The Psychotomimetic Drugs: An Overview
Jonathan O. Cole, M.D. & Martin M. Katz, PH.D.*
from: Journal of the American Medical
Association, Vol 187, No. 10, March 7, 1964
note: The criticisms expressed in the following
paper, relatively typical of those workers whose
establishment opinions helped to bring on the current era of
Prohibition, are answered by Humphrey Osmond and Abram Hoffer
in their 1967 book, The Hallucinogens. An
excerpt from that book dealing with the Cole And Katz
criticisms can be found in this library.
For many years several pharmacologically similar
drugslysergic acid diethylamide (LSD-25), psilocybin, and
mescaline, among othershave been of special scientific
interest. In volunteer subjects, they have been known to produce
a variety of intense and unusual psychic effects. These include
bizarre visual phenomena, ranging from heightening of the
apparent brightness or beauty of colored objects in the
environment, through distortions in the perceived nature or
meaning of real objects (illusions) to true visual hallucinations
of colors, shapes, or even of complex scenes or events. These
visual phenomena are usually accompanied by intense and often
rapidly shifting emotional experiences (ranging from mild
apprehension to panic, severe depression or mystical elation) or
by concurrent emotions (such as depression and joy) which are not
experienced simultaneously under ordinary conditions. Subjects
describe changes in body image, the body or its parts appearing
larger or smaller, intense feelings of depersonalization,
including states in which the subject believes he is outside his
own body viewing it from afar, or even sensations of death and
Occasionally there may be loss of insight into the
drug-induced nature of these sensations, with paranoid delusions
about other people in the environment who are believed to be
trying to harm or kill the subject. Intense self-loathing with
suicidal impulses or great feelings of mystical revelation can
also occur. Distortions in experiencing passage of time and, more
rarely, disorientation as to time and place can occur. The exact
quality, nature, and content of these experiences appear to
depend in a complex manner on the personality and expectations of
the subject, the dose of the drug, and the setting in which the
drug is administered (1, 2).
Particularly since the synthesis of LSD-25 in 1943,
there has been intense scientific interest in the possibility
that these agents reproduce naturally occurring schizophrenic
states. After twenty years of research, it seems most reasonable
to state that these drugs can produce a state which is similar
but not identical to naturally occurring schizophrenia, and which
may also resemble the toxic deliria caused by other agents such
as atropine or scopolamine. Since subjects acquire tolerance to
LSD, psilocybin, and mescaline after repeated administration
(3-6), the possibility that such compounds are of etiological
significance in naturally occurring schizophrenia seems remote.
Because of the assumed similarities of the state
produced by these agents to schizophrenia, they have been termed
"psychotomimetics" or mimickers of psychosis. Even less
accurately, because of the visual effects, they have been termed,
"hallucinogenics." These names reflect a careful
scientific concern with potentially dangerous, though unique
drugs. More recently Osmond (7) has coined a term,
"psychedelic," meaning "mind manifesting,"
which has begun to be used widely. Its implications are certainly
more vague than those of the other terms. In the contexts in
which it is used, it seems to imply that these drugs bring to the
fore aspects of the subject's mind previously hidden or at least
less manifest, and suggests that these effects may be
"good." Assuredly, many investigators believe that the
effects of these drugs result in an intensity of personal
experience and emotion more meaningful than the terms
"psychotomimetic" or "hallucinogenic" imply.
Therein lies the present problem in the use or
abuse of these agents. Rather than being the subject of careful
scientific inquiry, these agents have become invested with an
aura of magic, offering creativity to the uninspired,
"kicks" to the jaded, emotional warmth to the cold and
inhibited, and total personality reconstruction to the alcoholic
or the psychotherapy-resistant chronic neurotic. On the West
Coast, the effects are judged by some to be related to the
insights of Zen Buddhism; on the East Coast, they are judged by
others to lead the way to a new and free social order. Like the
broom in "The Sorcerer's Apprentice," the drugs seem to
have walked out of the laboratory into the outside world on their
own feet and to have turned on the unsuspecting apprentice.
To be sure, the therapeutic uses of these agents
have been pioneered by psychiatrists in many instances, including
Abramson (8), Frederking (9), Osmond (7), Savage (10, 11), and
Sandison (12, 13). With much of the published work, however,
there is an implicit or explicit attitude that the self-knowledge
of the leverage for self-change allegedly effected by these drugs
may be of value or benefit to individuals who do not ordinarily
consider themselves psychiatrically ill. At the extreme of this
attitude-dimension is the International Foundation for Inner
Freedom, formed by two psychologists, Doctors Leary and Alpert,
who claim that these agents (14) should not be considered drugs
at all but should be classed with poetry, music, literature, and
art, and should be available to all men wishing to improve their
minds and "expand their consciousness." There is,
apparently, an active black market in these drugs in major urban
centers, where these drugs may have more snob appeal than
diacetyl morphine (heroin), marihuana, or dextroamphetamine.
Major attention has been focused on these drugs,
their effects, and the personal eccentricities and misadventures
of the more notorious people advocating their use by a series of
articles in national popular magazinesLook (14), The
Reporter (15), Cosmopolitan (16), Time (17),
the Saturday Evening Post (18), and the Ladies' Home
Journal (19). As with other forms of illicit drug abuse, it
is hard to tell the real extent or seriousness of the
psychotomimetic problem, despite this rather florid publicity.
The present article has two purposes: first, to
underline the real and important dangers inherent in the
self-administration of these agents or in their administration by
uncritical enthusiasts and inadequately trained individuals;
second, to stress that some of the therapeutic claims made for
these drugs are of sufficient potential importance to warrant
serious, unprejudiced study.
Psychotomimetic Agents as Therapy
We take the second issue first, since the first
issue has already been outlined above. There have been an
increasing series of studies reporting LSD-25 and/or mescaline to
be effective in the treatment of chronic alcoholism, with
remission rates of approximately 50 percent being usually
Similar results have been observed in the treatment
of chronic neuroses (9, 10-13, 26, 27). The claims for the
utility of these drugs in the treatment of chronic neuroses range
from dramatic improvement to modest descriptions of improved
communication with the therapist, emotional release, and ability
to talk about difficult personal topics. There have also been
informal claims that these drugs are useful in producing valuable
personality changes in juvenile delinquents and other individuals
with serious personality disorders.
In brief, it is claimed that these agents are of
striking value in some groups of patients who are highly
resistant to more conventional forms of psychotherapy or
pharmacotherapy. Many of these claims stress, further, the
occurrence of basic changes in attitudes or personality, not mere
symptom reduction. If these claims are confirmed, this new
therapeutic approach could add substantially to the
psychiatrist's tools. We must stress that none of these claims
are based on detailed, carefully controlled studies designed to
be free from possible distortions due to bias or enthusiasm.
Further, the terms in which the effects are often explained are
not formulations common either to medicine in general or to
psychiatry in particular. "Our own conception is that people
live an inauthentic existential modality (i.e., alienation), and
that illness arises from an inability to see meaning in life. LSD
provides an encounter which brings a sudden liberation from
ignorance and illusion, enlarges the spiritual horizon and gives
a new meaning to life" (11).Such explanations may have a
mystical or philosophical sound which appeals to the enthusiast,
but they are likely to produce doubt or even violent disbelief
and concern in physicians used to a more pragmatic approach and
in scientists used to a more communicative language. The present
authors occupy a skeptical middle position, favoring the Scotch
verdict of "not proven." We feel strongly that this
approach to therapy should neither be rejected out of hand as
"crazy," nor accepted and applied in an uncritical
manner, but should be subjected to careful study under closely
It is important also to note that the
"treatment" discussed above is not a drug therapy in
the conventional sense. It is, rather, a complex mixture of drug
therapy and brief psychotherapy, with one or more prolonged
sessions, lasting eight to ten hours, during which the patient
experiences the drug effect and discusses his experiences and the
light they throw on his problems, needs, and past experiences in
a prolonged and intensive manner. The drug session is usually
preceded by several interviews in which the patient's problems
and the changes he desires from treatment are explored, a
relationship with the therapist is established, and strong
positive expectations concerning the drug session are developed.
The treatment, as administered by many, seems to include strong
suggestion, aspects of dynamic insight-oriented psychotherapy,
mystico-religious exhortation, catharsis, and pressure on the
patient to confront his problems head on. It is possible that
with all these components the intense and bizarre drug experience
may indeed permit an impact on the subject not obtainable by any
other means. It is difficult to break down the therapeutic
process into its component parts. The proportions of the
components may vary from therapist to therapist or from patient
to patient, especially with regard to the amount of therapist
interpretation and the extent of his active participation in the
solution of the patient's problems.
When this treatment is given in a hospital setting,
there is also considerable personal interaction between the
individual patient and other patients who have already undergone
this experience or are about to undergo it. The whole milieu has
an aura of intense conviction that change will occur and that the
experience will be highly meaningful and highly therapeutic.
Intensive group therapy sessions may occur before and after the
actual LSD experience. The entire therapeutic process, including
preparation for the psychotomimetic experience and subsequent
reinterpretation of it, may resemble the group interaction common
to successful experience with Alcoholics Anonymous. It may
resemble also the intense personalinteraction used at the
National Training Laboratory, at Bethel, Maine (16), where
revelations and emotional experiences are created by intensive
interpersonal and group interaction alone, without the aid of any
Problems in Evaluation
This form of treatment is, therefore, highly
intense and highly complex, necessitating strong convictions and
great sensitivity on the part of the therapist, and requiring the
creation of a social milieu in which all patients not only share
in a strong conviction that change will occur but also hold a
personal commitment to make certain that change does occur.
Dramatic short-term effects under such conditions have been
described. The durability on prolonged follow-up study of acute
changes in behavior, induced by therapy or perhaps even changes
in personality, is yet to be determined.
Several problems face investigators who wish to
make careful studies of such a complex treatment. It seems likely
that people who administer the treatment effectively must be
convinced of its efficacy. Further, they must be highly biased in
favor of it for the treatment to have the described effect. The
physician may be so involved in the treatment that he can not
evaluate its effects objectively. Independent evaluation of
outcome is, therefore, essential to any good research design in
this area. This independent procedure should make it easier to
evaluate the efficacy of treatment in a condition like chronic
alcoholism where an objective index of success or failure,
namely, excessive drinking, exists.
A much more complex problem must be faced in
evaluating the effects of these drugs on individuals with
personality disorders, severe or mild. Here a value judgment must
be made concerning the goodness or badness of the changes which
occur, if any. For example, how should one evaluate outcome if an
individual were to divorce his wife and take a job which paid him
less but which he said he enjoyed more than his previous job? If
a person becomes more relaxed and happy go lucky, more sensitive
to poetry or music, but less concerned with success or
competition, is this good? There are suggestions that individuals
who take drugs like LSD either illicitly or as therapy may become
more detached from reality or less concerned with the real world,
more "transcendental." A few of the reports concerning
this treatment, both published and unpublished, mix a variety of
poetic metaphors and occasionally bizarre-sounding elaborations
with serious descriptions of the details of treatment and the
valuable changes to be expected. For example, certain kinds of
artistic experience, certain types of music, etc., are said to be
particularly valuable in inducing the desired effects. Specific
components of the therapeutic process described may often have a
bizarrealmost schizophreniccomponent, which tends to
make serious investigators discount this whole area as a
delusional belief shared by a group of unstable clinicians and
lay enthusiasts. Whether or not this criticism is justified can
be judged only by future studies designed to be immune to such
criticism. Future studies must decide whether these treatments do
indeed have promise for specific clinical conditions which are
now highly resistant to conventional psychiatric approaches.
The Current Situation
At present a small number of facts are
strikingly clear. None of these drugs has been proved to be
effective or safe therapies for any psychiatric condition.
Because of the apparent potential of these agents for producing
bizarre behavior, suicidal impulses, or undesirable personality
change in some subjects or patients receiving them (28, 29),
there is some question as to whether they should be administered
outside a hospital. They are not available for general
prescription use, and there is some question whether they should
ever be so available. Because neither their safety nor their
efficacy has been adequately demonstrated, two of these agents,
LSD-25 and psilocybin, are being controlled as investigational
drugs in conformity with the existing Food and Drug
Administration regulations under the sponsorship of the drug
company which holds the patent rights for both substances. It is
our understanding that this company is at present providing these
agents for scientific study only to investigators functioning
within federal or state agencies with formal approval of the
agency, or to investigators doing research under ,rants from
these agencies. This policy decision has been made presumably to
insure that these drugs will not be misused by unqualified or
unscientific investigators without adequate checks and balances
necessary for safe and careful research. The other agent,
mescaline, is not to our knowledge being sponsored currently by
any pharmaceutical company, although it can be obtained for
animal or biochemical research from certain biochemical supply
Legally none of these agents can be used, even on
an investigational basis, except by investigators who have filed
a formal research plan with the FDA through a sponsoring
pharmaceutical company, or by investigators who have themselves
assumed sponsorship and satisfied the FDA concerning the safety
of the agents and their proposed research use in man. Any
reported use of these agents outside of these approved channels
should be reported to the FDA. Since there have been a number of
reports of suicide attempts or prolonged psychotic reactions
requiring psychiatric hospitalization in persons obtaining these
drugs outside of approved medical channels, their indiscriminate
unsupervised use is clearly dangerous. In addition, there have
been reports of insidious personality changes occurring in
individuals who have indulged in repeated self-administration of
these agents. It is, of course, difficult to determine whether or
not some of the bizarre behaviors of such individuals are a
product of the drug itself or are a product of the underlying
personality aberrations which lead the individuals to seek out
these agents. In any case, there is no evidence that uncontrolled
self-administration of these drugs is either safe or desirable.
There has also been concern over the possibility that
investigators who have embarked on serious scientific work in
this area may have been subject to the deleterious and seductive
effects of these agents.
Thesee statements are made in hope that warranted
concern over illicit abuse of these agents will not prevent
systematic study of their possible potential in the treatment of
psychiatric conditions which are otherwise severely treatment
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* Dr. Cole is chief and Dr. Katz is research
psychologist of the Psychopharmacology Service Center, National
Institute of Mental Health, National Institutes of Health.