ORCID Profile
0000-0001-7933-2865
Current Organisation
University of Zurich
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Publisher: MDPI AG
Date: 22-04-2021
DOI: 10.3390/MOLECULES26092451
Abstract: Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin silocin, and 2,5-dimethoxy-4-meth hetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL) displacement with the non-radioactive competitor ketanserin confirmed that the majority of [11C]-MBL specific binding was to serotonin 5-HT2A receptors. However, interactions at serotonin 5HT1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT2A/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([15O]-water) or metabolism ([18F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.NEUBIOREV.2019.11.016
Abstract: Across numerous studies, in iduals with substance use disorders (SUDs) differed from non-using controls regarding valuation of delayed gratification and feedback processing. However, it remains unclear whether the magnitude of the effect sizes is different across these two cognitive processes and how specific SUDs as well as demographic and clinical moderators influence these effects. In this study we thus performed multilevel linear mixed-effects meta-analyses and meta-regressions to examine the effects of SUDs on the Delay Discounting Task (DD) and on the Iowa Gambling Task (IGT). We found a moderate to large effect for SUD on both, the IGT and DD. While the effect on the DD was generalized to all substance classes, a smaller effect for cannabis-related disorder when compared to other SUDs was found with regard to the IGT. Early onset of substance use and psychiatric comorbidities were associated with stronger effects on the DD. Our findings suggest that feedback processing is more vulnerable to specific substance effects, while valuation of delayed gratification depends more on developmental and clinical factors.
Publisher: Cold Spring Harbor Laboratory
Date: 18-04-2023
DOI: 10.1101/2023.04.18.537293
Abstract: Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33 controls: N=43). In an additional analysis using 11 C-ABP688 positron emission tomography (PET) in a male subs le (CU: N=18 controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subs le, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence.
Publisher: Springer Science and Business Media LLC
Date: 03-03-2021
DOI: 10.1038/S41386-021-00977-9
Abstract: Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total s le of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.BBR.2019.112386
Abstract: Chronic cocaine use has been consistently associated with decision-making impairments that contribute to the development and maintenance of drug-taking. However, the underlying cognitive processes of risk-seeking behaviours observed in chronic cocaine users (CU) have so far remained unclear. Here we therefore tested whether CU differ from stimulant-naïve controls in their sensitivity to gain, loss, and probability of loss information when making decisions under risk. A s le of 96 participants (56 CU and 40 controls) performed the no-feedback version of the Columbia Card Task, designed to assess risk-taking in relation to gain, loss, and probability of loss information. Additionally, cognitive performance and impulsivity were determined. Current and recent substance use was objectively assessed by toxicological urine and hair analysis. Compared to controls, CU showed increased risk-seeking in unfavourable decision scenarios in which the loss probability was high and the returns were low, and a tendency for increased risk aversion in more favourable decision scenarios. In comparison to controls, CU were less sensitive to gain, but similarly sensitive to loss and probability of loss information. Further analysis revealed that in idual differences in sensitivity to loss and probability of loss information were related to cognitive performance and impulsivity. Reduced sensitivity to gains in people with CU may contribute to their propensity for making risky decisions. While these alterations in gain sensitivity might directly relate to cocaine use per se, the in idual psychopathological profile of CU might moderate sensitivity to loss information.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.NEUBIOREV.2019.07.006
Abstract: Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating in idual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.
No related grants have been discovered for Boris B. Quednow.