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← Psilocybin, Addiction, and End of Life - Stephen Ross

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Showing Revision 24 created 08/28/2016 by Christine Kyauk.

  1. It's a real pleasure to be here today.
  2. Today I'm going to tell two narratives.
  3. One is I'm going to tell you
    about our research
  4. using psilocybin-assisted psychotherapy
  5. with cancer patients and our
    preliminary results.
  6. And then I'm going to tell a story
  7. that's a little bit similar to Michael's.
  8. We have a planned study at NYU
  9. to use psilocybin-assisted psychotherapy
    for alcoholics.
  10. So, disclosures: I'm a member of the
    Heffter Research Institute,

  11. and I receive my research funding
    from NIDA, Heffter,
  12. and the NYU Langone Medical Center.
  13. So I have an 11-year-old son, and he's
    been doing montages at school,
  14. so I think I borrowed from him because
  15. it's more entertaining to tell
    a story in pictures.
  16. So, pop quiz: Now, when I did this,
    this is the story of the use,

  17. the history of psychedelics
    to treat addiction,
  18. and I'm going to tell the story today
    by going through these rows,
  19. and some of you are sitting
    in the audience, so...
  20. Who's that right there?
    [inaudible from audience]
  21. So that's William James. Dave Nichols.
    Who's that?
  22. That's Arthur Heffter. Who's that?
    [inaudible from audience]
  23. That's Carl Jung. Bill Wilson.
    Albert Hoffman.
  24. Right, so this is the... I'm going to tell
    a story here,
  25. but then the next story here, who's that?
  26. Humphry Osmond. You know that guy?
  27. Sidney Cohen. That handsome man?
  28. Walter Pahnke.
  29. Stan Grof.
  30. And I won't go through the rest here,
  31. but I'm going to
    come back to this picture.
  32. Now, there's another picture here,
  33. this has to do with the use of
    psychedelics and terminal cancer.
  34. And that's a young Irving Yolm.
  35. And you can notice,
  36. when I did all these pictures,
    I realize it's mostly men.
  37. All men, right?
  38. So, what I did for the ladies,
  39. is I went through the history of
    psychedelic women, right?
  40. So... [applause] You gotta do that. Yeah!
  41. So who's that? Marie Sabina. Who's that?
  42. Valentina Wasson, right?
    She's very important.
  43. Betty Eisner, UCLA.
  44. Loretta Bender, who's the first
    psychedelic researcher at NYU.
  45. Who's that? Laura Huxley. Helen Bonnie.
  46. Who's that?
  47. That's a young Ann Shulgin, yeah.
    And Mary Cosimano.
  48. I'll talk about Mary today,
  49. 'cause I had dinner with her,
    and it was a lot about love,
  50. there was a lot of love going on.
  51. And Annie Mithoefer.
  52. All of these people here
    are part of our NYU team.
  53. They are therapists,
    and then we have Alicia,
  54. and we'll go through all of these people
    here as well.
  55. Okay, and some more pictures.
    So, I'm going to talk about

  56. the serotonergic hallucinogens today
  57. and the indolealkylamines include
  58. the drugs like ayahuasca
    and psilocybin and LSD...
  59. and the phenylalkylamines,
    the prototype is mescaline.
  60. And you guys have heard a lot about
    a mystical experience.
  61. You know,
    when I was a psychiatric trainee,
  62. I didn't hear anything about psychosis
  63. that had a positive valence.
  64. If you talked about
    having unitary experiences,
  65. or being transcended to another place,
    time, and reality,
  66. we'd call that psychosis.
  67. At the Bellevue ER,
    we would admit you in-patient.
  68. So, mystical experiences provoke a kind of
  69. crisis of nomenclature within psychiatry:
  70. How do you define these kinds of
  71. alterations of consciousness that have
    a positive attribute to them?
  72. So I think we need a better
    definition system.
  73. And to think about psilocybin...
  74. psilocybin is very interesting because
    it's doable in the laboratory.
  75. It's very hard to sit there from 8
    in the morning to 5 at night
  76. to do a session, and I think
    if we did LSD,
  77. my wife would divorce me, you know,
    because I'd be home too late,
  78. so with psilocybin, it's doable
  79. within the laboratory setting, but still
    hard, still hard to sit there.
  80. Now, we have two neuroimaging teams,
  81. one in Switzerland,
  82. and one in Great Britain,
  83. that have come to two different
    conclusions in terms of what happens
  84. when you give psilocybin.
  85. Franz Vollenweider's team gave
    oral psilocybin
  86. and found marked activation of
    prefrontal cortical regions
  87. and temporal medial cortex,
  88. and that was interesting.
  89. This was PET because the group at
    Imperial College of London --
  90. and I feel that at today's lecture,
    I'm going to say a lot of "ditto,"
  91. or "what he said," because
    a lot of these lectures have been given.
  92. So, I think Robin is here in the audience,
    so he's going to talk all about this,
  93. but this was interesting,
    this was IV psilocybin,
  94. and what they found was deactivation
  95. of prefrontal cortical regions,
    not activation,
  96. and interestingly, they found
    deactivation of the default mode network,
  97. and when they did functional connectivity,
  98. there was increased connectivity between
    the default mode network
  99. and the task positive network,
  100. which is something that you see in
    certain states of psychosis and meditation
  101. and Robin is going to talk more about that
  102. but these were divergent findings,
    and the more we learn
  103. about the neurobiology of psychedelics
    it's really, really interesting.
  104. So, these drugs are all Schedule I, and,
    by definition,

  105. that means there's
    no accepted medical use,
  106. there's lack of safety for use under
    medical supervision,
  107. and that these drugs are the highest
    addictive liability.
  108. So, we're going to go back in history
    to take a look at this, and to look
  109. specifically at the serotonergic
    hallucinogens to understand
  110. how addictive they are or not.
  111. All right, so back to history here,

  112. back in the early days
    of psychopharmacology,
  113. what the great psychopharmacologists did,
  114. well they all self-ingested, right?
  115. That's what you did.
  116. People got in trouble later for doing
    that, and we don't do that anymore.
  117. But both Arthur Heffter and Louis Lewin
    got samples of mescaline
  118. and self-experimented, and
  119. Louis Lewin was so intrigued by it all,
    he wrote a book, Fantastica,
  120. which I think is probably the most apt
    term of all of these terms
  121. that come hard to truly describe
    these states.
  122. So this was the beginning of research in
    psychedelics from an academic perspective,
  123. and there was some interest in mescaline
    that endured,
  124. but essentially things picked up again in
    Switzerland in 1943,
  125. so we had Albert Hoffman, who's a
    Swiss chemist at Sandoz,
  126. and you all know the story,
    but he accidentally,
  127. while trying to make these ergot
    derivatives to help women that
  128. had blood loss during pregnancy,
    happened upon these lysergamides.
  129. He made them in '38, but in '43,
    he had some premonition to go back,
  130. and accidentally dosed himself and
    discovered LSD.
  131. He went back to Sandoz, and
    they started testing LSD among each other,
  132. among animals,
  133. and they found
    that it had no known toxic dose,
  134. and in '47 Sandoz makes LSD
    and makes it available to
  135. psychiatric researchers and
    psychiatrists throughout the country,
  136. which starts this interesting experiment
    of psychedelics within academia,
  137. and people thought that these states
    were similar to psychotic states, so,
  138. there was excitement about understanding
    the biological basis of psychosis,
  139. and in addition, the psychoanalysts --
  140. this was the heyday of psychoanalysis --
  141. and the analysts loved it because they
  142. were constantly looking for
    the "royal road" to the unconscious,
  143. and dreams was the one mechanism
    to do that,
  144. but this real sort of "royal road"
    and had some favor among the analysts,
  145. especially in European models.
  146. So articles start to appear with LSD.
    LSD is brought to the United States;
  147. work begins at Boston and Los Angeles.
  148. And a very interesting time, psychiatrists
    start to self-administer LSD.
  149. Psychiatry clerkship organizers take LSD
    with their medical students.
  150. This happened at places like UCSF
    and NYU,
  151. so the medical student or the psychiatrist
    could have empathic resonance
  152. with the mind of the psychotic patient,
  153. so it was an interesting time
    to go to medical school.
  154. And psychiatrists started using it
  155. I mean, it was not only available
    through research, you could get it -
  156. and I'll tell the tale of Oscar Janiger in
    Los Angeles.
  157. He gave it to thousands of people,
    including celebrities, etc.,
  158. So it becomes available and is used
    clinically, and then of course, you know,
  159. the CIA gets involved to try to
    weaponize hallucinogens.
  160. And very interestingly,
  161. Gordon Wasson is a banker in New York,
  162. but his wife Valentina is an
    amateur mycologist,
  163. and she is looking for this agent
    that is used by indigenous cultures
  164. in Mexico. And that's about all she knew.
    In fact, she thought that maybe peyote,
  165. there's something about these agents
  166. where they create a lot of excitement,
  167. and then something happens and
    they are repressed,
  168. and it's happened throughout time.
  169. It's happened within academia, and we now
    are, sort of, need to learn from the past
  170. to not repeat it.
  171. But they went to Mexico and they found
    Maria Savina,
  172. and Gordon Wasson and Valentina become
    the first Westerners
  173. to undergo a psilocybin experience.
  174. And Gordon Wasson is friends with
    Albert Hofmann.
  175. He sends the mushrooms to Albert Hofmann.
  176. He isolates the psychoactive alkaloid,
  177. and then Life magazine in like 1957
    does an article about all this,
  178. and Timothy Leary reads that
    and takes psilocybin in Cuernavaca,
  179. and in 1960 starts
    the Harvard Psilocybin Project.
  180. And we'll talk about
    the Spring Grove group as well,
  181. And I'll get to Humphrey Osmond a little
    bit later, but he does a lot of work
  182. with alcoholics in Canada. And this was
    part of mainstream, academic psychiatry.
  183. You know, most psychiatrists,
    when you ask them about LSD, they say,
  184. "Oh, you know, seven hits makes you
    insane. It's a very dangerous drug."
  185. None of them have any clue that this
    was part of American psychiatry
  186. for a considerable period of time, with
    a considerable number of
  187. research participants that were treated.
    And they ended up
  188. being hundreds of patients
    and tens of thousands of participants.
  189. And there's two models that emerged,
    and that's been discussed. This really was
  190. the psychedelic dream team,
    and Bill Richards is here in the audience.
  191. This was this amazing team
    that was assembled at Spring Grove,
  192. and I think if the work continued here, we
    would have psychedelics as medicines now
  193. for a whole host of conditions. This
    really was the right way to do it.
  194. They had a multidisciplinary team, they
    did a cancer study by working
  195. with an oncologist who sent them
    all of the patients.
  196. And these were a team of very experienced
    psychiatrists and psychologists,
  197. And, unfortunately, before things really
    got cooking and going well here,
  198. it all came to an end.
  199. So, what did happen?
  200. Well, unfortunately, the agents escaped
    from clinical laboratory research settings
  201. and they went out into the public. And the
    American public, I don't think was ready.
  202. It was, you know, the end of the '50s, and
    there was a lot of political turmoil.
  203. And what happened is,
  204. LSD was starting to be used by the mass
    public, and these drugs are not drugs that
  205. should be used indiscriminately by anyone.
    They have a down side and a danger.
  206. They're sacred, medicinal compounds that
    should be used in a certain kind
  207. of setting and only
    with a certain kind of individuals.
  208. And the problem is, you know,
    they were... they created problems.
  209. So, people that are predisposed to
  210. the 18-year-old who goes to college and
    tries LSD for the first time
  211. and becomes psychotic, and
    that starts his schizophrenia, even though
  212. LSD does not cause schizophrenia,
    there are a lot of casualties.
  213. And Richard Nixon got very concerned about
    this, and essentially [passed] the
  214. Controlled Substance Act of 1970, which
    was the beginning of the war on drugs...
  215. which really has been a disaster
    for addicts,
  216. because we've taken a
    medical illness and criminalized it.
  217. And in many ways it was because there was
    a grave concern about
  218. what these consciousness-
    expanding drugs were doing to
  219. the American public, and so this system
    was put in place in 1970. And we'll talk
  220. about if the serotonergic hallucinogens
    really belong in that category or not.
  221. But at the end there were a thousand
    articles, tens of thousands of
  222. participants, and, interestingly, as
    Michael mentioned,
  223. alcoholism
    was the most studied indication.
  224. If you take Humphrey Osmond
    by himself, he did open-label trials,
  225. there were several thousand alcoholics.
    And if you look at the other trials in the
  226. US, there were close to a thousand people
    and about 536 in the well-designed trials.
  227. Methodology of use, and set and setting,
    were all put in place,
  228. and safety was the term.
  229. Most of the serotonergic hallucinogens,
    except maybe ibogaine, are incredibly safe
  230. from a medical perspective. They have very
    low physiologic toxicity. The main
  231. problem has to do with the adverse
    psychological effects, and if you properly
  232. screen individuals, the safety data is
    very robust, both historically and also
  233. in the last 40 years the 400 or so
    participants that have received psilocybin
  234. in the United States, there have been no
    major or serious adverse events,
  235. which is a testament to the safety of
    doing this in a clinical setting.
  236. And I won't go over this -
    you've heard this enough.
  237. Hopkins: I'm going to show a dose response
    study that they've done recently... to get
  238. a sense of what the optimal dose is.
    And interestingly, a new therapy model.
  239. When I was training as a psychiatrist, you
    know, there was you as a psychiatrist, and
  240. there was the patient.
    One doctor, one patient.
  241. But, interestingly, they developed a model
    of two therapists, in a dia-team,
  242. usually male-female, and there was therapy
    training that went on - in fact, Jeff Gus
  243. is going to talk about our psychedelic
    psychotherapy training program at NYU -
  244. but it's an interesting model of training
    two therapists,
  245. and this is how Jeff does it:
  246. You go to Hawaii, and this is the
    final ceremony [audience laughs],
  247. you get to sit by the water -
    [responding to audience] I wish -
  248. but you know, two therapists, one patient,
    which for me has been very interesting
  249. to take a look at that. And this is the
    psilocybin that we have in our study.
  250. It is one gram that is stored in a
    thousand-pound safe.
  251. It's the only substance that's
    stored there.
  252. And here's a compounded pill.
  253. This is our treatment room,
    and this is the Hopkins treatment room.
  254. And this is exactly what the methodology,
    '50s to '70s was:
  255. the comfortable, living-room-like setting,
    two therapists. In many ways we have
  256. sort of left off from the old group. But
    people always ask me,
  257. "Why two therapists? Why male-female?
    Why music? Why introspection?"
  258. And I don't know, because they said so!
    [audience laughs].
  259. We'll figure it out later.
  260. All right, so back to the montage.
  261. So, this is the montage that has to do
    with cancer and anxiety.

  262. And you guys who went to Dr. Bossis's
    lecture have seen this slide.
  263. But who wants to die in an ICU setting in
    the hospital? Raise your hand.
  264. Yes, there's always the near-death
    experience people that like that one.
  265. Who'd like to die in a nursing home?
  266. How about in a hospice?
  267. Who'd like to die a good death at home
    with your family all around you, and -
  268. yeah, with hospice, yeah.
    [Audience laughs.]
  269. You know, unfortunately, the human
    encounter with death in the United States
  270. has been farmed out to academic medicine
    or medicine in general,
  271. and medicine is just not trained how to
    deal with patients.
  272. We don't... I was never trained how to
    administer a good death.
  273. That really...
    that construct was never taught to me.
  274. And so, as physicians, we're trained
    to save and extend life and...
  275. but I think in many ways we're failing our
    patients, because they're really dying
  276. in places they don't want to die.
    Most individuals are dying within
  277. hospital settings, and they're not dying
    where they want to die,
  278. and it's a real problem.
  279. Dr. Bossis mentioned this yesterday, but
    [in] palliative care the domain of
  280. spirituality comes up again and again,
    and it's a vital domain to understand
  281. the needs of patients that have
    existential distress
  282. associated with having a terminal illness.
  283. And terminal illnesses, like addiction,
    are a type of spiritual disorders,
  284. and if you define spiritual distress as
    unable to find sources of hope, love,
  285. meaning, value, comfort, strength,
  286. You really see this with cancer patients.
    You know, we all are going to die,
  287. but we all have, you know, cognitive
    illusions that allow the distance to death
  288. to be somewhere off in the future.
    But then when you go see your oncologist,
  289. and your oncologist says, "Well, actually,
    it's much closer. You have terminal cancer
  290. and you'll be dead in nine to twelve
    months," it really is awful for patients.
  291. And we've had young patients now in this
    study. We've treated a 26-year-old,
  292. and he developed illness when he was 19,
    and it really provoked a kind of crisis of
  293. meaning for him, which was interesting
    because his session sort of restored that
  294. faith in God as part of it. But cancer is
    a disaster, and there's a kind of
  295. differential responsivity to having
  296. You have some people that sort of cope
    through denial. They say,
  297. "Yeah, I have this cancer, but it's okay,
    I'm going to be fine. It's not a big deal.
  298. "It's not impacting my life that much."
  299. And then you have the kind of meaning-
    makers that take cancer, and for them,
  300. they're able to say, "Oh, you know,
    cancer's like this amazing gift, you know.
  301. It helped me realize that I was wasting
    my time doing X, Y, and Z,
  302. and what's really important,
    what's really fundamental is,
  303. you know, being home with my family,"
    or whatever the case might be.
  304. "I'm glad, grateful that I got cancer."
  305. And then there's a group of people that we
    deal with in this study that have
  306. existential distress, and for them, they
    fall apart psychologically,
  307. and it's a real nightmare for them.
  308. They have remorse, powerlessness,
    futility, meaningless[ness] of life.
  309. They're unable to connect to their loved
    ones. They're unable to connect to sources
  310. of transcendence. And they're depressed,
    hopeless, and suicidal,
  311. and they have a hastened desire to
    want to die. And so, this is,
  312. from a psychiatric perspective, this is a
    group of people that we really have to
  313. pay a lot of attention to
    to prevent really bad outcomes.
  314. And if you look at the prevalence of
    psychiatric illness in people that have
  315. advanced illness with cancer, it's very
    high. If you look at anxiety disorders,
  316. you know, you have as much as 2 out of 3
    people, or 50%, and same thing
  317. with depression. It's really interesting
    that you have also high rates of distress
  318. amongst family members.
  319. The cancer is more than an
    illness of the patient.
  320. It's an illness of the family system. And
    the family members are very distressed.
  321. In fact, several people have mentioned,
  322. "Why don't we do a study, you know,
    that includes family members."
  323. And I think that's a great idea,
  324. because they really are going through
    their own turmoil,
  325. and it's important to think of them,
    and to think of the person getting better
  326. within a family system.
    So, there's been a lot of work - a lot
  327. of it at Sloan-Kettering - looking at the
    correlation between people that are
  328. terminally ill that have a hastened desire
    to die. And it's correlated with being...
  329. having major depression, hopelessness,
    pain, and diminution of spiritual states.
  330. And another way of looking at it in these
    studies is: increased spiritual states
  331. are correlated with a decrease in desire
    for hastened death, hopelessness,
  332. depression, and suicidal ideation.
    So it sort of makes one think:
  333. Well, how can we improve spiritual states
    and end-of-life?
  334. How can we do it psychopharmacologically?
  335. And are there any psychosocial
    treatments - psychotherapies
  336. that are specifically designed
    to enhance meaning, to make meaning,
  337. in people that have terminal illness?
    And I'll talk about several that exist.
  338. And Dr. Bossis has mentioned this, but,
    you know, a good death really...
  339. you need to be to control pain, to prepare
    for death, people still want to be able to
  340. contribute to others. And spiritually
    and meaning keep coming up again and again
  341. in people that... have terminal illness.
    And so, how can we figure out a construct,
  342. both pharmacologically and [on] a
    psychosocial platform,
  343. to treat these kinds of patients?
  344. So, Kirkegaard and Jean-Paul Sartre were
    existential philosophers.

  345. And it was actually Jean-Paul Sartre who
    also became a psychologist.
  346. And the... there was the application of
    existential philosophy within psychiatry
  347. and mental health as a treatment. And,
    you know, we have people like Irving Yalum
  348. and Viktor Frankl that helped establish it
    within psychiatry. And then other people
  349. who were psycho-oncologists who have come
    up with a whole group of
  350. different treatments, psychotherapies,
    that are existentially based. And in
  351. designing our study, we picked for several
    of these to have some sort of platform
  352. to be able to leverage the experience
    that the patients have in the study.
  353. Now, Eric Kast was
    a really interesting guy.

  354. During the time that LSD was available,
    he was an internist in Chicago.
  355. He heard about this new drug, LSD.
  356. He didn't know anything about it, but
    he decided to order some LSD.
  357. And we now know that preparation is key
    for patients, but Kast didn't know that.
  358. So he had a lot of patients that had
    terminal illness, hundreds of them,
  359. that were essentially within three to six
    months of death. And what he started to do
  360. is he came by in the morning
    with the LSD and he said,
  361. "Hi, I'm Dr. Kast. I have a new compound
    for you that we're going to try."
  362. He would have them stick out their tongue,
    he would give it to them and he would say,
  363. "Well, I'll see you later in the day."
    Right? So, that's not a model of
  364. how you want to do it. But he did it like
    hundreds of times that way.
  365. I mean, really interesting stuff. And what
    he found was pretty fascinating.
  366. He did a controlled trial comparing LSD
    to opiate pharmacotherapy and looked at
  367. patients acutely and in a sustained manner
    and found that the LSD group,
  368. especially in the long term,
    had diminution of pain,
  369. and it was sustained for several weeks,
    which was a really interesting finding.
  370. That's one of the reason that groups that
    are doing cancer research
  371. are looking at pain.
    But in addition, he also found that
  372. patients had had decreased depressed mood,
    improved sleep, and he noticed,
  373. interestingly, that their fear of death
    was diminished. And he just kept doing it with little preparation and kept finding the same sort of thing:
  374. decreased fear of death, and lasting several weeks, people describing "happy oceanic feelings."
  375. And he was actually one of the people when LSD was put into Schedule I that went to congress and said,
  376. "No, this was [is] a really interesting thing, and we really thing this was [is] a novel treatment for pain."
  377. So I think that, I don't know... you know psilocybin and LSD pharmacologically are different.
  378. I don't know if there's something specific about LSD in terms of anti-pain, but it's interesting to consider.
  379. And pain is one of these things in terminal illness that you really have to control,
  380. or this drives people to be very distressed and to become suicidal, as well.
  381. So back to Spring Grove.

  382. Now, this was the group lead by Stan Grof, and this was really the data set that existed
  383. for terminal cancer. And, as Bill Richards knows, the group was starting out to study addiction,
  384. and what happened was one of the nurses at Spring Grove became sick with terminal breast cancer,
  385. and she wanted to know could this treatment be available for someone like her.
  386. And so the whole team shifted to this focus, and there was a study done, and essentially
  387. the inclusion and exclusion criteria are essentially the same ones used in all of our studies,
  388. that they included people that had cancer... terminal cancer and anxiety. They excluded people
  389. with major mental illness, major medical illness, and measured anxiety, depression, pain, mystical states.
  390. And there's no control group here. And what they found was that, you know, within the one group
  391. there was significant reduction pre-post in depression, anxiety, pain, fear of death.
  392. And they found that there was global improvement in the majority of people. And then some people
  393. didn't get better, and a small percentage got worse. But they never were able to go on
  394. to a controlled trial because the music had to stop. But if we were to do a controlled trial,
  395. and if we were to look at the right way to do it, this is Chuck Brown at Penn that goes through the ways
  396. that we want to do it. And, essentially, this is the model that we all use now in our centers.
  397. So, going back to this, how can we increase spiritual states? And this really has to do, I think,
  398. with a therapeutic mysticism. And I think this was something Carl Jung was trying to introduce
  399. within medicine but failed because [Freud... no, [?]] there was a concern that religion and spirituality
  400. would get mixed with medicine, and... But I was hanging out with Mary Cosimano yesterday,
  401. where... Mary, where are you? So, there's Mary was just emanating love, and it was all about love, right?
  402. And Mary and Tony, I think are going to write a book about love, I think are going to tour about it.
  403. But I think, Mary, that you'd gotten a contact buzz from all the psilocybin that you've administered,
  404. and I think that love has oozed into you, and now it's just oozing out. But it's almost a cliché,
  405. but it's really true that the majority of patients, they say the same thing: "I have a profound sense of love,
  406. "of feeling love, the, you know, the power of love." And even though, as corny as it sounds,
  407. there really is... there's something there, that patients have a profound sense of love and peace,
  408. and it makes them feel better, which really is, I think - and we have to ultimately analyze our data -
  409. but it's really interesting to see. And that's Roland Griffiths there. You know, the team
  410. that's really leading the way in the world in psychedelic research is the John Hopkins team.
  411. These guys are amazing. They're doing so many different studies and really have inspired
  412. so many of us, and really just an awesome group of individuals that keeps growing over time.
  413. And so, thank you, to them. And they have published so much interesting stuff that's been so important
  414. for all of us. And in a normal volunteer study of 36 hallucinogen-naive individuals
  415. in a controlled trial with Ritalin, they found... you know, this was the sort of, like,
  416. Good Friday Experiment redo, but excellent data showing that psilocybin acutely... and in
  417. 14 months later the participants attribute having a mystical experience. And these data always
  418. blow me away, the majority of people thinking that... experiencing these events
  419. as the top five most significant experiences of their entire lives, up there with having kids.
  420. These are profound experiences that have stuck with these individuals that have... at 14 months later,
  421. they continue to attribute positive changes in their attitudes, and even altruism.
  422. You know, in medical student... in medical school we try to train medical students
  423. to be warmer and more empathic, and I think unless you have good parents and you're already altruistic,
  424. I'm not sure how you get people to be like this, but it would be interesting if pharmacologically
  425. we could induce altruism. I think there would be a lot of applications to that. But I think these people were,
  426. you know, spiritual seekers already. Maybe they were already in that direction. But I think it's interesting
  427. to consider pharmacologically. You think of antisocial personality disorder,
  428. or narcissistic personality disorder. These have core deficits in empathic resonance.
  429. So at 14 months later, the mysticism... so the degree of mysticality is correlated with lasting benefit,
  430. you know, over a year later, and that is a novel finding within medicine.
  431. So you know this handsome fellow, Dr. Grob. And this is another really amazing team, the UCLA team.
  432. You know, Sidney Cohen was an amazing psychedelic researcher
  433. that sort of everyone forgets about. But he was doing excellent work with Betty Eisner and Gary Fisher,
  434. and Carl Janiger [?] was in private practice in LA. But Charlie picked this whole thing up
  435. and completed his trial, and you know Aldous Huxley here and Laura Huxley and Felicia Danforth [?],
  436. and... And this was published in the Archives of General Psychitry. This study's very similar to ours.
  437. There was a slightly lower dose, but same inclusion/exclusion criteria,
  438. preparatory psychotherapy, taking a narrative of the patient's life, taking a narrative of the cancer
  439. and how it's disproportionately affected them, taking a spiritual history, focusing on safety,
  440. and then the methodology of lying on the couch, pre-selected music, focus internally,
  441. and then integrative psychotherapy. The UCLA room pre and post. That's how they do it
  442. on the west coast, you just throw up some tie-dye stuff [audience laughs] and... I like that.
  443. And these results, it was a small sample, 12, but in most of them, interestingly, women.
  444. And we're finding in our study as well, two-to-one women-to-men. Why is that?
  445. 'Cause, women are just better, right? They're braver or, I don't know.
  446. But there were no major adverse medical events or psychiatric events, and compared to placebo,
  447. the psilocybin group was much more likely to induce alterations of consciousness
  448. that are consistent with mysticism. And what Charlie found was very interesting.
  449. If you look at this, this is the Spielberger Trait Anxiety Inventory, and this is a measure
  450. of trait anxiety here. At one month and three months, the participants... and the crossover I think occurred
  451. at a month, so they both had gotten one dose of psilocybin and placebo. But, interestingly,
  452. trait anxiety, which is a measure more of sort of longer-term how anxious you are,
  453. was diminished at one month and three months, so that was an interesting finding.
  454. And depression at six months, at the end of the trial - and, again, we don't know if this is the psilocybin,
  455. the placebo, psychotherapy, tincture of love being in a clinical trial - but at six months later,
  456. there was a significant drop in depression from the base line. And if you look at the POMS,
  457. which is another measure of depression, there were some acute trend changes
  458. between the different groups that probably if the N were higher and the dose were higher
  459. would have been significant, and you would have seen acute reductions in distress.
  460. So at NYU we are racing to finish our trial, and John Hopkins is, as well. Our trial is nine months long.
  461. It's a crossover at 7 weeks, our dose of psilocybin is a sort of moderate to high dose. We include people...
  462. we initially included people that had terminal cancer only, but we, since then, have increased that
  463. to include people who had any stage of cancer because, you know, you don't have to
  464. be dying of cancer to have death anxiety. We realized we were meeting people that had cancer -
  465. and they could even be in remission - but they still were traumatized by the cancer
  466. and had enormous distress, couldn't get beyond it, and they kept asking us, you know,
  467. "Couldn't we benefit from this as well?" So we have changed our protocol, and we now include
  468. any stage of cancer as long as you have distress associated with the cancer.
  469. And it's interesting to treat people who are dying and then those that are not
  470. and the differences that come out. Now, we rule out major medical illness, and we rule out
  471. certain medications. From a psychiatric perspective, you most certainly want to rule out
  472. people that have psychotic spectrum illness, either schizophrenia, schizoaffective,
  473. or affective psychoses, like bipolar I disorder with psychotic features. These are agents
  474. that should not be used on people that are psychotic or who have psychotic diathesis.
  475. Those people should be ruled out, and so we do that in the study.
  476. And we have a bunch of outcome measures: anxiety's the first one, and then depression, pain,
  477. acceptance of disease progression. And, again, we have preparatory psychotherapy,
  478. the dosing sessions, and integrative psychotherapy. And our integrative model we've drawn
  479. from a whole host of different psychotherapies, including ones that are existentially oriented.
  480. I think to do this kind of work you have to have psychodynamic or analytically oriented training,
  481. because the imagery is so rich. In a way it's like being with patients that are having a waking dream,
  482. so you really have to think symbolically and be able to understand and extract the enormous meaning
  483. that these experiences can occasion. And we also use CBT models and some other models, as well.
  484. It took a couple years to get approval to do the study. It's hard to get approval,
  485. but it's much, much easier now because of the work of people like Charlie and Roland and others,
  486. who really were pioneers in this field. It's much easier to work with the FDA.
  487. Interestingly, we had full approval for this study, but we did not have a site to do it.
  488. We had approval from the FDA and the DEA and the medical school, but the problem is
  489. we just didn't have a host, and so the NYU College of Dentistry came out of the blue,
  490. and I didn't even know we had a College of Dentistry at NYU, but they came out of the blue to save us,
  491. and I love those dentists. So I think this is the only psychedelic study ever that's taken place
  492. in a dental center, so... But they've really been amazing, and they've given us an entire room
  493. that we can use, which looks like this. It used to look like a hospital-looking room,
  494. but they were really gracious and allowed us to make it into a very beautiful-looking room
  495. with all the requisite icons and suggestive symbols. And here's our team. That's Tony Bossis,
  496. who you heard yesterday, Jeff Gus, Gabby... Gabby, are you here in the audience? There's Gabby.
  497. Gabby's our awesome project manager who saved our project because she's been able...
  498. [applause] Yeah! We got a scary letter from the cancer center - this was like a year and a half ago -
  499. and it said, "Dear Dr. Ross, We hereby inform you that you have fallen below your recruital target
  500. "for the study," and that "We are an affiliate of the National Cancer Institute,
  501. and if you don't get to this number in six months, you're finished." And I was like, "Oh, boy."
  502. So we had our existential crisis moment for the study, which we've had many, and for some reason,
  503. things just keep buoying us along, whether it's dentists, or specific individuals.
  504. So we went to one of our donors and said, you know, "We really need more personnel."
  505. So we were able to hire Gabby and to recruit cancer patients. I thought that it was maybe political
  506. why we weren't getting patients, but the reality is, cancer patients, they very rarely go
  507. into clinical trials. Only 3% do, and you have to be in the flow of traffic. And so we essentially were
  508. given entrer into the NYU Clinical Cancer Center. We've parked ourselves there,
  509. and we are now in the direct flow of patients, and now we have more patients than we can treat,
  510. and we have a very steady flow, and I think we're poised well to move on to Phase III trial.
  511. And this is the rest of our team. So, so far we have those 21 individuals, 2-to-1 women-to-men,
  512. and this is the age range and the average. Very interesting that the majority of people
  513. have been hallucinogen-naive. Now I thought these would be biased people from the '60s
  514. that did psychedelics that thought they were awesome and amazing and they're coming back
  515. to do them again. But the reality is that these... the typical patient is a woman in her 50s
  516. with terminal breast cancer who is scared and anxious and who's never done psychedelics
  517. and, in fact, stayed away from them because was concerned in the '60s for what may happen
  518. in uncontrolled settings. So I think it's more powerful when you have people... you know,
  519. you have less sort of expectancy bias. The majority of our patients have been toward the sicker end
  520. of the spectrum, in terms of staging. We've made a great connection with our guy in [??],
  521. but you can see we've treated people with a variety of different cancers. Now, the data
  522. is yet to be formally analyzed, but anecdotally, it's been really remarkable. These are findings
  523. that I've never sort of seen as a psychiatrist. I've, you know, heard of people, "Hey, when you work
  524. "in the addiction world, you're used to people having near-death experiences and dramatic change,"
  525. so I was sort of used to that. But what we've found here has been really interesting in that
  526. we've had both acute and sustained reductions in death anxiety. One patient in particular
  527. had resolution of death anxiety that's persisted now for 14 months. We've seen improvements in mood,
  528. people have greater integration back into their lives, improved family functioning,
  529. improved spiritual states. And it's very interesting that half of the day, it's sort of
  530. the psychedelic model: patients are sort of deep down having the mystical experience,
  531. but they inevitably come out of that and then start to tell us these amazing stories
  532. of places they've been and things that they've felt, and it becomes in the latter part of the day
  533. more of a psychoanalytically oriented therapy, a little bit like someone who's having a waking dream,
  534. and so in a way we sort of use both models. The majority of patients say, "Oh, you know,
  535. "I wish I could have another experience." Especially the ones that are naive. They say, you know,
  536. "I understand the terrain now, I would have gone deeper into it." And so, you know,
  537. we have to think about that in future studies. So this is data from the first five patients,
  538. and we're... we don't know whether, you know, dose A or dose B was psilocybin. But, you know,
  539. we see in almost all the patients a sort of tincture of "people here to help me",
  540. and almost, just engagement with the study, people start to feel better. But this person here -
  541. and most likely this was probably a psilocybin dose - this person had a very dramatic reduction of anxiety,
  542. and you can see it persisted until the end of the study, here. And here's another example
  543. of somebody that had a big drop in anxiety from the first dosing session. You know, with cancer, though,
  544. the problem is that people have scans, and they get super anxious, so we've had people that feel better,
  545. but then, on a particular day, had a scan that was bad, and their anxiety can fluctuate,
  546. so it's a difficult illness. This may be an example of someone that got a dosing session after dose B,
  547. and you can see reduction here, but you know, then it sort of comes up. In everyone, from the beginning
  548. to the end, everyone is less anxious at the end of the study than the beginning. But you can see
  549. that there's big fluctuations. And this person had some bad news here, at this moment,
  550. but you can see sort of, you know, the general trend is down. But there are fluctuations.
  551. This is only the first five, so, you know, cautious to interpret too much. We really have to look
  552. at the data. I think we have to be clear that even though it looks as if there's an effect, it may not be.
  553. We have to be open. So, that's it for the cancer story. I want to switch.
  554. And Michael's really made this a lot easier for me.

  555. But Humphrey Osmond really was a pioneer. He was a British psychiatrist
  556. who relocated to Canada, and he heard about this LSD treatment, and he started treating
  557. thousands of alcoholics. And he... his initial model, as Michael mentioned,
  558. was aversive counter-conditioning. There's people who... the delirium tremens
  559. could scare people, you know, straight, essentially, that, "Oh, that was so scary. I almost died.
  560. I want to get sober." So that was his initial model. But he started treating people,
  561. and he realized people were having these positive experiences and mystical experiences -
  562. and he thought that the experiences were so unique that you couldn't have blinded integrity
  563. and didn't bother with that - and found rates of abstinence that were pretty high,
  564. but we don't really know how to interpret this. But this was really interesting, what Michael mentioned,
  565. that you put all of the well-controlled trials together for alcoholism - it was amazing -
  566. there was a treatment effect in this meta-analysis. And this is a big number. If you do a Phase III trial,
  567. you know, you need three, four hundred. So in a way they did something close to a Phase III trial
  568. and had a treatment effect. So this is very encouraging data for a group of us to go back
  569. and to try hallucinogen treatment models for addiction. So back to the definition of Schedule I.
  570. And let's see if the seratonergic hallucinogens really fall into this. So, you know a drug of abuse
  571. is addictive... there are various models. So, if you give an animal the ability to self-administer
  572. any drug of abuse that's self-reinforcing, they will continue to press for that, either intravenously
  573. or intrathecally. So this happens with cocaine, alcohol, tobacco. But if you give a lab animal LSD,
  574. it will not continue to self-administer it. Or psilocybin. He might put on a tie-dye t-shirt and, you know,
  575. put on the Grateful Dead [audience laughs] and dance around and get lost for several hours,
  576. lose its sense of rat self [more laughter],
  577. and it always comes back, you gotta tell a little... it'll come back. And the other model is
  578. conditioned place preference, right? That if you... initially the animal forages back and forth.
  579. It gets a hit of something that's rewarding, goes back to this area. And this... you can get
  580. every drug of abuse to do this, except psilocybin and LSD do not do this. The nucleus accumbens
  581. is a very special part of the brain that's involved with reward, learning, it's part of our survival.
  582. Every normative reward, like food aquisition, water, sex, nurturing, go through this pathway.
  583. Every drug of abuse hijacks this pathway and leads to super-physiologic dopaminergic activation.
  584. And so when you give drugs of abuse to animals and humans, you image them,
  585. the nucleus accumbens lights up very dramatically. When you give drugs like psilocybin to individuals,
  586. although you get dopaminergic activation and increased signalling, the nucleus accumbens
  587. does not light up appreciably. And epidemiologically, the third generation studies that have been done,
  588. when you go out and you look, is there such a thing as LSD dependence or addictive syndrome,
  589. or psilocybin, it really doesn't exist. And so in no... in all the ways that we measure whether a drug
  590. has true addictive liability, these drugs really fail the test to be in Schedule I. And I'll get back to this
  591. in a moment. The drugs, though, that really are interesting in terms of addictive liability...
  592. The most addictive drug is tobacco, and alcohol is in the middle, and the psychedelic drugs
  593. are toward the least addictive. And these really are the NMDA antagonist drugs - like ketamine and PCP -
  594. they have real addictive liability. But if you factor out the seratonergic hallucinogens,
  595. they really are not drugs that produce addictive syndromes. And if you look at drugs
  596. that are damaging in our society, the most damaging drug of abuse in the world is what?
  597. In terms of morbidity, mortality, preventable death? What is it? Alcohol.
  598. Alcohol is the number three cause of global disability. Tobacco's a very close second.
  599. So these are drugs that are highly addictive and highly damaging, and they're scheduled...
  600. what are they scheduled again? They're... I think... [faint laughter in audience]
  601. I don't think they made the scheduling system. So that's interesting. Alright, now, going back here
  602. for a second. If you think of hallucinogen treatment models, there really are several ways to look at it.
  603. One is that the drugs have some biological effect, that is inducing sobriety. And how might that be?
  604. And a really interesting model for that is ibogaine. Ibogaine treats opiate withdrawal.
  605. Now, if you give LSD to someone in opiate withdrawal, what will happen?
  606. They will be in opiate withdrawal, and they'll be on LSD. Right? But it won't help them at all.
  607. Ibogaine, very interestingly, in one dose, can get rid of opiate withdrawal. And that really
  608. has nothing to do with its mystical, medic properties. That must have something to do with signalling
  609. at the mu opiate receptor or some other biologic process. So that's a biological model.
  610. And 18-MC is, you know, ibogaine without psychoactive stuff and the cardiac toxicity.
  611. And I'll talk a little bit [about] the history of ibogaine and NIDA funding. And the other way to think of it is
  612. mystical mimetic experiences and spiritually induced experiences as helpful for addiction.
  613. And we have really good models through AA, the Native American Church of Peyote,
  614. and the ayahuasca-based religions. And with these models, it's really important to talk about
  615. what comes next and how you link spiritually-induced states from pharmacology
  616. with psychosocial treatments and how to put those two together because recovery is not
  617. a quick, one-shot thing. Big experiences may help occasion long-term sobriety,
  618. but that's rare and unlikely. You have to have something that contains and continues recovery.
  619. That's why AA is so interesting, because it's a ready-made recovery community.
  620. The number of people that have used seratonergic hallucinogens is very large.
  621. There's tens of millions of individuals that have tried these agents. The prevalence rates have gone down,
  622. but the United States had a big dose of consciousness expansion in the '60s.
  623. And the story of ibogaine is interesting. Howard Lotsof was a heroin addict in Staten Island,
  624. and he ended up in the '60s trying ibogaine as a way to try another drug that he had not been high from,
  625. but he had something weird happen to him. His opiate withdrawal symptoms went away.
  626. He had a mystical experience, and this led him to long-term sobriety. And he became such an advocate
  627. for ibogaine. NIDA eventually spent some money in the early '90s, several million, to study ibogaine,
  628. but the politics of ibogaine became quite toxic. And ibogaine has a dark side, too.
  629. It can cause bradyarrhythmias, and QT prologations, and there have been, you know,
  630. at least 20 deaths associated with ibogaine. So ibogaine has sort of fallen off in terms of research.
  631. But 18-MC, which is an ibogo [?] congener, NIDA now has just committed about six and a half million dollars
  632. to Savant to study it, so NIDA has recognized there's something unique about ibogo [?] congeners
  633. that could be leveraged to treat addiction. Now, again, addiction, as I mentioned,
  634. is a kind of spiritual disorder. Addicts lose sense of meaning and hope and connection,
  635. and anyone who treats enough addicted individuals, you have the scenario where at some point
  636. the person picks the drug over their kids. And that really always amazes me, that a drug
  637. can be so powerful and so compelling, that you literally can go down the route of using the drugs
  638. over taking care of you kids. And that's really how insidious and terrible addiction can be.
  639. And so part of the path of recovery is reconnecting within oneself and in the relational matrix of the world
  640. and in one's community and community of meaning, and so we know that spirituality
  641. has a protective impact on addiction. We know that spirituality has been described
  642. within the addictive field for a long time as having therapeutic force. And so, can...
  643. how can we facilitate spiritual growth? And, I would say AA and the UDV and the Native American Church
  644. are quite similar in this way. It's just that in two of them they prescribe a sacramental hallucinogen.
  645. But otherwise they are very similar organizations. With - and Michael talked about this -
  646. as far as we can tell, ethnographically, epidemiologically - the Native American Church
  647. has very low rates of addiction. The highest rates of alcoholism are in certain communities
  648. within the Native American community. They have very high rates of alcoholism,
  649. so it's particularly interesting the Native American Church does not. Now they prescribe
  650. a sacramental hallucinogen, and they proscribe the use of drugs and alcohol. And so if they indeed -
  651. we need better epidemiologic studies - but if they indeed have these very low rates of addiction,
  652. it's important to kind of untangle why and what part the sacramental hallucinogen plays in all that.
  653. We know that individuals that receive peyote, you know, hundreds of thousands of doses
  654. over their lifetime, long-term, that there are no adverse medical or psychological effects
  655. associated with that. We know that ayahuasca is already being used to treat addicted individuals
  656. in their communities where this is happening. Takiwasi's an example of that. And we know, as well,
  657. similar to the peyote studies that individuals that use ayahuasca long-term do not have ill health effects.
  658. It tends to be the opposite. So, back to the montage here and back to this interesting story up here.
  659. So, Carl Jung is treating this alcoholic, his name is Rowland H. And, you know,

  660. when you take an alcoholic or schizophrenic patient, and you put them on the psychoanalytic couch
  661. for five days, what happens? For a week. How does that methodology work? It doesn't work that well.
  662. So, they remain psychotic, and it doesn't help your drinking. And we now know that psychoanalysis
  663. is not helpful for people who are actively using. So Carl Jung said to this alcoholic, Rowland H.,
  664. "That's it. You're done, buddy. I did all I can, and I can't help you." Now if Carl Jung can't help you
  665. and says it's over, you know things are not looking so good. So, actually, he told this guy, Rowland H.,
  666. "Go join this group, the Oxford Group. It's this amazing group where people
  667. have religious conversions, and they get sober." So Rowland H. goes and joins the Oxford Group,
  668. has a religious conversion, and ends up coming to America to proselytize. And Bill Wilson
  669. is a stock broker in New York, he's living in Westchester, and he's hopelessly alcoholic.
  670. He, in a way, has end-stage alcoholism. He's going to die from his illness. He has a doctor,
  671. William Silkworth, who says, "There's nothing I can do, but in Towns Hospital in New York, there's a guy,
  672. Charles Town, giving belladonna alkaloids as a novel treatment for addiction." And belladonna alkaloids
  673. have anti-muscarinic effects and can induce delirium and can induce mystical states.
  674. So Bill Wilson undergoes this treatment in 1934 and, either having a little bit of the DTs
  675. or certainly on belladonna alkaloids, he has the white light experience that Michael described,
  676. and he says, "In utter despair, I cried out, 'If there be a God, will He show Himself'.
  677. There immediately came to me an illumination of enormous impact and dimension,
  678. something which I have tried to describe in the book Alcoholics Anonymous...
  679. my release from the alcohol obsession was immediate. I knew I was a free man."
  680. So, so far, so good. Bill W. has a mystical experience. He doesn't want to drink anymore.
  681. But what happened when he went to Ohio a couple weeks later? So he goes to Ohio, and there he is
  682. at a bar. It's like, "Oh, my God, you know, it's all going to come undone." He freaks out.
  683. He goes to the phone booth. He calls the local Oxford Group chapter, and they put him in touch
  684. with Dr. Bob. Dr. Bob was a physician in recovery, and so they end up having this very long,
  685. first AA meeting. And really what sustained Bill Wilson was this: So, actually, Rowland H.
  686. comes to him in the hospital, gives him The Varieties of Religious Experience. He [Bill] said,
  687. "This book gave me the realization that most conversion experiences, whatever their variety,
  688. do have a common denominator of ego collapse at depth. In the wake of my spiritual experience
  689. there came a vision of a society of alcoholics, each identifying with and transmitting his experience
  690. to the next - chain style. This concept proved to be the foundation of Alcoholics Anonymous."
  691. So it really is... was the connectivity, and we've looked at studies now that look
  692. at the therapeutic ingredients of Alcoholics Anonymous, and although enhanced spirituality
  693. and spiritual states and even spiritual conversion are important, it's actually the size
  694. of your sober network being large and the size of your user network being small
  695. that is the greatest predictor or how well you do in this ready-made recovery community.
  696. And I think this is important because if we're going to design trials of addicts, I think we need a container,
  697. something like AA, which is there and goes along, you know, with this model.
  698. And Bill Wilson and Carl Jung communicated.
  699. You've heard a lot about mystical experience and transformation,

  700. and we've seen this with the John Hopkins work, and the work with
  701. Kast and McLean [?] is really, really interesting. Personality is supposed to be fixed in your early 20s.
  702. Your personality is set through genetics and temperament, and kind of, you know, how extroverted
  703. or introverted or open or not is relatively set except in this trial here, psilocybin, 14 months later,
  704. and those that had a higher degree of mystical experience were much more likely to have
  705. enduring changes in the openness domain, so more open to fantasy, and interested
  706. in aesthetics and feelings. And these people were more open. From a discrete pharmacologic event,
  707. they had greater degrees of the dimension of openness 14 months later. It was really remarkable,
  708. because in psychotherapy, isn't that what we try to do? We try to make people more open
  709. to change and experience? It's certainly what we try to do in addiction psychotherapies,
  710. like motivational interviewing. So, we... to treat addiction, if we induce mystical and spiritual states,
  711. if we can increase the domain of openness, how can we leverage that therapeutically
  712. to treat addicted individuals? And the important thing is, what's in the container?
  713. Are we going to use standard addiction psychotherapies, such as motivational interviewing
  714. or relapse prevention? And the evidence base for these psychotherapies for addiction
  715. has been well established, and so we have a lot of good addiction psychotherapies.
  716. But I think because we're inducing these spiritual states, I think it's important to have
  717. some part of the psychotherapy that has some component of this, whether it's mindfulness
  718. or whether it's 12-step facilitation, I think that they go well together. And I really love the idea
  719. of doing a study of including something like AA, because I think you really need to be
  720. in a community of recovery for it to be sustained. I really think that that's viable, after treating addicts
  721. for a long time. And we're trying to figure out single versus multiple dosing. And, again,
  722. the data that Michael has shown, the effect has worn off after, you know, a year or so,
  723. and so we really don't know the dosing frequency, and that's important to figure out.
  724. But we do know in terms of dose, this study done by Roland at Hopkins shows that
  725. as you increase dose, you reliably increase the intensity of the mystical state, and not only that,
  726. [you order an[?]] orderly way, you increase positive attributes related to the drug that's dose-dependent.
  727. And, again, individuals that had 20 or 30 mg, almost 100% of them said it was the single or top five
  728. most significant experience in this dose response study, so... But there is... between 20 and 30,
  729. the rate of adverse psychological events does go up, so... And Michael's data is interesting, that it...
  730. around, you know, this dose here, some alcoholics are having almost no experience.
  731. So maybe there's something biologically that's different that their sensitivity to the drug is altered
  732. in some way through alcohol's effects, perhaps on glutamate and other compounds.
  733. So, just two more slides. So, this is Michael, and, actually Rick Strassman restarted the field

  734. of hallucinogen research in the early '90s, so he was a real pioneer that go this restarted
  735. and really provoked the FDA and NIDA to take a look at this, and Rick was able to get research going
  736. at New Mexico, and Michael really is picking up the torch from that. And we have Bill Miller here,
  737. who was the founder of motivational interviewing, and I think it's just brilliant for Michael to come up
  738. with the idea of psilocybin-assisted motivational interviewing. And so Michael's data is really great,
  739. and we've been talking about having a multi-site [?] trial now with alcoholics. But for me,
  740. I'm particularly interested in a similar design, but how can we use, at the end of this 12-step facilitation
  741. and entry into AA... and in a way this is sort of like the reverse of what happened to Bill Wilson,
  742. or, you know, I think Bill... It's interesting that AA has sort of changed from this organization
  743. that was founded by a guy that had a drug-induced experience who believed in antidepressants, which...
  744. there were sort of splinter groups that... where... it got to the point you couldn't be
  745. on psychotropic medication and go to AA, you can't be on methadone because it means you're still using.
  746. So I wonder what it would be like to go to an AA meeting and say, "Well, I'm sober, day 14,"
  747. and they're, "Ah!" They clap for you, "That's great." And you say, "And I just did psilocybin,
  748. and it was awesome," you know, "Whoa..." and then... [audience laughs] you know.
  749. So that part... so we're trying to figure out how do you... You know it doesn't matter what got you sober,
  750. whether it was a near-death experience or psilocybin or whatever. You're here, sober now,
  751. and you don't want to use drugs. And so, I think that it would be important to think of this link
  752. and optimizing that. And, again, to just think of what would be the mechanisms of action.
  753. And it could be more than one, you know: Is it the biology of the compound, and if that's the case,
  754. what sort of neuroplastic changes or long-term changes at the gene level or otherwise
  755. could encounter [?], structural brain changes for effects - you know, one dose, one experience,
  756. positive effects months later - and what kind of learning mechanisms are involved,
  757. and psychological change mechanisms, and spiritual, religious. And, again, I think it's important to look
  758. at the social domain. We're social creatures, and social influences can really help us
  759. sustain positive changes. So, I'm going to stop there, and take questions.
  760. Thank you very much for your time. [Applause.]
  761. [Question] Thanks for your talk. You gave a really nice historical overview of the trajectory

  762. of psychedelics research in clinical use, and you talked in part about the cultural backlash
  763. coming from this idea that, you know, a kid somewhere took a psychedelic and... which coincided
  764. with a schizophrenic or psychotic break, and then you said something like,
  765. "Psychedelics don't cause schizophrenia"? I've encountered that sentiment a lot
  766. from skeptics of clinical research into psychedelics, and can you say just a little more about that?
  767. [Answer] Well, if you give someone LSD, if someone takes LSD who does not have a family history of psychosis,

  768. who is not predisposed to psychosis, acutely, within the order of hours or so, it can create a state that,
  769. within psychiatry, we would call psychosis or psychotic-like. If people retain the sense
  770. that they're on a drug, and they have reality testing that they're altered, then they're not psychotic.
  771. If they lose track of time and who they are, they can become psychotic, but that does not endure.
  772. The psychosis from the seratonergic hallucinogens does not endure. Only drugs
  773. like crystal methamphetamine, PCP, and alcohol can occasion enduring psychosis in people
  774. that don't have an underlying diathesis. But people that are prone to schizophrenia,
  775. these drugs, like other drugs, like cannabis and amphetamines, can induce psychotic states,
  776. either first break or relapses, so they're problematic in that population, for sure.
  777. [Audience member] So I'm a private capitalist, and I'm most interested in the mechanism of private industry

  778. in making these types of interventions more widely available. One of the... one of, perhaps,
  779. the most significant criticisms that, in private industry, we're likely to encounter is that,
  780. even though we know these aren't necessarily novel treatments, these are novel treatments,
  781. and there is insufficient research to support the efficacy of these interventions.
  782. And, so, I'm particularly interested, really, as a function of business practice,
  783. as a function of business model, a tighter integration between the research that's necessary
  784. to inform the very clinical practices that private industry provide to patients.
  785. Stephen, do you have any thoughts about how best to do that, or... [Dr. Ross] Yeah.
  786. [Audience member] That's my question.
  787. [Dr. Ross] It's very hard to do the research, in part, among others, the resource issue, that...

  788. The studies that I run at NYU Bellevue that are funded by NIDA, you have a real research budget
  789. that, you know... you have a whole team. When we first started doing this research,
  790. because NIH will not yet fund it, we had a very tight budget. It really was not powered enough
  791. from a resource perspective. And once we had enough resources, it changed everything.
  792. Once we had a project manager, we were able to pay our therapists, it powered the study.
  793. And the NIH and governmental agencies will not yet fund these studies, so we absolutely need
  794. private individuals and private venture philanthropy to get these studies going and to move forward.
  795. And we can more so much more quickly, but we're limited by resources.
  796. So there needs to be some help from, you know, these private entities to kind of power the research.
  797. [Audience member] Thank you.
    [Stephen] Yep.
  798. [New audience member] Hi Dr. Ross. I'm a medical student at UCSF, but I guess I'm there

  799. for the wrong era of empathy research. I was wondering a little bit about, in your cancer study,
  800. why you're allowing both psychedelic-naive and psychedelic-experienced patients,
  801. given that that could be a confounder. Or you think there's not a substantive difference
  802. in potential outcomes between those groups?
  803. [Dr. Ross] Well, there may be. We don't exclude people. And there's some places

  804. where they'll exclude people if they've had more than a certain number of experiences.
  805. We decided not to do that. We wanted to see, you know... I mean, in a way this is a pilot study,
  806. and I think in future studies we would want to look at and correlate: does it matter if someone's
  807. had an experience or not. But certainly, if someone's hallucinogen-naive, it decreases
  808. some of the expectancy effects. But it's really important... not only is it important to know
  809. if they've had a prior experience, their religious or spiritual frame is vital, and that's why we do
  810. an extensive spiritual history. Someone who's an atheist is... might have a much different experience
  811. than someone who's very religious, although we've had atheists in the trial that have had
  812. profound experiences. We had one woman, she had an encounter with a transcendental force,
  813. which was very important for her therapeutically, but she came back and said, "Well, I still don't believe
  814. in God. I'm still an atheist. But, wow, that was pretty powerful," [audience laughs] and she developed
  815. a kind of spiritual practice based on that. So, it will ultimately be interesting to understand
  816. one's frame of reference due to, you know, pharmacologic agents they've taken or experiences.