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Title: Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast tomore » other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. - Highlights: • We tested the toxic properties of a synthetic cannabinoid. • Acute cytotoxic effects were detected with doses ≥ 7 μM. • No hormonal effects were found. • DNA damage was detected at levels ≥ 10 μM in comet assay and micronucleus tests. • Effects in directly exposed tissues may occur in humans.« less
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [1] ;  [1]
  1. Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria)
  2. Institute of Forensic Medicine, University Medical Center Freiburg, Albertstraße 9, 79104 Freiburg (Germany)
  3. German Federal Environmental Agency, Heinrich-Heine-Str., 12, 08645 Bad Elster (Germany)
Publication Date:
OSTI Identifier:
22439727
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 277; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BONE MARROW; DNA; DNA DAMAGES; DOSES; DRUGS; GENE MUTATIONS; HORMONES; HUMAN POPULATIONS; IN VITRO; LIVER; LUCIFERASE; MEMBRANES; MICROSOMES; MIXTURES; OXIDATION; RECEPTORS; SALMONELLA; SYNTHESIS; TOXICITY