KURT

A STUDY

ON

SALOMON,’

BEVERLY

Biochemical

Research

MESCALINE

Laboratory

WESCOTT of the

Washington

Mescaline,

3 ,4

,

modality.

psychiatric are

fate

a psychological

in man

concerning

the

THOMAS

AND

been

but

available,

physiology

hallucinations

only

very

few

to our

visual

in the

investigated

while

of the

Radiology,

13, 1948

extensively

of view,

and

Missouri

produces

are

THALE

of Neuropsychiatry Louis,

December

has point

of mescaline

data

no

St.

publication

phenomenon

SUBJECTS’

GABRIO,’

5 , trimethoxyphenylethylamine, This

and

chemical

for

HUMAN

Departments

University,

Received

visual

IN

from

studies

of the

knowledge,

mechanism

a

there

in response

to

mescaline.

The presence

hallucinations of methoxyl

produced by groups in the

amine,

a homologous

substance

lucinations. hallucinations acid, the phenomena chain

also

Slotta

this drug mescaline

without

However, the methoxyl since Slotta and MUller oxidation in man. It

in

product is evident,

vitro

plays and

an

essential

Muller

methoxyl

of mescaline, therefore,

that

are that

does

not

cause

able

to isolate

Richter

from

the

group Their

(2)

showed

groups renders the mescaline investigation of mescalinized with two points: 1. A quantitative

of the methoxyl groups medication to determine with visual hallucinations. Six

EXPERIMENTAL. given

:

1 and

200 mgm.

This investigation the Simon Grant

eration of American ‘Present address:

New

York. mescaline

of

mescaline.

if changes

subjects

mescaline

were

sulfates was

for

side

urine

of mescaline-fed

only, thus experiments

that

after

oral

humans

indicating revealed

that some also that

decomposition process. excreted unchanged in ingestion

of mescaline

molecule more resistant to human subjects, we were estimation of the urinary

oxidation. concerned excretion

2.

and after correlated

in this

used

(137.8

Color perception before physiological function are

in this investigation.

mgm.

in the urine with the presence of

base)

The following

to one schizophrenic

female;

doses

were

300 mgm.

supported

in part by funds of the Frank Phillips Foundation, Presented in part at the annual meeting of the Fedfor Experimental Biology, Chicago, Illinois, May 19-23, 1947. of Rochester School of Medicine and Dentistry, Rochester,

Research.

Societies University

sulfate

hal-

does not produce hallucinatory the amino group in the

hydrochloride (191 mgm. base), 58 per cent was excreted unchanged about 18 hours after ingestion. This observation is in agreement findings of Bernheim and Bernheim (3), and Blaschko (4) that the methoxyl In this primarily

the

not sufficient to produce trimethoxyphenylacetic

acid is not a step in the in vivo whether or not mescaline was

However,

a great extent to since beta-phenylethyl-

part.

were

trimethoxyphenylacetic They did not investigate urine.

to

groups,

groups alone (1) showed

a substance which contained one methoxyl of the mescaline ingested is metabolized.

the

are due molecule,

was

generously

supplied 455

by the Hoffmann-La

Roche

Company.

456

K.

SALOMON,

B.

W.

GAI3RIO,

AND

T.

THALE

mescaline sulfate (206.7 mgm. base) to one schizophrenic male and one schizophrenic female; 400 mgm. mescaline sulfate (275.6 mgm. base) to two schizophrenic males and one neurotic male. All doses were given orally in the morning while the subjects were in a fasting state. Detailed information concerning the subjects used, the hallucinatory responses, and changes in visual imagery, will be published elsewhere. 1 . Urinary excretion of methozyl groups. Urine specimens were collected prior to medicstion and at stated intervals for 18 hours (2, 4, 6, 10, 14, 18) thereafter. A 40 cc. aliquot from each urine sample was extracted for mescaline by first adjusting the pH to about 9 with KOH and then extracting twice with an equal volume of a 1 : 1 mixture of toluene and isobutylalcohol. Preliminary experiments had shown that this mixture was superior for the extraction of mescaline. The extract was dried with anhydrous sodium sulfate. An appropriate aliquot of the dried extract was used for the determination of methoxyl groups following a modification of the Zeisel method (5). The validity of the forementioned method was tested for known amounts of mescaline added to urine samples. The error of recovery was plus or minus 4 per cent. Methoxyl groups were never found in urines of nonmedicated subjects. After the content of methoxyl groups of aliquots of urines was determined, the remainder of all the urine samples of one particular patient was combined and extracted after alkalinization with the toluene-isobutylalcohol mixture. These extracts were used for the identification of mescaline and the investigation of the presence of possible breakdown products. Mescaline was isolated and identified as the picrate by the following method. The solvent (toluene-isobutylalcohol) was evaporated in vacuo. The browi residue thus obtained was treated with hot water, and the undissolved material was filtered off. The latter was dried in vacuo and then developed a resin-like consistency. From the filtrate, crystalline mescaline picrate was obtained and purified by repeatedly dissolving in acetone and precipitating with petroleum ether. Mescaline picrate thus obtained melted at 217-220#{176}C. uncorrected. The mixed melting point with an authentic sample of synthesized mescaline picrate showed no depression. A sample of the resin-like material mentioned above was analyzed for the presence of methoxyl groups. The Zeisel test revealed that the material contained methoxyl groups. In addition a qualitative test for methoxyl and other alkoxyl groups’devised by Tobie (6) was applied to the resin-like material and gave a positive result. Identification of the methoxyl-containing substance or substances present in the resin-like material was not attempted. 2. Color perception. Color perception was tested within two days prior to the administration of the drug and again 30 to 180 minutes after the drug was given. The apparatus used was devised by H. B. Molholm4 who will describe it in a forthcoming publication. It is based on the principle that when lights of different intensity are seen in rapid alternation, the effect is one of flicker. When the intensity of the two sources is nearly equivalent, the flicker disappears, and the subject perceives one steady light. In this device a single source was used to produce a white light of constant intensity, and a second beam alternated with it. The second beam was modified by passage through a variable density Eastman film, manipulated by the subject. In addition, the second beam could be presented untinted or could be passed through a color filter. The following filters were used: nile green, sextant green, emerald green, lighthouse red, red-yellow, and blue. The variable light was always presented in greater intensity than the fixed. The subject was instructed to turn a dial which increased the density of the film. When he signified that the light no longer flickered, he was told to reverse the movement and find the point at which flicker was barely apparent. This was used as the end point. The threshold for each color was determined three to five times at each testing and the mean value was used, numbers being read from a scale fixed to the variable film. The threshold for white was We investigation.

wish

to

thank

Dr.

Moihoim

for

making

this

apparatus

available

to us

for

this

MESCALINE

determined corrected

457

HUMANS

before and after each battery of color tests. for any shift in the threshold for white, the latter

illumination, the speed flicker as distinguished RESULTS

AND

various

data

of

methoxyl

the

IN

mescaline

of the motor which from color sensitivity.

1.

COMMENTS.

obtained

in this groups

excreted

alternated

Urinary

are

determined

are

in the

excretion

of

shown

to

bg,n.

P. Ja

C. S..

A’

,

93.6 63.0 70.5

55.5 43.4 63.2

of material

TOTAL ILETHOXYL

VOLUME

mgm.

resin-like

corn pounds

Methoxyl

URINE

IN

18

EXCRETED

118.5 118.5 118.5 88.9 88.9 59.3

18

IN

‘

METHOXYL EXCRETED

‘

METHOXYL

HOURS

TO

INGESTED

cc.

mgtu.

per cent

990 975 1520 2195 690 665

43.2

36.4

31.0

26.1

16.3 34.7 14.5 5.1

13.7 38.9 16.2 8.6

mgm.

275.6 275.6 275.6 206.7 206.7 137.8

majority

representative

the

HOURS

M M M M F F

The

I

DOSE

Et

The

groups.

I.

be

However,

nethoxyl-containing

Mescaline

SEX

SUBJECT

in table

considered

urine.

TABLE Urinary

of met hoxyt

excretion

investigation

unchanged

All color determinations were accounting for changes in the lights, and the ability to perceive

‘Schizophrenic.

t Neurotic. TABLE Change DOSE MESCALINE

in

color

EMERALD GREEN

II

perception lIE ,

after

GREE

N

mescaline

ingestion

SEXTANT N

RED-YELLOW

GREEN

LIGHTHOUSE

BLUE

-5

-15

mgm.

E

‘

P J

275.6 275.6

-4 39 -17 -15 -3 -6

275.6 206.7

C S A

206.7 137.8

‘

-10

-1 -6 -5 -14 -10 -9

-2 1 0

0

0 13

-14

-12 -4

‘

-7

-8

-24

-9 -1

-22 -16

4 6

‘

-22

-6 -2

which remained after water the toluene-isobutylalcohol cent of the total methoxyl

extraction of tile residue of the combination of all extracts of all the subjects contained less than 10 per groups extracted. It might be assumed that this

resin-like mescaline.

one or conclusions

molecule Essentially

material contained Therefore, no to which these this finding

claimed that Although tO breakdown

not only

methoxyl groups is in accordance

all of the mescaline a small percentage

products

a mixture may be

of mescaline

of the drawn

breakdown concerning

in the resin-like material with that of Slotta and

ingested of the according

leaves methoxyl

the

to our

body groups experiment,

products the type are Muller

unchanged. excreted

of of

attached. (1) who belonged

we have

pre-

458

K.

SALOMON,

B.

W.

GABRIO,

ferred to express The percentage

the excretion of the drug of total methoxyl groups

groups

ingested

varied

values

are

than

lower

excretion mescaline

be

indicated

that

In

addition,

explained

by

extract The

the

value

whereas average

medication

subjects

the

subject.

fact

agreement

It is worth of each urinary

had

8.6 and

we

with

mentioning

the

groups of our

maximum

at this

point

2.

Color

perception.

perception. green, and ceived

Table

mescaline following

II shows

ingestion. the drug.

that

the

mgm.

275.6

mescaline

were greater were ranked

of hallucinations,

amount

and

perception,

change

with from

individual

Sizable,

doses

but were

not associated

statistically with

significant more

the

vivid

intense

increase

Thus

the

by large

Vividness

before as the

response for

color

a decreased a decrease in for who

emerald also re-

The

decreases

dose,

vividness

in blue.

change subject

in color having

the

1 for that variable, the subject ex2, etc. Each of these variables was rank order method. be significant at the 5 per cent level: perception

-

.94

-

.89

+ .94

correlations hallucinations,

suggested greater

that

absolute

excretion of methoxyl groups and, to a lesser degree, with total excreted. The initial suppression of urine was compensated flow in the latter hours of observation. On the other hand, particularly for lighthouse red and nile green, was more impaired than

case

in scores

average

post

Richter’s

subjects of view

indicates is toward

excreted,

urinary

hallucinatory

in each

changes

of

might

hours of

hallucinatory

value trend

color.

in color green green

of hallucinations-Change of hallucinations-Nile in color perception-Nile

most

the smaller doses. following variables:

groups

greatest excretion would receive a rank of creting the next greatest amount a rank of correlated with each other by means of the The following correlations were found to Vividness Vividness Change

six

a series of normal a metabolic point

corrected

a slight receiving to the

of methoxyl of each

at

showed a marked increase while another schizophrenic

showed for those according

the

period

of the

time

occurred

A negative The general

One of the schizophrenics a slight increase in blue,

in perception All subjects

the

These while

of data

groups

excretion

difference mentioned by Slotta and MUller between to mescaline of normal and schizophrenic subjects. perception after color perception

sets

present. subjects

subject as reported to the observers excretion of methoxyl groups.

Further experimentation along this line well as schizophrenic subjects may explain

cent. but

in this

two

methoxyl

the amino of mescaline

per cent,

excreted

in these

determined

38.9

groups. methoxyl

at 18 hours after medication similar excretion curves of our

all been

difference

methoxyl to total

of

of 58 per

that line,

not

TRALE

I in terms in 18 hours

between

showed the zero

mescaline that

T.

by Richter

quantitative

Richter meaured peak excretion

is in

response the peak

the

the

in table excreted

reported

curve of Richter’s subject excretion had approached

subjects time.

among the

AND

the

larger

and relative

amount of urine for by a greater color perception, by small doses

ones. of hallucinations

was

definitely

not

associated

with

impairment

of

MESCALINE

color

perception

change The suggest

any

as

is shown

by

IN

the

459

HUMANS

large

negative

in color perception and with nile green. correlations involving average color change

that particular

the

effect range.

is manifested

throughout

the

correlations

and

with

the

entire

individual

range

average colors

rather

than

in

over

an

SUMMARY

The

urinary

18-hour gestion

excretion

of methoxyl

period in 5 schizophrenic of mescaline sulfate.

was followed

groups

subjects Mescaline

quantitatively

and 1 neurotic subject after the inwas identified in the urinary extracts,

and the majority of methoxyl groups determined present as mescaline. Methoxyl groups belonging mescaline were found in a resin-like residue of the

may be considered to to breakdown products urinary extract.

Orally lucinations

mgm.) Large

administered mescaline sulfate (200-400 and impairment of color perception.

with

greater

The

greatest

excretion impairment

smaller

doses.

We -nterest

wish to in this

thank Dr. investigation.

and

more

of color

Edwin

vivid vision

F.

hallucinations

was observed

Gildea,

Dept.

produced doses were than

in those

were

visual halassociated small

subjects

of Neuropsychiatry,

REFERENCES 1. SIorrA,

2. 3.

BERNHEIM,

4.

BLASCHKO,

RICHTER,

5. J. Assoc. 6. T0BIE,

be of

K. H., AND MULLER, J.: Ztschr. f. Physiol. Chem., 237-238: 14: 1936. D.: Biochem. J., 32: 1763, 1938. F., AND BERNHEIM, M. W. C.: J. Biol. Chem., 123: 317, 1938. H.: J. Physiol., 103: 13P, 1944. Official Agric. Chem., 22: 100, 1939. W. C.: md. Eng. Chem. (Anal. Ed.), 15: 433, 1943.

doses. receiving

for

his