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Journal of Psychoactive Drugs

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Psychoactive Properties of Benztropine and

Trihexyphenidyl
a
James A. Wilcox
a
Department of Psychiatry , University of Iowa College of Medicine , Iowa City , Iowa ,
52242
Published online: 19 Jan 2012.

To cite this article: James A. Wilcox (1983) Psychoactive Properties of Benztropine and Trihexyphenidyl, Journal of
Psychoactive Drugs, 15:4, 319-321, DOI: 10.1080/02791072.1983.10471970

To link to this article: http://dx.doi.org/10.1080/02791072.1983.10471970

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 PSYCHOACTIVE PROPERTIES OF
BENZTROPINE AND TRIHEXYPHENIDYL
James A. Wilcox, D.O. •
Benztropine mesylate (Cogentin®) and trihexy-
phenidyl hydrochloride (Artane®) are anticholinergic
drugs commonly used to treat Parkinson's disease. They
are also widely employed to counteract the extra-
pyramidal symptoms caused by antipsychotic drugs. The
clinical and pharmacological literature contains many
references to the side effects of these agents (Goodman
& Gilman 1975; Woody & O'Brien 1974; Stephens 1967;
Bolin 1960), and it has generally been felt that their
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primary psychoactive effect was in the form of anti-
cholinergic delirium seen in cases of acute intoxication.
A growing body of literature suggests that, aside from
toxic psychosis, these chemicals also possess a mood-
elevating potential, and several authors have reported
that this euphorigenic effect is quite significant in some
individuals (Kaminer, Munitz & Wijsenbeek 1982; Gog-
gin 1979; jellinek 1977; MacVicar 1977).
PHARMACOLOGY
Benztropine and trihexyphenidyl are synthetic anti-
cholinergics. Benztropine mesylate is produced as a
white crystalline powder, which is soluble in both water
and alcohol. When the chemical structure of benztropine
is compared with atropine (a potent natural anti-
cholinergic substance) and diphenhydramine (a sedating
antihistamine), similarities are apparent. Benztropine
actually demonstrates both antihistaminic and atropine-
like effects. The usual daily dose of benztropine varies
from 0.5-6.0 mg orally or parenterally.
Trihexyphenidyl is also produced as a white, crystal-
line powder. Like benztropine, it is soluble in both water
and alcohol. This substance antagonizes acetylcholine
much like atropine, but with less intensity. The usual
daily doses are similar to those of benztropine.
These substances have been especially useful in the
treatment of Parkinson's disease, many of the symptoms
of which appear to result from an imbalance of
excitatory ganglia and inhibitory dopaminergic pathways
of the nigrostriatal tract. The beneficial effects of
benztropine and trihexyphenidyl are felt to be due to
partial blockade of striatal cholinergic receptors and also
because of their ability to block the reuptake of
dopamine in the striatum (Goodman & Gilman 1975:
236-239).
*Medical Director, Mid-Eastern Council on Olernical Abuse,
Iowa City, Iowa; Resident, Department of Psychiatry, University
of Iowa College of Medicine, Iowa City, Iowa 52242.
journal of Psychoactive Drugs
Both benztropine and trihexyphenidyl have direct
inhibitory effects on the parasympathetic nervous sys-
tem. At low doses, each of these drugs causes depression
of the central nervous system. At doses above the
general therapeutic level, cerebral stimulation may occur
(Medical Economics 1983). These drugs are frequently
used to control the the extrapyramidal side effects of
neuroleptic drugs and are particularly useful in treating
muscle rigidity and dystonia produced by agents such as
haloperidol and fluphenazine. Both benztropine and
trihexyphenidyl can produce anticholinergic delirium
similar to that described by Hall and colleagues (1978a,
1978b). Additionally, they can also produce a variety of
other undesirable effects including dry mouth, rashes,
paralytic ileus, urinary hesitancy and increased intra-
ocular pressure (Medical Economics 198 3 ). These effects
are potentially dangerous.
The treatment of acute intoxication from either
benztropine or trihexyphenidyl is largely supportive.
Severe anticholinergic symptoms may be treated with
physostigmine salicylate (one to two milligrams given
intravenously as a slowly pushed infusion). Psychological
manifestations are best managed with a quiet reassurance
in a darkened room. Phenothiazine drugs are contra-
indicated because of their inherent anticholinergic
properties.
PSYCHOACTIVE PROPERTIES
Benztropine and trihexyphenidyl are known to
produce changes in perception. They have been reported
to induce vivid visual hallucinations, confusion and
delusions (Stephens 1967; Bolin 1960). These experi-
ences are similar to those found in anticholinergic
delirium. The signs of intoxication on routine doses have
been reported to have an incidence of 2.0-19.2 percent
depending on the age of individuals in the sample
(Stephens 196 7). The risk of delirium appears to be
higher for those over the age of 60.
The hallucinations associated with ingestion of large
amounts of trihexyphenidyl have led to nonmedical use
of this drug among those unable to obtain more
conventional mind-altering substances. Benztropine has
also been used, both orally and by smoking, as a
recreational drug in prison populations (Woody &
O'Brien 1974). Doses associated with hallucinosis range
from 6.0-75.0 mg, with the greatest sensitivity in the
elderly. The subjective experience of these intoxications
frequently is marked by vivid visual imagery and the
hallucinations frequently center on a group of similar
objects, such as several identical children or many
uniformed men (Stephens 1967). There is a relative
absence of distortion of body image and space.
319 Vol. 15(4) Oct-Dec, 1983
 WILCOX
These substances also appear to have a mood-
elevating effect that is separate from toxic delirium. This
condition is described as a sense of well-being and is not
necessarily accompanied by changes in visual perception.
There are more than 11 case reports in the literature of
people obtaining euphoria through the use of these
agents (e.g ., Kaminer, Munitz & Wijsenbeek 1982;
Jellinek 1977).
CASE REPORTS
This author has treated numerous psychiatric
patients suspected of using benztropine or trihexy-
phenidyl for mood-elevating effects. Many individuals
taking these drugs considered them to be an important
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part of their psychopharmacological therapy and often
resisted being parted from the drugs. It is difficult to
evaluate this kind of general response because of the
often subtle nature of this euphoric experience. The
hallucinosis associated with the use of these substances is
much more obvious and perhaps more easily and
accurately described. The two cases presented here are
of psychiatric patients who experienced temporary
hallucinations that were related to benz tropine usage.
easel
Patient A was a 29-year-old single White male with a
history of chronic paranoid schizophrenia. He was
known to be quite lucid when in a state of remission,
and he was living in a normal fashion when his behavior
suddenly changed. He was brought to the emergency
room because of disorientation. He appeared confused
and reported having had visual hallucinations over
several days, including vivid scenes of devils and apes.
His sensorium gradually cleared and he reported that he
had ingested 40 rng of benztropine two hours prior to
his episode of hallucinosis. He also reported that he
often used this drug for its mood-altering effect, when
other agents were unavailable. He reported that it
produced a euphoria similar to cannabis. When his
normal level of function was achieved, the patient was
transferred to a drug rehabilitation center and then
released.
Case2
Patient B was a 24-year-old single White male with a
history of chronic disorganized schizophrenia. When
considered ill, the patient was troubled by auditory
hallucinations and disorganized thoughts. He was being
treated with fluphenazine and was noted to develop
journal of Psychoactive Drugs
SHORT COMMUNICATIONS
Parkinsonian rigidity as an undesired side effect of his
medication. He was given two milligrams of benztropine
orally to relieve the rigidity. Approximately 45 minutes
after receiving benztropine, the patient experienced
visual hallucinations of colorful geometric designs. His
sensorium was otherwise intact and without clouding of
consciousness. The hallucinations disappeared after
approximately four hours and did not recur.
DISCUSSION
The precise psychopharmacological mechanisms for
the euphoria and hallucinosis induced by benztropine
and trihexyphenidyl are unclear. It is possible that these
substances produce a form of anticholinergic delirium.
Other cholinergic antagonists cause hallucinations, but
also produce confusion as well as physical signs of
toxicity (dilated pupils, flushing, anhydrosis) not gen-
erally observed in reported cases of benztropine or
trihexyphenidyl abuse. It may also be possible that the
mood-elevating effect seen with these agents is mediated
via catecholamines. This notion is consistent with the
observation that these drugs increase cerebral dopamine
levels (Goodman & Gilman 1975) and have been noted
to have a stimulating effect (] ellinek 1977; Goodman &
Gilman 1975).
One possible problem with these reports is that
most of them deal with people who have been diagnosed
as schizophrenic, but this criticism does not account for
the use of these drugs among prisoners and other
nonschizophrenic individuals. In addition, this author's
experience indicates that the subjective experience of
benztropine intoxication is quite separate from the
experience of illness. It should also be noted that the
majority of reports concerns euphoria, which is not a
symptom of schizophrenia. There is no reason to suspect
that schizophrenics have any greater tendency to be-
come euphoric from these drugs than anyone else.
Another consideration is whether the relief that
these drugs provide from Parkinsonian symptoms may
be misinterpreted as euphoria. This notion is inconsis-
tent, however, with the observation that individuals
without Parkinsonian symptoms also experience eu-
phoria (Woody & O'Brien 1974; Stephens 1967).
Benztropine and trihexyphenidyl indeed appear to
have psychoactive properties, which are characterized by
induction of euphoria and hallucinosis. Research beyond
the level of case reports is warranted to further clarify
the potential of these agents.
320 Vol. 15(4) Oct-Dec, 1983
 WILCOX
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