PMID- 37855335
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240105
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 260
IP  - 1
DP  - 2024 Jan 1
TI  - Gestational exposure to cannabidiol leads to glucose intolerance in 3-month-old 
      male offspring.
LID - 10.1530/JOE-23-0173 [doi]
LID - e230173
AB  - Reports in North America suggest that up to 20% of young women (18-24 years) use 
      cannabis during pregnancy. This is concerning given clinical studies indicate 
      that maternal cannabis use is associated with fetal growth restriction and 
      dysglycemia in the offspring. Preclinical studies demonstrated that prenatal 
      exposure to Delta9-tetrahydrocannabinol, the main psychoactive component of cannabis, 
      in rat dams led to female-specific deficits in beta-cell mass and glucose 
      intolerance/insulin resistance. Yet to date, the contributions of cannabidiol 
      (CBD), the primary nonpsychoactive compound in cannabis, remain elusive. This 
      study aimed to define the effects of in utero cannabidiol (CBD) exposure on 
      postnatal glucose regulation. Pregnant Wistar rat dams received daily 
      intraperitoneal injections of either a vehicle solution or 3 mg/kg of CBD from 
      gestational day (GD) 6 to parturition. CBD exposure did not lead to observable 
      changes in maternal or neonatal outcomes; however, by 3 months of age male 
      CBD-exposed offspring exhibited glucose intolerance despite no changes in 
      pancreatic beta/alpha-cell mass. Transcriptomic analysis on the livers of these 
      CBD-exposed males revealed altered gene expression of circadian rhythm clock 
      machinery, which is linked to systemic glucose intolerance. Furthermore, 
      alterations in hepatic developmental and metabolic processes were also observed, 
      suggesting gestational CBD exposure has a long-lasting detrimental effect on 
      liver health throughout life. Collectively, these results indicate that exposure 
      to CBD alone in pregnancy may be detrimental to the metabolic health of the 
      offspring later in life.
FAU - Vanin, Sebastian R
AU  - Vanin SR
AD  - Departments of Obstetrics and Gynaecology, and Physiology and Pharmacology, 
      Schulich School of Medicine and Dentistry, University of Western Ontario, London, 
      Ontario, Canada.
FAU - Lee, Kendrick
AU  - Lee K
AD  - Departments of Obstetrics and Gynaecology, and Physiology and Pharmacology, 
      Schulich School of Medicine and Dentistry, University of Western Ontario, London, 
      Ontario, Canada.
FAU - Nashed, Mina
AU  - Nashed M
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Ontario, Canada.
FAU - Tse, Brennan
AU  - Tse B
AD  - Department of Pathology and Laboratory Medicine, Schulich School of Medicine and 
      Dentistry, The Lawson Health Research Institute and Children's Health Research 
      Institute, University of Western Ontario, London, Ontario, Canada.
FAU - Sarikahya, Mohammed
AU  - Sarikahya M
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Ontario, Canada.
FAU - Brar, Sukham
AU  - Brar S
AD  - Department of Pathology and Laboratory Medicine, Schulich School of Medicine and 
      Dentistry, The Lawson Health Research Institute and Children's Health Research 
      Institute, University of Western Ontario, London, Ontario, Canada.
FAU - Tomy, Gregg
AU  - Tomy G
AD  - Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
FAU - Lucas, Amica-Mariae
AU  - Lucas AM
AD  - Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
FAU - Tomy, Thane
AU  - Tomy T
AD  - Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
FAU - Laviolette, Steven R
AU  - Laviolette SR
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Ontario, Canada.
FAU - Arany, Edith J
AU  - Arany EJ
AD  - Department of Pathology and Laboratory Medicine, Schulich School of Medicine and 
      Dentistry, The Lawson Health Research Institute and Children's Health Research 
      Institute, University of Western Ontario, London, Ontario, Canada.
FAU - Hardy, Daniel B
AU  - Hardy DB
AUID- ORCID: 0000-0001-5445-273X
AD  - Departments of Obstetrics and Gynaecology, and Physiology and Pharmacology, 
      Schulich School of Medicine and Dentistry, University of Western Ontario, London, 
      Ontario, Canada.
AD  - The Lawson Health Research Institute and the Children's Health Research 
      Institute, London, Ontario, Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231123
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 19GBJ60SN5 (Cannabidiol)
SB  - IM
MH  - Pregnancy
MH  - Rats
MH  - Female
MH  - Male
MH  - Humans
MH  - Animals
MH  - Infant
MH  - *Cannabidiol/toxicity
MH  - *Glucose Intolerance/chemically induced
MH  - Rats, Wistar
MH  - *Insulin Resistance
MH  - *Insulin-Secreting Cells
PMC - PMC10762538
OTO - NOTNLM
OT  - cannabidiol
OT  - endocannabinoid system
OT  - glucose intolerance
OT  - insulin signaling
OT  - liver
OT  - pancreas
COIS- We do not have any conflicts of interest to disclose.
EDAT- 2023/10/19 12:42
MHDA- 2023/11/27 12:42
PMCR- 2024/01/03
CRDT- 2023/10/19 07:44
PHST- 2023/05/31 00:00 [received]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/11/27 12:42 [medline]
PHST- 2023/10/19 12:42 [pubmed]
PHST- 2023/10/19 07:44 [entrez]
PHST- 2024/01/03 00:00 [pmc-release]
AID - JOE-23-0173 [pii]
AID - 10.1530/JOE-23-0173 [doi]
PST - epublish
SO  - J Endocrinol. 2023 Nov 23;260(1):e230173. doi: 10.1530/JOE-23-0173. Print 2024 
      Jan 1.