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Stimulants and psychedelics
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
Hallucinogens produce sensory perception abnormalities in a variety of modalities, including visual and auditory senses. A variety of terms have been used for these drugs including ‘psychedelic’ and ‘psychomimetic’ (Farré et al., 2015). It is believed that the majority of the effects of hallucinogens are mediated by the serotonin 5-HT2A receptor (Halberstadt, 2015) despite the fact that hallucinogenic substances come from multiple chemical families. Hallucinogens can produce alterations and distortions in sensory processing and are reported to produce synaesthesias, in which, for example, music may be perceived as colour patterns (Nichols, 2015).
Spice Drugs, Synthetic Cannabinoids, and ‘Spiceophrenia’
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Duccio Papanti, Laura Orsolini, John M. Corkery, Fabrizio Schifano
In the literature, there are controversial views on the treatment of substance-related/‘dual’ psychotic disorders. Although, according to San et al. (San, Arranz, & Martinez-Raga, 2007), second-generation antipsychotics may confer some advantages over first-generation antipsychotics, for the treatment of substance-induced psychotic disorders, other authors found no evidence of better outcomes with second-generation antipsychotics (Petrakis, Leslie, Finney, & Rosenheck, 2006). Furthermore, other studies found that both clozapine and olanzapine may present distinct advantages in reducing substance-induced psychotic symptoms without increasing craving in patients with concomitant cannabis-use disorders in comparison to patients treated with risperidone (MacHielsen et al., 2012; Machielsen, Veltman, van den Brink, & de Haan, 2018). Finally, clozapine has been reported to reduce substance misuse and improve psychosis, potentially ameliorating the dysfunction within the dopamine-mediated brain reward circuitry implicated in addiction (Green, Noordsy, Brunette, & O’Keefe, 2008). Additionally, second-generation antipsychotics act as antagonists at serotonin 5-HT2A receptors, the main target of most hallucinogenic drugs (Papanti et al., 2018; Valeriani et al., 2015). Further studies clearly need to be carried out to clarify these treatment and management issues.
Lympho-Neuric Syncytium and the Somatodelic Hypothesis
Published in Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen, Harmal, 2017
Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen
Further suggestive evidence had been developed by Rivera-Baltanas et al. (2014) who had used immunocytochemistry to assess 5-HT2A receptor clusters in lymphocytes of patients with depression. Genetic variation in the serotonin receptor gene affected immune responses in rheumatoid arthritis (Snir et al. 2013). The serotonin-receptor 5-HT(2C) was specifically expressed in natural killer lymphocytes of patients with Alzheimer’s disease (Martins et al. 2012). In mice, pharmacological stimulation of the 5-HT2A receptor led to a blocking of the immune response whereas its suppression led to immunological enhancement as measured by CD8(+)T cell counts (Davydova et al. 2010). Serotonin 3A receptors were expressed on B lymphocytes even if they had become neoplastic (Rinaldi et al. 2010). Yin et al. (2006) elucidated the role that serotonin 5-HT1B receptors on T lymphocytes had played in their proliferation.
Has the utilization of serotonin receptor antagonism made an impact on schizophrenia treatment?
Published in Expert Opinion on Pharmacotherapy, 2022
The introduction of atypical, i.e. second generation, antipsychotics (AAPs) since the discovery of clozapine, has been a big step in schizophrenia treatment. They are ‘atypical’ as their clinical profile differs from typical (first-generation) antipsychotics. All AAPs share dopamine and serotonin receptor antagonism (except for amisulpride, which preferentially binds to dopamine D2/D3 receptors). Besides antagonism to the dopamine D2 receptor, the AAPs also block other dopamine receptors such as D1, D3, or D4 [1]. The serotonergic system modulates a broad spectrum of the central nervous system functions through 5-HT binding to 5-HT receptors. The overwhelming majority of research has focused on 5-HT2A receptors antagonism. However, a variety of 5-HT receptors, such as 5-HT2A/2C, 5-HT1A, 5-HT3, 5-HT6, and 5-HT7 receptors, may contribute to the mechanisms of action of ‘atypicality’ [2]. For example, we have data indicating that 5-HT3 receptor antagonists (ondansentron) as adjunctive therapy can improve negative symptoms in schizophrenia [3]. Other molecular targets are also relevant for further AAPs characterization. Some AAPs act at adrenergic alpha 1/2, histamine (especially H1) and muscarinic receptors. Targeting glutamatergic neurotransmission may be also involved. Clinical characteristics of individual AAPs can be predicted according to their molecular profile [1].
The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes
Published in Clinical Toxicology, 2022
Angela L. Chiew, Nicholas A. Buckley
There are at least seven families of 5-HT receptors (5-HT1 to 5-HT7), some of which have multiple subtypes [4,5]. It is likely that no single receptor is responsible for serotonin toxicity. However, stimulation of the 5-HT1A and 5-HT2A receptors have been implicated in serotonin toxicity. The 5-HT1A receptors possibly contribute to some of the milder symptoms of serotonin toxicity including anxiety and hyperactivity [8,9]. Activation of 5HT2A receptors at high serotonin concentrations is implicated in severe serotonin toxicity in animal studies [10,11]. The 5-HT1A receptors have a higher affinity for serotonin than the low-affinity 5-HT2A receptors and are likely to be nearly fully occupied at much lower extracellular 5-HT concentrations [10]. This means that changes in 5-HT1A receptor occupancy and effects are likely to be dominant with small increases in 5-HT.
Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia
Published in Expert Opinion on Drug Safety, 2019
Wade Marteene, Karl Winckel, Sam Hollingworth, Steve Kisely, Erin Gallagher, Margaret Hahn, Bjørn H Ebdrup, Joseph Firth, Dan Siskind
Antagonism of the serotonin receptors, particularly the 5-HT2A and 5-HT2C receptor subtypes, is a characteristic of many SGAs and is widely implicated as a pathway involved in weight gain [38]. Serotonin is a key component of the homeostatic control of satiety and appetite, with expression of the 5-HT2C receptor on POMC and NPY neurons in the ARC [38,57]. Mice treated with olanzapine have shown greater appetite and corresponding weight gain but locaserin – a 5-HT2C agonist – diminished this [58]. This suggests that antagonism of 5-HT2C induces weight gain [58]. Further substantiating the significance of the 5-HT2C receptor in terms of weight gain, olanzapine and clozapine are inverse agonists and induce more weight gain than ziprasidone and aripiprazole, which are partial agonists [6,55,59]. Limited data is available concerning the involvement of the 5-HT2A receptor. However, a study in 15 antipsychotic-naïve patients experiencing their first-episode of schizophrenia has shown a possible link [60]. In this study, neocortical binding of 5-HT2A by quetiapine positively correlated with an increase in BMI [60].