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Article ; Online: Understanding the Association of Childhood Tobacco Use With Neuropathological Outcomes and Cognitive Performance Deficits in Vulnerable Brains.

Laviolette, Steven R

JAMA network open

2022 Volume 5, Issue 8, Page(s) e2226001

MeSH term(s)	Brain/pathology ; Cognition ; Cognition Disorders ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/pathology ; Humans ; Tobacco Use
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2022.26001
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Article ; Online: Molecular and neuronal mechanisms underlying the effects of adolescent nicotine exposure on anxiety and mood disorders.

Laviolette, Steven R

Neuropharmacology

2020 Volume 184, Page(s) 108411

Abstract: Tobacco addiction is highly co-morbid with a variety of mental health conditions, including schizophrenia, mood and anxiety disorders. Nicotine, the primary psychoactive compound in tobacco-related products is known to functionally modulate brain ... ...

Abstract	Tobacco addiction is highly co-morbid with a variety of mental health conditions, including schizophrenia, mood and anxiety disorders. Nicotine, the primary psychoactive compound in tobacco-related products is known to functionally modulate brain circuits that are disturbed in these disorders. Nicotine can potently regulate the transmission of various neurochemicals, including dopamine (DA), γ-amino-butyric acid (GABA) and glutamate, within various mesocorticolimbic structures, such as the ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC), all of which show pathologies in these disorders. Many neuropsychiatric diseases have etiological origins during neurodevelopment, typically occurring during vulnerable periods of adolescent or pre-natal brain development. During these neurodevelopmental periods, exposure to extrinsic drug insults can induce enduring and long-term pathophysiological sequelae that ultimately increase the risk of developing chronic mental health disorders in later life. These vulnerability factors are of growing concern given rising rates of adolescent nicotine exposure via traditional tobacco use and the increasing use of alternative nicotine delivery formats such as vaping and e-cigarettes. A large body of clinical and pre-clinical evidence points to an important role for adolescent exposure to nicotine and increased vulnerability to developing mood and anxiety disorders in later life. This review will examine current clinical and pre-clinical evidence that pinpoints specific mechanisms within the mesocorticolimbic circuitry and molecular biomarkers linked to the association between adolescent nicotine exposure and increased risk of developing mood and anxiety-related disorders. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.
MeSH term(s)	Adolescent ; Adolescent Behavior/drug effects ; Adolescent Behavior/psychology ; Animals ; Anxiety Disorders/chemically induced ; Anxiety Disorders/metabolism ; Anxiety Disorders/psychology ; Brain/drug effects ; Brain/metabolism ; Electronic Nicotine Delivery Systems ; Humans ; Mood Disorders/chemically induced ; Mood Disorders/metabolism ; Mood Disorders/psychology ; Nicotine/administration & dosage ; Nicotine/adverse effects ; Tobacco Use/adverse effects ; Tobacco Use/metabolism ; Tobacco Use/psychology ; Vaping/adverse effects ; Vaping/metabolism ; Vaping/psychology
Chemical Substances	Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2020-11-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2020.108411
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Article ; Online: Exploring the impact of adolescent exposure to cannabinoids and nicotine on psychiatric risk: insights from translational animal models.

Laviolette, Steven R

Psychological medicine

2019 Volume 51, Issue 6, Page(s) 940–947

Abstract: Adolescence represents a highly sensitive period of mammalian neurodevelopment wherein critical synaptic and structural changes are taking place in brain regions involved in cognition, self-regulation and emotional processing. Importantly, neural ... ...

Abstract	Adolescence represents a highly sensitive period of mammalian neurodevelopment wherein critical synaptic and structural changes are taking place in brain regions involved in cognition, self-regulation and emotional processing. Importantly, neural circuits such as the mesocorticolimbic pathway, comprising the prefrontal cortex, sub-cortical mesolimbic dopamine system and their associated input/output centres, are particularly vulnerable to drug-related insults. Human adolescence represents a life-period wherein many individuals first begin to experiment with recreational drugs such as nicotine and cannabis, both of which are known to profoundly modulate neurochemical signalling within the mesocorticolimbic pathway and to influence both long-term and acute neuropsychiatric symptoms. While a vast body of epidemiological clinical research has highlighted the effects of adolescent exposure to drugs such as nicotine and cannabis on the developing adolescent brain, many of these studies are limited to correlative analyses and rely on retrospective self-reports from subjects, making causal interpretations difficult to discern. The use of pre-clinical animal studies can avoid these issues by allowing for precise temporal and dose-related experimental control over drug exposure during adolescence. In addition, such animal-based research has the added advantage of allowing for in-depth molecular, pharmacological, genetic and neuronal analyses of how recreational drug exposure may set up the brain for neuropsychiatric risk. This review will explore some of the advantages and disadvantages of these models, with a focus on the common, divergent and synergistic effects of adolescent nicotine and cannabis exposure on neuropsychiatric risk.
MeSH term(s)	Adolescent ; Animals ; Brain/drug effects ; Cannabinoids/adverse effects ; Disease Models, Animal ; Drug Synergism ; Humans ; Mental Disorders/epidemiology ; Mental Disorders/physiopathology ; Mental Disorders/psychology ; Nicotine/adverse effects ; Risk Factors ; Smoking/adverse effects
Chemical Substances	Cannabinoids ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2019-12-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	217420-0
ISSN	1469-8978 ; 0033-2917
ISSN (online)	1469-8978
ISSN	0033-2917
DOI	10.1017/S0033291719003325
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Article ; Online: Cannabidiol Exposure During Gestation Leads to Adverse Cardiac Outcomes Early in Postnatal Life in Male Rat Offspring.

Lee, Kendrick / Vanin, Sebastian / Nashed, Mina / Sarikahya, Mohammed Halit / Laviolette, Steven R / Natale, David R C / Hardy, Daniel B

Cannabis and cannabinoid research

2024

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2023.0213
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Article ; Online: Reversing the Psychiatric Effects of Neurodevelopmental Cannabinoid Exposure: Exploring Pharmacotherapeutic Interventions for Symptom Improvement.

De Felice, Marta / Laviolette, Steven R

International journal of molecular sciences

2021 Volume 22, Issue 15

Abstract: Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and ...

Abstract	Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.
MeSH term(s)	Animals ; Cannabis/adverse effects ; Dronabinol/adverse effects ; GABA Agents/therapeutic use ; Humans ; Neurodevelopmental Disorders/chemically induced ; Neurodevelopmental Disorders/drug therapy ; Psychology, Adolescent
Chemical Substances	GABA Agents ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2021-07-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22157861
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Article ; Online: Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life.

Lee, Kendrick / Laviolette, Steven R / Hardy, Daniel B

Pediatric research

2021 Volume 90, Issue 3, Page(s) 532–539

Abstract: Background: Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing ... ...

Abstract	Background: Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods: Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results: Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions: Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact: To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.
MeSH term(s)	Animals ; Birth Weight ; Dronabinol/pharmacology ; Female ; Heart/drug effects ; Maternal Exposure ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar
Chemical Substances	Dronabinol (7J8897W37S)
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-021-01511-9
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Article: Prenatal Cannabinoid Exposure: Emerging Evidence of Physiological and Neuropsychiatric Abnormalities.

Nashed, Mina G / Hardy, Daniel B / Laviolette, Steven R

Frontiers in psychiatry

2021 Volume 11, Page(s) 624275

Abstract: Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing ... ...

Abstract	Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing global legalization and the overall perceptions of safety, even during pregnancy. These trends are further compounded by a lack of evidence-based policy and guidelines for prenatal cannabis use, which has led to inconsistent messaging by healthcare providers and medically licensed cannabis dispensaries regarding prenatal cannabis use for treatment of symptoms, such as nausea. Additionally, the use of cannabis to self-medicate depression and anxiety during pregnancy is a growing medical concern. This review aims to summarize recent findings of clinical and preclinical data on neonatal outcomes, as well as long-term physiological and neurodevelopmental outcomes of prenatal cannabis exposure. Although many of the outcomes under investigation have produced mixed results, we consider these data in light of the unique challenges facing cannabis research. In particular, the limited longitudinal clinical studies available have not previously accounted for the exponential increase in (-)-Δ9- tetrahydrocannabinol (Δ9-THC; the psychoactive compound in cannabis) concentrations found in cannabis over the past two decades. Polydrug use and the long-term effects of individual cannabis constituents [Δ9-THC vs. cannabidiol (CBD)] are also understudied, along with sex-dependent outcomes. Despite these limitations, prenatal cannabis exposure has been linked to low birth weight, and emerging evidence suggests that prenatal exposure to Δ9-THC, which crosses the placenta and impacts placental development, may have wide-ranging physiological and neurodevelopmental consequences. The long-term effects of these changes require more rigorous investigation, though early reports suggest Δ9-THC increases the risk of cognitive impairment and neuropsychiatric disease, including psychosis, depression, anxiety, and sleep disorders. In light of the current trends in the perception and use of cannabis during pregnancy, we emphasize the social and medical imperative for more rigorous investigation of the long-term effects of prenatal cannabis exposure.
Language	English
Publishing date	2021-01-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2020.624275
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Article ; Online: Maternal Delta-9-Tetrahydrocannabinol Exposure Induces Abnormalities of the Developing Heart in Mice.

Robinson, Gregory I / Ye, Fang / Lu, Xiangru / Laviolette, Steven R / Feng, Qingping

Cannabis and cannabinoid research

2022 Volume 9, Issue 1, Page(s) 121–133

Abstract: Introduction: ...

Abstract	Introduction:
MeSH term(s)	Humans ; Mice ; Animals ; Pregnancy ; Female ; Dronabinol/adverse effects ; Stroke Volume ; Mice, Inbred C57BL ; Ventricular Function, Left ; Cannabis/adverse effects ; Fetal Heart ; Cannabinoid Receptor Agonists/pharmacology ; Heart Defects, Congenital
Chemical Substances	Dronabinol (7J8897W37S) ; Cannabinoid Receptor Agonists
Language	English
Publishing date	2022-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2022.0180
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Article: Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?

O'Sullivan, Saoirse E / Stevenson, Carl W / Laviolette, Steven R

Cannabis and cannabinoid research

2021 Volume 6, Issue 1, Page(s) 7–18

Abstract: Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), ...

Abstract	Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), a chemical isolated from
MeSH term(s)	Anxiety Disorders/drug therapy ; Anxiety Disorders/etiology ; COVID-19 ; Cannabidiol/pharmacology ; Cannabinoid Receptor Modulators/pharmacology ; Humans
Chemical Substances	Cannabinoid Receptor Modulators ; Cannabidiol (19GBJ60SN5)
Language	English
Publishing date	2021-02-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2020.0102
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Article ; Online: Reversing the Psychiatric Effects of Neurodevelopmental Cannabinoid Exposure

Marta De Felice / Steven R. Laviolette

International Journal of Molecular Sciences, Vol 22, Iss 7861, p

Exploring Pharmacotherapeutic Interventions for Symptom Improvement

2021 Volume 7861

Abstract	Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.
Keywords	cannabis ; marijuana ; THC ; endocannabinoid system ; adolescence ; neurodevelopment ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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