Clinical Investigation of EA 1729 (CRDLR 3074)

Introduction

(S) CLINICAL. INVESTIGATION OF EA 1729 (U)

I. (5) INTRODUCTION.

(S) The ability of EA 1729 (lysergic acid diethylamide, LSD25) to

produce aberrant mental behavior in humans came to the attention of the U. S. Army Chemical Corps about 1947, and this material has been one of the most promising CW incapacitating compounds since that time. It is the most potent of the incapacitating agents studied to date and has the very important attribute of a large safety margin between the incapacitating and lethal doses.

(U) The objectives of the project under which the reported work was

carried out are:

1. To supply fundamental knowledge concerning the nature of the mechanism and sites of action in man of CW agents and of prophylactic and therapeutic drugs.

1. On the basis of this information, to suggest the development of novel or more effective agents, as well as to develop diagnostic, protective, antidotal, and therapeutic devices and procedures applicable to poisoning by such compounds.

(U) A research and development program on agents that temporarily

incapacitate but do not kill requires a more complex structure of research than is necessary for a program on lethal agents. Quantitating the lethality of a compound does not require the extensive knowledge of the physiological and pharmacological effects of the material that is required when dealing with an incapacitating compound, especially one that produces effects on the mind. It has therefore been necessary to extend the program of these Laboratories to include studies that will yield the more detailed information on incapacitating agents required to meet the program objectives.

(C) Because of its profound effect on the mental processes of man,

EA 1729 is of interest to investigators in many parts of the world. It has been used extensively to produce experimental model psychoses that sometimes mimic the acute schizophrenic patient. The survey of open publications continues, keeping the Laboratories cognizant of the work being done and permitting an economy of effort. These Laboratories have restricted studies to those questions that would probably not be considered by private research because they are especially applicable to the search for and evaluation of CW agents and the treatment of casualties therefrom.

(U) Since the establishment of the Medical Research Volunteer Program

in 1955, numerous studies in volunteers have yielded sufficient data to delineate essentially the physiological and psychological effects of this material in man. Dose-response relationships also have been determined, and the effectiveness of a number of antidotal and blocking agents has been evaluated.

(C) The effect of EA 1729 on the ability of small groups of individuals

to participate in activities that require group cooperation has been assessed. These demonstrations were followed by field tests designed to* measure this agent's disorganizing and disrupting influence on a disciplined military unit.

(U) An extensive and systematic investigation of the nervous system of

lower animals has been undertaken as a step toward arriving at a more complete understanding of the mechanism and site of action of psychotomimetic agents in man. The continuing need for improved methods of recognizing potent psychochemical agents in animals, in order to permit the effectual and expeditious evaluation of the large number of compounds that the Chemical Corps must screen, motivated many of the animal studies reported.

(C) The potency of several analogs and homologs of EA 1729 has been

studied to determine whether they merit consideration as CW incapacitating agents.

(U) The data reported fall into two categories:

1. Work that has been done in these Laboratories or performed in cooperation with other military organizations which is being reported for the first time.

1. Work in universities by contractors, which may have been reported in the open literature, as a classified contractor's report, or in a collaborative study at this facility.

[Objectives and background of the Army Chemical Corps program on EA 1729 continue; paragraph break only, no text omitted here]

Human Studies: General and Psychological Effects

II. (C): HUMAN STUDIES.

1 2 4

A. (C) Clinical, Physiological, and Psychiatric Studies. ' '

(C) A conservative estimate is that approximately 3, 000 doses of

EA 17 29 have been given to some 1, 500 individuals either in clinical studies at Army Chemical Center, in group demonstrations and exercises conducted at other military installations, or in contract programs at the University of Maryland Psychiatric Institute; Tulane University, Department of Neurology and Psychiatry; New York Psychiatric Institute; and University of Washington Medical School, Department of Pharmacology. These studies indicated that

the effects elicited by EA 1729 increase more or less proportionately to the dosage, up to 2/jig/kg. Above this dose, there was no clear-cut relationship between dose and response. Subjects have had very distinct effects from only 25 jitg(total dose), but they were relatively mild compared with those produced by higher doses. Most subjects received total doses of approximately .

70 to 150 fig. At this dose range, the majority of men had marked effects.

After considerable numbers of clinical trials, it was found that, for field demonstration purposes, total doses of 100 to 150 fig (without strict regard to body weight) were sufficient to cause incapacitation.

(C) The general physiological effects of EA 1729 are mild, consisting

of pupillary dilatation and a slight increase in blood pressure and pulse rate. Nausea and dizziness and an increase or a decrease of appetite are also reported by some subjects. The only consistent neurological change noted was an increase in deep tendon reflexes, such as knee, ankle, wrist, and elbow hyperreflexia. The major and most consistent physiological effect was disturbance of visual perception, evidenced by distortion of shapes and objects, and, subjectively, by hallucinations of colors and geometrical patterns. The latter were more pronounced in darkened rooms.

(U) Psychological changes were, consistent and profound. Almost all

the subjects had difficulty in concentrating, making decisions, and communicating. The particular type of observed reaction depended on the total personality of the individual. The broad term "personality" in this sense means the evaluation of psychological and psychometric testing, as well as the psychiatric evaluation of the individual's ability to cope with his social environment, either in military or in civilian life.

(U) The observed reactions ranged from tenseness to panic and from

friendliness to (rarely) verbal manifestation of aggressiveness without physical action.

Field Demonstration of Effects of EA 1729 in Humans

B. (C) Field Demonstration of Effects of EA 1729 in Humans. .

(C) On 17 December 1957, a demonstration was conducted primarily

to determine the problem of controlling a small group influenced by EA 1729 and also to provide a filmed record of the effect of the agent.

•

(C) Nine soldiers were ordered by a typical Army drill sergeant to

"fall in." The squad responded like well-trained soldiers; the drill sergeant's commands were obeyed accurately and with precision. After the squad was given 2 fig/kg of EA 1729 orally and the undrugged drill sergeant again ordered the men to fall in, the response was entirely different. The men were euphoric and disorganized; commands were either disregarded or obedience was haphazard and indifferent. In a marching exercise, the men started fairly well but soon began to break ranks and straggle out. When a second drill sergeant who was drugged was given command of the squad, he did not perform effectively. In fact, when an officer ordered him to drill the squad, he responded with, "You want 'em drilled? You drill 'em! "

(C) On 18 December 1957, in another demonstration, eight volunteers

were each given 2 ^ig/kg of EA 1729 orally. This group, before receiving the drug, had defeated another group in a volleyball game by a score of 21-5.

After receiving the drug, they again defeated their undrugged opponents 21-17.

It is believed that one individual, an Army private who demonstrated exceptional leadership, was instrumental in holding the group together. When he was removed from the game, there was a tendency for his team to slacken play.

(U) These two demonstrations indicated that individual reactions to this

agent are varied: a drugged group can continue simple functions, but there is reduction in their effectiveness and teamwork is less efficient. '

[Dose-response pharmacology, physiological measurement tables (blood pressure, pupillary size, nausea/vomiting incidence), tracking and self-rating test results, personality and body-image studies, and the account of the demonstration to Chemical Corps School personnel at Fort McClellan are omitted.]

Demonstration of Effects of EA 1729 to XVIII Airborne Corps, Fort Bragg, North Carolina

1. (C) Demonstration of Effects of EA 1729 to XVIII Airborne

Corps, Fort Bragg, North Carolina.

(C) After enough experiments in individual and small groups of

volunteers had been carried out to ascertain that large-group studies were feasible, arrangements were made by CG, USCONARC, to conduct a test at Fort Bragg, North Carolina, in September 1958. Chemical Corps personnel supplied the necessary medical support for all test operations, but operational evaluation of the tests was made by members of the XVIII Airborne Corps.

All scoring was based on standard artillery proficiency tests. Such an evaluation allows some judgment to be made of the military effectiveness of the agent. All evaluations of test results that appear in this report were furnished by the evaluation team of the XVIII Airborne Corps.

(U) Of the 70 men from the XVIII Airborne Corps Artillery who volunteered to compose the teams, 11 were rejected for either psychiatric or medical reasons. The crews selected represented above-average, skilled Army units, with exceptional morale. The tests were conducted in the field under anticipated operating conditions, with only minor deviations from normal procedure to insure the safety of individuals and to allow for photographic coverage.

(C) The total dose of 150 pg/man of EA 1729 was selected on the basis

of previous clinical experience as a dose which would (1) produce measurable effects that would endure for the period of the test; (2) permit the degree of physical activity necessary; and (3) not be so severe as to result in a termination of the test before missions were accomplished. Although several of the volunteers received the compound more than once during the 5 -week testing period, there was no evidence that the performance of these men was improved by previous drug experience.

(C) A double- blind procedure was used on all tests; EA 1729 in water

and plain water as placebo were administered to the volunteers.

(U) The criteria used for selecting the types of teams to be used in the

test were;

(U) a. Team missions should require the collective efforts of

the individual team members to produce results.

(U) b. The success or failure of the accomplishment of the

team mission should have a maximum effect on related operations.

(U) c. Maximum opportunity to supervise the safety of individuals composing the team should be possible.

(U) Two of each of the following groups participated in the tests outlined

below:

(1) (C) Meteorological Section,

The mission of this section is to furnish necessary weather data' that will affect artillery projectiles or rockets in flight and will furnish winds- aloft data for prediction of fallout after an atomic burst.

• (C) Data obtained by this section are disseminated to artillery units through out the Corps sections and can affect the firing accuracy of several artillery units.

(C) At 0820 on 3 September 1958, EA 1729 in water was administered

to one of the meteorological sections; the other section received placebo.

Both sections were assigned the mission of making weather balloon. releases at 0830, 0930, and 1030 hours and reporting weather data gained from the releases. The section which received placebo disseminated completed messages at 0900, 1000, and 1100 hours. The drugged section disseminated a completed message at 0900 hours, but* was unable to produce any part of a message after the next two balloon.releases.

(U) Identical results were achieved when the same procedure was

followed on 9 September 1958, the only change in the procedure being that the drugged and control sections were reversed.

(C) The evaluation team of the XVIII Airborne Corps

concluded from this phase of the test that a meteorological section subjected to attack with EA 1729 would not be able to fulfill its mission.

(2) (C) Survey Section.

(C) The mission of this section is to furnish survey control data

needed by artillery units to locate firing positions and targets.

(U) On 4 September 1958, both survey sections were given data for a

survey control point and the mission of extending this control to another area. Under normal conditions successful accomplishment of this mission should be achieved within 2-1/2 hours.

(C) Immediately after EA 1729 and placebo were administered, the

teams began survey operations. The drugged team required 5 hours 50 minutes to complete the task. The accuracy of the survey was within allowable tolerances only because the recorder was undrugged and was able to assure that all angles and taped distances were rechecked until he was certain of their accuracy, ('When the test was repeated on 10 September and all members of the same section were drugged, the team required 3 hours 40 minutes to complete the survey, and accuracy was not within tolerable limits..} The undrugged (control) section completed its mission in 2 hours 5 minutes, and the results were accurate.

(C) The evaluation team of the XVIII Airborne Corps

concluded that although a survey team subjected to attack with EA 1729 might be able to produce acceptably accurate results, the time required for completion of even the simplest type of survey would be so great as to make the survey section's accomplishment of its mission unsatisfactory.

(3) (C) Fire Direction Team.

(C) The mission of this section is to control battery or battalion firing

by converting information furnished by an observer into commands for guns to fire; to convert without adjustment data furnished by survey and meteorological sections into commands to deliver fire on targets when no observer is available.

(C) On 16 September 1958, the two fire direction teams were given a

series of identical fire missions that were typical of their normal operations. An hour after receiving EA 1729, the drugged team was much slower in processing fire commands than the control section. Although the members of the drugged team were able to perform the necessary computations for delivering area-type fire on target with acceptable results, they could not fire precision missions with any degree of accuracy, mainly because of their inability to concentrate.

(U) _ Identical results were obtained when the test was repeated on

23 September 1958, the only change in procedure being that the drugged and control teams were reversed,

(C) The evaluation team of the XVIII Airborne Corps

concluded that an artillery fire direction team would be unable to perform its mission satisfactorily while experiencing the effects of EA 1729.

(4) (C) 40-mm Antiaircraft Automatic Weapons Gun Section.

The mission of this section is to provide air defense for forward combat arms and to attack and destroy hostile targets on land or water, as required,

• (U) It should be borne in mind that the recorder was not drugged in the

test on which this conclusion is based. That this would be the case in an actual situation is not probable.

(C) On 5 September 1958, the 40-mm antiaircraft automatic weapons

gun sections were emplaced on a ridge which afforded a field of fire in all directions. Cameras were mounted parallel. to the gun tubes, and an L-19 aircraft was used as the target. The tracking by the undrugged group was smooth and continuous, and the gun camera film indicates this group was able to accomplish its mission of defense against hostile aircraft. The tracking by the drugged group was jerky and not coordinated; the gun camera film proved that the only hits obtained by this group were accidental.

(U) When the test was repeated on 11 September, with the drugged and

control groups alternated, similar results were obtained.

(C) The evaluation team of the XVIII Airborne Corps

concluded that a 40-mm antiaircraft automatic weapons gun section subjected to attack with EA 1729 would be unable to track an aircraft that was using evasive tactics and, therefore, would not be able to accomplish its mission of furnishing antiaircraft protection.

Overall Results

(C) The over-all results of the tests conducted at Fort Bragg (XVIII

Airborne Corps) indicate that an artillery unit attacked with EA 1729 would be unable to deliver artillery fire effectively in support of ground operations.

[A further field demonstration at the U.S. Army Special Warfare School, polygraph and sensory-isolation demonstrations, animal studies, biochemical studies, and the pharmacological-summary subsections are omitted.]

Discussion

VI. (C) DISCUSSION.

(C) In 1955, the chairman of the Technical Advisory Panel on Biological and Chemical Warfare'^ appointed an ad hoc study group ( the so-called Wolff Committee) to examine the problem of psychochemical agents , with a view to advising the Chemical Corps in regard to its future program. Based on an intensive investigation into the preliminary work the Corps had completed on psychochemicals and a survey of the open literature, the Wolff Committee recommended that:

(C) 1. A quasi-realistic experiment (outlined in detail in its report)

be carried out with EA 1729 and volunteer units as soon as practicable.

(C) 2. The potential and promise of the use of psychochemical

agents in warfare be re-evaluated upon completion of the experiment,

(C) 3. Increased efforts be placed on screening chemicals in the

lysergic acid class to find a substitute for EA 1729.

(U) 4. Conditioned reflex studies, using psychochemical agents, be

made on dogs and additional higher animals other than man.

(U) 5. The dog or similar larger animals be employed in long-term

intoxication and lethal-dosage studies.

(C) All of the Wolff Committee's recommendations concerning EA 1729

have been carried out and are reported either in this document or in those mentioned in the bibliography.

(C) EA 1729 was selected as the model to be used in studies to provide

some conception of the worth in warfare of materials that produce aberrant mental behavior because of its known action and because a tremendous amount of work already had been done with this compound in psychiatric research with humans.

Office of the Assistant Secretary of Defense, R&D

(C) Among the conclusions of the Wolff Committee is the following;

The promise offered in this field can be determined . only by assaying the effect of psychochemical agents

on military units. If LSD25, used as outlined in the experiment, should fail to produce disorganizing and disrupting effects on the military unit, it would be evident that there is no military promise in this field.

However, if the use of these agents should, under the specified conditions, produce serious disruptions in the ability of the unit to carry out its missions, then it could be reasonably stated that these agents offer great promise for use in military operations,

(C) The Fort Bragg field test described in this report is comparable to

the experiment recommended by the Wolff Committee and certainly proved that EA 1729 will "produce serious disruptions in the ability of the unit to carry out its missions, " If more realistic doses had been used (250 jug to 300 jug total per man), the men probably would have been so incapacitated that they would never have attempted to perform their mission requirements.

[The remainder of the Discussion (effective dose by route, safety margin, type and degree of incapacitation, species variation), the one-paragraph Conclusions, and the Literature Cited list are omitted.]