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Dr. Rarris Isball
United States Public Health Service
Lexington,Kentucky

Dear Dr. Isbell:

In continuation of our drug antagonisn program, ve have recently performed axarirents to test the antagonism batveen the effects of corynanthine hydroehloride, Zanthine, and LSD-25. Ve are sendirg you a sempla of corymanthine in case you wish to repeat our cparisants. Bonthire is, of ccurse, available on prescription.

In surzary, a 15.0 mm. dose of corynanthine takon orally 15-30 ninutes bofore a dose of ko nicresrans of LSD-25 seened to dlrinish or prevent nost df the rental and psychological syuptoms usually prccuced hy t.sp-25: at the sore tine. scuatic and vogetative sytcza and signs of LSD-25 wore largely unaffected or vere .inoreased in intansity. The proteotive effect of comnanthine porsiotel for only L to 2y hours; subsequsnt 15.0 ms. doses of corynanthine scemed to produce less proteetion than did the first dose, for a shorher poricd of time. Aninistration of éormerthine after LSp-25 had teen taken gave little protection from the effects of LSD. Adminiotration of Banthine (lO0 mg. per oc) and corymenthine (15 mea. per os) 15 to 30 ninutos before LSD-25 (ho mierograms) seemed to prevent even the somntic and visseral syeptomo noually produced by LsD. The adaition of Banthine to the rogise, hovaver, proluced a "heavy," trugged" feeling in the suojects. Corynanthine givon alone in doses up to 45 mga. per os, had no noticeable paychological or physiolozical effects. Subjective acecunta of five of the exoorinents are attached.

Shonlá vou aish to investizate such drug combinstions as these, ve woula puzzest that vcu first atteot to confira cur rasuito usin: bhe druzs anl dose schedules given above; it is augjested that the Eanthine be reducnd to 50 ns. total dosa. Hodification of the prouant regime might then be triel; for exaple, the use of other adrenargic blocking drugs, other paraoyapathetic blcoking scents (such es tinetue of Lelladonna or atropine) or even gangiionie blccking ogents (such as honomathonium) might be vorchraile. tcdirication of she doses used in Our triala aná the time relationships between doses could, of courso, be made.

June 11, 1954

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Dr. Isbell

Jume:11, 1954

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le lod': foremrd to hearins the results of any such "antagonismexporinents" such as thase vhich you right be abla to yerfoim. It voull bo appraciated if you vould senl the usual lotter to tho above adáress in order to roport any results of these entidoting experironts, In cddition, it woula be anpreciated if you vould send an original and a carbon of such reports.

Sincerely yours,

SG: