DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE 3 Tanuar 1961 Addlctioa Restuch Cantef U.S. P"U4: He2ith Stivi" Hospitsl Cantacky I am enclosing herewith copies of three tables: "Co=.L-oarison of the total course of t4e LSD, mescaline and ps,Uocin reactions, " "Mean increase in pu-oillary diameter over control, 11 and "Mean incr---1-2se in number T)ositive answers over control. " All dr-,igs were given intramuscularly, a de-arture fr2om our orevious practice. The 10 subects used received all drugs. The methods used were those that have become standard with us for psychotomimetic ttudies.. Tne experiments were done oartly to get equivalent dosages of LSD and mescaline, and also to get some information on osilocin (delohosphorylated psilocybin). As expected, the effects of all three drugs were quite similar quantktatively. All thr@ee induce the same sort of autonomic changes including puaillary dilataticn, terlperature elevation, blood -oressure rise, et,,. , and all induce similar mental-changes including ilterations in mood,, body image, sensory slk"ortion an ucinations, chi y o e visu type. e chief differences relate to potency and time course. As i2s apoarent from the tables,, the onset of the psL' ocin reaction is quite rapid, nearly ma)d.-nal effect being attained in the first half-hour. After 2-1/2 hours the psilocin reaction is a.Iready declining sharioly, and, after 3-1/2 to 4-1/2 hours has declined to negligible t)rooortions. It is of some interest that psilocin is the most consistent agent we have studied, insofar 6as the induction of hallucinations is concerned. All 10 men who received a 150-mcg/kg dose had hallucinations and 9 of them lost insight. Des,oite this, psilocli seems less anr)leasant than either LSD or mescaline, per@aps because of the short time course. -age -2 The calculation of relative potency presents something of a problem because of the marked differen c-- in the time courses. Tne relative slowness and long persistence of the mescaline reaction should be noted in this regard. However it is aocarent that 1. 5 mcg/.kg of LSD is equivalent to 75 mcg@kg of psil(@@in substance and to 5000 mcg/kg of mescaline hydrochloride. currently we are running a small study on the relative pote.,icy @f osilocin and psil.ocvbin. Psilocin is of course,;nore r)otent in terms of weight, but pro",,ab'ly there will be vety little aLFference in terms of moles. Cross tolerance between mescaline and LSD is:well along2 and I --Feel almost certain that a higli, grade of cross tolerance wll exist. Ampheta.-nine is next on the agenda insofar as cross tolerance is concerned. It was very pleb@sant to s,-.e you during my last trio to 1,@,ashington, and I am sending kindest personal regards for the New Year. Sincerely yours, 1--iL- b w 3s Enclosures Tables (3) m! i c, r UP s '.T' h rc 2 I d C', i re rt -U 2 0. r@9 7 0. 75 -rncg/kj .+3. 41 Al +bJ. 15 +., 10. 11) +45. 50 12. 4 -3 + 12. 9,@ 1. 51 -54. CO 9. +4..31 -h Z). 4, 7.70 3'. 20 2 10. 10 GU r#7c-,kllna 2. 5 MZ/ +3. 4,3 0. 41 t3l. 43 + 9. 27 +45.45 13.53 +10. 43 1. ('j2 -2Z@. 5 0. 1 5. 35. 1) r, c.,-tl 1 n,3 +4. 51 0. 3-2 +71. 10 17. 7D +7(,@'.!35 12. 45 +17.33 1.10,1 7 i3 -4 1 3 C-'7. IF'2k n 3 7. 5 +3. f,15 44 +3 7. 25 I'). 0.0 + 3'4-10. V 5 1 4 ..I r.4 + 6. Zi4 1. 10 :.-47. -15. 74 1'6'. 1.0 3 1 - r@') 2 0. r -3-3. 5f.,, V. 1,,@ 7. il. e,ln 75 rncg/t,,g i, 0. 42 411. 5'0 12. 41 i-4.@l. n5 1".t. 51 + -P). 74 0. 83 0. "5 +41. 10 12. 2,9 457. O-J d. 10. 43 +14. 5C 1. 5,3 t3 7. ,I2 .I 1 7. 1 D n 150 mcg/kg if-5. 17. at,,*t t'lie i-fic@anr, @3rrors of ttc.),, "2rlio rigns or In the er.-Orp t.,f of po.-,Iitlvc-1,7 In. tti,3 7-Ile@ 1,-,@@urs a.!t,,,Ir til@, er,!-, 6 tw,,hleli re n.,ot qandar-I error-s of tn'@,<@n:Dtty o f irlntv! rcactlc)n on a rcale of 0-4. t:-) r-4 W-4 2 + + .4.6 P-4 + + 2 Lf) CN) 0 *-I r-4 2 + + + + 4 + en 2 ,@ll It:c3 t- (--.I it@) C,4 -4 V-4 rq 2 + + + + t u) L n 4Cqr) 2 v 'A 0 9 6'. f.11 e4 w (4,..3 cl: C4 2 4- + + + + + V) (VI to C,4 L:4 .11-14 ri 2 + + + + 4U LO 2 1(') LI) 0 2 Lc; il73 C> tn SiO 2 ti 0 0 10, IU'k ta tr4 2 CQ PI C"l 2 0 CA 0 CA3 9-M 2 fj) NI) tk@) flu 2 cli C.> C-) ci 6 L-) E3 ci (.@o C)