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Declan W. AliDepartments of Biological Sciences and Physiology
University of Alberta
Embryonic Exposure to Cannabinoids and Alcohol Alters Early Development in Zebrafish and May Have Long-term Consequences in Adults
Presenter Disclosure
Declan W. Ali
Relationship with commercial interests:
None
50 µm
…from a few of cells…
Animal Models of FASD
• Nematode (C. elegans)• Fruit flies (D. melanogaster)• Xenopus laevis• Zebrafish, Medaka• Chicks• Mice, Rats (third trimester equivalent is post-natal) • Guinea pigs (true in utero exposure over three trimester
equivalents)• Non-human Primates such as macaques (“gold standard” but
expensive, time consuming, ethics)
http://www.seriouslyfish.com/species/oryzias-latipes/
In 2002, about 2.4 % of women admitted to smoking pot while pregnant.
By 2014, about 4% said they got high during their pregnancy.
Increasing marijuana use in
adults
Potency trends of marijuana
Prenatal exposure of marijuana
https://www.ncbi.nlm.nih.gov/pubmed/22103415
Cognitive Behavioral and Neuropsychiatric defects
Cannabinoids
CBDA CBD
THCA THC CBNA CBN
(+) δ9 - THC (-) δ9 - THC
Gaoni and Mechoulam, 1964
Our study:
• Effect of THC, cannabinol, cannabidiol and alcohol (ethanol) on neurodevelopment and neuromuscular activity in embryos
• Effects on zebrafish locomotion• What role do endocannabinoids play in
communication between cells• Expose zebrafish embryos to THC, cannabinol and
cannabidiol during the gastrulation stage of development and then determine the effect on neuronal function.
Zebrafish Development
FertilizationCleavage Gastrulation
0h 5h 10h 24h
Segmentation
48h
PharyngulaHatching
Effects Studied
Drug Exposure
Exposure Timelines
Häggström, Mikael. "Medical gallery of Mikael Häggström2014". Wikiversity Journal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 20018762.
Gestational Timeline in Humans
Gastrulation
Organogenesis
Embryonic exposure to cannabinoids alters morphology
Ahmed et al, Scientific Reports (2018)
36 hpf
Adapted from Devoto et al. Development (1996) 122, 3371-3380.
sc
nc
Transverse section through the trunk of a zebrafish embryo
Exposure to cannabinoids alters neuronal growth and branching
Ahmed et al, Scientific Reports (2018)
Embryonic exposure to cannabinoids alters responses to sound
Controls
THC
Embryonic exposure to alcohol alters motor neurons
Amin et al ( Unpublished)
Time spent in Thigmotaxis
Distance moved
Embryonic exposure to CBD alters adult behavior/locomotion
* ***
Amin et al ( Unpublished)
Summary
• Zebrafish embryos exposed to THC or CBD experience
morphological defects.
• Zebrafish embryos exposed to THC or CBD exhibit reduced
hatching, survival and heart rates.
• Zebrafish embryos exposed to THC or CBD exhibit reduced
branching patterns of motoneurons and fewer neuromuscular
junctions.
• Zebrafish embryos show reduced sensation to sound
Acknowledgements
• Trevor Hamilton (Collaborator at Grant Macewan University.
• Jeffrrey Crook (undergraduate student, Grant Macewan University)
• Md Ruhul Amin (PhD student)• Kazi T, Ahmed(PhD student)• Janatul Ferdous (MSc student)
Learning Objectives
1. To recognize the effect of cannabinoids on early development.
2. To describe the combined effects of cannabinoids and alcohol on early development and maturation.
3. To identify or review the implications of cannabinoid exposure for pregnancy.
USA
According to National Survey on Drug Use and Health in the United States-
In 2009-2010 - 3.6%In 2011-2012 - 5.2%.
During the first trimester - 10.7%
Canada
In 2008, illicit drug use during pregnancy was about 5% (According to Canadian Perinatal Health Report)
In 2013, the percentage was reported as 11% (According to Health Canada)
http://www.poppot.org/category/addiction/
(Substance Abuse and Mental Health Services Administration [SAMHSA], 2013)
Illicit drug usage during pregnancy is increasing
References
Ahmed, K.T. et al. Scientific Reports (2018) 8:10518.
Devoto, S.H. et al. Development (1996) 122: 3371-3380.
Mechoulam, R. and Gaoni Y., J Am Chem Soc (1965) 87:3273-3275.
Häggström, M. "Medical gallery of Mikael Häggström 2014". Wikiversity Journal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 20018762.
Shan, S. et al. Neurotoxicology and Teratology (2015) 48: 18-27.
Substance Abuse and Mental Health Services Administration [SAMHSA], 2013)
Managing Potential Bias
Not required.