Effects of the hallucinogen psilocybin on covert orienting of visual attention in humans.

Hallucinogenic drug-induced states are considered as models for acute schizophrenic disorders (experimental psychoses). In a double-blind study with healthy volunteers we investigated the influence of the serotonergic hallucinogen psilocybin, the ecstasy-like drug 3,4-methylenedioxyethylamphetamine (MDE), the stimulant d- methamphetamine and placebo on covert orienting of spatial attention (n = 8 in each group). Reaction times were prolonged after ingestion of psilocybin > MDE, but not after d-methamphetamine. In addition, subjects on psilocybin exhibited particularly slow reaction times in invalid trials at short cue target intervals and failure of response inhibition in valid trials at long cue target intervals for right visual field targets. Despite some methodological limitations, these results are in line with both bilateral impairment of disengagement of attention and a lateralized impairment of inhibition of return (IOR) in productive psychotic states. Additional investigations with larger samples, different hallucinogenic substances (serotonergic agonists vs. NMDA antagonists) and different dose regimens are needed in order to further explore the suggested relationship between visuospatial attentional dysfunction and acute psychotic conditions.

[Therapeutic experiences with alcohol-related Korsakoff syndrome]. / Therapeutische Erfahrungen beim alkoholbedingten Korsakow-Syndrom.

Korsakoff's psychosis (Wernicke-Korsakoff-Syndrome) following severe, long-term alcoholism is considered to be widely resistant to treatment. We report two cases with beneficial effects of treatment by a combination of clonidine and fluvoxamine.

Interdisciplinary clinical assessment of patients with illness attributed to environmental factors.

Patients with health problems attributed to environmental factors such as chemical pollutants and electromagnetic fields often do not present evidence of an environmental aetiology of their symptoms. It has been postulated, that their problems are due to disorders diagnosed by other medical disciplines, especially allergology and psychiatry. Our study was designed to subject these patients to a comprehensive diagnostic program involving several medical disciplines in order to achieve diagnoses appropriate to explain the patients' symptoms. Fifty patients consecutively referred to the department of environmental medicine in the university hospital of Aachen, Germany, were submitted to the following examinations: (i) environmental medicine (history, clinical examination, biological and/or ambient monitoring for environmental agents); (ii) allergological examination (history, clinical examination, skin tests); (iii) psychiatric examination (psychopathological examination, psychometric and neuropsychological testing). In addition, the patients were examined in other hospital departments according to the symptoms presented. The findings were discussed in case conferences attended by the physicians involved in order to achieve individual diagnoses. The numbers of patients to whom diagnoses were given by different medical disciplines are as follows: psychiatry (32 patients), dermatology (4), allergology (2), neurology (2), rheumatology (2), gynaecology (1), haematology (1). The most frequent mental disorders diagnosed by the psychiatrists were somatoform disorders (19), followed by schizophreniform and delusion disorders (7). In spite of extensive diagnostic efforts, patients with health problems attributed to the environment usually do not present sufficient evidence of an environmental aetiology of their symptoms. On the other hand the symptoms often meet the diagnostic criteria of other diseases, especially of mental disorders.

Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study.

The aim of this study was to contribute to the characterization of the entactogen (ecstasy) substance group. The psychopathological, neuroendocrine and autonomic effects of common recreational doses of the entactogen 3,4-methylenedioxyethylamphetamine (MDE), the hallucinogen psilocybin, the stimulant d-methamphetamine and placebo were investigated in a double-blind study with healthy volunteers (n = 32). Psychological effects of the drugs were assessed by means of standardized rating scales, self assessment inventories and free descriptions. The most characteristic effects of MDE were pleasant emotional experiences of relaxation, peacefulness, content and closeness to others. However, significant stimulant and hallucinogen-like effects were also present, although the latter were weaker than the effects of psilocybin. MDE elicited the strongest endocrine and autonomic effects among the three drugs, including robust rises of serum cortisol and prolactin, elevations of blood pressure and heart rate, and a moderate, but significant rise of body temperature. The apparent contrast between psychological and autonomic effects (subjective relaxation versus physical activation) was a unique feature of the MDE state. Our findings are in line with both users' reports and results from previous experimental studies, and support the view that entactogens constitute a distinct psychoactive substance class taking an intermediate position between hallucinogens and stimulants.

Effects of the hallucinogen psilocybin on habituation and prepulse inhibition of the startle reflex in humans.

Schizophrenic patients exhibit deficits in indices of sensorimotor gating, such as habituation and prepulse inhibition (PPI) of the startle reflex. Hallucinogenic drug-induced states are putative models for the early and acute stages of schizophrenic and schizophrenia-spectrum disorders. Hallucinogenic drugs have been shown to disrupt PPI and/or retard habituation of the startle reflex in animal models of schizophrenia, consistent with the view of hallucinogen-induced states as 'model psychoses'. We evaluated the effects of the hallucinogen psilocybin on PPI and habituation of the startle reflex in a double-blind, placebo-controlled human study with 12 healthy subjects. In contrast to animal studies, in our small human sample, psilocybin increased PPI, while having no clear effect on habituation (n = 6). These findings must be considered preliminary because several factors, including dose regimens and experimental parameters, may influence the results of studies on startle plasticity. Further investigations both with psychotic patients in different stages of the disease and with human and animal models of schizophrenia are needed in order to explore the effects of hallucinogens on sensorimotor gating and the relationship between information processing in hallucinogenic drug-induced states and the naturally occurring psychoses.

History, rationale and potential of human experimental hallucinogenic drug research in psychiatry.

Systematic scientific interest in psychedelic substances has a tradition of about 100 years. Numerous human experimental studies have confirmed the existence of a common nucleus of experiences in hallucinogen-induced states and the acute stages of schizophrenic psychoses. However, the degree of resemblance between endogenous and drug-induced psychotic states has been an issue of controversial debate. After the scheduling of psychedelics in the 1960s, human research became highly restricted worldwide and scientific interest in this field faded. The debate about the appropriateness of the psychedelic state as a model for endogenous psychosis therefore seemed to have little practical relevance. Currently there is a revival of scientific interest in human experimental psychedelic research. Consequently, the appropriateness of hallucinogen-induced states as models for psychosis needs to be reappraised. The arguments for and against are summarized in this paper. In conclusion, the drug-induced model psychosis is shown to be a useful model for acute psychotic stages, but not for the nosological entity schizophrenia.

Methodological issues of human experimental research with hallucinogens.

Human experimental research with hallucinogenic drugs is potentially able to identify linking variables between the psycho(patho)logical conditions and neurobiological alterations involved in both pharmacologically induced and naturally occurring acute psychotic states. A number of methodological aspects should be considered when planning modern experimental studies with hallucinogenic drugs. The issues of subject selection, repeated measures, and adequate control groups are discussed in this paper. Examples of recent experimental studies are presented which take these aspects into account. The first study examined psychopathological changes, facial expression and semantic priming effects during a psilocybin-induced state. In the second study, semantic priming effects after intake of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE), and d-methamphetamine were investigated. Results confirmed time-dependent effects of psilocybin and the restriction of increased priming effects in the psilocybin group.

Multiresolution detection of coherent radar targets.

We develop and investigate several novel multiresolution algorithms for detecting coherent radar targets embedded in clutter. These multiresolution detectors exploit the fact that prominent target scatterers interfere in a characteristic manner as resolution is changed, while multiresolution clutter signatures are random. We show, both on simulated and collected synthetic aperture radar data, that these multiresolution algorithms yield significant detection improvements over single-pixel, single-resolution constant false alarm rate (CFAR) methods that use only the finest available resolution.

Phase-diversity correction of turbulence-induced space-variant blur.

Space-variant blur is encountered when objects extend beyond the isoplanatic patch associated with the intervening atmospheric turbulence. The method of phase diversity, used to estimate jointly the object and the aberrations, is generalized to accommodate turbulence-induced space-variant blur. This generalization utilizes a parametric model for the blur function that is constructed with multiple phase screens. Simulation results are presented that demonstrate the recovery of near-diffraction-limited imagery from phase-diversity imagery that has been degraded with rather severe anisoplanatism.