Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice

Carvalho, Renata Karine de; Santos, Mateus Pereira dos; Souza, Maingredy Rodrigues; Rocha, Thiago Lopes; Guimarães, Francisco Silveira; Anselmo-Franci, Janete Aparecida; Mazaro-Costa, Renata

doi:10.1002/jat.3631

Cited by 48 publications

(28 citation statements)

References 37 publications

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“…While sperm quantity was not measured in the previous study, 24 h post-fertilization (hpf) survival can be influenced by sperm quality. A reduction of sperm quantity and quality following exposure to CBD has been observed in other animal models including mice and sea urchins (Carvalho et al 2018;Schuel et al 1987). Notably, these exposures were conducted in adolescent or adult organisms, not during embryonic development.…”

Section: Discussionmentioning

confidence: 90%

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)

et al. 2020

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Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown. This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life. Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5 μM) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30 months later. F0 exposure to CBD significantly increased survival (~20%) and reduced size (wet weight and length) of female fish. While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5 μM CBD significantly reduced sperm concentration in males, but 0.1 μM increased egg production in females. Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16 ink4ab , tnfα, il1b, il6, and pparγ) in the liver. Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls. The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.

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Section: Discussionmentioning

confidence: 90%

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)

et al. 2020

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“…When Swiss mice received 30 mg/kg oral CBD or placebo in sunflower oil for 34 consecutive days, CBD decreased total circulating testosterone by 76% (still within normal ranges), significantly increased abnormalities in spermiation and meiotic stages [104]. CBD-treated mice had a 38% reduction in spermatozoa in the epididymis tail and more head abnormalities in the sperm and cytoplasmic droplets in the flagella medial region.…”

Section: In Vivo Reproductive Effectsmentioning

confidence: 96%

Cannabidiol Adverse Effects and Toxicity

et al. 2019

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Background: Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidiolex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug Administration in 2018. The World Health Organization considers rescheduling cannabis and cannabinoids. CBD use around the world is expanding for diseases that lack scientific evidence of the drug’s efficacy. Preclinical and clinical studies also report adverse effects (AEs) and toxicity following CBD intake. Methods: Relevant studies reporting CBD’s AEs or toxicity were identified from PubMed, Cochrane Central, and EMBASE through January 2019. Studies defining CBD’s beneficial effects were included to provide balance in estimating risk/benefit. Results: CBD is not risk-free. In animals, CBD AEs included developmental toxicity, embryo-fetal mortality, central nervous system inhibition and neurotoxicity, hepatocellular injuries, spermatogenesis reduction, organ weight alterations, male reproductive system alterations, and hypotension, although at doses higher than recommended for human pharmacotherapies. Human CBD studies for epilepsy and psychiatric disorders reported CBD-induced drug-drug interactions, hepatic abnormalities, diarrhea, fatigue, vomiting, and somnolence. Conclusion: CBD has proven therapeutic efficacy for serious conditions such as Dravet and Lennox-Gastaut syndromes and is likely to be recommended off label by physicians for other conditions. However, AEs and potential drug-drug interactions must be taken into consideration by clinicians prior to recommending off-label CBD.

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“…Subsequent to the publication of the paper by Carvalho et al (), it was noticed that the data on Table are the same with Table 2. The correct Table is given below:…”

Section: Sperm Count and Dsp On Testis Of 90‐day‐old Swiss Mice Orallmentioning

confidence: 83%