Amphetamine Psychosis Research Articles

Thought Disorder in Amphetamine Psychosis: A Case Report

Back to table of contents Previous article Next article AbstractsNo AccessThought Disorder in Amphetamine Psychosis: A Case ReportLeanne G. Domash, Ph.D.Leanne G. DomashNew York, N.Y.Search for more papers by this author, Ph.D.Published Online:30 Apr 2018https://doi.org/10.1176/appi.psychotherapy.1977.31.3.487aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Thought Disorder in Amphetamine Psychosis: A Case Report." American Journal of Psychotherapy, 31(3), pp. 487–488 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - APT - American Journal of Psychotherapy $35.00 Add to cart PPV Articles - APT - American Journal of Psychotherapy Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byNone Volume 31Issue 3 1977, pp. 341–499Pages 487-488 Metrics PDF download History Published online 30 April 2018 Published in print 1 July 1977

Dopaminergic agonist properties of ephedrine-theoretical implications

Reports of ephedrine-induced psychoses resembling amphetamine psychosis prompted studies of this classic sympathomimetic agent in systems that indicate central dopaminergic actions. Ephedrine induced dose-related stereotyped behavior in rats. This behavior was antagonized by haloperidol, but not by alpha- or beta-adrenergic blockers. Pretreatment with AMPT, but not reserpine, attenuated the stereotypy induced by ephedrine under one of two sets of conditions. Consistent prolactin suppression in humans was not seen. These findings are discussed in the context of clinical and pharmacologic data regarding other dopamine agonist drugs (the central nervous system stimulants, apomorphine, ET 495). These data suggest the possibility that synergistic noradrenergic and dopaminergic facilitation may be important in the induction of the stimulant psychoses.

DOPAMINE AND SCHIZOPHRENIA

The antipsychotic actions and extrapyramidal side-effects of neuroleptic drugs are strongly correlated with their ability to block central dopaminergic transmission. It is argued that the former are more closely related to actions on dopaminergic mechanisms in the "mesolimbic dopamine" system, and the latter to similar actions in the striatum. Although the amphetamine psychosis closely resembles paranoid schizophrenia and may be due to excess dopamine release, clinical, biochemical, and endocrine studies suggest that dopaminergic overactivity is not a necessary concomitant of schizophrenic illnesses. It is suggested that the primary defect in schizophrenia does not lie in the dopamine neuron. It remains to be excluded that the receptors, particularly in the mesolimbic dopamine areas, become supersensitive, or that there is a deficit in a system which normally acts in antagonism to the mesolimbic dopamine system.

Biochemistry and behavior: some central actions of amphetamine and antipsychotic drugs.

tempted to presen t a relatively broad coverage of the different levels of analysis of amphetamin e action s. We have chosen to emphasize two promin ent behavioral effects of amphetamin e on spontaneous behavior, i.e. increased locomotor behavior and stereotyped behavior, and the biochemical and neurophysiological studies that relate primarily to these behavioral effects. One of the most interestin g aspects of this emphasis will be the provocative effects of lon g-term amphetamin e admin istra­ tion , which in experimen tal animals leads to a progressive augme nta tion of these behavioral effects, and which in humans produces the condition termed ampheta­ mine psychosis. Clinically the symptoms associated with this syndrome are difficult to distin guish from those characteristic of paran oid schizophrenia, and without a prior knowledge of the history of drug abuse, amphetamine psychosis has often been misdiagn osed as an idiopathic schizophrenic disorder. A large number of books and reviews on amphetamin e and related drugs has been published within the past 5 years, many of which are cited in this review for the interested reader. However, this topic has not been treated previously in the Annual Review of Psychology. The literature search for this manuscript ended in March 1975 .

Multiple Drug Interviews as a Diagnostic Technique: A Clinical Case Study

Diagnostic information obtained from a single drug interview is subject to conscious and unconscious distortion by the patient and to interviewer effects. Rationales for the various provocative techniques are reviewed, with particular reference to the amphetamine psychosis and to state-dependent learning. A format for a controlled series of multiple provocative interviews which "triangulates" on the same clinical problem from several theoretical perspectives is proposed, and a clinical case is presented in which this format was employed. Used in this way, drug interviews may provide useful diagnostic information.

Sympathomimetics and Schizophrenia

To the Editor.— Amphetamine psychosis has long been known to mimic schizophrenia. 1,2 Some experiences in my practice suggest that limited, continuing use of amphetamine and related substances may exert a deregulating effect on chronic schizophrenia. In particular, it appears that several sympathomimetic materials can yield subtle or dramatic exacerbations in the course of schizophrenia, the origin of which may not be visible without precise inquiry. Of a group of 575 schizophrenics under my care, and all on phenothiazine therapy, 26 are thought to have shown such exacerbations, which abated on stopping simultaneously taking a sympathomimetic material. This number is likely an understatement, because many of the events were not recognized because of our only recent appreciation of this matter. It is not mainly sympathomimetics prescribed by physicians that constitute the bulk of this problem; it is the presence of these materials in over-the-counter pharmaceuticals, particularly in diet pills and

Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats

After rats were trained to differentiate between the effects of d-amphetamine and saline in a state-dependent task, pretreatment with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, significantly decreased amphetamine discrimination. Pretreatment with the dopamine-beta-hydroxylase inhibitor, disulfiram, or with the tryptophan hydroxylase inhibitor, p-chloro-phenylalanine, was observed to have no effect on the rats' ability to discriminate d-amphetamine. Administration of haloperidol, a selective dopamine receptor blocker, completely abolished the amphetamine discrimination, whereas alpha- and beta-adrenergic receptor blockade had no effect. Apomorphine, a dopamine receptor stimulant, produced amphetamine-like responses and this was, likewise, abolished by pretreatment with haloperidol. These data suggest that dopaminergic systems mediate the interoceptive cue produced by d-amphetamine in rats, and these results are discussed in relation to possible dopamine mediation of amphetamine psychosis and paranoid schizophrenia.

Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis.

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.

Exogene Psychose eines Patienten mit Karzinoidsyndrom nach Behandlung mit <i>p</i>-Chlorophenylalanin (PCPA)

A case is reported of a patient with carcinoid syndrome who developed a exogenous psychosis while under treatment with the serotonin-inhibitor Ρ-chlorophenylalanine (PCPA). Partial symptoms similar to delirium and schizophrenia were exhibited. The attached literature survey focuses on the psychological side effects of PCPA treatment. A discussion follows concerning noteworthy phenomenological similarities between the case reported and certain forms of amphetamine psychosis. Common biochemical mechanisms are hypothetically stated.

Gilles de la Tourette's disease--a review.

The author describes Gilles de la Tourette's disease, noting that it is characterized by sudden involuntary movements, explosive involuntarty utterances, and imitative phenomena; the pathognomonic feature is the sudden, uncontrolled repetitive utterance of obscenities. The general progression of symptoms is cephalocaudad, with frequent waxing and waning; symptoms become worse during affective arousal and improve with relaxation. Etiology is unclear, with recent evidence suggesting catecholaminergic overactivity. Although this disease and schizophrenia are clearly two separate entities, the author suggests that Gilles de la Tourette's disease may be behaviorally related to schizophrenia and biochemically related to the amphetamine psychosis. The treatment of choice is haloperidol.

Amphetamine and methylphenidate psychosis

Publisher Summary This chapter discusses the amphetamine and methylphenidate psychosis. A total of 17 actively ill schizophrenic patients, who were in good health without cardiovascular or other physical illness were administered active drug by a single injection, preceded and followed by placebo injections every 5 min. In actively schizophrenic patients, methylphenidate produced a marked worsening of the schizophrenic symptoms causing a doubling of the psychosis scores. d -amphetamine worsened psychotic symptoms somewhat, but was less potent than methylphenidate. l -amphetamine was the least potent of three drugs. l -amphetamine 10 mg, and d -amphetamine 4 mg were less potent than l -amphetamine 28 mg. The results from each of several experiments were combined to arrive at drug potencies relative to the psychosis worsening effects of l -amphetamine. In the experiment in which methylphenidate was given followed by physostigmine, methylphenidate produced a 50% increase in psychosis ratings. It is found that when physostigmine was administered after methylphenidate, there was essentially no net increase in psychosis, so that physostigmine effectively reversed the psychosis worsening property of methylphenidate. Methylphenidate also increased interactions, and this effect was blocked by physostigmine.

Interaction of low-dose amphetamine use with schizophrenia in outpatients: three case reports.

The similarities between amphetamine psychosis and schizophrenia have been noted by several authors. Recently, an exacerbation of acute schizophrenia by amphetamine has been demonstrated. The case histories presented in this paper suggest that the dosages of amphetamine often prescribed for dieting may precipitate psychotic symptoms in outpatient schizophrenics who are not known to be clinically ill when the drugs are prescribed.

Amphetamine psychosis: Behavioral and biochemical aspects

Publisher Summary This chapter discusses the behavioral and biochemical aspects of amphetamine psychosis. Amphetamine psychosis was characterized by a brisk emotional reaction, usually in the direction of anxiety amphetamine psychosis was rather strikingly similar to schizophrenia in its presentation; however, these two conditions could be differentiated by the presence of thought disorder that is prominent in schizophrenia and lacking in amphetamine psychosis The pharmacologic manipulation of dopaminergic mechanisms is almost certainly not without effect on other central nervous system systems and certain effects considered dopaminergic may indirectly be mediated by these other systems. Physostigmine can both block and abolish the stereotypy in rats induced by the administration of methylphenidate.

Dopamine and the pharmacology of schizophrenia: The state of the evidence

Publisher Summary This chapter discusses the connection between dopamine and schizophrenia. The evidence connecting dopamine transmission with schizophrenia comes primarily from three areas of research, namely, the blocking effects of antipsychotic drugs on amphetamine- and apomorphine-induced stereotyped behavior, the approximate equality of potency of d - and l -amphetaminein eliciting psychosis, and the ability of the antipsychotics to enhance brain dopamine turnover. It is true, in a general way, that tranquilizing drugs block amphetamine- and apomorphine-induced stereotyped behavior. Thiethylperazine is a phenothiazine used in the treatment of motion sickness but regarded as without antipsychotic effects the relative potency of d -amphetamine as compared with the l -form is 1–3 to 1. The similarity of the effects of the stereoisomers in man would constitute intriguing evidence for the involvement of a dopaminergic system, at least in amphetamine psychosis, and perhaps also in schizophrenia. Conceivably, there are regional differences in the effect of phenothiazines on dopamine receptors so that thioridazine might have a large effect on limbic dopamine endings but a small effect in the caudate.

Stereoselective features of catecholamine disposition and their behavioral implications

The post-synaptic receptor actions of norepinephrine but not of dopamine are strikingly stereospecific. A considerably lesser “stereoselectivity” characterizes the presynaptic uptake and release properties of norepinephrine neurons in the peripheral sympathetic nervous system and in the brain. Dopamine nerve terminals display still less stereoselectivity in their uptake mechanism, none being demonstrable at the β-carbon while a variable degree can be detected at the α-carbon. The differential stereoselectivity of dopamine and norepinephrine neurons has prompted the use of isomers of amphetamine in attempts to discern whether particular behaviors in animals, such as turning after unilateral nigrostriatal lesion, stereotyped behavior, locomotor activation and hypothalamic or midbrain self-stimulation, are predominantly dopamine or norepinephrine mediated. In man, amphetamine isomers have been evaluated for central stimulant effects, production of “amphetamine psychosis” and exascerbation of schizophrenic symptoms.

Central dopamine neurons and sensory processing

THERE ARE several indications that the function of central dopamine (DA) neurons is associated with schizophrenia: Amphetamine psychosis is thought to resemble schizophrenia while treatment with neuroleptic drugs are used against the disease. Amphetamine may cause DA hyperfinction by increasing DA release while neuroleptic drugs probably cause DA hypofunction as they inhibit DA receptors, It is possible to induce this state of hyperor hypofunction in animal models which may increase our understanding of the kind of functional changes that occur. The syndrome of hyperfunction, after e.g. amphetamine, is well known in animal models and associated with the typical stereotyped behaviouP while hypofunction, after neuroleptic drugs, causes a profound hypoactivity and catalepsy.’ The DA system is thrown off balance in both instances but in different directions. However, the functional effect may sometimes be the same as in the case of anorexia which is caused by amphetamine as well as neuroleptic drugs. 4 It may be speculated that normal function requires a rather narrow balance between hyper- and hypofunction. In a recent series of experiments (Ljungberg and Ungerstedt, to be published), we have studied the functional deficits occurring after a unilateral removal of the ascending DA neurons. The degeneration was induced by a stereotaxic injection of 6-hydroxydopamine (6-OH-DA) in among the DA cell bodies in the substantia nigra.2s5 The animals were tested for their ability to orient towards visual, auditory, olfactory and tactile stimuli to either side of the body. The unilaterally DA denervated animal wasunable to orient towards any sensory stimuli applied to the side of the body that is contralateral to the lesion while it reacts normally to all stimuli applied to the side ipsilateral to the lesion. In connection with the postulated involvement of the central DA pathways in “extrapyramidal” motor control it may be argued that the lack of orienting reaction is due to motor disability. However, the time course of recovery differs among the different sensory modalities and at a given time point the animal may react to certain sensory stimuli while not to others indicating that there is no non-specific motor disability preventing him from performing the orienting response. These deficits in responding to sensory stimuli after lesions of the DA neurons are also evident in a more complex situation e.g. running a maze to get water reward. Bilateral removal of the ascending DA neurons induces serious akinesia, adipsia and aphagia and abolishes the ability to perform an already well trained response. If the degeneration of the DA neurons is the cause of this disruption of learned behaviour it should be possible to restore the behaviour by compensating for the lost DA with e.g. the DA precursor Dopa or the DA receptor stimulating drug apomorphine. In fact, both these drugs are able to

Evolving behavior in the clinical and experimental amphetamine (model) psychosis.

A parallel is drawn between several behavioral constellations observed in the evolution of the human amphetamine psychosis and the motor-postural-attitudinal manifestations induced in animals by chronic amphetamine intoxication. On the basis of the results reported, a triple-layered model of psychosis is suggested and the roles played by participating neurotransmitters and mechanisms are further elaborated.

Amphetamine metabolism in amphetamine psychosis.

The metabolism of 3H‐d,l‐amphetamine was investigated in 11 subjects with amphetamine psychosis. In 3 patients with acidic urine (pH < 6.6), renal elimination of unchanged amphetamine (67% to 73%) was associated with plasma half‐life of 7 to 14 hours and rapid clearing of psychotic symptoms. In 4 patients with alkaline urinary pH metabolism became the dominant route of elimination and plasma half‐life increased to 18 to 34 hours. In these subfects the psychosis was also more long‐lasting. Parahydroxyamphetamine, p‐hydroxynorephedrine, and norephedrine constituted 3% to 8% and hippuric acid 14% to 16% of the metabolites in acidic urine, and 6.8% to 13% and 22% to 52%, respectively, in alkaline urine. The intensity of the psychosis was positively correlated to the amount of basic polar metabolites of amphetamine excreted in urine but not to the amphetamine level in the plasma. Our results indicate that amphetamine metabolites may be of importance in the development of the paranoid psychosis in chronic amphetamine abusers.

The experimental reproduction of amphetamine psychosis.

A large dose of intravenous methamphetamine hydrochloride reproduced the amphetamine psychosis in 12 of 14 patients dependent on amphetamine sulfate and failed to produce a psychosis in two patients who were eventually found to have not used amphetamine regularly above the therapeutic dose range. The psychosis was the facsimile of the disorder observed during drug abuse—a schizophrenic-like state of paranoia in a setting of clear consciousness accompanied by auditory or visual hallucinations, or both, but without thought disorder. Since in some cases the onset of the psychosis was sudden and occurred within one hour of commencing the intravenous injection, hypotheses about depletion of catecholamines and long term metabolites may need to be reconsidered.

Amphetamine psychosis: a "model" schizophrenia mediated by catecholamines.

Because of its close clinical similarity to acute paranoid schizophrenia, amphetamine psychosis may serve as a useful experimental model for schizophrenia. Molecular and clinical studies suggest that both the schizophrenia-like symptoms of amphetamine psychosis and the specific ability of phenothiazines to relieve the symptoms of schizophrenia and amphetamine psychosis may be the result of interactions with dopamine systems in the brain. The author discusses some implications of the roles dopamine and norepinephrine may play in mediating some schizophrenic symptoms.