Effects of Adolescent Cannabinoid and Nicotine Exposure...

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Effects of Adolescent Cannabinoid and Nicotine Exposure

Christie Fowler, PhDAssistant Professor

Department of Neurobiology and BehaviorUniversity of California, Irvine

cdfowler@uci.edu

Disclosures

I have no competing interests to disclose.

2019 North American Cannabis Summit 2

Tobacco and Nicotine Addiction

• 6 million premature deaths each year worldwide

• 600,000 deaths second-hand exposure in non-smokers

• Quitting success rate <10% after 1 year• Main psychoactive component in

tobacco: Nicotine

Presenter
Presentation Notes
Size of a larger USB drive JUUL has 78% of market share at the end of 2018

E-Cigarettes and Adolescence

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Chadwick et al., Frontiers in Psychiatry, 2013

High Comorbidity of Nicotine and Cannabis Co-use

Presenter
Presentation Notes
Poster advertising the 1936 film Reefer Madness

Cannabis Exposure During Development

A natural and safe herb? Are there limitations to

this characterization?

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112019 North American Cannabis Summit

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www.the-scientist.com

Drugs and the Brain

How do cannabinoids and nicotine act to

modulate function of the brain?

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THC and CBD act on

cannabinoid receptors in

the brain

2019 North American Cannabis Summit 15www.drugabuse.gov

Nicotine acts on

nicotinic receptors

in the brain

16Jasinska et al. 2013 Neuropharmacology

Presenter
Presentation Notes
Nicotine is taking over the receptors in the brain, so not as much radioligand binding for a4b2 receptors

Research Question

Is adolescence a sensitive period for the

detrimental effects of drug exposure?

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Chadwick et al., Frontiers in Psychiatry, 2013

Dynamic changes in endogenous cannabinoid signaling during adolescence

Presenter
Presentation Notes
4-7 times more likely than adults to develop a marijuana use disorder: Romanowski KS, Barsun A, Kwan P, et al. Butane Hash Oil Burns: A 7-Year Perspective on a Growing Problem. J Burn Care Res Off Publ Am Burn Assoc. 2017;38(1):e165-e171. doi:10.1097/BCR.0000000000000334 Frequent adolescent use of cannabis related to decreased adult IQ May be caused by other factors – shared familial factors (e.g., genetics, family environment, SES, nutrition) Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A. 2012;109(40):E2657-E2664. doi:10.1073/pnas.1206820109

Human and rodent development

2019 North American Cannabis Summit 19Yuan et al., J Physiology, 2015

Adolescent Drug Exposure Paradigm

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PND 38 39 40 41 42 43 44 45 46 47 48 49 70

ControlNIC – NicotineWIN – Cannabinoid receptor agonistNIC/WIN – Nicotine and WIN co-exposure

Cannabinoid exposure in females, but not male, decreases body weight in adolescence

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Research Question

Does adolescent nicotine and/or cannabinoid exposure alter the ability to learn an operant task

in adulthood?

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Adolescent drug exposure does not alter operant learning for food reward in males

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Adolescent drug exposure does not alter operant learning for food reward in females

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Enhanced cognitive flexibility in the reversal task in cannabinoid-exposed males

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Male Female

Research Question

Does adolescent nicotine and/or cannabinoid exposure alter affective behaviors?

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Decreased anxiety-associated behaviors in males, but not females, during adulthood

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Increased sucrose reward exhibited in cannabinoid exposed males, and an opposing effect in females

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Male Female

Group differences not found in a measure of depression

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Male Female

Research Question

Do the reward-related effects predispose groups to altered nicotine reinforcement in adulthood?

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Increased nicotine intake found in cannabinoid-exposed males, whereas decreased intake found in females

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Male Female

Summary

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In males, long-lasting effects of adolescent cannabinoid exposurelead to decreased anxiety-like behaviors, increased reward-related cognitive flexibility, and increased nicotine intake duringadulthood.

Female mice exhibited differential effects than males, withcannabinoid treatment leading to decreased weight gain duringadolescence, and decreased natural reward consumption andnicotine intake during adulthood.

Together, these data provide evidence of long-term effects ofcannabinoid exposure on later affective, cognitive and nicotinetaking behaviors in adulthood.

NIH K99/R00 DA-032543NIH DP1 DA-039658

Fowler LabValeria Lallai, PhDYasmine SherafatAngeline EugeneYen-Chu (Andrew) ChenJP FowlerAmina AhmedAndres Staben RamirezMalia BautistaEashan KothaAdriana Hernandez VasquezMiguel Ruiz RomoRachel Meek

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