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L. The writer and Dr, Felikan visited Dr. Isbell at Lexington oa the 2ni and 3rd of Septenber to observe and discuss project (bX3) à good deal of the single . dose work has now been done and several interesting developrents have occurred.

2. Ths experizent was started by establishing the subjects (5). in the test ward and-alloyirg them to bacome used to the personnel, environnent, etc. for a few weeks. Mhe norral values for these subjects for a large battary of tests were then deterained. The tests include physiological, neurológical, psycholcgical, and such thinzd as clinical abservation and EEg, etc. The subjects were then given daily doses o LSD and placebo and the testing continued. The doses given were of. the order of l00 germa. All of theusual syeptoms were reported on the first doset-hovevnr, when that same dose was repeated on the next day, no ayptoms. develooed. In the course of further testing it becane more evident that a tolerance was rapidly developed by the subjects. At the present tine. the data indicate that after a dose of lCC garna on a given day, at least 4 days have to elapse before he will again show symtoms of the drug. ke observed one suojact who was showing no symptors on 135 gamca after having had 80 garaa the previous day and then we saw him the next day after he had been given l20 garma. The only symptoms he was showing at this level were slight patellar hyperreflexia and very slight mydriasis. He indicated in ell these trials that. he feltsho drug action rhile on the orig inal g0 gamma cose he had reported intensereaction in all departnents. It. would seen at first glance that this property would impose a most sericus linitation on the usefulness of this-drug.

3. Dr. Wikler has gotten very interesting results from photic stimulation while runnint the SEGs on reacting suhiects. Fis general conclusion is that LSD potentiates the visual illusions brought on by this tyre of stimulation. One aubject had clonus and approached an epileptic sèizure under this treatnent. He' sav himself beccge first larger and. then progressivelt sraller until he had to conclude that he was observinz himself in the erbryonic state. At this point a man with a shotgn entered the picture in a threatening way and the patient was so close to corvulsion that the arperiment had to be terninated. The subject interpreted the erisode as an attempt on his mother's part to abort while she was carrying himHe also felt that Dr. aikler was shocking him with the electrodes and that hs (Dr. wikler) could read his subconscious aind.. Another subject mo got. a atrong centered around nis reoressed desire to kill a wnise min.

4. The supply situaticn with regard to LSD is critical. Dr. Isbell is. in contäct with Kr. Erickson at Sandoz and has been prcnised whatever racerial becore available but the outlcok is not scod. A supply of LaE has also been ordered and whils there is very little in this country at the present tize, the cutlcck for core is very good. Dr. Isbell plaad to go to high doses of LSD to test reversal of the tolerance, so. the experirent is using zuch mere raterial than was orizinally indicated. Even if Sandoz can supply all of the LSD that has been créered, it probably will not be possible to complete the present experiment as originally plarned. The LaE was ordered as a first attempt to fili this gap.

5. To suri up the results so far, it has been found that tolerance developys en the first dose of L3D and four or five days are recuired to overccze it even with a 5Os increase in dose, LSD plus photic stimulation carries the subject back in tine and treresses atl cubiastive Fsalines, the rain distovefrrs cbsetrrd in the subsoote hove been those involving the size and color of hands and feet, and L3D potentiates the effects of phctic stimulaticn. In addition, ro toxic ranifescations as exibited ey liver, urine, or blood changes have been foumd. There is ac groas change in the EBo. Te oubjects slsep all riht the nirht follovirs a dces, but soretizes corrlain of a tanscyar tre next day. They don't sac so nuch under tho influence as norally (50) cal vs usual 2ic0). Several physical changes during intoxication have been observed. Thd blcod pressure is reliably eleveted Ercn around ll5 to near 1/o kr about loo gawra, and the pulse rate inoreases along with the respiratory rate. The pupils ars wniforly dilated by about 3mm. Hyperreflexda seens always to occur.

6. In proceedins, Dr. Isbell will feel his vey to ticher doses in an atcorgt to break doum the tolerance. . lie also plans to camy cut the chronic testing sore or leas as criginally sanned, but it vill no Couot so at sach lisher lsvels of dre. Fe wiil begin work witk Las xhen he has a stpply and ich the LoD exporiaent will 1ox it.

DRAFT 4 Septenber 1953

Hemorandum For the Record

Subjact: Visit to the USPaS a Lengton, Ky.

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7. Dr. Ishell has talked to. Charley Winters of Nerks about the new Nalline derivatives that were discussed at the last reeting. He found that all of the good materials had already been turned over to him. He felt that there would be little profit to us to try any more of these materials, since none of them show any real promise. Uniforzly, they have such serious side and after effects that they are quite dangerous to use. He pointed out that e, while testing one of the acetylrethadols in a patient, alnost lost. the ran and had to make a wild tslephone call to Le:dngton to find out what to do to bring the man out of it.

8. The writer nakes hurble apology for the interminable length of this report.