Experimental Psychosis Research and Schizophrenia-Similarities and Dissimilarities in Psychopathology.

The aim of experimental psychopathology is to delineate overlapping functional disorders of psychoneurobiologically-defined systems where a set of common symptoms may correspond to a variety of nosological entities. According to the vulnerability model of psychosis, experimental research needs to go beyond categories such as "schizophrenia". Prospective studies of the effects of psychoactive substances in normal control subjects offer several methodological advantages over routine clinical reviews of schizophrenic patients, especially in terms of standardization. Carefully designed studies utilizing a model psychosis paradigm are a step toward symptom-oriented research. Combining psychological and neurobiological techniques, the experimental psychopathological approach can provide us with a valuable tool for psychiatric research.

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review.

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, 'psychedelics') like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N=445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N=30). The 4 more recent randomized controlled trials (RCTs) (N=104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.

[Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges]. / Psychotherapie mit adjuvanter Gabe von serotonergen psychoaktiven Substanzen ­ Möglichkeiten und Hindernisse.

Background Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances. Method A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000. Results Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA). Discussion Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future.

Hallucinogen-persisting perception disorder.

A 33-year-old female patient developed a hallucinogen-persisting perception disorder (HPPD) after lysergic acid diethylamide (LSD) abuse for a year at the age of 18. Specifically, she reported after images, perception of movement in her peripheral visual fields, blurring of small patterns, halo effects, and macro- and micropsia. Previous treatment with antidepressants and risperidone failed to ameliorate these symptoms. Upon commencing drug therapy with lamotrigine, these complex visual disturbances receded almost completely. Based on its hypothesized neuroprotective and mood-stabilizing effects, the antiepileptic lamotrigine may offer a promising new approach in the treatment of HPPD.

Increased unconscious semantic activation in schizophrenia patients with formal thought disorder.

Formal thought disorder (TD) is a core symptom in schizophrenia, but the underlying neurocognitive mechanisms have yet to be determined. This pilot study tested the hypothesis that unconscious semantic activation in conceptual memory is increased in thought disordered patients with schizophrenia. Twenty-eight right-handed individuals with a DSM-IV diagnosis of schizophrenia or schizophreniform disorder (2 patients) and 14 healthy comparison participants performed lexical decisions on target words that were preceded by semantically related and unrelated unconsciously perceived masked prime words (masked priming paradigm). Fourteen patients showed more severe thought disorder symptoms (TD patients), 14 patients showed weaker TD symptoms (non-TD patients). Groups did not differ significantly with regard to gender, age, education and premorbid verbal intelligence. Rigorous tests demonstrated that the masked word could not be consciously identified in either group. Schizophrenia patients with TD showed increased masked semantic priming in comparison to non-TD schizophrenia patients and healthy comparison participants. The present results suggest that the unconscious automatic spread of activation within semantic memory is increased in schizophrenia patients with TD. Increased unconscious activation of several related concepts may interfere with conscious goal-directed thinking in TD patients.

Risperidone monotherapy in manic inpatients: an open label, multicentre trial.

OBJECTIVE: The efficacy of risperidone in acute mania has been established in several controlled clinical studies. However, this may not necessarily resemble the clinical effectiveness of this treatment, as patient populations in controlled studies are considered as being not representative. This study examined risperidone monotherapy in a sample of severe manic patients in admission ward settings. METHODS: Open label monotherapy with risperidone was examined for 3 weeks in 30 inpatients. Subjects were evaluated with structured clinical rating scales: Young Mania Rating Scale (YMRS), Clinical Global Impression, bipolar version (CGI-BP), and the Extrapyramidal Symptom Rating Scale (ESRS). In addition, the amount of concomitant use of benzodiazepines was documented. Data were analysed using a last observation carried forward method on all subjects given medication at baseline. RESULTS: Significant improvement from baseline to exit was observed both for the YMRS and CGI-BP. Responder analysis revealed that two-thirds of the patients showed a reduction of 50% in the YMRS score, and 69% of the patients were rated as very much improved or much improved on the CGI-BP mania scale at study exit. Only three patients dropped out due to adverse events, in one case due to extrapyramidal symptoms. CONCLUSIONS: The efficacy of risperidone in the acute treatment of mania as observed in controlled studies could be replicated in this open monotherapy study in a severely manic inpatient population. Considering the mean maximal dosage of 5.5+/-0.9 mg risperidone, the tolerability and safety profile appeared satisfactory.

Enantioselective quantitation of the ecstasy compound (R)- and (S)-N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma and urine.

An enantioselective HPLC method has been developed and validated for the stereospecific analysis of N-ethyl-3,4-methylenedioxyamphetamine (MDE) and its major metabolites N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA). These compounds have been analyzed both from human plasma and urine after administration of 70 mg pure MDE-hydrochloride enantiomers to four subjects. The samples were prepared by hydrolysis of the o-glucuronate and sulfate conjugates using beta-glucuronidase/arylsulfatase and solid-phase extraction with a cation-exchange phase. A chiral stationary protein phase (chiral-CBH) was used for the stereoselective determination of MDE, HME and MDA in a single HPLC run using sodium dihydrogenphosphate, ethylendiaminetetraacetic acid disodium salt and isopropanol as the mobile phase (pH 6.44) and fluorimetric detection (lambda(ex) 286 nm, lambda(em) 322 nm). Moreover, a suitable internal standard (N-ethyl-3,4-methylenedioxybenzylamine) was synthesized and qualified for quantitation purposes. The method showed high recovery rates (>95%) and limits of quantitation for MDE and MDA of 5 ng/ml and for HME of 10 ng/ml. The RSDs for all working ranges of MDE, MDA and HME in plasma and urine, respectively, were less than 1.5%. After validation of the analytical methods in plasma and urine samples pharmacokinetic parameters were calculated. The plasma concentrations of (R)-MDE exceeded those of the S-enantiomer (ratio R:S of the area under the curve, 3.1) and the plasma half time of (R)-MDE was longer than that of (S)-MDE (7.9 vs. 4.0 h). In contrast, the stereochemical disposition of the MDE metabolites HME and MDA was reversed. Concentrations of the (S)-metabolites in plasma of volunteers were much higher than those of the (R)-enantiomers.