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(b)3)

1 am enclosing copy of proposed budget for fiscal year 1958 which has already been sent to Mr. Robert E. Motley, Administrative Assistant for Basic Research, National institute of Mental Health. He will submit it shortly to the Office of Naval Research. Also enclosed is letter to Mr. Motley asking him to increase Item 3, unier travel, by

The material I have been using is designated as l-methyilysergic acid diethylamide. it bears the Sandoz code number MLD-41, Lot No. 060001273001.

Animal pharmacology indicates toxicity is about equal to that of LSD in mice. The material is 3.7 times as active as LSD in inhibiting serotonin. it is pyrogenic in the rabbit, but less so than LSD. in mice it is said to produce only minimal excitation and no mydriasis.in the cat, effects are a little different than those produced by LSD, but studies are not complete.

Evaluation here, although incompiete, indicates that the material produces effects in man somewhat like LSD, but that mLD is less potent. it induces mydrlasis, elevation in blood pressure, facilitaticn of deep tendon reflexes and the usual constellation of LSD-like subjective symptoms. The dose required to incuce a Grade 3 reaction is prchably on the order of 4-6 mcg./kg. as compared with 2 mcg./kg. of LSD.

Other materials 1 have are t-acetyl-lysergic acid diethylamide bitartrate (ALD-52) and Pyrcolidid of d-lysergic acid (LpD-824).

Sincerely yours, Harris ishel1, M.D. Director

A-355

H RELYING AGDRE3S THE NARAL  O  L AEON REAR CN . U.\$. FULIC HtALT JCRVICE NOsmITAL P. O. 80 2000

-n HEALTH, EDUCATION, AND FAREblic Heaith Service NATIONAL INSTITUTES OF HEALTH 25 Apri1 1957

Ht:ra Enclosures

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to the Abramson-larvik questlonnaire, and assessment of the degree of the reaction by the clinical grading system prevlously deserlbed. Methods of handling these data have been prevlously. reported.

Results. The results are shown In the accompanying table and are suggestive of a reductlon ln the Intensity of the. LSD reactlon. They show a reduction In every aspect of the LSD reaction measured. The dlfferences between the response seen after BOl plus LSD and those seen after BOL-placebo pius LSD reached tatistical signlficance in the case of effects on the kneejerks and on blood pressure, but were not signlflcant on measurements of puplllary size, number of questions, and elinical grade.

The experlment actually was unsatisfactory for several reasons: {ll The number of subjects was smali because of the shortage of BOL; l2) Six of the subjects were new, and 4 of these proved to be non-responders {had no mental symptoms with the dose of LSD used) w1th resulting skewness In the statistics;. l3) the results of Ginzel and Maver-Gross suggest that cross-tolerance to LSD is. developiag which Iikely would not be complete in 2 days.

In the only 2 experienced subjects available, the LSD reactlon was almost totally blocked by pretreatment with 8OL.

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