ATTEMPTED BLOCKING OF THE LSD REACTICN WITH BAS These experlments were carried' out because -'It 13 known that BAS Is a powerful anti-serotonin and the .posstblltty existed that the LSD psychosis was due to an accen t ua t to n of th e ef f cc t s o f sero to n I n w I t h I n the cen t ra I ner vous s yste2m t LSD I n low con cc n t ra t to n po te n f la f e s rather than blocks the effects of scrofonin In smooth muscle preparations). The subjects used were IC of the same 15 Negro male, -in the experiments dealing foreer drug addicts who served with the acute effects of BAS. These patients received the2 following drug combtnaflons In a randomized order (Latin square)** SAS placebo plus LSD placebo; BAS plus LSD placebo; BAS placebo plus LSD; and BAS plus LSD. Doses of BAS were 150 mg. ever,/ s Tx hours for four doses (total dose 600 mg.). The last dose was given two hours before LSD. LSD was administered orally In doses ranging between 0.5-1.5 mcgm./kg. (aver3age of 1.1 mcgm./kg.). The smaller doses were given to the men %-ihid were tested first since the posslbiltty-existed that. BAS and LSD Might synergize. Methods. The methods used Included determination *f-pupillary size, threshold for knee Jerk, resting sysfol.ic blood: pressure,@..response to a modification of the Abramson-larvik questionna ire, and eva luation of the cttnlcal grade of the LSD reaction based on short psychiatric 2examinaf Tons. These methods and the means of statist tcal analysis employed have been previously described In other reports. The ee suits are shown In the accompanying fable. The only Important change noted was significant blocking of LSD Induced elevation in blood pressure by the SAS. All other aspects of.the reaction. Including mental response., were unaffected. A number of patients withdrew from all experiments after these tests were completed, primarily because of Ion persistence of the unpleasant SAS effects. 9 Discussion. The-results do not favor the hypothests that LSD psychosis Is due to potentiation of scrotonin effects within the central nirvous system. They, however, do not-exclude this possibl'lify since we do not know whether the symptoms caused by SAS are ctue to pe ripherat or to cenfrat a c t I o n s lit A TTEMPTED BLOCKING OF LSD REACTIL)N ',"II TM BAS E@ JPI E DRUG 2 BAS PLACEBO 4. BAS BA'3 PLACEBO LSD PLACEBO LSD PLACEBO LSD LSr) ",-I lae Pef lex 0.13 4- 0. 14 4- 1.17 4- 0.17 4. 2.04 0. 29 2 2. 02 0. 4'.' ) @:@,'uptllary Size 0,11 1 0.22 1.37 0.55 4. 3.79 0.35 4.&j4 O.QP '.@ystol IC Blood Pressure 0.59 4. 0.18 0.12 4. 0.31 0.76 0436 41 20.118 0.46 n. e r of Quest tons 0.7 0.9 5 0.3 43 4. 1 2 404 13 linical Grade 0.3 4- 0.3 1.1 0.1 0.1 0 4.. 02 (,ave. 0. 9 Dose of LSD 0.5 1.5 mcgi/kg6 5 mcg./kg.) Dosage of BAS 600 mg. In 24 hours given In 4 doses of 150 rng. Figures are,means of observations o7n 10 subjects sfandar(I errors* ACUTE EFFECTS OF LARGE DOSES OF EOL IN IVAN D-2-Brom-lysergtc acid diethylamlde (SC)L) differs fron, LSD only In the presence of a bromine atom at carbon No. 2. This material Is a potent anfl-serofonin In vitro. Rofhlin e t a I ha ve repo r ted th a tthe doses of SOL 20 firr;es 2 grea ter than those of LSD do not Induce a psychosis In man. Since.t like LSD, SOL reverses prolongation of hexobarbifat sleeping-tl me by scrotonin If must be presumed that the drug does reach the central nervous system. These expIert- ments have been Interpreted as not favoring the hypothesis which attributes the LSD psychosis to lnh 2lbltion of brain serctonin.by LSD. If occurred to us that, because of the chemical of the two compounds SOL might possibly block the LSD reaction. It was first necessary to re-evaluate the acute effects of this substance In man. Subjects used were 15 Ne@gro male addicts who had been abstinent' from opiates for a@IL least2 1111-.ree Al I of these sub'ects had had considerable ex perience with the subjective effects induced by LSD. BOL was given orall-Y. lnifial doses were S megm./kg. of bodyweighf, which was Tncreasec' in sfep-wise fashion, as the experiments proceeded to almost §O rrcgm1./kg. The highest total dose given was 8 mg. Page Obse r v.a t I 0 n sThe fol lowing obser,vations were made two hours before and for one hour after the administration of BOL: rectal temperatures resting pulse rates"respirafory rafts resting systolic and diastolic blo od pressures, threshold for elicitation of kneelerkt PUPTIlary size, mdlffcation of the Abramson-larvik questionnaire, and a short psychiatric examination-* Results* Doses of BOL up to 4 mg /70 kg. cause-d neither subj.edtive nor objective effects. Doses of' 4 mg. or more per 70 kg. of bodyweighf Induced mild effects, which are presented In 2the tab,le. These Included small Increases In systolic blood pressures diameter of the pupil, and In the threshold for knecierks. The 'mental" symptoms. Included nervousness, nauseas chilly sensations, blurred vision and, In some patients, colored lights and hallucinations. Reactions are described as resembling those of a ver2y small dose of LSD and were milder than the- effects of 0.5-1.5 mcgm. of LSD In the same subjects (see fable). It Is estimated that the effects are no greater in degree than fsose induced by 0.25-0.5 mcgm./kg. of LSD. BC)L Is, therefore, at least 100-200 times less,p7otent tha.n LSD* If Is, in facf..,. far less pofent than lysergic acid monoefhylamlde FLAE). Discuss Ion. ' These results confirm those of Rofhlln and do not favor the hypothesis which attributes the LSD psychbsis to a 'deficiency' of serotonin. EFFECTS OF 5-8 IVG. /7 0 KG. OF D-2-BR@.ki-LYSERGIC ACID D I E TLIY LAM I DE %SURE DRUG I -60 2 PL2ACR. BOL LSD fellar Reflex 3 4- 0.15 4. 0.12 0.68 4 0.2 2.29 4 0.32 of I far i/ Si ze 0.16 4 0.18 4. 1.54 .4 0.33 4.93 0.36 stolic B-lood Pressure 4- .6 8 0.2 0. 95 4. 0.3 2.69 4 0.1 .2 4. 1 . 12 1 34. 4.7 ,iber of Ouestions 61 4. 1 1 inical Grade 04 0 0.6 4 0.15 -2.0 I 9Average dose of BOL 6.@'i mg./70 kg. 86 mcg./kg. 2 O.S to 1.5 mcg. of LSD/kg. (.Average 1.1 mcg./kg.). 3 Figures are means on 15 subjzc.ts 4. standard errors.