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COMPARISUN CF THE EFFECTS CF NLD-AI ANO LSD-OS

Mlo-4l Is l-methyl-dlethylenldr.of lysergic acld. Studles on thls aggat were undertakea in order to cbtala data on structure-ectlvity reletlcaships in the LSD gerles.

The purposes of ths present experlmznts verel ll) to determine 1f MLD induced L5-llte efiectst and 12) to assess roughly. the poteney af MiLD as ewmpared elth iSD.

WETHODS

Subierts. Fourteen Negro.metes aged 24 to 45 years voiunteered for the experimentt. All vare prtsoners sho were tervlng eantenees for violation of the U. S. narectie lows and all had been abstinent fros aarcctle drugs for at least six months pricr to sarvine ln these experlments. èll were la gcod phyelcal and mentel health, noan were psvthotlc, and all had taken L5D on previcus uecasions.

Frurt- The drugs were glven vrally ia soiutlon. Identifies ef the drugs were uatnswn to both the pallents and cbetrvars. wbssrvers dis nst kous of the purpctes of ths experimsats, end, furthermore, were not aware that a nes tsD-llke drug sas delng

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given. Sslutlons, of the druga were orepored wlth freshly distilled water and preserved in brown bottles; c-ncentrallcn of stcck rolutions was l00 mcgm./cc. Doses for esch Individual were measured with mlero-plpettes and drugs diluted to 30 cc. with freshly distilled water and administered whlle patiente were fasting.

Methots cf biessurecent. Patlentt were housed In & soeclel ward which is reserved fur experlmentatlcn elth psychct\_mimetic drugs.. The patlents entered this ward ca the aight baiore teets. All were eccustcsed to the envircnment. At hourly intervals, two hours befare end elght huurs after abalnistrstiun uf drugs, the puplllary dlamster wat measured uader ccnditions of controlled light and accammodatlcn. The distance thrcugh which a callbratad barmer must fall to elleif a kpeejerk vas detern alned. Systolle blood pressure vas mcasured after ten mlnutes rest In bed. Potlents fllled cut e modificalicn of the Abremson-Jarvlk questicaaaire hcurly, aad sh-rt sental-status examinetlcns were made by the eftendiag physlcian. Data ca pupillary size, biusd pressure, and threshold Icr elleitatien of laeeierk sere plotfed un graph paper and ths avsrage of the twe pre-drug cbservati ns usad as a boseline. Data unier the curve for the B-hcur perlod ci cbservatlen eas measurad elth a planineter, thus reduclng all dete ca these partleuiar mrasurements t. a tingle flgure. -uestions were counted, eliminatisg any that wers also

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scored pesitively prlor to Ingestion of the drug. Clinicel Grode was assessed accordtng to the nethod of isbell, ar descrlbed in the attached reprlat.

Dusess. Patients rocelved, in randamlzed ordert placeboi LSD 1 mcgm./kg. (10 subjects); t5) 1.5 mega./kg. 110 subjects); ead LSD 2 mcgm./kg. (8 subjectelj and varlous doses of hilD-41. In order to sscertaln the dporoxinate desege range, prellminary ruas wero done eith MlD4l. sith detes of .25 mcga./kg. tt patleat), 0.5 mega./kg. (l paticat), 0.75 acga./kg. 1l patlent), or I mcga./tg. il patlent!, no objective or subjective effects vere qbseryed. tiowever, whee 1.5 ncga./tg. 13 patlenta) or 2 mega./kg. (l patlent) were givea, deflnite, but pild,LsD-ilks mental syaptoms uere cbserved. It was, theraf-re, deelded that experimental deses wculd be hlgher than " acga. of HAlDn4l par kg. Six patients recelved 3 mega./kg. ef MlD41, 10 recelved 4 ms./kg., and 6 received ó acga./kg.

RESUETS

Tesults are shewn in the table. in reading the tahle, figuret represant the mesn fur the particular Deasurenent L the staadard errer. The data, however, ors suiflclent to shew thstt (ll LlD creates autoncnlc disturbanccs simllar to. those cdused by. L5g 121 llD ereates pavchle disturbances sinlier tu t'ese caused by t5; 131 110 1s less potent than l30. The data parolt a rcugh eatimate that LSD Is oae-third t.. vne-half co polant os

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lSD.. Such a figure is only an eppruzimatlcn slace true dosze responss curves cannet be constructed because number of otlents at each deso wos tuo mall, scoe satiants did not recelvs all deses, and, epparentty, flat pcrtlon of the dota-response curve had already been reoched with the 4-ocçm-/tg. dose ln caze of kneejerks, pupltlary size, and blood pressure.

Sublective phenoneaa reported after Ingestloa of MlDnl Inctyded enxtety, feelings of uareatlty, coafuslon, haptlc sonsatlons, alterett-es lo-tactile, visual, and acdifory perccoticr, the presence of deluslors eat optle telluslraticns, depers.nalle zaifa srd fetcailzeti-a. The Lcn-retctt:p began mcre stcaty iusvaily I to l-l/2 hours as cunpared to 30 mlnutec after LSD) end dis net persist es lcñc.

CACLUSINS

hlO-4l is 4 paychstcmaimetic drug whlch laduces mentol effects similar to those of lSD. lt ls Fcughty cae=third fo one-hali as pctent os 150.

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Number of subjecte ot vari-us desest lsD 1.0 mclo./kg. (l) rubjeciel: 1sD 1.5 mcgm./kg. 110 rublests11.lsn 2.0 mcgm./kg. (0 subjects1; lln 3.0 mcgm./ku. lá subjectsl; ALo 4.0 mcgn./g- (10 subjecte); LilD. 6.0 mcgm./kg. 1o subjectel.