Florian Jeffry, Salcedo Pablo, Burkhart Keith, Shah Aanchal, Chekka Lakshmi Manasa S, Keshishi Dro, Patel Vikram, Yang ShanChao, Fein Melanie, DePalma Ryan, Matta Murali, Strauss David G, Rouse Rodney
Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
Now with Nurix Therapeutics, San Francisco, California.
JAMA Intern Med. 2025 Jul 7. doi: 10.1001/jamainternmed.2025.2366.
The wide use of unregulated cannabidiol (CBD) products among consumers raises safety concerns. Most research on CBD has studied the relatively high doses used by patients taking prescription CBD. However, limited safety data are available at lower doses.
To study the effects of 4-weeks of twice-daily CBD use on the liver and endocrine hormones using a dose within the range consumers are taking with unregulated CBD products.
DESIGN, SETTING, AND PARTICIPANTS: This randomized double-blinded placebo-controlled trial from January to August 2024, using per protocol analysis, included healthy adults recruited from a clinical pharmacology unit (Spaulding Clinical Research in West Bend, Wisconsin).
Healthy participants were randomized to CBD, 5 mg/kg/d (2.5 mg/kg/d twice daily), or placebo for 28 days with weekly laboratory assessments.
The primary end point was the percentage of participants with an alanine aminotransferase or aspartate aminotransferase level elevation greater than 3 times the upper limit of normal during the study.
In 201 healthy participants (median age, 36 years [IQR, 30-43 years]; 89 women [44%]), 8 participants (5.6%; 95% CI, 1.8%-9.3%) in the CBD group and 0 participants (0%; 95% CI, 0%-7.6%) in the placebo group had liver enzyme level elevation greater than 3 times the upper limit of normal. Seven participants met withdrawal criteria for potential drug-induced liver injury, detected at day 21 in 2 participants and day 28 in 5 participants. No differences in change from baseline were observed between the CBD and placebo groups for total testosterone and inhibin B in male participants or thyrotropin, total triiodothyronine, and free thyroxine in all participants.
In this study, the incidence of elevated alanine aminotransferase or aspartate aminotransferase coupled with the finding of increased eosinophilia, underscores the need for further investigation on the long-term effects of CBD use, its impact on various populations, and the safety of lower doses commonly used by consumers.
ClinicalTrials.gov Identifier: NCT06192589.
消费者中不受监管的大麻二酚（CBD）产品广泛使用引发了安全担忧。大多数关于CBD的研究都集中在服用处方CBD的患者所使用的相对高剂量上。然而，低剂量时的安全数据有限。
使用消费者在使用不受监管的CBD产品时所服用剂量范围内的一种剂量，研究每天两次服用4周CBD对肝脏和内分泌激素的影响。
设计、地点和参与者：这项于2024年1月至8月进行的随机双盲安慰剂对照试验，采用符合方案分析，纳入了从临床药理学单位（威斯康星州韦斯特本的斯波尔丁临床研究中心）招募的健康成年人。
健康参与者被随机分为CBD组，5毫克/千克/天（每天两次，每次2.5毫克/千克），或安慰剂组，为期28天，每周进行实验室评估。
主要终点是研究期间丙氨酸氨基转移酶或天冬氨酸氨基转移酶水平升高超过正常上限3倍的参与者百分比。
在201名健康参与者中（年龄中位数为36岁[四分位间距，30 - 43岁]；89名女性[44%]），CBD组有8名参与者（5.6%；95%置信区间，1.8% - 9.3%），安慰剂组有0名参与者（0%；95%置信区间，0% - 7.6%）的肝酶水平升高超过正常上限3倍。7名参与者符合潜在药物性肝损伤的退出标准，2名参与者在第21天被检测出，5名参与者在第28天被检测出。在男性参与者中，CBD组和安慰剂组的总睾酮和抑制素B，以及在所有参与者中促甲状腺激素、总三碘甲状腺原氨酸和游离甲状腺素从基线的变化没有差异。
在本研究中，丙氨酸氨基转移酶或天冬氨酸氨基转移酶升高的发生率以及嗜酸性粒细胞增多的发现，凸显了对CBD使用的长期影响、其对不同人群的影响以及消费者常用低剂量安全性进行进一步研究的必要性。
ClinicalTrials.gov标识符：NCT06192589。
