Molecular Mechanism and Cannabinoid Pharmacology

Schurman, Lesley D.; Lu, Dai; Kendall, Debra A.; Howlett, A­llyn C.; Lichtman, Aron H.

doi:10.1007/164_2019_298

Cited by 63 publications

(39 citation statements)

References 221 publications

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“…As the effect of these changes, impairment in cholinergic transmission follows, which then results in typical symptoms of this disease [1]. Pharmacotherapy of AD focuses primarily on alleviating memory impairment and employs two strategies for this purpose: cholinergic and glutamatergic [11]. The decrease in the concentration of the neurotransmitter crucial for cognitive processes, i.e., ACh still remains the main target of symptomatic treatment of AD (cholinergic strategy).…”

Section: Discussionmentioning

confidence: 99%

The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice in the Passive Avoidance Test

2022

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Background: Dysfunction of the cholinergic system is associated with the development of Alzheimer’s disease (AD). One of the new possible strategies for the pharmacological modulation of memory-related problems typical of AD, is connected with the endocannabinoid system (ECS) and the cannabinoid (CB: CB1 and CB2) receptors. Methods: The aim of the study was to determine the influence of the selective CB2 receptor ligands: agonist (JWH 133) and antagonist (AM 630) on different stages of memory and learning in mice, in the context of their interaction with cholinergic pathways. To assess and understand the memory-related effects in mice we used the passive avoidance (PA) test. Results: We revealed that co-administration of non-effective dose of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the non-effective dose of cholinergic receptor agonist - nicotine (0.05 mg/kg) enhanced cognition in the PA test in mice; however, an acute injection of JWH 133 (0.25 mg/kg) or AM 630 (0.25 mg/kg) had no influence on memory enhancement induced by the effective dose of nicotine (0.1 mg/kg). Co-administration of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the effective dose of the cholinergic receptor antagonist scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice. Conclusion: Our experiments have shown that CB2 receptors participate in the modulation of memory-related responses, especially those in which cholinergic pathways are implicated.

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Section: Discussionmentioning

confidence: 99%

The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice in the Passive Avoidance Test

2022

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“…Cannabinoids have been used for many centuries to counter pain. The endocannabinoid system (ECS) is an evolutionarily conserved signalling pathway, which has diverse regulatory functions [4]. In the last two decades, a growing body of evidences had shown the role of ECS in a diverse scope of diseases, such as psychological disorders, motion disorders like Parkinson's and Huntington's disease, neuropathy, disseminated sclerosis, spinal cord trauma, atherosclerotic disease, heart attack, hemorrhagic stroke, high blood pressure, eye disease, abnormal weight and bone diseases.…”

Section: Introductionmentioning

confidence: 99%

“…In the last two decades, a growing body of evidences had shown the role of ECS in a diverse scope of diseases, such as psychological disorders, motion disorders like Parkinson's and Huntington's disease, neuropathy, disseminated sclerosis, spinal cord trauma, atherosclerotic disease, heart attack, hemorrhagic stroke, high blood pressure, eye disease, abnormal weight and bone diseases. For each of these diseases the potential positive effect of cannabidiol (CBD), a good candidate for ECS modulator and/or regulator, has been demonstrated [4][5][6][7][8][9]. Several studies have demonstrated that cannabinoids also have antineoplastic effect and are usually accompanied with no negative side effects such as the ones produced by the conventional chemotherapy treatment [10,11].…”

Section: Introductionmentioning

confidence: 99%

The antitumor activity of cannabidiol on lung cancer cell lines A549 and H1299: the role of apoptosis

Todorova

Lazarov

Petrova

et al. 2021

Biotechnology & Biotechnological Equipment

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In the recent years, the application of new antitumor drugs has focused on the replacement of conventional chemotherapeutics with compounds derived from natural products. Cannabidiol (CBD) is one of the 113 cannabinoids derived from the plant Cannabis sativa and is characterized with complex and not entirely understood biological function. Unlike the other most abundant cannabinoid in Cannabis sativa -tetrahydrocannabinol, cannabidiol has low affinity to the endocannabinoid receptors and the manifestation of its activity does not appear to rely on the endocannabinoid system. Cannabidiol is used in the treatment of many diseases including some types of cancer. The aim of our study was to evaluate the cytotoxic activity of cannabidiol and its effect on the process of programmed cell death. This process is directly involved in the antitumor effect of many drugs. Two lung cancer cell lines, A549 expressing р53 and H1299-p53 negative, were used. Apoptosis was monitored by Anexin V assay and the activation of Caspase 3/7. We found that CBD treatment led to a dose-dependant apoptosis increase in p53 positive A549 cells. The level of apoptosis in p53 negative H1299 cells was much lower and did not seem to be dose dependent. However, the total cell viability was similar for the two cell lines, which was due to the increased necrosis observed in H1299 cells.

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“…Phytocannabinoids are bioactive ingredients of cannabis and include Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), the former being the major psychoactive component. These compounds exert their effects via CB1R, CB2R, and/or other receptors, with CB1R responsible for mediating the major neurobehavioral effects of THC (Lu & Mackie, 2020; Schurman et al , 2020). Importantly, THC and CBD inhibited HH signaling similarly to endocannabinoids, whereas structurally unrelated CB1R and CB2R agonists/antagonists did not (Khaliullina et al ., 2015).…”

Section: Introductionmentioning

confidence: 99%

Δ9-tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development

Hong

Szutorisz

et al. 2021

Preprint

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Many birth defects are thought to arise from a multifactorial etiology; i.e., interaction between genetic and environmental risk factors. The Hedgehog (HH) signaling pathway regulates myriad developmental processes, and pathway inhibition is associated with birth defects, including holoprosencephaly (HPE). Cannabinoids are HH pathway inhibitors, but little is known of their effects on HH-dependent processes in mammalian embryos, and their mechanism of action is unclear. We report here that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) induces two hallmark HH loss-of-function phenotypes (HPE and ventral neural tube patterning defects) in Cdon mutant mice, which have a subthreshold deficit in HH signaling. THC therefore acts as a “conditional teratogen”, dependent on a complementing but insufficient genetic insult. In vitro findings indicate that THC is a direct, albeit relatively weak, inhibitor of the essential HH pathway component, Smoothened. In contrast, the canonical THC receptor, cannabinoid receptor-type 1, is not required for THC to inhibit HH signaling. Cannabis consumption during pregnancy may contribute to the combination of risk factors underlying specific developmental disorders. These findings therefore have significant public health relevance.

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Molecular Mechanism and Cannabinoid Pharmacology

Cited by 63 publications

References 221 publications

The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice in the Passive Avoidance Test

The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice in the Passive Avoidance Test

The antitumor activity of cannabidiol on lung cancer cell lines A549 and H1299: the role of apoptosis

Δ9-tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development

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