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

Reiche, Simon; Hermle, Leo; Gutwinski, Stefan; Jungaberle, Henrik; Gasser, Peter; Majić, Tomislav

doi:10.1016/j.pnpbp.2017.09.012

Cited by 102 publications

(81 citation statements)

References 87 publications

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“…However, little is known about 5HT 2A levels in patients with anxiety disorders. While 5HT 2A antagonists have been used for the treatment of anxiety disorders (46), 5HT 2A agonists (serotonin hallucinogens) have provided improvement of anxiety and depressive symptoms in patients suffering from life-threatening diseases (49). Thus, the role of cortical 5HT 2A in the regulation of anxiety may depend not only on the specific brain area and type of behavior but also on the emotional context.…”

Section: Discussionmentioning

confidence: 99%

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Santangelo

Sawiak

Fryer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Genetic variation in the serotonin transporter gene (SLC6A4) is associated with vulnerability to affective disorders and pharmacotherapy efficacy. We recently identified sequence polymorphisms in the common marmoset SLC6A4 repeat region (AC/C/G and CT/T/C) associated with individual differences in anxiety-like trait, gene expression, and response to antidepressants. The mechanisms underlying the effects of these polymorphisms are unknown, but a key mediator of serotonin action is the serotonin 2A receptor (5HT2A). Thus, we correlated 5HT2A binding potential (BP) and RNA gene expression in 16 SLC6A4 genotyped marmosets with responsivity to 5HT2A antagonism during the human intruder test of anxiety. Voxel-based analysis and RNA measurements showed a reduction in 5HT2A BP and gene expression specifically in the right posterior insula of individuals homozygous for the anxiety-related variant AC/C/G. These same marmosets displayed an anxiogenic, dose-dependent response to the human intruder after 5HT2A pharmacological antagonism, while CT/T/C individuals showed no effect. A voxel-based correlation analysis, independent of SLC6A4 genotype, revealed that 5HT2A BP in the adjacent right anterior insula and insula proisocortex was negatively correlated with trait anxiety scores. Moreover, 5HT2A BP in both regions was a good predictor of the size and direction of the acute emotional response to the human intruder threat after 5HT2A antagonism. Our findings suggest that genetic variation in the SLC6A4 repeat region may contribute to the trait anxious phenotype via neurochemical changes in brain areas implicated in interoceptive and emotional processing, with a critical role for the right insula 5HT2A in the regulation of affective responses to threat.

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Section: Discussionmentioning

confidence: 99%

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Santangelo

Sawiak

Fryer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…To our knowledge, this work was the first to demonstrate a direct effect of a naturally occurring psychoactive compound in adult neurogenesis. New lines of investigation have suggested that serotoninergic hallucinogens can significantly improve severe depression and anxiety (Reiche et al, 2018 ). Thus, the effect of 5-MeO-DMT in modulating neurogenesis could throw light on the mechanism behind the beneficial effects of hallucinogenic compounds in mood disorders.…”

Section: Discussionmentioning

confidence: 99%

A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus

Cruz

Moulin

Petiz

et al. 2018

Front. Mol. Neurosci.

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The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.

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“…Young people living on the street use prescription drugs rather than heroin and cocaine at a time when, paradoxically, illicit drugs are being considered to treat psychiatric pathologies, reawakening the 1980s theory of drug use as self-medication. (52)(53)(54)(55)(56). They are easily accessible and inexpensive at the street level.…”

Section: Discussionmentioning

confidence: 99%

Is precariousness the blind spot of prevention and treatment of the use of psychoactive substances?

Chossegros

Nino

2020

Preprint

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Background and aims: Prevalence of the use of psychoactive substances is high in precarious populations. Yet the influence of precariousness on the trajectory of drug users (DUs) has rarely been studied. For the first time, we conducted such a study with a representative group of DUs.Methods: We combined a recruitment through a respondent driven sampling (RDS) with a 250 items questionnaire. The answers of our sample of 327 UDs were studied according to a precariousness score (PS).Results: The prevalence of precariousness ranged from low PS 48.9 %, average PS 30.9 % to high PS 20.2 %. Access to health services at the time of our survey concerned 61.8 % of DUs. Its prevalence was lower among DUs with the highest precariousness score (Low PS 72.5 %, Average PS 61.4 %, High PS 36.4 %) with an Odds ratio of 5.01 (CI95% 2.52-9.97; p<0.0001) between low and high PS for a continuous follow-up. A higher dropout rate was also observed among the highest PS (p<0.0001).Despite differences in their socio-economic characteristics, DUs represented a homogeneous community with respect to their use of drugs. The more precarious DUs were younger, had an earlier age of initiation of injection, of experimentation of cannabis, alcohol, heroin as well as diverted opioid substitution treatments (OST). They had a more frequent and durable use of alcohol. Precariousness was also associated with lower educational levels, less contacts with one’s parents, less search for information on the Internet for drugs and GPs for health and more housing and social rights as plans for the future.Conclusion: In France, despite the fact that specialized care is free of charge, the lower access to for the most precarious DUs and their higher drop-out rates suggest that it is not adapted to their demand, which is more oriented towards socio-economic problems than towards drug use or harm reduction. This observation is all the more important as it concerns the youngest users. Our data suggest that precariousness influences the course of drug addiction from its onset. Lack of consideration of this population limits the ability to develop effective health policies.

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

Cited by 102 publications

References 87 publications

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus

Is precariousness the blind spot of prevention and treatment of the use of psychoactive substances?

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