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1625
1.7

As you undoubtedly know, I had a vislt week before last from Mr. Kornetsky. We went over the data obtalned so far, end are in the process of making dupllcates of the graphs in the doseeffect experiment.

Since Mr. Kornztsky has been here, we have completed another tolerance experlment. in this experlment patlents. were given LSD for cight days lá doses increasing from 20 mcg. to 75 mcg. once dally at 9 a.m. On the ninth day, the 75=mcg. dose was repeated. The results appear in Table l. As expected, a conslderable dsgree of tolerance was developed to the subjective effects of LSD-2s. Patients gave an average of only l8 pos:itive answers, as compored to 88 positive answers after three days of water. The clinical 37 grade after elght days was estimated as O.625 as compared with 1.7 after three days of weter. In scoring e number of positive answers and clinical-grades, the same criterla were used as described in my prior letter. The grade of tolerance, however, taking into account the ladividuals concerned, does not appear to be any greater than thet developed after three days on two small doses daiiy Isee prlor reportl. Moreover, patients on the elght-day schedule reported more side effects as tolerance was developing, more particulariy in the middle part of the schedule.

We have some preliminary informatlon on attempts to break through the LSD-tolerance by inereasing the dose. The number of patlents is not yet sufflcient to permit aay conclusions but, howevzr, the information is being submitted for what lt is worth, since it is not likely that I will be able to do more prior to the Federatlon mecting.

In one experlment, 4 patients were made tolerant by the three-day schedule (10, 20, and 30 mcg. LSD-25 at 9 a.m. and 9 p.m.), the test dose being given on the fourth day. Two of the patlents received a l00 mcg. test dose lincrease of33 per cent] and 2 recelved 125 mcg. lan lacrease of 6ó per cent). No significant"break-through" occurred In any of fhese 4 patients.

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DEPARTMENT OF HEALTH. EDUCATION. AND V.ELFA CSORRAILCCCURIYAGENY PUBLIC HEALTH SERVICE LEXINGTON, KENTUCKY

IN REPLYING, ADORESS THEもPUALIC HEALTH SERYICE HCSPITAL

NIMH Addictlon Research Center

29 March 1954

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Mir. (hifa)March 1954

Doc bhea p 1 2    g 20-1 th200-.250/

Sincerely yours,

7 Harris Isbell, M.D. Director of Research

Hi:Én

At ta chmen ts

cc: Mr. Kornetsky

A-95

Poge 2

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TCLERANCE

TAELE 1

LSD-25 - Eight Day Schedule

75. mcg. Test Dose

Control not yet obtained

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TABLE 3