00:50:32,367 --> 00:50:33,768 SUMMARY OF THE STORY WE HAVE THE 1098 00:50:33,768 --> 00:50:35,837 NATURE PAPER THAT SHOWS ALL THE 1099 00:50:35,837 --> 00:50:37,105 EXPERIMENTS THAT I JUST 1100 00:50:37,105 --> 00:50:38,606 SUMMARIZED AND IT'S BEEN 1101 00:50:38,606 --> 00:50:41,910 REPLICATED IN OVER 30 PLUS OTHER 1102 00:50:41,910 --> 00:50:46,881 PAPERS VERY BRIEFLY THAT LED TO 1103 00:50:46,881 --> 00:50:51,586 THE KEY INNOVATION. TOXICOLOGY, 1104 00:50:51,586 --> 00:50:54,889 WE ESTABLISHED THAT IT WAS SAFE 1105 00:50:54,889 --> 00:50:57,926 AND PRODUCED ONLY LEGIONS CAUSED 1106 00:50:57,926 --> 00:50:59,861 BY THE ANTAGONIST. PRECLINICAL 1107 00:50:59,861 --> 00:51:02,630 PHASE ONE AND PHASE TWO STUDY 1108 00:51:02,630 --> 00:51:04,299 SUGGESTED SAFE. THE STUDIES IN 1109 00:51:04,299 --> 00:51:06,534 HUMANS DOES NOT SHOW IT PRODUCES 1110 00:51:06,534 --> 00:51:08,770 DISSOCIATIVE SIDE EFFECTS AND WE 1111 00:51:08,770 --> 00:51:11,039 ARE ABOUT TO START STUDIES IN 1112 00:51:11,039 --> 00:51:14,676 THE FALL WITH HYDROXY NOR 1113 00:51:14,676 --> 00:51:16,945 KETAMINE AND TREATMENT RESISTANT 1114 00:51:16,945 --> 00:51:17,479 DEPRESSION. 1115 00:51:17,479 --> 00:51:19,948 SO I'M GOING TO CONCLUDE HERE 1116 00:51:19,948 --> 00:51:22,517 SHOWING THAT KETAMINE, I HOPE I 1117 00:51:22,517 --> 00:51:24,919 CONVINCED YOU THAT KETAMINE DOES 1118 00:51:24,919 --> 00:51:27,555 HAVE BROAD THERAPEUTIC EFFECTS 1119 00:51:27,555 --> 00:51:29,357 AND SUICIDE AND ANXIETY. NOT 1120 00:51:29,357 --> 00:51:30,458 EVERYBODY RESPONDS TO KETAMINE I 1121 00:51:30,458 --> 00:51:33,294 WANT TO MAKE THAT CLEAR. BUT 1122 00:51:33,294 --> 00:51:37,098 WHEN YOU DO RESPOND, IT SEEMS TO 1123 00:51:37,098 --> 00:51:40,935 LAST. WORK BY COLLABORATORS, 1124 00:51:40,935 --> 00:51:42,504 ACADEMIA, INDUSTRY GOVERNMENT 1125 00:51:42,504 --> 00:51:46,241 HAS LED TO APPROVAL BY THE EMA 1126 00:51:46,241 --> 00:51:48,810 OF KETAMINE FOR TWO INDICATIONS 1127 00:51:48,810 --> 00:51:51,012 FOR TREATMENT RESISTANT 1128 00:51:51,012 --> 00:51:52,714 DEPRESSION AND SUICIDAL 1129 00:51:52,714 --> 00:51:56,050 IDEATION. WE THINK THAT 1130 00:51:56,050 --> 00:51:57,852 METABOLISM OF KETAMINE TO 1131 00:51:57,852 --> 00:52:00,355 HYDROXY NOR KETAMINE IS KEY AND 1132 00:52:00,355 --> 00:52:03,558 IMPORTANT TO ITS THERAPEUTIC 1133 00:52:03,558 --> 00:52:04,359 EFFECTS. WE CAN ONLY DO SO MUCH 1134 00:52:04,359 --> 00:52:05,927 IN PRECLINICAL STUDIES. WE HAVE 1135 00:52:05,927 --> 00:52:10,532 TO TEST THIS IN OUR DEPRESSED 1136 00:52:10,532 --> 00:52:11,966 PATIENTS TO SEE IF THIS IS THE 1137 00:52:11,966 --> 00:52:14,869 CASE AND IT IS UNDER DEVELOPMENT 1138 00:52:14,869 --> 00:52:16,538 BY MULTIPLES OF THE IMPORTANCE 1139 00:52:16,538 --> 00:52:18,873 OF PARTNERSHIPS IS CRITICAL SO 1140 00:52:18,873 --> 00:52:21,443 HERE THERE'S SO MANY TO 1141 00:52:21,443 --> 00:52:22,277 ACKNOWLEDGE. FIRST OF ALL ALL 1142 00:52:22,277 --> 00:52:23,812 THIS WONDERFUL WORK WAS DONE AT 1143 00:52:23,812 --> 00:52:26,347 THE CLINICAL CENTER. WOULD NOT 1144 00:52:26,347 --> 00:52:28,049 BE POSSIBLE WITHOUT THE SUPPORT 1145 00:52:28,049 --> 00:52:29,551 OF ALL THE WONDERFUL STAFF AND 1146 00:52:29,551 --> 00:52:31,419 THE NURSES: I'D LIKE TO THANK 1147 00:52:31,419 --> 00:52:34,923 THEM OUR TRAINEES. OUR 1148 00:52:34,923 --> 00:52:36,958 WONDERFUL 7 SOUTHEAST NURSES WHO 1149 00:52:36,958 --> 00:52:38,493 HAVE BEEN PART OF THE JOURNEY 1150 00:52:38,493 --> 00:52:41,529 FOR TWO DECADES. INTRAMURAL AND 1151 00:52:41,529 --> 00:52:43,264 EXTRAMURAL COLLABORATORS HERE IS 1152 00:52:43,264 --> 00:52:46,034 OUR STAFF AND MORE IMPORTANTLY, 1153 00:52:46,034 --> 00:52:48,570 AND AS IMPORTANTLY, I'D LIKE TO 1154 00:52:48,570 --> 00:52:51,206 THANK THE HNKERS, WE CALL 1155 00:52:51,206 --> 00:52:52,740 OURSELF, WE HAD WEEKLY MEETINGS 1156 00:52:52,740 --> 00:52:57,445 GOING BACK TO THE 2015 OR '14 1157 00:52:57,445 --> 00:52:58,880 AND IF YOU REMEMBER THAT VALLEY 1158 00:52:58,880 --> 00:52:59,981 OF DEATH WE SUPPORT EACH OTHER 1159 00:52:59,981 --> 00:53:02,417 TO TRY TO GET THROUGH THIS 1160 00:53:02,417 --> 00:53:05,220 PERIOD OF TIME. WE ARE WORKING 1161 00:53:05,220 --> 00:53:09,691 HARD. AND I'D LIKE TO THANK 1162 00:53:09,691 --> 00:53:13,962 TODD GOULD, PATRICK MORRIS FOR 1163 00:53:13,962 --> 00:53:16,431 THEIR COLLABORATION AND MOST 1164 00:53:16,431 --> 00:53:18,700 IMPORTANTLY, THANKS TO OUR 1165 00:53:18,700 --> 00:53:22,170 PATIENTS SUCH AS MICHELE, TO THE 1166 00:53:22,170 --> 00:53:23,605 FAMILIES, WHO HELPED SUPPORT OUR 1167 00:53:23,605 --> 00:53:26,007 RESEARCH SO. I WOULD LIKE TO 1168 00:53:26,007 --> 00:53:28,943 STOP THERE AND THANK YOU FOR 1169 00:53:28,943 --> 00:53:38,887 YOUR ATTENTION. . 1170 00:53:38,887 --> 00:53:41,322 >> ANYONE QUESTIONS, FEEL FREE 1171 00:53:41,322 --> 00:53:43,157 TO GO TO THE MICS. 1172 00:53:43,157 --> 00:53:44,826 >> CARLOS: ANY QUESTIONS OR 1173 00:53:44,826 --> 00:53:55,003 COMMENTS. 1174 00:54:03,611 --> 00:54:05,780 >> AUDIENCE: ABOUT 104 PATIENTS 1175 00:54:05,780 --> 00:54:07,448 IN A RANDOM IDEAS CLINICAL 1176 00:54:07,448 --> 00:54:08,249 CONTROL TRIAL. 1177 00:54:08,249 --> 00:54:11,619 WHICH SHOWED ALSO RAPID ONSET 1178 00:54:11,619 --> 00:54:13,454 AGAINST MAJOR DEPRESS I DISORDER 1179 00:54:13,454 --> 00:54:15,590 AND WHAT I'M WONDERING IS IF YOU 1180 00:54:15,590 --> 00:54:18,192 COMMENT ON THE FUTURE OF NATURAL 1181 00:54:18,192 --> 00:54:20,662 PRODUCTS LIKE SILL LA SAY BEN 1182 00:54:20,662 --> 00:54:22,830 PERHAPS IN CONJUNCTION WITH 1183 00:54:22,830 --> 00:54:23,264 KETAMINE THERAPY. 1184 00:54:23,264 --> 00:54:24,532 >> CARLOS: THANK YOU FOR THE 1185 00:54:24,532 --> 00:54:27,435 QUESTION. SEVERAL POINTS, ONE 1186 00:54:27,435 --> 00:54:29,671 IS THAT PSYCHEDELIC RESEARCH HAS 1187 00:54:29,671 --> 00:54:32,407 GONE ON FOR MANY, MANY DECADES 1188 00:54:32,407 --> 00:54:34,409 BUT IT SEEMED IN -- THERE HAVE 1189 00:54:34,409 --> 00:54:37,278 BEEN, YOU KNOW, STUDIES IN, YOU 1190 00:54:37,278 --> 00:54:40,315 KNOW, A THOUSAND STUDIES IN THE 1191 00:54:40,315 --> 00:54:42,650 PAST AND MANY 40,000 PATIENTS 1192 00:54:42,650 --> 00:54:44,886 EXPOSED TO PSYCHEDELICS AND, YOU 1193 00:54:44,886 --> 00:54:47,922 KNOW, FOR MANY REASONS THE LAW 1194 00:54:47,922 --> 00:54:49,857 AND IT BECAME A CONTROLLED 1195 00:54:49,857 --> 00:54:50,858 SUBSTANCE THAT KIND OF WENT AWAY 1196 00:54:50,858 --> 00:54:54,862 BUT IT SEEMS TO ME THAT THE 1197 00:54:54,862 --> 00:54:58,866 RESULTS OF THE KETAMINE DID 1198 00:54:58,866 --> 00:55:00,001 RESURRECT THIS IN LARGE PART 1199 00:55:00,001 --> 00:55:02,337 THAT IT WAS OKAY TO HAVE A DRUG 1200 00:55:02,337 --> 00:55:04,639 THAT PRODUCES DISSOCIATIVE SIDE 1201 00:55:04,639 --> 00:55:05,873 EFFECTS. I DON'T MEAN OKAY THAT 1202 00:55:05,873 --> 00:55:08,876 IT'S A GOOD THING BUT THAT MEANS 1203 00:55:08,876 --> 00:55:10,111 THAT YOU CAN HAVE A GREATER 1204 00:55:10,111 --> 00:55:12,013 THRESHOLD FOR TESTING OTHER 1205 00:55:12,013 --> 00:55:14,882 TYPES OF PRODUCTS THAT EFFECTS 1206 00:55:14,882 --> 00:55:16,551 THIS. AND THAT WAS VERY 1207 00:55:16,551 --> 00:55:18,686 IMPORTANT. THE OTHER IS THAT, 1208 00:55:18,686 --> 00:55:21,255 THE RECENT STUDIES, UNTIL 1209 00:55:21,255 --> 00:55:25,159 RECENTLY, THE STUDY YOU 1210 00:55:25,159 --> 00:55:26,628 MENTIONED, THE WORLD LITERATURE 1211 00:55:26,628 --> 00:55:31,733 HAD ONLY BEEN ABOUT 257 PATIENTS 1212 00:55:31,733 --> 00:55:33,901 RANDOMIZED ON THIS. AND YET, 1213 00:55:33,901 --> 00:55:36,871 THE AMOUNT OF ATTENTION IS 1214 00:55:36,871 --> 00:55:38,873 INCREDIBLE. I MEAN, IT'S TAKEN 1215 00:55:38,873 --> 00:55:42,110 OFF, 75 VENTURE CAPITALIST. 1216 00:55:42,110 --> 00:55:43,845 BILLIONS OF DOLLARS INVESTED AND 1217 00:55:43,845 --> 00:55:46,414 I CERTAINLY BELIEVE, YOU KNOW, 1218 00:55:46,414 --> 00:55:47,982 THAT IT'S IMPORTANT TO CONTINUE 1219 00:55:47,982 --> 00:55:49,817 TO UNDERSTAND IT BUT IT'S REALLY 1220 00:55:49,817 --> 00:55:52,954 TAKEN OFF VERY QUICKLY AND 1221 00:55:52,954 --> 00:55:55,657 THERE'S ALWAYS MY CONCERN 1222 00:55:55,657 --> 00:55:56,691 SOMETHING COULD GO WRONG AND YOU 1223 00:55:56,691 --> 00:55:59,227 COULD ARGUE THAT THE RESEARCH WE 1224 00:55:59,227 --> 00:56:01,629 TOOK WAS SLOW. IT TOOK A LONG 1225 00:56:01,629 --> 00:56:03,097 TIME. I WOULD ARGUE THAT WAS 1226 00:56:03,097 --> 00:56:05,099 APPROPRIATE UNDER THE ETHICAL 1227 00:56:05,099 --> 00:56:06,801 CONSIDERATIONS, THE SIDE 1228 00:56:06,801 --> 00:56:08,770 EFFECTS, THE MISUSE POTENTIAL, 1229 00:56:08,770 --> 00:56:11,839 AND THINGS THAT COULD GO WRONG 1230 00:56:11,839 --> 00:56:14,776 IN THIS SLOW AND DELIBERATE WAS 1231 00:56:14,776 --> 00:56:16,611 BENEFICIAL TO THE FIELD. AND SO 1232 00:56:16,611 --> 00:56:19,247 I THINK THAT WHAT I WOULD SAY 1233 00:56:19,247 --> 00:56:21,916 THAT THESE ARE INTRIGUING AND 1234 00:56:21,916 --> 00:56:23,985 INTERESTING RESULTS BUT WE HAVE 1235 00:56:23,985 --> 00:56:25,153 TO BE CAREFUL. 1236 00:56:25,153 --> 00:56:26,387 >> AUDIENCE: THANK YOU. 1237 00:56:26,387 --> 00:56:28,890 >> CARLOS: YES, NEXT QUESTION. 1238 00:56:28,890 --> 00:56:31,325 >> AUDIENCE: YOU SAID WITH THE 1239 00:56:31,325 --> 00:56:34,762 SPROE HAVE A DO YOU HAD SEVEN 1240 00:56:34,762 --> 00:56:36,698 DAYS OF EFFECTIVENESS SO HOW 1241 00:56:36,698 --> 00:56:38,866 MANY DOSAGE DO YOU HAVE TO GET 1242 00:56:38,866 --> 00:56:39,701 TO A REMISSION? 1243 00:56:39,701 --> 00:56:43,137 >> CARLOS: YEAH, SO, RIGHT NOW 1244 00:56:43,137 --> 00:56:46,307 THE WAY -- THERE'S A -- AN ACUTE 1245 00:56:46,307 --> 00:56:48,443 DOSING STRATEGY WHICH IS YOU 1246 00:56:48,443 --> 00:56:51,345 GIVE -- AND IT'S VERY SIMILAR 1247 00:56:51,345 --> 00:56:54,015 FOR THE INTRAVENOUS KETAMINE YOU 1248 00:56:54,015 --> 00:56:55,416 GET TWO INFUSIONS A WEEK FOR TWO 1249 00:56:55,416 --> 00:56:57,819 WEEKS SO THAT'S FOUR INFUSION. 1250 00:56:57,819 --> 00:56:59,787 SOME MIGHT GO ANOTHER WEEK AND 1251 00:56:59,787 --> 00:57:01,956 THEN YOU GO TO ONE INFUSION A 1252 00:57:01,956 --> 00:57:05,560 WEEK AND TRY TO COME UP WITH 1253 00:57:05,560 --> 00:57:06,861 THAT SWEET POINT FOR THAT 1254 00:57:06,861 --> 00:57:09,330 INDIVIDUAL. AND SO NOW THERE IS 1255 00:57:09,330 --> 00:57:11,999 DATA WITH SPRO HAVE A DO IN 1256 00:57:11,999 --> 00:57:14,268 TERMS OF SAFETY AND EFFICACY FOR 1257 00:57:14,268 --> 00:57:15,803 SIX AND A HALF YEARS SO THERE 1258 00:57:15,803 --> 00:57:18,639 IS -- IT'S OPEN LABEL DATA. 1259 00:57:18,639 --> 00:57:20,508 IT'S NOT CONTROLLED. SO THAT'S 1260 00:57:20,508 --> 00:57:23,978 GENERALLY HOW YOU PRESCRIBE IT. 1261 00:57:23,978 --> 00:57:24,579 >> AUDIENCE: SO YOU'RE SAYING 1262 00:57:24,579 --> 00:57:26,380 THAT SOME PEOPLE ARE ON, LET'S 1263 00:57:26,380 --> 00:57:27,815 SAY MONTHLY FOR SIX AND A HALF 1264 00:57:27,815 --> 00:57:30,017 YEARS OR THEY OBTAIN A REMISSION 1265 00:57:30,017 --> 00:57:33,254 OR WHAT DO YOU MEAN? 1266 00:57:33,254 --> 00:57:33,855 >> CARLOS: WHAT IS GENERALLY 1267 00:57:33,855 --> 00:57:37,091 TRIED IS WE TRY TO FOCUS ON 1268 00:57:37,091 --> 00:57:38,593 USING THE EXISTING MEDICATIONS 1269 00:57:38,593 --> 00:57:40,795 AND NOT TO GIVE IT CONTINUOUSLY. 1270 00:57:40,795 --> 00:57:42,029 YOU TRY WITH THAT, IF NOT 1271 00:57:42,029 --> 00:57:44,499 ANOTHER CLASS, AND IF NOT SOME 1272 00:57:44,499 --> 00:57:46,467 PEOPLE MIGHT NEED IT FOR LONGER 1273 00:57:46,467 --> 00:57:48,002 PERIODS OF TIME SO WE TRY TO 1274 00:57:48,002 --> 00:57:50,471 WORK ON THAT BECAUSE THERE IS 1275 00:57:50,471 --> 00:57:54,275 STILL NOT A LOT OF LONG-TERM 1276 00:57:54,275 --> 00:57:56,144 SAFETY DATA WITH SPRO HAVE A DO 1277 00:57:56,144 --> 00:57:58,613 OR S KETAMINE WE NEED A LARGER 1278 00:57:58,613 --> 00:58:00,181 AND LONGER TERM STUDY TO REALLY 1279 00:58:00,181 --> 00:58:03,317 KNOW WHAT THE EFFECT IS. SO WE 1280 00:58:03,317 --> 00:58:04,886 ALWAYS TRY WITH EXISTING 1281 00:58:04,886 --> 00:58:05,987 TREATMENTS AND BUILD UP TO GET 1282 00:58:05,987 --> 00:58:08,256 INTO THAT POINT WE WOULD NEED IT 1283 00:58:08,256 --> 00:58:10,124 MONTHLY BUT IF YOU DON'T MIND IT 1284 00:58:10,124 --> 00:58:14,095 WITHIN ONE MONTH I TRY SOMETHING 1285 00:58:14,095 --> 00:58:14,295 ELSE. 1286 00:58:14,295 --> 00:58:15,196 >> LET ME SLIP IN AT LEAST ONE 1287 00:58:15,196 --> 00:58:17,198 QUESTION OVER HERE. HI. FROM 1288 00:58:17,198 --> 00:58:17,999 ONLINE, JUST BEFORE WE GO THERE 1289 00:58:17,999 --> 00:58:21,869 SO FROM OUR COLLEAGUES AT NCBI, 1290 00:58:21,869 --> 00:58:25,473 IF ONLY R KETAMINE IS 1291 00:58:25,473 --> 00:58:31,612 METABOLIZED BY 2R 6R-HNK HOW 1292 00:58:31,612 --> 00:58:34,515 DOES IT EXPLAIN THE LASTING 1293 00:58:34,515 --> 00:58:36,417 EFFECTS OF S KETAMINE? 1294 00:58:36,417 --> 00:58:37,485 >> CARLOS: ONE IS IMPORTANT 1295 00:58:37,485 --> 00:58:40,822 BECAUSE OF THE TIME IS IN OUR 1296 00:58:40,822 --> 00:58:42,590 NATURE PAPER. WE STUDIED THE 1297 00:58:42,590 --> 00:58:46,594 TWO PATH, THE S AND THE R. SO 1298 00:58:46,594 --> 00:58:52,033 THERE'S ALSO 2S HYDROXY NOR 1299 00:58:52,033 --> 00:58:57,972 KETAMINE WE ALSO FOUND THAT 2 S. 1300 00:58:57,972 --> 00:59:05,279 WHAT WE DID FIND IS THAT THE 2S 1301 00:59:05,279 --> 00:59:08,182 HAS MISUSE POTENTIAL. SO IT'S 1302 00:59:08,182 --> 00:59:10,051 NOT DISSIMILAR FROM S KETAMINE 1303 00:59:10,051 --> 00:59:13,487 AND HAS THE SIDE EFFECTS OF 1304 00:59:13,487 --> 00:59:16,190 KETAMINE THAT IS THE MODELS THAT 1305 00:59:16,190 --> 00:59:18,826 OCCUR IN HUMANS AND WE WENT WITH 1306 00:59:18,826 --> 00:59:20,428 THE DRUG THAT WAS BETTER 1307 00:59:20,428 --> 00:59:22,730 TOLERATED. DID NOT HAVE THE 1308 00:59:22,730 --> 00:59:23,331 ABUSE POTENTIAL AND THAT WE 1309 00:59:23,331 --> 00:59:25,700 COULD DEVELOP AND SO THAT WAS 1310 00:59:25,700 --> 00:59:27,602 THE REASON. IT'S POSITIVE THERE 1311 00:59:27,602 --> 00:59:30,438 MIGHT BE OTHER METABOLITES WITH 1312 00:59:30,438 --> 00:59:35,109 OTHER EFFECTS. THAT'S A GOOD 1313 00:59:35,109 --> 00:59:35,376 QUESTION. 1314 00:59:35,376 --> 00:59:36,644 >> AUDIENCE: GOOD MORNING 1315 00:59:36,644 --> 00:59:41,015 DR. ZOO RAH ZARATE. 1316 00:59:41,015 --> 00:59:42,149 SOMETHING THAT STOOD OUT IS THAT 1317 00:59:42,149 --> 00:59:45,786 KETAMINE LIKES YOU SAID, AS GOOD 1318 00:59:45,786 --> 00:59:49,590 AS OR BETTER IN TREATMENT THAN 1319 00:59:49,590 --> 00:59:51,626 ECT AND I THINK THAT -- I MEAN 1320 00:59:51,626 --> 00:59:54,929 FROM MY UNDERSTANDING ECT IS A 1321 00:59:54,929 --> 00:59:56,330 PRETTY INTENSE TREATMENT I 1322 00:59:56,330 --> 00:59:58,332 WANTED TO KNOW AND I COMMEND YOU 1323 00:59:58,332 --> 01:00:00,668 FOR TAKING AS LONG AS YOU DID 1324 01:00:00,668 --> 01:00:06,674 BECAUSE IT IS -- IT IS FOR A 1325 01:00:06,674 --> 01:00:07,775 TREATMENT RESISTANT DEPRESSION 1326 01:00:07,775 --> 01:00:10,878 R. THE SIDE EFFECTS OF KETAMINE 1327 01:00:10,878 --> 01:00:13,347 AS SEVERE AS THOSE OF ECT? IN 1328 01:00:13,347 --> 01:00:15,149 MY EXPERIENCE OF SEEING FATIGUE, 1329 01:00:15,149 --> 01:00:17,418 BRAIN FOG, AFTER TREATMENT. AND 1330 01:00:17,418 --> 01:00:22,523 IF SO, WOULD THAT DEPEND ON THE 1331 01:00:22,523 --> 01:00:23,724 METHOD OF ADMINISTRATION WHETHER 1332 01:00:23,724 --> 01:00:28,663 IV OR NASALLY? 1333 01:00:28,663 --> 01:00:29,764 >> CARLOS: THANK YOU FOR THAT 1334 01:00:29,764 --> 01:00:30,798 QUESTION. KEEP IN MIND THAT 1335 01:00:30,798 --> 01:00:32,533 WHAT I HOPE I SAID WAS THAT IT 1336 01:00:32,533 --> 01:00:34,869 IS AS EFFECTIVE I DIDN'T SAY IT 1337 01:00:34,869 --> 01:00:35,670 WAS SUPERIOR EVEN THOUGH YOU MAY 1338 01:00:35,670 --> 01:00:38,706 HAVE NOTICED THE NUMBERS TENDED 1339 01:00:38,706 --> 01:00:40,308 TO FAVOR KETAMINE. BUT IS WHAT 1340 01:00:40,308 --> 01:00:42,877 WE REFER TO AS A NON INFERIOR 1341 01:00:42,877 --> 01:00:44,345 DESIGN SO IT'S NOT POWER TO SHOW 1342 01:00:44,345 --> 01:00:46,047 THAT ONE IS BETTER THAN THE 1343 01:00:46,047 --> 01:00:47,715 OTHER. THAT'S ONE POINT. ECT 1344 01:00:47,715 --> 01:00:50,151 IS A VERY EFFECTIVE TREATMENT 1345 01:00:50,151 --> 01:00:52,753 BUT THE INDIVIDUALS WERE MAINLY 1346 01:00:52,753 --> 01:00:54,889 OUTPATIENTS WITH NON PSYCHOTIC 1347 01:00:54,889 --> 01:00:58,592 DEPRESSION. IN INDIVIDUALS WHO 1348 01:00:58,592 --> 01:01:02,730 HAVE PSYCHOSIS IMPAIRED REALITY 1349 01:01:02,730 --> 01:01:04,865 TESTING AND INPATIENTS MIGHT 1350 01:01:04,865 --> 01:01:06,000 BENEFIT MORE FROM ECT WE DO NOT 1351 01:01:06,000 --> 01:01:08,803 KNOW. THOSE STUDIES HAVE TO BE 1352 01:01:08,803 --> 01:01:10,638 DONE. THE SIDE EFFECTS ARE 1353 01:01:10,638 --> 01:01:12,006 DIFFERENT. ONE CANNOT GENERALLY 1354 01:01:12,006 --> 01:01:14,041 SAY ONE IS BETTER THAN OTHER SO 1355 01:01:14,041 --> 01:01:15,843 DO YOU PREFER TO HAVE MORE 1356 01:01:15,843 --> 01:01:18,512 MEMORY IMPAIRMENT OR PREFER TO 1357 01:01:18,512 --> 01:01:20,748 HAVE MORE DISSOCIATIVE SIDE 1358 01:01:20,748 --> 01:01:22,950 EFFECTS WHICH ARE TRANSITORY, 1359 01:01:22,950 --> 01:01:24,685 KEEP IN MIND AND THE RISK OF 1360 01:01:24,685 --> 01:01:26,287 ABUSE POTENTIAL. A LOT OF THIS 1361 01:01:26,287 --> 01:01:28,956 HAS TO DO WITH SAFETY AND IT'S A 1362 01:01:28,956 --> 01:01:30,858 PERSONAL CHOICE. SO WHAT MORE 1363 01:01:30,858 --> 01:01:33,094 AND MORE PROFESSIONALS ARE DOING 1364 01:01:33,094 --> 01:01:36,364 IS THEY ARE REFERRED FOR ECT 1365 01:01:36,364 --> 01:01:37,431 BECAUSE THEY HAVE REALLY BAD 1366 01:01:37,431 --> 01:01:39,266 DEPRESSION. AND SAY, WELL, 1367 01:01:39,266 --> 01:01:41,135 WHY -- AND FOR THEM, THEY REALLY 1368 01:01:41,135 --> 01:01:45,506 DEPEND ON THEIR MEMORY AND THEIR 1369 01:01:45,506 --> 01:01:46,707 CONCENTRATION EXECUTIVE FUNCTION 1370 01:01:46,707 --> 01:01:49,076 WHY NOT TRY KETAMINE ONE OR TWO 1371 01:01:49,076 --> 01:01:51,145 DOSES BEFORE I DECIDE TO GO TO 1372 01:01:51,145 --> 01:01:53,314 ECT? SO IT'S REALLY ALL THE 1373 01:01:53,314 --> 01:01:55,449 MEDICATIONS IS BASED -- THE SIDE 1374 01:01:55,449 --> 01:01:57,251 EFFECTS ARE BASED UPON YOUR 1375 01:01:57,251 --> 01:01:58,886 INDIVIDUAL PREFERENCE. 1376 01:01:58,886 --> 01:02:01,455 >> AUDIENCE: I SEE. THANK YOU. 1377 01:02:01,455 --> 01:02:02,289 >> AUDIENCE: HI, GOOD MORNING, 1378 01:02:02,289 --> 01:02:04,258 THANK YOU FOR THE TALK. I HAD A 1379 01:02:04,258 --> 01:02:05,893 QUICK QUESTION FROM ALL YOUR 1380 01:02:05,893 --> 01:02:06,861 EXPERIENCE AND ESPECIALLY 1381 01:02:06,861 --> 01:02:09,697 CONSIDERING WHAT YOU SAW WITH 1382 01:02:09,697 --> 01:02:11,465 HYDROXY NOR KETAMINE DO YOU 1383 01:02:11,465 --> 01:02:13,167 THINK THAT THE ACTUAL MENTAL 1384 01:02:13,167 --> 01:02:16,804 EPISODES OF DISASSOCIATION HAVE 1385 01:02:16,804 --> 01:02:17,538 ANYTHING THERAPEUTIC BENEFIT 1386 01:02:17,538 --> 01:02:18,873 THAT COME FROM DRUGS OF KETAMINE 1387 01:02:18,873 --> 01:02:22,576 OR OTHER TYPES OF HALLUCINOGENIC 1388 01:02:22,576 --> 01:02:23,611 TYPE COMPOUNDS? 1389 01:02:23,611 --> 01:02:27,448 >> CARLOS: WE TAKEN ADVANTAGE OF 1390 01:02:27,448 --> 01:02:29,417 THE DATA WE'VE COMMITTED OVER 1391 01:02:29,417 --> 01:02:31,652 THE YEARS. WE LOOKED AT THAT IN 1392 01:02:31,652 --> 01:02:34,021 108 INDIVIDUALS WHO RECEIVED 1393 01:02:34,021 --> 01:02:35,689 KETAMINE UNDER THE SAME 1394 01:02:35,689 --> 01:02:38,059 CONDITIONS AND NOTICED THAT THE 1395 01:02:38,059 --> 01:02:40,594 VARIANCE, THE RELATIONSHIP OF 1396 01:02:40,594 --> 01:02:41,929 DISASSOCIATION WITH RESPONSE WAS 1397 01:02:41,929 --> 01:02:46,400 ABOUT 12-14-16%. SO IT'S STILL 1398 01:02:46,400 --> 01:02:47,935 IMPORTANT BUT THERE ARE OTHER 1399 01:02:47,935 --> 01:02:51,872 FACTORS THAT ARE IMPLICATED IN 1400 01:02:51,872 --> 01:02:53,674 THE RESPONSE. THE OTHER IS WE 1401 01:02:53,674 --> 01:02:55,242 HAD THOSE WHO RESPONDED AND 1402 01:02:55,242 --> 01:02:56,077 OTHERS DID NOT RESPOND AND SOME 1403 01:02:56,077 --> 01:02:58,279 WHO -- SORRY, ANY DISASSOCIATION 1404 01:02:58,279 --> 01:03:02,383 WHO RESPONDED. AND SO AFTER 1405 01:03:02,383 --> 01:03:03,517 REVIEWING ALL THE LITERATURE, 1406 01:03:03,517 --> 01:03:06,053 AND LOOKING AT DIFFERENT STUDIES 1407 01:03:06,053 --> 01:03:07,955 AND I THINK EVEN SPRO HAVE AED 1408 01:03:07,955 --> 01:03:10,991 DO HAS LOOKED AT THAT. 1409 01:03:10,991 --> 01:03:13,327 THEY DON'T FIND A STRONG 1410 01:03:13,327 --> 01:03:14,361 RELATIONSHIP BETWEEN 1411 01:03:14,361 --> 01:03:16,497 DISASSOCIATION AND THEIR PUT 1412 01:03:16,497 --> 01:03:17,965 IMEFFECTS. ONE WOULD HAVE TO 1413 01:03:17,965 --> 01:03:20,167 DESIGN THE SPECIFIC STUDY TO 1414 01:03:20,167 --> 01:03:21,702 TEST THAT QUESTION AND TO MY 1415 01:03:21,702 --> 01:03:22,870 KNOWLEDGE IS ONGOING AT THIS 1416 01:03:22,870 --> 01:03:23,104 STAGE. 1417 01:03:23,104 --> 01:03:25,573 THAT DOES NOT MEAN, FOR EXAMPLE, 1418 01:03:25,573 --> 01:03:27,708 THAT YOU CAN TAKE THIS LESSON 1419 01:03:27,708 --> 01:03:30,010 AND APPLY TO THE PSYCHEDELICS, 1420 01:03:30,010 --> 01:03:30,678 RIGHT? BECAUSE THAT WOULD BE 1421 01:03:30,678 --> 01:03:32,246 ANOTHER QUESTION, YOU KNOW, 1422 01:03:32,246 --> 01:03:34,148 WELL, IF DISASSOCIATION IS NOT 1423 01:03:34,148 --> 01:03:36,784 IMPORTANT THAT PROBABLY MEANS WE 1424 01:03:36,784 --> 01:03:38,219 DON'T NEED THESE SIDE EFFECTS ON 1425 01:03:38,219 --> 01:03:40,588 THE PSYCHEDELICS BUT THESE ARE 1426 01:03:40,588 --> 01:03:42,556 SEPARATE DRUGS, SEPARATE 1427 01:03:42,556 --> 01:03:43,390 COMPOUNDS, SEPARATE TARGETS AND 1428 01:03:43,390 --> 01:03:44,058 THOSE QUESTIONS HAVE TO BE 1429 01:03:44,058 --> 01:03:47,795 LOOKED AT. I THINK. THANK YOU. 1430 01:03:47,795 --> 01:03:51,599 >> TAKE ONE LAST QUESTION THEN, 1431 01:03:51,599 --> 01:03:52,766 PLEASE. 1432 01:03:52,766 --> 01:03:54,001 >> AUDIENCE: THANK YOU VERY MUCH 1433 01:03:54,001 --> 01:03:56,504 DR. ZARATE FOR YOUR GREAT 1434 01:03:56,504 --> 01:03:58,672 PRESENTATION. SO I JUST WANT TO 1435 01:03:58,672 --> 01:04:00,441 ASK, IF YOU DETERMINE THE 1436 01:04:00,441 --> 01:04:04,411 BINDING POCKET FOR HNK AND IF IT 1437 01:04:04,411 --> 01:04:08,415 IS THE SAME ONE THAT IS USED BY 1438 01:04:08,415 --> 01:04:09,984 KETAMINE, TO BIND INTO THE 1439 01:04:09,984 --> 01:04:10,885 RECEPTOR AND THE SECOND QUESTION 1440 01:04:10,885 --> 01:04:14,121 REGARDING THIS ONE, IF YOU HAVE 1441 01:04:14,121 --> 01:04:16,657 DETERMINED WHETHER THERE ARE BUY 1442 01:04:16,657 --> 01:04:25,099 INS, YES GENOMIC BUY INS THAT 1443 01:04:25,099 --> 01:04:27,501 YOU CAN REPORT NOW THAT COULD 1444 01:04:27,501 --> 01:04:30,871 RESULT IN THAT ME TOO DRUG LATER 1445 01:04:30,871 --> 01:04:34,842 O 1446 01:04:34,842 --> 01:04:35,009 ON: 1447 01:04:35,009 --> 01:04:39,613 >> CARLOS: WHAT WE KNOW IS THAT 1448 01:04:39,613 --> 01:04:46,887 THIS IS WITH S KETAMINE AND NDA 1449 01:04:46,887 --> 01:04:50,624 AN IT'S AIST -- ANTAGONIST. 1450 01:04:50,624 --> 01:04:51,358 THAT DOESN'T MEAN IT'S 1451 01:04:51,358 --> 01:04:52,860 FUNCTIONAL HI RESPONSIBLE FOR 1452 01:04:52,860 --> 01:04:54,862 THE ANTIDEPRESSANT EFFECTS. 1453 01:04:54,862 --> 01:04:57,765 KETAMINE HAS A LOT OF DIFFERENT 1454 01:04:57,765 --> 01:04:59,800 TARGETS. AND HYDROXY NOR 1455 01:04:59,800 --> 01:05:01,969 KETAMINE WE KNOW THAT REALLY 1456 01:05:01,969 --> 01:05:05,706 DOES NOT BLOCK AN NMDA. YOU 1457 01:05:05,706 --> 01:05:09,443 REALLY HAVE TO PUSH IT TO GET 1458 01:05:09,443 --> 01:05:11,478 ANYWHERE NEAR AN NMDA ANTAGONISM 1459 01:05:11,478 --> 01:05:12,713 SO WE DON'T SEE THAT AND THE 1460 01:05:12,713 --> 01:05:14,181 SECOND PART OF THE QUESTION. 1461 01:05:14,181 --> 01:05:16,817 AND WE STILL DON'T KNOW WHAT THE 1462 01:05:16,817 --> 01:05:20,020 TARGET MIGHT BE OF HNK. 1463 01:05:20,020 --> 01:05:24,024 >> AUDIENCE: OKAY. GOT IT. 1464 01:05:24,024 --> 01:05:25,793 PERFECT. THANK YOU. 1465 01:05:25,793 --> 01:05:26,327 >> CARLOS: WELL THANK YOU. 1466 01:05:26,327 --> 01:05:28,729 >> OKAY, I'D LIKE TO THANK YOU 1467 01:05:28,729 --> 01:05:31,398 FOR COMING HERE TODAY. 1468 01:05:31,398 --> 01:05:34,868 >> AUDIENCE: (APPLAUSE). 1469 01:05:34,868 --> 01:05:38,472 >> I JUST WANT TO THANK DR. 1470 01:05:38,472 --> 01:05:42,710 DR. ZARATE REALLY FOR A 1471 01:05:42,710 --> 01:05:43,844 MAGNIFICENT EXAMPLE FOR 1472 01:05:43,844 --> 01:05:46,714 EVERYTHING THAT NIH STANDS FOR 1473 01:05:46,714 --> 01:05:49,483 THE DISCOVERY OF BASIC SCIENCE 1474 01:05:49,483 --> 01:05:51,819 OF BIOLOGIC SYSTEMS AND THE 1475 01:05:51,819 --> 01:05:53,087 APPLICATION OF THOSE DISCOVERIES 1476 01:05:53,087 --> 01:05:57,791 TO THE RELIEF OF SUFFERING IN 1477 01:05:57,791 --> 01:06:02,229 PATIENTS. SO THANK YOU SO MUCH. 1478 01:06:02,229 --> 01:06:12,229 AUDIENCE: (APPLAUSE).