International Journal of Molecular Sciences
February 15, 2023
Martina di Bartolomeo, Tibor Stark, Serena di Martino et al.
23 citations
Rats exposed to the toxin methylazoxymethanol acetate (MAM) before birth or to THC shortly after birth showed adult behaviors resembling schizophrenia, such as social withdrawal and memory problems, along with increased expression of cannabinoid and dopamine receptor genes in the prefrontal cortex linked to DNA methylation changes. Giving THC during adolescence impaired social behavior in otherwise healthy rats but did not worsen the schizophrenia-like traits in rats already exposed to THC after birth. In rats exposed to MAM before birth, adolescent THC paradoxically reversed their memory deficit by altering dopamine receptor gene expression. The effects of adolescent THC exposure appear to depend on individual differences in dopamine signaling.
Metabolites
November 12, 2021
Jitka Nykodemová, Anna Šuláková, Petr Palivec et al.
14 citations
The metabolism of the psychoactive compound 2C-B-Fly-NBOMe was investigated using three systems: human liver microsomes, the fungus Cunninghamella elegans, and live rats. Thirty-five phase I and nine phase II metabolites were identified. Major metabolic pathways include hydroxylation, O-demethylation, oxidative debromination, and N-demethoxybenzylation, followed by glucuronidation or N-acetylation. Human liver microsomes produced the most metabolites at highest concentrations. Two poly-hydroxylated metabolites appeared only in rat urine, while the fungus generated dehydrogenated, N-oxygenated, and dibrominated metabolites. These findings clarify how the body processes this substance, aiding understanding of its effects and potential toxicity.
Metabolites
March 31, 2021
Anna Šuláková, Jitka Nykodemová, Petr Palivec et al.
11 citations
N-Benzylphenethylamines, including 25CN-NBOMe, are novel psychedelic substances with limited metabolism data. This study investigated the metabolic profile of 25CN-NBOMe in rats in vivo and in human liver microsomes and Cunninghamella elegans mycelium in vitro. Major metabolic pathways include mono- and bis-O-demethylation, hydroxylation, and combinations, followed by glucuronidation, sulfation, or N-acetylation of primary metabolites. The cyano group was either hydrolyzed to an amide or carboxylic acid or remained unchanged. Differences between species should be considered in metabolism studies of novel substances.
Addiction Biology
August 4, 2022
Klára Šíchová, Kateřina Syrová, Edita Kofroňová et al.
8 citations
25CN-NBOMe, a substance related to LSD, readily crosses the blood-brain barrier in rats. After a 5 mg/kg dose, drug concentration peaked in blood and brain at 1 hour, with half-lives of 1.88 and 2.28 hours. The drug is classified as toxicity category 3, with a lethal dose of 300 mg/kg and an estimated LD50 of 200 mg/kg. Histological findings suggest acute cardiovascular arrest from malignant arrhythmia at lethal doses. A 5 mg/kg dose reduced body temperature in individually housed rats. Lower doses (0.2 and 1 mg/kg) reduced locomotor activity and increased anxiety, while 5 mg/kg also impaired sensorimotor gating. The drug's behavioral effects are comparable to other NBOMes.
Scientific Reports
April 22, 2024
Oleh Durydivka, Petr Palivec, Matej Gazdarica et al.
7 citations
Hexahydrocannabinol (HHC) activates cannabinoid receptor 1 (CB1R) in ways only broadly comparable to Δ9-tetrahydrocannabinol (Δ9-THC), with each HHC epimer showing unique signaling properties. HHC's greater chemical stability than Δ9-THC makes it a potential candidate for modern medicine. The study examined the pharmacodynamics of HHC epimers and their activation of CB1R-mediated signaling pathways, comparing them to those activated by Δ9-THC.
The international journal of neuropsychopharmacology
August 1, 2025
Klára Šíchová, Barbara Mallarino, Lucie Janeckova et al.
1 citation
Hexahydrocannabinol (HHC), a new psychoactive substance used as a legal alternative to ∆9-tetrahydrocannabinol, crosses the blood-brain barrier, exhibits mild toxicity, and induces behavioral effects similar to tetrahydrocannabinol in male Wistar rats. A 1:1 mixture of (9R)-HHC and (9S)-HHC was given at doses of 1, 5, and 10 mg/kg. Two hours after the highest dose, peak concentrations appeared in blood and brain tissue. The OECD 423 test classified HHC as Category 4, with an estimated lethal dose of 1000 mg/kg. Compared to controls, 10 mg/kg HHC reduced movement, increased anxiety, and impaired sensory processing, highlighting dose-dependent anxiogenic properties and impact on information processing.
Journal of pharmaceutical and biomedical analysis
August 1, 2026
Magdaléna Vágnerová, Petr Palivec, Monika Mrňavá et al.
The metabolism of the recreational drug 25E-NBOH was investigated in human liver microsomes, rat urine, and Cunninghamella elegans fungus. Using untargeted LC-HRMS/MS, 56 metabolites were annotated, many as isomers. Primary metabolic pathways included hydroxylation, O-demethylation, and N-debenzylation, followed by conjugation. Ten reference substances were synthesized; seven matched detected metabolites by retention time and MS/MS spectra, enabling structural assignment. The known psychoactive substance 2C-E was confirmed as a metabolite. Three main biomarkers are proposed. This work provides the first comprehensive metabolic profile of 25E-NBOH, supporting future pharmacological and toxicological studies and aiding clinical diagnosis of intoxication.
October 2, 2024
Klára Šíchová, Barbara Mallarino, Lucie Janeckova et al.
Hexahydrocannabinol (HHC), a psychoactive cannabinoid used as a legal alternative to THC, readily crosses the blood-brain barrier in male Wistar rats. After oral administration, both HHC epimers peaked in blood and brain tissue at two hours. The estimated lethal dose was 1000 mg/kg, classifying HHC as a Category 4 substance with mild toxicity. At the highest dose (10 mg/kg), HHC reduced locomotor activity, increased anxiety, and impaired sensorimotor gating, producing behavioral effects similar to THC-like cannabinoids.