Hexahydrocannabinol (HHC): pharmacokinetics, systemic toxicity, and acute behavioural effects in Wistar rats.

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY

International Journal of Neuropsychopharmacology Pub Date : 2025-07-11 DOI:10.1093/ijnp/pyaf041

Klára Šíchová, Barbara Mallarino, Lucie Janečková, Petr Palivec, Magdaléna Vágnerová, Čestmír Vejmola, Marek Nikolič, Lucie Ladislavová, Kristýna Mazochová, Pavel Ryšánek, Martin Šíma, Adam Šafanda, Bui Quang Hiep, Isis Rita Anzel Koutrouli, Martin Kuchař, Tomáš Páleníček

{"title":"Hexahydrocannabinol (HHC): pharmacokinetics, systemic toxicity, and acute behavioural effects in Wistar rats.","authors":"Klára Šíchová, Barbara Mallarino, Lucie Janečková, Petr Palivec, Magdaléna Vágnerová, Čestmír Vejmola, Marek Nikolič, Lucie Ladislavová, Kristýna Mazochová, Pavel Ryšánek, Martin Šíma, Adam Šafanda, Bui Quang Hiep, Isis Rita Anzel Koutrouli, Martin Kuchař, Tomáš Páleníček","doi":"10.1093/ijnp/pyaf041","DOIUrl":null,"url":null,"abstract":"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 EU and UK as a legal alternative to ∆9-tetrahydrocannabinol (∆9-THC), 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 behaviour 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. Behavioural 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 OECD 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 bloodbrain barrier, exhibits mild toxicity, and induces behavioural effects similar to THC. Its dose-dependent anxiogenic properties and impact on information processing highlight the importance of the appropriate dosing in any potential therapeutic use.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ijnp/pyaf041","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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 EU and UK as a legal alternative to ∆9-tetrahydrocannabinol (∆9-THC), 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 behaviour 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. Behavioural 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 OECD 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 bloodbrain barrier, exhibits mild toxicity, and induces behavioural effects similar to THC. Its dose-dependent anxiogenic properties and impact on information processing highlight the importance of the appropriate dosing in any potential therapeutic use.

查看原文本刊更多论文

六氢大麻酚（HHC）： Wistar大鼠的药代动力学、全身毒性和急性行为效应。

背景：六氢大麻酚（HHC）是一种新的精神活性物质，以其改变精神的作用和暂时的法律地位而闻名。在欧盟和英国的部分地区，它被广泛用作∆9-四氢大麻酚（∆9-THC）的合法替代品，但很少有研究探讨其效果和安全性。本研究考察了HHC在体内的加工过程、毒性及其对雄性Wistar大鼠行为的影响。方法：将(9R)-HHC与(9S)-HHC以1:1的比例按1、5、10 mg/kg灌胃。行为效应评估使用开放场试验和脉冲前抑制声惊吓反应。结果：最大剂量（10 mg/kg）后2 h，血液和脑组织中均检测到HHC的峰值浓度。经合组织423毒性试验将六氯环己烷列为第4类物质，估计致死剂量为1000毫克/公斤。与对照组（使用葵花籽油）相比，10 mg/kg HHC减少了运动，增加了焦虑，并损害了感觉处理。结论：总体而言，HHC穿过血脑屏障，表现出轻微的毒性，并诱导与四氢大麻酚相似的行为效应。其剂量依赖性的焦虑特性和对信息处理的影响突出了在任何潜在治疗用途中适当剂量的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

International Journal of Neuropsychopharmacology 医学-精神病学

CiteScore

8.40

自引率

2.10%

发文量

230

审稿时长

4-8 weeks

期刊介绍： The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.