Current opinion in toxicology最新文献

Cannabidiol and neurodevelopment: Is perception outpacing proof? 大麻二酚和神经发育：感觉超过证据吗？

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-31 DOI: 10.1016/j.cotox.2025.100569

Gurugowtham Ulaganathan , Susan K. Murphy

Cannabidiol (CBD) use has rapidly increased among adolescents, young adults, and pregnant individuals over the last decade. This trend is, in part, fueled by the perception of CBD as relatively harmless, a notion bolstered by its nonpsychoactive nature and the expanding legalization of cannabis products across the United States. CBD readily crosses both the placenta and blood–brain barriers, raising concerns about its impacts on fetal development. This concern is further heightened because its antiemetic and anxiolytic properties are most sought after in early pregnancy, during a time spanning the foundational stages of neurodevelopment. Despite this, CBD's effects on embryonic and fetal development, including neurodevelopment, remain poorly understood. Neurodevelopment is an extended and tightly structured process marked by multiple developmental windows of susceptibility to external perturbations. CBD-induced disruption of early ontogenic trajectories can result in long-term structural and functional deficits. Yet, given the increase in gestational CBD use and the absence of recommended thresholds for use from regulatory or advisory bodies, CBD safety needs to be revisited in the context of its recreational, self-medicating, and therapeutic uses. This lack of understanding must be urgently addressed as CBD use continues to expand while the vulnerability of the developing brain remains a pressing and persistent concern.

在过去十年中，大麻二酚（CBD）在青少年、年轻人和孕妇中的使用迅速增加。这一趋势在一定程度上是由于人们认为CBD相对无害，而CBD的非精神活性和大麻产品在美国各地的合法化也支持了这一观点。CBD很容易穿过胎盘和血脑屏障，这引起了人们对其对胎儿发育影响的担忧。这种担忧进一步加剧，因为它的止吐和抗焦虑特性在怀孕早期最受追捧，在神经发育的基础阶段。尽管如此，CBD对胚胎和胎儿发育（包括神经发育）的影响仍然知之甚少。神经发育是一个扩展和紧密结构的过程，其特征是对外部扰动的敏感性的多个发育窗口。cbd诱导的早期个体发生轨迹的破坏可导致长期的结构和功能缺陷。然而，鉴于妊娠期CBD使用量的增加，以及监管机构或咨询机构没有推荐的使用阈值，CBD的安全性需要在其娱乐、自我用药和治疗用途的背景下重新审视。由于CBD的使用不断扩大，而发育中的大脑的脆弱性仍然是一个紧迫而持久的问题，因此必须紧急解决这种缺乏理解的问题。

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引用次数: 0

Toxicological effects of cannabis on reproduction and human development 大麻对生殖和人类发育的毒理学影响

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-29 DOI: 10.1016/j.cotox.2025.100568

Alexandra Kane , Gillian Watson , Daniel J. Corsi

Cannabis is a recreational drug that is also widely used for its potential therapeutic benefits. Cannabis use has increased in recent years, and products are increasingly accessible in jurisdictions where it has been legalized and commercially distributed. In addition, higher-potency forms of cannabis are now frequently available than in previous decades. In this paper, we discuss the epidemiology and toxicological aspects of cannabis use in relation to its impacts on reproductive function and offspring development. Cannabis and its chemical components tetrahydrocannabinol and cannabidiol demonstrate mild to moderate reproductive and developmental toxicity and adverse effects on exposed humans and animals. A robust biological plausibility exists for a causal association between cannabis use and outcomes through endocannabinoid system disruption and other mechanisms; however, the epidemiological data remain challenging to interpret due to potential confounding. Despite these limitations, continued monitoring of cannabis use in the human population for associations with reproductive and developmental outcomes remains an important public health concern, especially with recent increases in cannabis use prevalence and the move toward legalization in several countries.

大麻是一种娱乐性药物，也因其潜在的治疗益处而被广泛使用。近年来，大麻的使用有所增加，在大麻合法化和商业分销的司法管辖区，大麻产品越来越容易获得。此外，与过去几十年相比，现在可以经常获得效力更高的大麻。在本文中，我们讨论了流行病学和毒理学方面的大麻使用有关其对生殖功能和后代发育的影响。大麻及其化学成分四氢大麻酚和大麻二酚显示出轻度至中度的生殖和发育毒性，并对接触大麻的人和动物产生不利影响。通过内源性大麻素系统破坏和其他机制，大麻使用与结果之间存在强大的生物学合理性；然而，由于潜在的混淆，流行病学数据的解释仍然具有挑战性。尽管存在这些限制，但继续监测人口中大麻使用情况与生殖和发育结果之间的关系仍然是一个重要的公共卫生问题，特别是考虑到最近一些国家大麻使用率上升和走向合法化。

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引用次数: 0

Identification of reference values intended to be protective of human health for potential contaminants in hemp plant material and hemp-based products: Part I. Microbial and elemental contaminants 大麻植物材料和大麻产品中潜在污染物保护人体健康参考值的鉴定：第1部分：微生物和元素污染物

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-15 DOI: 10.1016/j.cotox.2025.100567

Marissa L. Smith , Autumn J. Bernal , Roxana E. Weil , Willie J. McKinney , Julia Hoeng

Cannabis use is rising globally in consumer and medicinal products that are ingested, inhaled, or applied topically. Due to cultivation and manufacturing processes, cannabis plant materials and plant-based products may contain detectable levels of microbial and elemental contaminants of human health concern. A review of regulations and identification of toxicological reference values for these compounds in cannabis is necessary to protect public health and guide manufacturers in regions lacking contaminant regulations.

This review evaluated international and U.S. state regulations and guidance for impurities in cannabis plant material and final consumer products to identify toxicological reference values for common contaminants. A three-step process was used to identify reference values protective of public health for common microbial and elemental contaminants. An initial literature review of contaminants in cannabis and cannabis-based products was conducted, followed by a focal review of international and U.S. state contaminant regulations. A tiered approach was developed to assess the reliability and relevance of each data source, selecting reference values from Tier 1 and Tier 2 sources. The most conservative values were recommended to best protect human health.

While some regions have developed regulations for evaluating contaminants in cannabis products, these vary widely, and significant gaps remain across the industry. In regions without regulations, these discrepancies make it difficult for manufacturers aiming to protect human health to determine which guidance and reference values to follow.

在全球范围内，在摄入、吸入或外用的消费和医药产品中使用大麻的情况正在上升。由于种植和制造过程，大麻植物材料和植物基产品可能含有可检测到的与人类健康有关的微生物和元素污染物。有必要审查法规并确定大麻中这些化合物的毒理学参考值，以保护公众健康并指导缺乏污染物法规的地区的制造商。本综述评估了国际和美国各州关于大麻植物材料和最终消费产品中杂质的法规和指南，以确定常见污染物的毒理学参考值。采用三步法确定常见微生物和元素污染物的公共健康保护参考值。对大麻和基于大麻的产品中的污染物进行了初步文献综述，随后对国际和美国各州的污染物法规进行了重点审查。开发了一种分层方法来评估每个数据源的可靠性和相关性，从第一级和第二级数据源中选择参考值。建议使用最保守的数值以最好地保护人体健康。虽然一些地区已经制定了评估大麻产品中污染物的法规，但这些法规差异很大，整个行业仍存在重大差距。在没有法规的地区，这些差异使旨在保护人类健康的制造商难以确定应遵循哪些指导和参考值。

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引用次数: 0

The unexpected when expecting: Cannabinoid use in pregnancy and postpartum 怀孕时的意外：大麻素在怀孕和产后的使用

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-13 DOI: 10.1016/j.cotox.2025.100554

Maria Katsigeorgis, Terry Gordon

As cannabis legalization expands and its stigma declines, a growing number of pregnant and postpartum women are using cannabis products, often without medical guidance. These women, colloquially referred to as “canna-moms”, frequently turn to cannabinoids like tetrahydrocannabinol (THC) or cannabidiol (CBD) to manage peripartum symptoms such as nausea, insomnia, anxiety, and postpartum depression. Despite increasing popularity, there is cause for concern as THC has been shown to cross the placental barrier and transfer into the breast milk of users, potentially interfering with healthy neurodevelopment both in utero and ex utero. Additionally, inhaled cannabis products may exacerbate pulmonary inflammation during the physiologically sensitive periods of pregnancy and lactation. Belying CBD’s reputation as a safe and natural compound, its safety in peripartum populations is not well understood. This is compounded by labeling inconsistencies and contamination of commercial products. Regulatory gaps and disparities in risk perception create an additional layer of complexity in patient-provider conversations. Here we review toxicological evidence in both gestational and postpartum periods, highlight knowledge gaps particularly for CBD, identify urgent clinical and scientific research needs, and call for a patient-informed policy reform. Until safety and evidence-based guidelines are established, a precautionary approach to cannabis use surrounding pregnancy remains essential for the protection of maternal and fetal well-being.

随着大麻合法化的扩大及其污名的减少，越来越多的孕妇和产后妇女在没有医疗指导的情况下使用大麻产品。这些女性通常被称为“大麻妈妈”，她们经常求助于四氢大麻酚（THC）或大麻二酚（CBD）等大麻素来控制围产期症状，如恶心、失眠、焦虑和产后抑郁。尽管THC越来越受欢迎，但有理由担心，因为THC已被证明可以穿过胎盘屏障，进入使用者的母乳中，可能会干扰子宫内外的健康神经发育。此外，在怀孕和哺乳期的生理敏感期，吸入大麻产品可能加剧肺部炎症。与CBD作为一种安全天然化合物的声誉不符，其在围产期人群中的安全性尚不清楚。由于标签的不一致和商业产品的污染，情况更加复杂。风险认知方面的监管缺口和差异给医患对话带来了额外的复杂性。在此，我们回顾了妊娠期和产后的毒理学证据，强调了CBD的知识差距，确定了迫切的临床和科学研究需求，并呼吁进行患者知情的政策改革。在建立安全和循证指南之前，对怀孕前后使用大麻采取预防性措施对于保护孕产妇和胎儿健康仍然至关重要。

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引用次数: 0

Identification of reference values intended to be protective of human health for potential contaminants in hemp plant material and hemp-based products: Part II. Pesticides and solvents 大麻植物材料和基于大麻的产品中潜在污染物保护人类健康的参考值的鉴定：第2部分。农药和溶剂

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-07 DOI: 10.1016/j.cotox.2025.100555

Marissa L. Smith , Autumn J. Bernal , Roxana E. Weil , Willie J. McKinney , Julia Hoeng

Cannabis use is rising globally in consumer and medicinal products that are ingested, inhaled, or applied topically. Due to cultivation and manufacturing processes, cannabis plant materials and plant-based products may contain detectable levels of pesticides and residual solvents of human health concern. A review of regulations and identification of toxicological reference values for these compounds on cannabis is necessary to protect public health and guide manufacturers in regions lacking contaminant regulations.

This review evaluated international and U.S. state regulations and guidance for impurities in cannabis plant material and final consumer products to identify toxicological reference values for common contaminants. A three-step process was used to identify reference values protective of public health for pesticide and residual solvent contaminants. First, a literature review of contaminants in cannabis and cannabis-based products was conducted, followed by a review of international and U.S. state contaminant regulations. A tiered approach was developed to assess the reliability and relevance of each data source, selecting reference values from Tier 1 and Tier 2 sources. The most conservative values were recommended to best protect human health.

While some regions have developed regulations for evaluating contaminants in cannabis products, these vary widely, and significant gaps remain across the industry. In regions without regulations, these discrepancies make it difficult for manufacturers aiming to protect human health to determine which guidance and reference values to follow.

在全球范围内，在摄入、吸入或外用的消费和医药产品中使用大麻的情况正在上升。由于种植和制造过程，大麻植物材料和植物基产品可能含有可检测到的农药和对人类健康有影响的残留溶剂。为了保护公众健康和指导缺乏污染物法规的地区的制造商，有必要审查有关大麻的法规并确定这些化合物的毒理学参考值。本综述评估了国际和美国各州关于大麻植物材料和最终消费产品中杂质的法规和指南，以确定常见污染物的毒理学参考值。采用三步法确定农药和残留溶剂污染物的公共健康保护参考值。首先，对大麻和基于大麻的产品中的污染物进行了文献综述，然后对国际和美国各州的污染物法规进行了审查。开发了一种分层方法来评估每个数据源的可靠性和相关性，从第一级和第二级数据源中选择参考值。建议使用最保守的数值以最好地保护人体健康。虽然一些地区已经制定了评估大麻产品中污染物的法规，但这些法规差异很大，整个行业仍存在重大差距。在没有法规的地区，这些差异使旨在保护人类健康的制造商难以确定应遵循哪些指导和参考值。

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引用次数: 0

New approaches to historical challenges: Avoiding the early missteps of tobacco research in cannabis studies 应对历史挑战的新方法：避免大麻研究中烟草研究的早期失误

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-06 DOI: 10.1016/j.cotox.2025.100564

Emily T. Wilson , Nicole S. Heimbach , David H. Eidelman , Carolyn J. Baglole

As cannabis use becomes increasingly mainstream for both recreational and medicinal purposes, scientific evaluation of its health effects has not kept pace with legalization and market expansion. This gap echoes historical missteps seen in tobacco regulation, where decades passed before sufficient mechanistic and epidemiologic data on health effects prompted policy action. To avoid repeating such delays in action, this paper advocates for the integration of New Approach Methodologies (NAMs) in cannabis toxicology research, particularly for inhaled products; these tools prioritize human relevance, mechanistic insight, and reduction of animal testing. We highlight three key domains of innovation: (1) air–liquid interface (ALI) exposure systems that more accurately model inhaled cannabis products; (2) human-derived cell models and organoids, including those from induced pluripotent stem cells (iPSCs), which provide insight into tissue-specific toxicity; and (3) computational toxicology platforms such as quantitative structure–activity relationship (QSAR) and physiologically-based pharmacokinetic (PBPK) modeling, which support high-throughput, mechanism-based risk assessment. Together, these tools offer a robust framework for evaluating the diverse and complex constituents of cannabis products, enabling proactive risk assessment and regulation for cannabis-based products.

随着大麻的使用日益成为娱乐和医疗目的的主流，对其健康影响的科学评价没有跟上合法化和市场扩大的步伐。这一差距与烟草监管的历史失误相呼应，过去几十年，有关健康影响的充分机制和流行病学数据才促使政策行动。为了避免重复这种行动延误，本文主张将新方法方法（NAMs）纳入大麻毒理学研究，特别是吸入产品；这些工具优先考虑人的相关性、机制洞察力和减少动物试验。我们强调了三个关键的创新领域：(1)空气-液体界面（ALI）暴露系统，更准确地模拟吸入大麻产品；(2)人类来源的细胞模型和类器官，包括来自诱导多能干细胞（iPSCs）的细胞模型和类器官，可以深入了解组织特异性毒性；(3)计算毒理学平台，如定量构效关系（QSAR）和基于生理的药代动力学（PBPK）模型，支持高通量、基于机制的风险评估。这些工具共同为评估大麻产品的多样化和复杂成分提供了一个强有力的框架，从而能够对基于大麻的产品进行主动风险评估和监管。

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引用次数: 0

An overview of the nonclinical toxicology of cannabidiol oral solution, the first approved therapeutic cannabidiol 概述大麻二酚口服溶液的非临床毒理学，第一个批准治疗大麻二酚

IF 4.6

Current opinion in toxicology

Pub Date : 2025-12-04 DOI: 10.1016/j.cotox.2025.100553

Thomas Lancaster , Kevin Trouba , Dino Manca

Cannabidiol oral solution (CBD-OS; Epidiolex® [US]/Epidyolex® [Europe], 100 mg/mL oral solution) produced from the Cannabis sativa plant is indicated for the treatment of seizures associated with Lennox–Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. The toxicity of CBD-oral solution (CBD-OS) was extensively examined in a variety of in vitro and in vivo nonclinical safety studies. Regulatory-guided studies in the rat, mouse, dog, and rabbit evaluated short-term and chronic toxicity, carcinogenicity, and reproductive toxicity of CBD-OS. In vitro mutagenicity and genotoxicity studies complemented animal toxicology studies. In repeat dose oral toxicity studies of varying durations, noteworthy CBD-OS–related changes were evident in the liver but were not adverse and considered adaptive (consequent to enzyme induction). In reproductive toxicology studies in rats and rabbits, average litter size, embryonic viability, or fetal wastage was not influenced by oral CBD-OS. When administered to male rats, CBD-OS did not affect fertility. CBD-OS did not elicit mutagenic or cytogenetic alterations in genotoxicity assessments in vitro and in vivo and did not indicate a potential for translatable carcinogenicity in dedicated rodent studies. Furthermore, CBD-OS is considered to have limited abuse liability as demonstrated in dedicated in vivo behavioral and in vitro pharmacological studies. The nonclinical toxicology studies described herein (including those completed post approval) supported the initial marketing application of CBD-OS. As part of a series of postmarketing regulatory requirements, metabolite qualification studies remain ongoing at the time of authorship of this manuscript. Overall, the available preclinical data indicate that CBD-OS was well tolerated in animals at doses/exposures exceeding the maximum recommended therapeutic doses in pediatric and adult patients.

大麻二酚口服溶液（CBD-OS； Epidiolex®[美国]/Epidyolex®[欧洲]，100 mg/mL口服溶液）是从大麻植物中提取的，用于治疗lenox - gastaut综合征、Dravet综合征或结节性硬化症相关的癫痫发作。在各种体外和体内非临床安全性研究中，广泛检查了cbd口服溶液（CBD-OS）的毒性。在大鼠、小鼠、狗和兔子中进行的监管指导研究评估了CBD-OS的短期和慢性毒性、致癌性和生殖毒性。体外诱变性和遗传毒性研究补充了动物毒理学研究。在不同持续时间的重复剂量口服毒性研究中，值得注意的是，与cbd - os相关的变化在肝脏中很明显，但不是不利的，被认为是适应性的（酶诱导的结果）。在对大鼠和家兔的生殖毒理学研究中，平均产仔数、胚胎活力或胎儿损耗不受口服CBD-OS的影响。当给雄性大鼠服用CBD-OS时，不影响生育能力。在体外和体内的遗传毒性评估中，CBD-OS没有引起诱变或细胞遗传学改变，在专门的啮齿动物研究中也没有显示出可翻译的致癌性。此外，专门的体内行为和体外药理学研究表明，CBD-OS被认为具有有限的滥用责任。本文描述的非临床毒理学研究（包括批准后完成的研究）支持了CBD-OS的初始市场应用。作为一系列上市后监管要求的一部分，代谢物鉴定研究在撰写本文时仍在进行中。总的来说，现有的临床前数据表明，在儿童和成人患者中，当剂量/暴露超过最大推荐治疗剂量时，动物对CBD-OS的耐受性良好。

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引用次数: 0

Professional needs regarding cannabis: Learning about the endocannabinoid system and cannabinoid pharmacology 关于大麻的专业需求：学习内源性大麻素系统和大麻素药理学

IF 4.6

Current opinion in toxicology

Pub Date : 2025-11-15 DOI: 10.1016/j.cotox.2025.100552

Barbara L.F. Kaplan , Uma V.A. Dhanabalan

The endocannabinoid system (ECS) is a physiological system consisting of cannabinoids receptors (CBs), endogenous lipid-based ligands, known as endocannabinoids, and the enzymes responsible for synthesis and metabolism. Unlike other systems, the discovery of the ECS was relatively recent. Therefore, for many health professionals that currently support the use of medical cannabis for their patients, their knowledge about the ECS and cannabinoid pharmacology was independently acquired. This manuscript aims to provide foundational information about the ECS and cannabinoid pharmacology, advocate for increased education on these topics among all healthcare providers, particularly in regions with established medical cannabis programs, and to promote the inclusion of ECS-related content in curricula of biomedical education programs (e.g., medical, veterinary, pharmacy, nursing). We also recommend a consistent use of the term cannabis in place of marijuana as it reflects the plants’ formal name and helps avoid historical stigma. Staying informed about the ECS and cannabinoid pharmacology empowers healthcare professionals to offer optimal guidance regarding product selection, therapeutic efficacy, dosing, administration methods, and management of potential drug interactions and adverse effects.

内源性大麻素系统（ECS）是一个由大麻素受体（CBs）、内源性脂基配体（内源性大麻素）和负责合成和代谢的酶组成的生理系统。与其他星系不同，ECS的发现相对较晚。因此，对于目前支持为患者使用医用大麻的许多卫生专业人员来说，他们对ECS和大麻素药理学的了解是独立获得的。本文旨在提供有关ECS和大麻素药理学的基本信息，倡导在所有医疗保健提供者中增加这些主题的教育，特别是在已建立医用大麻计划的地区，并促进将ECS相关内容纳入生物医学教育计划的课程（例如，医学，兽医，药学，护理）。我们还建议一致使用大麻一词来代替大麻，因为它反映了植物的正式名称，并有助于避免历史上的耻辱。了解ECS和大麻素药理学使医疗保健专业人员能够提供关于产品选择、治疗效果、剂量、给药方法以及潜在药物相互作用和不良反应管理的最佳指导。

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引用次数: 0

Medicinal cannabinoid use and the risk of developing psychoses and suicidality 药用大麻素的使用与患精神病和自杀的风险

IF 4.6

Current opinion in toxicology

Pub Date : 2025-11-01 DOI: 10.1016/j.cotox.2025.100551

João Pedro Silva , Félix Carvalho

Cannabis and cannabinoid-based products (e.g., dronabinol, nabilone, cannabidiol, nabiximols) have been clinically used for the treatment of different symptoms (e.g., nausea and vomiting in patients subjected to chemotherapy, pain, seizures associated with Lennox-Gastaut and Dravet syndromes, or multiple sclerosis-associated spasticity) in which conventional treatments have failed. However, there is accumulating evidence suggesting that even the medically-supervised use of these substances may lead to the onset of especially critical neuropsychiatric outcomes, such as psychoses and suicidal ideation.

Considering that the medicinal use of cannabis and cannabinoids is expected to further increase as a result of recent legislation changes in different territories worldwide, it is critical to analyze the most recent data on their neuropsychiatric adverse effects. As such, we review recent clinical trials and pharmacovigilance evidence on the mechanisms underlying cannabinoid-induced psychoses and suicidality.

大麻和基于大麻素的产品（例如，屈大麻酚、纳比龙、大麻二酚、纳比ximols）已在临床上用于治疗常规治疗无效的不同症状（例如，化疗患者的恶心和呕吐、疼痛、与Lennox-Gastaut和Dravet综合征相关的癫痫发作或多发性硬化症相关的痉挛）。然而，越来越多的证据表明，即使在医学监督下使用这些物质，也可能导致特别严重的神经精神后果的发作，如精神病和自杀意念。考虑到大麻和大麻素的医疗用途预计将因全球不同地区最近的立法变化而进一步增加，分析其神经精神不良影响的最新数据至关重要。因此，我们回顾了最近的临床试验和药物警戒证据，大麻素诱发精神病和自杀的机制。

引用次数: 0

IUTOX 2023: Addressing complex toxicological endpoints with new approach methodologies IUTOX 2023：用新的方法方法解决复杂的毒理学终点

IF 4.6

Current opinion in toxicology

Pub Date : 2025-09-27 DOI: 10.1016/j.cotox.2025.100550

Emanuela Corsini, Heather Wallace

引用次数: 0