Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition DOI
Izaque de Sousa Maciel, Gabriel H Dias de Abreu,

Claire T. Johnson

et al.

Cannabis and Cannabinoid Research, Journal Year: 2021, Volume and Issue: 7(3), P. 318 - 327

Published: June 29, 2021

Introduction: There is widespread acceptance of cannabis for medical or recreational use across the society, including pregnant women. Concerningly, numerous studies find that developing central nervous system (CNS) vulnerable to detrimental effects Δ9-tetrahydrocannabinol (THC). In contrast, almost nothing on consequences perinatal cannabidiol (CBD) exposure. this study, we used mice investigate adult impact cannabinoid exposure (PCE) with THC, CBD, a 1:1 ratio THC and CBD behaviors. Furthermore, lasting PCE fluoxetine sensitivity in forced swim test (FST) was evaluated probe neurochemical pathways interacting endocannabinoid (ECS). Methods: Pregnant CD1 dams were injected subcutaneously daily vehicle, 3 mg/kg +3 from gestational day 5 postnatal 10. Mass spectroscopic (MS) analyses conducted measure brain levels their embryonic progenies. adults subjected battery behavioral tests: open field arena, sucrose preference test, marble burying nestlet shredding FST. Results: MS analysis found substantial brains. Our testing females receiving buried significantly more marbles than control mice. Interestingly, males THC+CBD had increased preference. While did not affect FST immobility, prevented decreasing immobility both females. Excitingly, fatty acid amide hydrolase (FAAH) inhibition dose URB597 behaviorally inactive rescued efficacy sexes. Conclusions: data suggest either alters repetitive hedonic behaviors phytocannabinoid sex-dependent manner. addition, prevents enhancing coping behavior. The restoration responsiveness by FAAH suggests causes reduction ECS enhancement anandamide signaling represents potential treatment deficits following PCE.

Language: Английский

Acute Cannabinoids Produce Robust Anxiety-Like and Locomotor Effects in Mice, but Long-Term Consequences Are Age- and Sex-Dependent DOI Creative Commons
Chelsea R. Kasten, Yanping Zhang, Stephen L. Boehm

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: Feb. 19, 2019

The rise in cannabinoid legalization and decriminalization the US has been paired with an increase adolescents that perceive marijuana as a "no risk" drug. However, comprehensive review of human literature indicates usage may have both beneficial detrimental effects, adolescent exposure being critical window for harming cognitive development. Although cannabinoids Δ9-tetrahydrocannabinol (THC) cannabidiol (CBD) are often used together recreational medical purposes, no study previously observed acute long-lasting effects THC+CBD battery behavioral assays analogous to subjective reports. current long-term THC, CBD, on object memory, anxiety-like behavior, activity levels adult mice sexes. Acute THC alone combination CBD resulted robust locomotor behavior. A history repeated treatment followed by period without drug administration minimal these assays. Most notably, strongest were seen females administered THC+CBD, which significantly impaired their recognition. No present hippocampal protein expression. These studies represent detailed examination age- sex-effects administration. additional behaviors adults will need be examined more complete picture effects.

Language: Английский

Citations

72
Effects of cannabidiol in males and females in two different rat models of depression DOI
Liat Shbiro, Danielle Hen-Shoval,

Noa Hazut

et al.

Physiology & Behavior, Journal Year: 2018, Volume and Issue: 201, P. 59 - 63

Published: Dec. 17, 2018

Language: Английский

Citations

70
Voluntary oral consumption of Δ9-tetrahydrocannabinol by adolescent rats impairs reward-predictive cue behaviors in adulthood DOI Open Access

Lauren C. Kruse,

Jessica K. Cao,

Katie Viray

et al.

Neuropsychopharmacology, Journal Year: 2019, Volume and Issue: 44(8), P. 1406 - 1414

Published: April 9, 2019

Language: Английский

Citations

56
Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice DOI Creative Commons

Nicole M. Wanner,

Mathia Colwell,

Chelsea Drown

et al.

Clinical Epigenetics, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 6, 2021

Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about underlying molecular mechanisms its effects. Previous work indicates that direct CBD exposure strongly impacts brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed animal human studies. The epigenome, particularly DNA methylation, responsive to environmental input can persistent patterns gene regulation impacting phenotype. Epigenetic perturbation impactful during embryogenesis, when exogenous exposures disrupt critical resetting epigenetic marks impart phenotypic lasting into adulthood. impact prenatal not been evaluated; however, studies using psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental on psychological outcomes developmentally exposed adult offspring. We hypothesized developmental would similar negative behavior mediated part by epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were 20 mg/kg or vehicle daily from two weeks prior mating through gestation lactation. Coat color shifts, a readout methylation at locus this strain, measured F1 Avy/a Young a/a offspring then subjected tests working spatial memory anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed both F0 cerebral cortex hippocampus identify genome-wide changes for exposure, respectively.F1 development exhibited increased anxiety improved sex-specific manner. Further, no significant coat shift offspring, thousands differentially methylated loci (DMLs) brain regions functional enrichment neurogenesis, substance use phenotypes, psychologically relevant terms.These findings demonstrate first time despite positive associated mixed behavioral

Language: Английский

Citations

50
Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review DOI Creative Commons

Nandi Niloy,

Tousif Ahmed Hediyal,

Chandrasekaran Vichitra

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 162 - 162

Published: Jan. 12, 2023

Cannabis is one of the oldest crops grown, traditionally held religious attachments in various cultures for its medicinal use much before introduction to Western medicine. Multiple preclinical and clinical investigations have explored beneficial effects cannabis neurocognitive neurodegenerative diseases affecting cognitive domains. Tetrahydrocannabinol (THC), major psychoactive component, responsible cognition-related deficits, while cannabidiol (CBD), a non-psychoactive phytocannabinoid, has been shown elicit neuroprotective activity. In present integrative review, authors focus on different domains, including learning, consolidation, retrieval. The study first attempt which significant imparted all three aspects cognition, thus linking usage. Furthermore, investigators also depicted current legal position India requirement reforms.

Language: Английский

Citations

17
Effects of Adolescent THC Exposure on the Prefrontal GABAergic System: Implications for Schizophrenia-Related Psychopathology DOI Creative Commons
Justine Renard,

Walter J. Rushlow,

Steven R. Laviolette

et al.

Frontiers in Psychiatry, Journal Year: 2018, Volume and Issue: 9

Published: July 2, 2018

Marijuana is the most commonly used drug of abuse among adolescents. Considerable clinical evidence supports hypothesis that adolescent neurodevelopmental exposure to high levels principal psychoactive component in marijuana, -delta-9-tetrahydrocanabinol (THC), associated with a risk developing psychiatric diseases, such as schizophrenia later life. This marijuana-associated believed be related increasing THC found within marijuana strains. Adolescence highly vulnerable period for development brain, where inhibitory GABAergic system plays pivotal role maturation regulatory control mechanisms central nervous (CNS). Specifically, neurodevelopment represents critical wherein connectivity between higher-order cortical regions and sub-cortical emotional processing circuits mesolimbic dopamine (DA) established. Emerging preclinical demonstrates selectively targets schizophrenia-related molecular neuropharmacological signaling pathways both regions, including prefrontal cortex (PFC) DA pathway, comprising ventral tegmental area (VTA) nucleus accumbens (NAc). Prefrontal hypofunction key feature schizophrenia-like neuropsychopathology. may lead loss PFC regulate proper neurotransmission, thereby leading symptoms. review summarizes demonstrating reduced neurotransmission has DAergic dysregulation behaviours observed following exposure.

Language: Английский

Citations

53
Effect of cannabidiol on endocannabinoid, glutamatergic and GABAergic signalling markers in male offspring of a maternal immune activation (poly I:C) model relevant to schizophrenia DOI

Ashleigh L. Osborne,

Nadia Solowij,

Ilijana Babic

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2019, Volume and Issue: 95, P. 109666 - 109666

Published: June 14, 2019

Language: Английский

Citations

51
Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment DOI
Tibor Štark,

Serena Di Martino,

Filippo Drago

et al.

Pharmacological Research, Journal Year: 2021, Volume and Issue: 174, P. 105938 - 105938

Published: Oct. 15, 2021

Language: Английский

Citations

33
Anxiolytic effects of endocannabinoid enhancing compounds: A systematic review and meta-analysis DOI Creative Commons
C. Kwee, N.A. Leen,

Rian C. Van der Kamp

et al.

European Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 72, P. 79 - 94

Published: April 23, 2023

The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed evidence anxiety-reduction by compounds that facilitate signaling in humans and animals. To identify areas of specific potential, effects moderators were assessed. Literature was searched Pubmed Embase up May 2021. A placebo/vehicle-control group required human studies, randomization. excluded studies co-administered other substances. Risk bias assessed with SYRCLE's RoB tool Cochrane 2.0. conducted three-level random meta-analyses explored sources heterogeneity using Bayesian regularized meta-regression (BRMA). systematic review yielded 134 studies. analyzed 120 (114 animal, 6 human) investigated cannabidiol (CBD, 61), URB597 (39), PF-3845 (6) AM404 (14). Pooled on conditioned unconditioned anxiety animals (with exception anxiety) experimentally induced favored investigational drugs over placebo/vehicle. Publication year negatively associated CBD anxiety. Compared approach avoidance tests, tests repetitive-compulsive behavior larger URB597, social interaction test smaller URB597. Larger observed when pre-existed. Studies reported few side at therapeutic doses. quality low indications publication bias. More clinical trials are needed translate overall positive results applications.

Language: Английский

Citations

16
Species‐specific susceptibility to cannabis‐induced convulsions DOI Creative Commons

Benjamin J. Whalley,

Hong Lin, Lynne Bell

et al.

British Journal of Pharmacology, Journal Year: 2018, Volume and Issue: 176(10), P. 1506 - 1523

Published: Feb. 21, 2018

Numerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9 -tetrahydrocannabinol (THC), variously reported to be pro- and anticonvulsant, cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects prolonged exposure different THC/CBD cannabis extracts on seizure activity associated measures endocannabinoid (eCB) system signalling.Cannabis extract in vivo neurological behavioural responses, bioanalyte levels, were measured rats dogs. Extract using electroencephalography telemetry rats. eCB signalling was also radioligand binding extract-treated treatment-naïve rat, mouse, chicken, dog tissue.Prolonged caused spontaneous, generalized subserved by epileptiform discharges rats, not dogs, produced higher THC, lower 11-hydroxy-THC (11-OH-THC) CBD, plasma concentrations versus In same impaired cannabinoid type 1 receptor (CB1 receptor)-mediated signalling. Profiling CB1 expression, basal activity, extent activation sensitivity THC suggested interspecies differences signalling, being more pronounced a species that exhibited extract-induced seizures (rat) than one did (dog).Sustained treatment differential seizure, levels between Supporting data suggest Interspecies variations may have important implications predicting cannabis-induced convulsions from animal models.This article part themed section 8th European Workshop Cannabinoid Research. To view other articles this visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.

Language: Английский

Citations

45