BACKGROUND: Hexahydrocannabinol (HHC) is a new psychoactive substance known for its mind-altering effects and temporary legal status. It is widely used in parts of the Europe and United Kingdom as a legal alternative to ∆9-tetrahydrocannabinol, yet little research has explored its effects and safety. This study examined how HHC is processed in the body, its toxicity, and its impact on behavior in male Wistar rats. METHODS: A 1:1 mixture of (9R)-HHC and (9S)-HHC was administered via intragastric gavage at doses of 1, 5, and 10 mg/kg. Behavioral effects were assessed using the open field test and the prepulse inhibition of acoustic startle response. RESULTS: Two hours after the highest dose (10 mg/kg), peak concentrations of HHC were detected in blood and brain tissue. The Organization for Economic Co-operation and Development 423 toxicity test classified HHC as a Category 4 substance, estimating a lethal dose of 1000 mg/kg. Compared to controls (administered by sunflower oil), 10 mg/kg HHC reduced movement, increased anxiety, and impaired sensory processing. CONCLUSIONS: Overall, HHC crosses the blood-brain barrier, exhibits mild toxicity, and induces behavioral effects similar to tetrahydrocannabinol. Its dose-dependent anxiogenic properties and impact on information processing highlight the importance of the appropriate dosing in any potential therapeutic use.

• Keywords
• acute toxicity, behavior, hexahydrocannabinol, pharmacokinetics, rat,
• MeSH
• Behavior, Animal * drug effects   MeSH
• Cannabinol * toxicity   pharmacokinetics   analogs & derivatives   MeSH
• Rats MeSH
• Brain metabolism   drug effects   MeSH
• Rats, Wistar MeSH
• Prepulse Inhibition * drug effects   MeSH
• Psychotropic Drugs * toxicity   pharmacokinetics   MeSH
• Dronabinol * analogs & derivatives   toxicity   pharmacokinetics   MeSH
• Reflex, Startle drug effects   MeSH
• Anxiety chemically induced   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cannabinol * MeSH
• Psychotropic Drugs * MeSH
• Dronabinol * MeSH