Pharmacological Research
February 1, 2025
Michaela Dvorakova, Ken Mackie, Alex Straiker
2 citations
Δ9-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, acts in the brain primarily via cannabinoid CB1 receptors. These receptors are implicated in several forms of synaptic plasticity - depolarization-induced suppression of excitation (DSE), metabotropic suppression of excitation (MSE), long term depression (LTD) and activation-dependent desensitization. Cultured...
Scientific Reports
April 22, 2024
Oleh Durydivka, Petr Palivec, Matej Gazdarica et al.
7 citations
Abstract The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the...
Cannabis and Cannabinoid Research
October 1, 2023
Pedro Henrique Gobira, Jacob LaMar, Jade Marques et al.
Introduction: The antidepressant properties of ketamine have been extensively demonstrated in experimental and clinical settings. However, the psychotomimetic side effects still limit its wider use as an antidepressant. It was recently observed that endocannabinoids are inolved in ketamine induced reward properties. As an increase in endocannabinoid signaling induces antidepressant effects,...
Molecular Pharmacology
December 2022
Taryn Bosquez-Berger, Sierra Wilson, Christos Iliopoulos-Tsoutsouvas et al.
The two main constituents of cannabis are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). While Δ9-THC pharmacology has been studied extensively, CBD-long considered inactive-is now the subject of vigorous research related to epilepsy, pain, and inflammation and is popularly embraced as a virtual cure-all. However, our understanding of CBD pharmacology remains limited, although CBD...
Cerebral Cortex
November 21, 2022
Miguel Garzón, June Chan, Ken Mackie et al.
Chronic adolescent administration of marijuana's major psychoactive compound, ∆9-tetrahydrocannabinol (Δ9-THC), produces adaptive changes in adult social and cognitive functions sustained by prelimbic prefrontal cortex (PL-PFC). Memory and learning processes in PL-PFC neurons can be regulated through cholinergic muscarinic-2 receptors (M2R) and modulated by activation of cannabinoid-1 receptors...
Journal of Psychopharmacology
May 25, 2021
Ashley M. Schnakenberg Martin, Dae-Jin Kim, Sharlene D. Newman et al.
Background: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state...
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
August 1, 2020
Hui-Chen Lu, Ken Mackie
The endocannabinoid system (ECS) is a widespread neuromodulatory network involved both in the developing CNS as well as playing a major role in tuning many cognitive and physiological processes. The ECS is composed of endogenous cannabinoids, cannabinoid receptors and the enzymes responsible for the synthesis and degradation of endocannabinoids. In addition to its endogenous roles, cannabinoid...
Biochimica et biophysica acta. Molecular and cell biology of lipids
May 2018
Emma Leishman, Michelle Murphy, Ken Mackie et al.
Exposing the adolescent brain to drugs of abuse is associated with increased risk for adult onset psychopathologies. Cannabis use peaks during adolescence, with largely unknown effects on the developing brain. Cannabis' major psychoactive component, Δ9-tetrahydrocannabinol (THC) alters neuronal, astrocytic, and microglial signaling. Therefore, multiple cellular and signaling pathways are...
Behavior genetics
May 2018
Chelsea R Kasten, Yanping Zhang, Ken Mackie et al.
Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity...
Biological Psychiatry
April 1, 2016
Hui-Chen Lu, Ken Mackie
The endocannabinoid system (ECS) is a widespread neuromodulatory system that plays important roles in central nervous system development, synaptic plasticity, and the response to endogenous and environmental insults. The ECS comprises cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes responsible for the synthesis and degradation of the endocannabinoids. The most...
Neurobiology of Disease
October 2015
Michael D Ballinger, Atsushi Saito, Bagrat Abazyan et al.
Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental illnesses before full-onset in early adulthood, it is particularly important to...
Journal of Neuroscience
April 9, 2014
Daniel J Morgan, Brian J Davis, Chris S Kearn et al.
For many G-protein-coupled receptors (GPCRs), including cannabinoid receptor 1 (CB1R), desensitization has been proposed as a principal mechanism driving initial tolerance to agonists. GPCR desensitization typically requires phosphorylation by a G-protein-coupled receptor kinase (GRK) and interaction of the phosphorylated receptor with an arrestin. In simple model systems, CB1R is desensitized...
British Journal of Pharmacology
June 2010
Brady K Atwood, John W Huffman, Alex Straiker et al.
'Spice' is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis-like effects and as a legal alternative to cannabis. However, a recent report identified a number of synthetic additives in samples of 'Spice'. One of these, the indole derivative JWH018, is a ligand for the cannabinoid receptor 1 (CB(1)) cannabinoid receptor and inhibits cAMP production in...
Molecular and cellular endocrinology
April 16, 2008
Ken Mackie
Because of the prominent psychoactive effects of cannabis and its preparations, much research has focused on the actions of cannabinoids, the primary psychoactive components of cannabis, on neuronal function. A convergence of research has identified (1) cannabinoid receptors, (2) endogenous compounds that activate these receptors (endocannabinoids), and (3) drugs that interact with these...