t T" Fit) @3D z%.iENIORAND FC)R: THE RECO'. 21-23 August 1956 on2, Kvt s, Trip to Lexing't SUBJECT* yl LSD 1-methyl I is obtaining supplies of acet 0 1. Dr. Isbel ck these olidide of LSD.. He will che2 LSD, BOL-148. and the pyrr L-aD-like reactions, for cross compounds in his subjects for of tolerance to LSD. and pay particular attention to time course the action in each case and the odd reactions. I agreed to furnish what data we have on 2the pvrrolidide compound. I ef- 2.. He will check the time course, potency and, genera fectiveness of the dispersed C-9 compound which I furnished in adequate supply. He is looking at the circulatory effects oi tlie C materials in,general. I-Te has approx-Lniately 15 pounds of fresh Charas that'he would like to give us. This would involve us seeinff Mr. Cunningham in Anslinger's office, since @,ilr. Cunninghar,@n is responsible for the material. 3. Dr. Isbell provided,=e with one grarr. of 1-6ro.-neran tartrate and 0. 5 grains of2 the Dhenett@vl derivative. ',he phenathvl derivative is -5 time's more po#.ent than 1-dromeran but in all other ways is strictly comparable in iis action. it is the most pote-nt of all morphire derivatives b,-,r far. Dr. Isbeli his no doubt of its oral potencv but is testincr @i. Th:e ralio of intra-@nuscular 4@-.o oral potepcy is est'iniated to be 1. 5 to 1. This par'%.icular substance T)robably will never be marketed by Hoffman La Roche beca-use it offers no advantage except the greater potency and is more difficult to make. The antidote for the respiratory deloressio-,.i is2 'Zia'Lline. I aucried Dr. isb--Il on ttie produced by the compound possible use of O.Z millia n -dle fo- ,rams of this co-rrpolind on ot.,r e- use against guam-as. He thoua-ht th3L+. -,-ery -t,ssibl..v tti2e F-.Aard i--t a -Y.---ul:i be z)arlor"-i acid verv possibly be unav-;are of his surroundings. 4. Dr. Isbell finds that tte Ri,.,ea rceds givf.-n him bv -oduce neuro'Lo,,,i.c-al si4nz 2 n,@N,.driasis, etc., bi--@-,. also so mu(,ho, gastro-i.nte.Bti.,ial ,-rruble +U'ne rcsi.ns) I'liat he :,-,nlt.evalua:e aliy psychological ea'fects. I e-@r,)Iained to hirn the confusio-i bet@,,veen types of seeds and gave Iiii-n an adequate of the the tnvo 6 @. A.- larger seeds fror-n the iVie.--cican mainl,:@n@,l for tri-:7,1 as he 1,,as 15eclassiftid EY -1087475, ?ate -3 7 2 I also in dicat hat as soon as it was available. I would send him an extract fr( ,,Yhich the resins have been re,-n@oved. Dr. Lsbell has the comt)ound@2, 2-diphenyt-4-rnorpholino- ethyl butyrate (note.- gamma amino butyrate) which can replace 2 morphine in Preventing abstinence symr-,toms but at the same time produces a rather acute.toxic psychosis of two to three dayst duration, More information will be available on this compound later. 6. I queried Dr. Isbell on the possible use of orinase to potentiate and/or pr2olong the LSD reaction (based on information that orinase lowers the capacity of the liver to perform its normal detoxifying function). He felt that a considerable amount of i,-iforn,,a- tion could be gotten about the feasibility of this through some animal work with the.compound prior to his human work. He suggested use of Dr. Winter's technique. If the animal work indica2tes that this is a feasible approach, he will be very glad to do the human work with the material. 7. Dr. Isbell is viery interested in testing- the French com- pound it we can furnish- him with *j'-,e substance and some animal data. His inleiest in t-he compourl'd comes from its possible con- nection with the active,compounds found :i-n nutmeg, etc. 8. In connection with the problem of cliecking the effects of druas on suggestibilitv ndard procedure @ . Dr. Isbell felt@ that a sta ' .could be Worked out which would not necessari y require the use of a hypnotist. The technique he suggests consists of the productio2n of a standard tape recording,@;,hich su,,Tgests that a person. is sway- ing on Iiis feet. The subject is olaced in a sway meter. There his tendencv for normal swavi.ng and swaying under stiggestion will be measured at different time,-z 4.,-, order to determine rer)rm- ducihili-tlv s2ari-,e iliu'ividillai. Later the drula, is ir,.troduced to determine whether the subject is then more susceptible to the pla ying of 'the tape. 'R@'e also discus5,ed th(,,- probl--ms of arriving -elatior at objective tests for de!-lt2h of hvonosis. In i i to th4s, Dr. Isbell felt t.l@.at it migii,@. be instructil,,e first to an,)Iv whati--lr--r 4ests that -we d-cide. are germa:,e to the problern to sorrnambu.Iiatic Subjects in states such as rigid @§uspension betnveen chairs or complete anesthe7sia, etc., in order to eliminate as far as possibl&e -187475- dat's 4 F@8 1977 doub,-s as to the enuineness of the co 9 ndition artd to get as large a change in the subject as is possible.' 9. D.-. Isbell suggest,?d that the problem of an anti- interro at;on mat--rial i-.,i,ht be solved bv the injection of between 2 30 and-60 m;.'J.Iigrams of d, I acetyl met@i'adol (alpha-d, 1-4, 4 d;phenyl-6-di,-rethylarnino-3-acetoxy-liepta,-ie). The effect would be p&-ofound, not too da,-igerous and would follow the time cotirse indicated below: Effect Begins Peak Effect 2 Mild Residual EfL'--cts 10-15 mins.- 1 1/2 2 hrs. 24 houris d- 3-4 hrs. 12 hours 72 hours Nalline wilIonly antidote the respiratory denression, 'not the anala,--sic effect, the emetic cffect, nor the psycl.ALloz;.C-al Therefore, it would be possible to keep the person alive in the event of an overctose bv the use of N'alline but it ivould not be t him in a condition for interrog4ti.on. possible to pu 10. Dr.- Wilr-.Ier has finished his review on the electro- 2 physiology of the central nervous system and Dr. Isbell' will send us a cqpy of t@;-- ir.-ar,.uscrit)t s.-)on. Dr. .-Isbell rrill be in Washinctor. part of the week ot 20 Sep,.Pembcir and ivill be glad to talk to us then. ";OWN 2 Chief, Branch II TSS/Chemical Divisio-a Dist- Orig 3 TSS/CD (24 At,,a st-19'1 'Declassified by -187475 ?ate 4 4 FEB1977