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These experiments were carrled -out because lt Is 口 known that BAS Is a powerful antl-serotonin and the posslbillty existed that the LSD psychosls was due to an accentuatlon of the effects of serotonin wlthin the central nervous system ILSD In low concentration potentiates rather than blocks the effects of serotonln in smooth muscle preparationsl.

The subjects used were l0 of the same 15 Negro male, former drug addtcts who served In the experiments dealIng wIth the acute effects of BAS. These patients recelved the followlng drug combInatlons in a randomized order (Latin squarel: BAS placebo plus LSD placebo; BAS plus LSD placebo; BAS placebo plus LSD; and BAS plus LSD. Doses of BAS were l50 mg. every six hours for four doses Itotal dose 600 mg.l. The last dose was given two hours before LSD. LSD was adminlstgred orally In doses ranging between 0.5-1.5 mcgm./kg. laverage of 1.l mcgm./kg.1. The smaller doses were glven to the men who were tested flrst sInce the possibiltty exlsted that BAS and LSD might. synergize.

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ATTEMPTED BLOCKING OF THE LSD REACTICN WITH BAS

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Methods. The methods. used Included determlnatlon of pupillary size, threshold for knee jerk, resting systolic blood pressure, response to a modificattan of the Abramson-jarvlk questlonnaire, and evaluation of the elInlcal grade of the LSD reaction based on short psychtatrlc examinations.These methods and the means of statlstlcal analysls employed have been prevlously described In other reports.

The results are shown in the accompanying table. The only Important change noted was slgatflcant blocking of LSD Induced elevatlon in blood pressure by the BAS. All other aspects of the reactlon. Including mentel response, were unaffected. A number of patlents withdrew from all experiments after these tests were completed, prImarily because of long persistence of the unpleasant BAS effects.

Discusslon. The results do not favor the hypothesls that LSD psychosis Is due to potentlation of seroton1n effects wlfhir the central nervous system. They, however, do not: exclude this posslbl'llty since we do not know whether the symptoms caused by BAS are due to peripheral or to central actions.

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[PAGE 3]
Flgures are means of observatlons on l0 subjects t standard errors.

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D-2-Brom-lysergic acld diethylamlde (8OL) differs from LSD oniy in the presence of a bromine atom at carbon No. 2. This material is s potent antl-serotonin in yitro. Rothlin et al have reported that the doses of BOL 20 times greater than those of LSD do not Induce a psychosis in man. Since, IIke LSD, BOL reverses prolongatlon of hexobarbltal sleeping-flme by serotonln It must be presumed that the drug does reach the central nervous system. These experiments have been lnterpreted as not favoring the hypothesls which attrlbutes the LSD psychosls to inhibltion of brain serctonin. by LSD.

It oceurred to us that, because of the chemical similarlty of the two compounds BOL might possibly block the LSD reactlon. It was first necessary to re-evaluate the acute effects of this substance In man.

Subjects used were 15 Negro male addicts who hed been abstlnent from oplates for at least three months. All of these subjects had had considerable experience with the subjective effects Induced by LSD.

BOL was glven orally. lniflal doses were 5 mcgm./kg. of bodyweight, which was Increased In step-wlse fashlon, as the experiments proceeded to almost 0 megm./kg. The highest totol dose given was 8 mg.

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ACUTE EFFECTS OF LARGE DOSES OF BOL IN MAN

5

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Observations. The following observations were made two hours before and for one hour after the administration of BOl: rectal temperature, resting pulse rate, respiratory rate, resting systolic and diastolic blood pressures, threshold for elicitation of kneejerk, puplllary size, modiflcatlon of the Abromson-Jarvik questionnafre, and a short psychiatrtc examinatlon.

Resuits. Doses of BOL up to 4 mg./70 kg. caused neither subjective nor objecttve effects. Doses of 4 mg. or more per 70 kg. of bodyweight Induced mlld effects, which are presented in the table. These included small increases In systolic blood pressure, dlameter of the pupil, and In the threshold for kneelerks. The "mental" symptoms. Included neryousness, nausea, chilly sensatlons, blurred vlslon and, In some patlents, colored lights and hallucinations. Reactions are descrlbed as resembling those of a very small dose of LSD and were mllder than the effects of O.5-l.5 mcgm. of LSD In the same subjects (see tablel. lt Is estimated that the effects are no greater in degree fhan those lnduced. by O.25-0.5 megm./kg. of LSD. BOL Is, therefore, at least 100-200 times less potent than LSD. It is, in fact, far less potent than lysergic acid monoethylamide [LAE).

Discussion. These results confirm those of Rothltn and do not favor the hypothesis which attributes the LSD psychosis to a "deficlency" of serotonin.

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[PAGE 6]
3 Figures are means on 15 subjects ± standard errors.

EFFECTS OF 5-8 MG./70 KG. OF D-2-BRUM-LYSERGIC ACID DIETHYLAMIDE

1 Average dose of B0L = 6.0 mg./70 kg. = 86 mcg./kg.