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(b)(3)

I am enclosing a table which gives data obtained In experiments concerned.with the development of tolerance to LSD-25. Eleven subjecis completed these experiments. The first 5 subjects werenegroes; the last 6 were uhite. Two negro sub-Jects, RE and GO, did not complete the experlment because they got into trouble with the authorlties lnot connected with the LSD expsrinentsl. The results obtained with these 2 subjects, for completeness sake, are shown below the totals and the averages. In the coatrol experiment, all the subjects were glven water at .9 a.m. and at 9 p.m. On the fourth day, they were given 75 mcg. of LSD-25 at 9 a.m.,and questionaalres were fllled out houriy for cight huurs. Ciinicai notes.on behavior were kept. In the other experiment. patlents received increaslng doses of LSD-25. ll0, 20 and 30 mcg.1 at 9 a.m. ond 9 p.m. for three days. On the fourih day, they were agaln tested with 75 mcg. of LSD-25. Half of the patients went through the water routine first; half weat through the LSD first.

-89 Declassified by ——187475 date 4 FEB 1977

TWX COOE NO LEX KY 477

IN PEPLYING, ADOOESS THE BEDCXCFSKEXARE PUULIC HEAITH SERYICE HOSPITAL

7 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE EZOZRA-SECURHSY-AGENY PUBLIC HEALTH SERVICE LEXINGTON, KENTUCKY 8 March 1954

NIMH Addictlon Research Ceater

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Results on the questionnalres were estimated simply by counfing the number of posltive aaswers (those scored posItive, after being scored negative prlor to ingesting the drugl. The degree of the symptom so recorded was ignored. "Clinical grades" were assigned by myself on the basis of lnterviews during the test day and the, day followiag. Crlteria for the grades were as follows:

O- Absence of nervousness and appreheasloa,

I - Nervousness and apprehension without distortion in shape or size of self, other persons, or inanlmate objects,

2 - Nervousness and apprehenslon, plus distortions in own body image, other persons, or inanimate objects, but without hallucinations and with retention of inslght, if

3- Nzrvousness, appreheaslon, distortions and elementery hallucinations. True hallucinations may be present, but iasight apparently retalned,

4. - Same as Grade 3, but true hallucinatlons present and insight lost. Grade 4 Is apparently qulte rare In my experience.

Tabulated data show that these patiants gave an average of
98 positive responses after three days on water and only 22 after
three days on LSD-25. In terms of clinical grade, the averages
were l.95 after three days of water, and O.6 after three deys
of LSD-25. :

88

Declassified by187475 date FE5 1977

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I interpret Phe data as 'indicatlng a very slgnificant degree of tolerance after three days cn these small amouats of LSD-25. Tolerance, however, was not complete in 5 of the patients. Two of the patlents, FO and GR, had very llftle response to the 75-mcg. dose, even after three days of water, so the presence or absence ,could not be determined.

2 I hope to coafirm these resulis, using pupillary, blood 1 pressures and reflex responses, in another experlment which will begin as soon as fhe dose-effect experlment which Is currently underway is completed.

I am currently carrylng out another tolerance experiment In which patients will recelve one dose of LSD-25 dally during an 8-day period in amounts increasing from 20 to 75 mcg. 1 belieye this particuiar schedule will result in complete, rather than partial tolerance. If.this is true, we will then be in position to attempt to determine how much the dose must be elevated to break through this degree of tolerance.

I am sending a copy of the toble and lefter to Mr. Kornetsky, whom I am expecting to arrive in Lexington about March ISth.

I have just received your letter of March Sth concerning BOL-l48,and three vials have arrived in the mall. This will not permit more than a very preliminary evaluatlon, but I will give you the results as soon as possible.

Yours very sincerely, Harris Isbell, M.D. Director of Research

487

HI:rA Enclosure

福

Declassified by \_ 1om

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RESPCHISE TO 75 MICG. LSD-25

Declassifiedby187475
date 4 FEb 1977