Toxicology and Analysis of Psychoactive Tryptamines

Abstract

Our understanding of tryptamines is poor due to the lack of data globally. Tryptamines currently are not part of typical toxicology testing regimens and their contribution to drug overdoses may be underestimated. Although their prevalence was low, it is increasing. There are few published data on the many new compounds, their mechanisms of action, onset and duration of action, toxicity, signs and symptoms of intoxication and analytical methods to identify tryptamines and their metabolites. We review the published literature and worldwide databases to describe the newest tryptamines, their toxicology, chemical structures and reported overdose cases. Tryptamines are 5-HT2A receptor agonists that produce altered perceptions of reality. Currently, the most prevalent tryptamines are 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT), 5-methoxy-N,N- diallyltryptamine (5-MeO-DALT) and dimethyltryptamine (DMT). From 2015 to 2020, 22 new analytical methods were developed to identify/quantify tryptamines and metabolites in biological samples, primarily by liquid chromatography tandem mass spectrometry. The morbidity accompanying tryptamine intake is considerable and it is critical for clinicians and laboratorians to be informed of the latest data on this public health threat.

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“…Over the last few years, synthetic tryptamine analogs (STs) show a growing demand among drug users. STs can offer increased potencies compared to natural tryptamines as a result of a functional group modification, specifically from decarboxylation of the amino acid tryptophan [ 71 ].…”

Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain

“…There are currently 14 5-HT receptor subtypes identified having varying affinities for serotonin, present presynaptically, postsynaptically in the CNS and throughout the brain being predominately G protein coupled receptors (except 5-HT3 receptor) [ 47 ]. Agonism of the 5-HT 2A receptors is involved in increasing cortical glutamate levels [ 48 ]. The neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis a natural pathway activated in times of stress also becomes hyperactive in states of depression.…”

“…Fungal biologics of therapeutic potential include lysergic acid diethylamide (LSD) a synthetic derivative of the precursor LSA (d-lysergic acid) or ergine from the rye ergot fungus Claviceps purpurea , muscimol and a DMT derivative from Amanita muscaria mushroom (amongst others) and psilocybin, a hallucinogenic pro-drug of psilocin found in Psilocybe mushrooms (magic mushrooms) ( Table 2 ). Psilocybe alkaloids are more recently obtained from magic truffles (fungis sclerotia) as this species is currently overlooked in the prohibition laws banning sale [ 48 ]. Non hallucinogenic fungal biologics showing potential for mental health treatment include compounds from the edible mushroom Hericium erinaceus and ergothioneine from Pleurotus cornucopiae .…”

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“…Apart from multiple fatalities due to NBOMes, namely 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe (for a review, see [39]), fatalities have also been associated with other novel SPs, e.g. tryptamines (AMT, 5-MeO-AMT, AET, 5-OH-DMT [68]) and derivatives of the phenethylamine groups 2C-x (2C-E [69,70], 2C-T-7, 2C-T-21 [71]) and DOx (DOB, DOC [62,72], Bromo-DragonFLY [73]) (see list of abbreviations). Even if the exact toxicological mechanisms are not well understood in humans, animal studies indicate neuro-and genotoxic properties of certain SPs, such as 5-MeO-DIPT [74], 2C-C, 2C-P [75], and 25B-NBOMe [76,77].…”

“…An analytical challenge is also presented by the substantial number of novel SPs, for which the reference standards or mass spectrum of recently evolved substances may not be available in libraries, so substances' identification may be missed [68]. As not all DC services have the means to quantify SPs with MS, qualitative techniques such as Fourier transform infrared (FTIR) spectroscopy [48], Raman spectroscopy (RS) [50], low-voltage paper spray ionisation quadrupole time-offlight (QTOF)-MS [90], thin-layer chromatography (TLC), or colorimetric reagent tests [4] may be used at least for qualitative analysis, i.e.…”