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Concept: Psychedelics, dissociatives and deliriants

806

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Concepts: Nervous system, Brain, Human brain, Cerebral cortex, Lysergic acid diethylamide, Psychedelic drug, Psychedelics, dissociatives and deliriants, Timothy Leary

145

Use of unauthorized synthetic drugs is a serious, forensic, regulatory and public health issue. In this scenario, consumption of drug-impregnated blotters is very frequent. For decades, blotters have been generally impregnated with the potent hallucinogen known as lysergic acid diethylamide (LSD); however, since 2013 blotter stamps with N-2 methoxybenzyl-substituted phenylethylamine hallucinogen designated as “NBOMes” have been seized in Chile. To address this issue with readily accessible laboratory equipment, we have developed and validated a new HPTLC method for the identification and quantitation of 25-C-NBOMe in seized blotters and its confirmation by GC-MS. The proposed method was validated according to SWGTOX recommendations and is suitable for routine analysis of seized blotters containing 25-C-NBOMe. With the validated method, we analyzed 15 real samples, in all cases finding 25-C-NBOMe in a wide dosage range (701.0-1943.5 µg per blotter). In this situation, we can assume that NBOMes are replacing LSD as the main hallucinogenic drug consumed in blotters in Chile.

Concepts: Drug, Lysergic acid diethylamide, Lysergic acid, Ergot, Psychedelic drug, Psychedelics, dissociatives and deliriants, Ergoline

144

People with schizophrenia who hallucinate show impairments in reality monitoring (the ability to distinguish internally generated information from information obtained from external sources) compared to non-hallucinating patients and healthy individuals. While this may be explained at least in part by an increased externalizing bias, it remains unclear whether this impairment is specific to reality monitoring, or whether it also reflects a general deficit in the monitoring of self-generated information (internal source monitoring). Much interest has focused recently on continuum models of psychosis which argue that hallucination-proneness is distributed in clinical and non-clinical groups, but few studies have directly investigated reality monitoring and internal source monitoring abilities in healthy individuals with a proneness to hallucinations. Two experiments are presented here: the first (N = 47, with participants selected for hallucination-proneness from a larger sample of 677 adults) found no evidence of an impairment or externalizing bias on a reality monitoring task in hallucination-prone individuals; the second (N = 124) found no evidence of atypical performance on an internal source monitoring task in hallucination-prone individuals. The significance of these findings is reviewed in light of the clinical evidence and the implications for models of hallucination generation discussed.

Concepts: Critical thinking, Schizophrenia, Hallucination, Psychosis, Psychedelics, dissociatives and deliriants, Hallucinations in the sane

113

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts towards openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol.

Concepts: Clinical trial, Clinical research, Serotonin, Clinical psychology, Psychotherapy, Adverse event, Psychedelic drug, Psychedelics, dissociatives and deliriants

96

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.

Concepts: Randomized controlled trial, Drug addiction, Lysergic acid diethylamide, Lysergic acid, Ergot, Psilocybin mushrooms, Psychedelics, dissociatives and deliriants, Dimethyltryptamine

31

Studies have highlighted psychosocial factors associated with drug use among adolescents. Association of specific psychiatric comorbidity with substance use has not been properly established in Brazil. This study aimed to investigate alcohol, tobacco, and marijuana use by 15-18-year-old high school Brazilian students and to estimate associations with psychiatric symptoms.

Concepts: The Association, Drug addiction, High school, Mental disorder, Psychiatry, Brazil, Psychedelics, dissociatives and deliriants

28

This case report offers rare insights into crossmodal responses to psychedelic drug use in a congenitally blind (CB) individual as a form of synthetic synesthesia. BP’s personal experience provides us with a unique report on the psychological and sensory alterations induced by hallucinogenic drugs, including an account of the absence of visual hallucinations, and a compelling look at the relationship between LSD induced synesthesia and crossmodal correspondences. The hallucinatory experiences reported by BP are of particular interest in light of the observation that rates of psychosis within the CB population are extremely low. The phenomenology of the induced hallucinations suggests that experiences acquired through other means, might not give rise to “visual” experiences in the phenomenological sense, but instead gives rise to novel experiences in the other functioning senses.

Concepts: Sensory system, Hallucination, Psychosis, Synesthesia, Psychedelic drug, Psychedelics, dissociatives and deliriants, Hallucinations in the sane, Psychedelic

28

The majority of patients with schizophrenia suffer from hallucinations. While the triple-network model, which includes the default mode network (DMN), the central executive network (CEN) and the salience network (SAL), has recently been applied to schizophrenia, how this framework could explain the emergence of hallucinations remains unclear. Therefore, complementary brain regions that have been linked to hallucinations, such as the left hippocampus, should also be considered and added to this model. Accordingly, the present study explored the effective connectivity across these four components (i.e., the quadripartite model) during the different stages of hallucinations. Twenty-five patients with schizophrenia participated in a single session of resting-state functional magnetic resonance imaging to capture hallucinatory experiences. Based on the participants' self-report of the psychosensory experiences that occurred during scanning, hallucinatory experiences were identified and divided into four stages: periods without hallucination (“OFF”), periods with hallucination (“ON”), transition periods between “OFF” and “ON”, and the extinction of the hallucinatory experience (“END”). Using stochastic dynamic causal modeling analysis, this study first confirmed that the SAL played a critical and causal role in switching between the CEN and the DMN in schizophrenia. In addition, effective connectivity within the quadripartite model depended on the hallucinatory stage. In particular, “ON” periods were linked to memory-based sensory input from the hippocampus to the SAL, while “END” periods were associated with a takeover of the CEN in favor of a voluntary process. Finally, the pathophysiological and therapeutic implications of these findings are critically discussed. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

Concepts: Brain, Magnetic resonance imaging, Hippocampus, Schizophrenia, Hallucination, Psychosis, Psychedelics, dissociatives and deliriants, Hallucinations in the sane

28

BACKGROUND: Cognitive models have postulated that auditory hallucinations arise from the misattribution of internally generated cognitive events to external sources. Several experimental paradigms have been developed to assess this externalizing bias in clinical and non-clinical hallucination-prone samples, including source-monitoring, verbal self-monitoring and auditory signal detection tasks. This meta-analysis aims to synthesize the wealth of empirical findings from these experimental studies. Method A database search was carried out for reports between January 1985 and March 2012. Additional studies were retrieved by contacting authors and screening references of eligible reports. Studies were considered eligible if they compared either (i) hallucinating and non-hallucinating patients with comparable diagnoses, or (ii) non-clinical hallucination-prone and non-prone participants using source-monitoring, verbal self-monitoring or signal detection tasks, or used correlational analyses to estimate comparable effects. RESULTS: The analysis included 15 clinical (240 hallucinating patients and 249 non-hallucinating patients) and nine non-clinical studies (171 hallucination-prone and 177 non-prone participants; 57 participants in a correlation study). Moderate-to-large summary effects were observed in both the clinical and analogue samples. Robust and significant effects were observed in source-monitoring and signal detection studies, but not in self-monitoring studies, possibly due to the small numbers of eligible studies in this subgroup. The use of emotionally valenced stimuli led to effects of similar magnitude to the use of neutral stimuli. CONCLUSIONS: The findings suggest that externalizing biases are important cognitive underpinnings of hallucinatory experiences. Clinical interventions targeting these biases should be explored as possible treatments for clients with distressing voices.

Concepts: Scientific method, Schizophrenia, Hallucination, Psychosis, Bias, Psychedelics, dissociatives and deliriants, Hallucinations in the sane

28

Mertin, P. & O'Brien, N. (2012). High emotional arousal and failures in reality monitoring: Pathways to auditory hallucinations in non-psychotic children? Scandinavian Journal of Psychology. Recent research has confirmed the presence of auditory hallucinations in non-psychotic children, with this research also suggesting that such hallucinations may be more common than previously thought. While auditory hallucinations in children have frequently been associated with high levels of emotional stress, there is still a poor understanding of how this stress may precipitate hallucinations, and why some children experience hallucinations while others seem not to. The current study assessed the association between high levels of trauma symptomatology, anxiety and depression, and the presence of hallucinations against matched controls. Results indicated that hallucinating children had significantly higher mean anxiety, depression and, in particular, re-experiencing scores than did the children in the control group. These results were examined within the framework of reality monitoring, that is, the ability to distinguish between externally or internally generated sources of information. The notion of high levels of emotional distress decreasing the efficiency of reality monitoring and leading to the possibility of confusion between internally and externally generated stimuli was discussed, with the conclusion advanced that the misattribution of an externally generated source - either held as a memory or as a traumatic re-experiencing - as an internally generated one, underlies hallucinatory experiences.

Concepts: Anxiety, Psychology, Schizophrenia, Hallucination, Psychosis, Psychedelics, dissociatives and deliriants, Hallucinations in the sane