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Ycu may bz interested In the progress of our exoeriments with LSD to date. Orlcinally we had planned to determine the thrzshetd dose for each patient individually, and this was attempted early in August, using a supply of' LSD which was more fhantwo years old.

Negetlve subjective reoorts were obtained with doses of 20 to 70 micrograms. Finally, patients were given l00 micrograms in divided doses, with marked subjective effects las well as otjectivel appearlng in all 5 patients. We then attempted to titrate: the effects in each patient, giving dases of 80 to. 90 microgrems. Very, little effect was observed. These doses were administered on the day following the lOo microgram dose. These doses were raisedprogressively until l20 tc 130 mlcrocrams were being given to 4 of the subjects and 90 micrograms to the other, withcut any signiflcant effects of any kind. It was found thet thc time of day dld not alter the lack-of effects and, alsc, that a fresh supply of LSD produced no changz In the effects, or lack of themi.

Since the lack of effects might be due to tolerence, administr ation of the drug was diseontinued and. after five days was again adminisfered, with markod suhjecfive' and objective changes aooeering with doses of 90 to l20 micrograms. Meaawhlle. tesis of the druc in individuals who had not been receteine it had shown strong oosltive results. The findings were very sugcesfive. of rasid develcoment of tolerance.

It was, therefore, necessary tc obtain measurements after single doses af widely scattered intervals. As long as the interyal was as. much as S days, there wes no noticeable

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HEALTH, EDUCATIÓN, AND WELF/ ERALSECUBITYNGENG PUBLIC HEALTH SERVICE LEXINGTON, KENTUCKY 1 16 Septcmber 1953

,  T MEDICACOFFEERIAEHARGK PUOLIC HEALTH SERVICE HOSPITAL NiMH Addictlon Research Center

187475 date 1977

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decreese In effect, but there may be some deerease in effect if the drug Is administered every third doy..

Then given at proper Intervels, LSD induces, very definlte. blood pressure rise, puoiliary dilatation, increase In deep tendon reflexes, and dimlnutlon in superficlal skin reflexes. The pupillary effects and blood pressure effects appear to be sultable for measurements of tolerance.

LSD appears to facllltate synchromizatlon of the electroencephalogram by photlc stimvlatton. Photlc sfimulatlion also seems to enhance. the perception of elementary hallucinatlens.

Apparently the supply of LSD ls qulte limited and we may be unable to obtaln sufficlent amounts cf the drug to carry out the study as orlginolly planned. However, we belleve we have sufftcient material to accomplish the follcwing: I} Effects of larger doses in non-tolerant patients; 21 Oeterminatlon of whether tolerance occurs after one singie dose of LSO: dose or L>y; 3} Controlied studies of tolerance. develooment in 5 patients; it:---5 1\_ta-sae duntanment tn 5 atients

41 Comparison of LSD:with LAE.

Sincerely yours,

Haini SHheee

Harris Isbell, M.D. Director of Resedrch

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Declassified by4 187475. date FEB1377