The Psychedelic Model of Schizophrenia: The Case of N,N-Dimethyltryptamine
by Gillin, Kaplan, Stillman & Wyatt
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EXCERPTS from:
The Psychedelic Model of Schizophrenia: The Case of N,N-Dimethyltryptamine
by Gillin, Kaplan, Stillman & Wyatt
Abstract:
The authors review the research on N,N-dimethyltryptamine (DMT) as a
possible "schizotoxin". DMT produces psychedelic effects when administered
to normal subjects, the means are present to synthesize it in man, it has
occasionally been found in man, and tolerance to its behavioral effects
is incomplete. Hovever, DMT concentrations have not been proven to differ
significantly in schizophrenics and normal controls. Also, in vivo synthesis
of DMT has not been convincingly demonstrated, and the psychological
changes it produces do not closely mimic the symptoms of schizophrenia.
The authors conclude that more data are necessary before the validity
of this theory can be determined.
DOES DMT PRODUCE SIGNIFICANT SCHIZOPHRENIC-LIKE SYMPTOMS?
In 1956 Szara (9) found that the effects of DMT on 20 normal volunteer
subjects were similar to those of LSD and mescaline: visual illusions and
hallucinations, distortions of spatial perception and body image, speech
disturbances, and euphoria. A striking finding was that the effects of DMT
began within 5 minutes and ended within 1 hour after injection. Similar
results have since been reported by Rosenberg and associates (10) and Turner
and Merlis (5).
In order to reexamine the psychological effects of DMT and to correlate them
with pharmacokinetic aspects, we administered .7mg/kg of DMT intramuscularly
to 15 make volunteers. Each subject was an experienced user of LSD,
mescaline, or other psychedelic substances who expressed an intention to
continue using these agents in the future. All subjects were intereviewed by
two psychiatrists and were given a complete medical history and examination
prior to testing in order to ensure the absence of psychiatric and physical
impairment.
Like previous investigators, we found that DMT was a hallucinogen with rapid
action and a short duration of effect. Psychological changes were evident
within 5 minutes of injection, peaked at about 10 to 15 minutes, and ended
within 45 to 120 minutes. The major psychological effects are shown in table
1. The subjects became so uncommunicative and withdrawn during the drug
experience that we were forced to inquire about the subjective effects with
simple "yes-no" questions. Although all subjects reported visual distortions
and illusions, these were color or spatial distortions rather than formed
visual hallucinations. Only 1 subject reported an auditory hallucination, a
"buzzing bee" in his ear. We did not observe formal loosening of
associations, although several subjects seemed to have thought blocking. Two
subjects had paranoid symptoms that lasted less than an hour.
These psychological changes were accompanied by mydriasis, tachycardia, and
increased blood pressure. Blood levels of DMT (see figure 2), assayed by a
gas chromatographic-mass spectrometric (GC-MS) isotopic dilution technique,
closely paralleled the psychological and autonomic changes (11). Peak
concentrations of DMT, which averaged approximately 100 ng/ml, were reached
about 10 to 15 minutes after injection; the concentration then fell rapidly
to baseline, undetectable levels within about 45 to 120 minutes after
administration.
TABLE 1.
Subjective Effects of DMT Experienced by 15 Normal Volunteer Subjects
Subjective Effects Percent<br>
Visual hallucinations 100<br>
Hallucinations with eyes closed 100<br>
Movement of surroundings 93<br>
Difficulty talking 93<br>
Difficulty describing feelings 93<br>
Relaxation 93<br>
Difficulty concentrating 93<br>
Colors seem brighter 87<br>
Excitation 87<br>
Thinking faster 87<br>
Dry mouth 87<br>
Tenseness 80<br>
People look different 75<br>
Depersonalization 60<br>
Nausea 60<br>
People have orange-red hue 53<br>
Hallucinating "real things" 27<br>
Paranoia 20<br>
Auditory hallucinations 7
DOES TOLERANCE TO DMT DEVELOP?
Tolerance to LSD, mescaline and psilocybin develops rapidly in man and
animals, for some if not all behavioral effects.
In our initial efforts, we found that tolerance did not develop to
unconditioned behavioral and EEG effects of DMT in cats administered DMT
twice daily for 15 days or every 2 hours for 24 hours (34). Also, lack of
behavioral tolerance has been reported in squirrel monkeys given DMT once
daily for 38 days (35).
More recently, we studied the issue of tolerance in normal male volunteers
who received 0.7 mg/kg of DMT intramuscularly twice daily for 5 days.
Repeated administration did not consistently alter the peak blood
concentration of DMT; autonomic changes in pupil size, pulse, or heart rate;
the number of psychological items changed in a psychological scale; or the
frequency of errors in a test requiring the subject to cross out a specific
number in a list of random numbers. Three of the 4 subjects reported
diminished subjective "highs" on a scale of 0 to 10 after two to four
injections of DMT, but their subjective responses were variable from trial to
trial and did not indicate a general loss of responsiveness to DMT. Rather,
these subjects exhibited a variable or aperiodic partial tolerance to DMT.
This pattern is reminiscent of Koella and associates' report of a cyclic
change in ambulation produced by LSD in goats (36). Further studies,
including longer or more frequent trials with DMT, are neccesary to fully
evaluate this phenomenon.
This type of variable tolerance has also been reported recently by Kovacic
and Domino(37), who studied the supressive effects of DMT on the operant
behavior of appetitively conditioned rats who were given DMT every 2 hours
for periods of up to 21 days.
Boszormenyi and Szara (38) reported that schizophrenics do show diminished
responsiveness to DMT, this may result from increased metabolism or variable
tolerance resulting from long-term endogenous synthesis of DMT.
(5) Turner WJ, Merlis S: Effect of some indolealkylamines in man.
Arch Neurol Psychiatry 81:121-129, 1959
...
(9) Szara S; Dimethyltryptamine: its metabolism in man:
the relation of its psychotic effect to serotonin metabolism.
Experientia 12:441-442, 1956
(10) Rosenberg DE, Isbell H, Miner EJ; Comparison of placebo,
N,N-dimethyltryptamine, and 6-hydroxy-N-methyltryptamine in man.
Psychopharmacol 4;39-42, 1963
(11) Kaplan J, Mandel LR, Stillman R, et al; Blood and urine levels of
N,N-dimethyltryptamine following administration of psychoactive
doses to human subjects. Psychopharmacologia 38;239-245, 1956
(34) Gillin JC, Cannon E, Magyar R, et al; Failure of N,N-dimethyltryptamine
to evoke tolerance in cats. Biol Psychiatry 7;213-220, 1973
(35) Cole JM, Pieper WA; The effects of N,N-dimethyltryptamine on operant
behavior in squirrel monkeys. Psychopharmacologia 29;107-112, 1973
(36) Koella WP, Beaulieu RF, Bergen JR; Stereotyped behavior and cyclic
changes in response produced by LSD in goats.
Int J Neuropharmacol 3;398-403, 1964
(37) Kovacic B, Domio EF; Tolerance to behavioral effects of
dimethyltryptamine (DMT) in the rat (abstract). Fed Proc 33;549, 1974
(38) Boszormenyi A, Szara S; Dimethyltryptamine experiments with psychotics.
J Mental Sci 104;445-453, 1958
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