From ancient Asian relics to contemporaneity: A review of historical and chemical aspects of Cannabis

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From the Himalayan mountains to the South American coast, Cannabis, a general term for plants of the
genus Cannabis, with thousands of years of contact with humankind, shows its versatility as food tools
such as hemp, religious and hedonistic input, and other purposes through the millennia, according to the
populations in question. In this paper, a review of the context of the use of Cannabis and its place in world
history is presented, from ancient Mesopotamian relics, traditional Chinese and Ayurvedic medicines, to
the reasoning behind the isolation and structural elucidation of three phytocannabinoids and the spread
of Cannabis throughout the world.

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The Pharmacological Case for Cannabigerol

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Medical cannabis and individual cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), are receiving growing attention in both the media and the scientific literature. The Cannabis plant, however, produces over 100 different cannabinoids, and cannabigerol (CBG) serves as the precursor molecule for the most abundant phytocannabinoids. CBG exhibits affinity and activity characteristics between Δ9-THC and CBD at the cannabinoid receptors but appears to be unique in its interactions with α-2 adrenoceptors and 5-hydroxytryptamine (5-HT1A). Studies indicate that CBG may have therapeutic potential in treating neurologic disorders (e.g., Huntington disease, Parkinson disease, and multiple sclerosis) and inflammatory bowel disease, as well as having antibacterial activity. There is growing interest in the commercial use of this unregulated phytocannabinoid. This review focuses on the unique pharmacology of CBG, our current knowledge of its possible therapeutic utility, and its potential toxicological hazards.

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Cannabidiol attenuates inflammatory impairment of intestinal cells expanding biomaterial-based therapeutic approaches

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Cannabis-based biomaterials have the potential to deliver anti-inflammatory therapeutics specifically to desired cells, tissues, and organs, enhancing drug delivery and the effectiveness of anti-inflammatory treatment while minimizing toxicity. As a major component of Cannabis, Cannabidiol (CBD) has gained major attention in recent years because of its potential therapeutic properties, e.g., for restoring a disturbed barrier resulting from inflammatory conditions. The aim of this study was to test the hypothesis that CBD has beneficial effects under normal and inflammatory conditions in the established non-transformed intestinal epithelial cell model IPEC-J2.

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Cannabis use to manage stimulant cravings among people who use unregulated drugs

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We sought to analyze the association between cannabis use to manage stimulant cravings and self-reported changes in stimulant use among structurally marginalized people who use unregulated drugs (PWUD). The data for this secondary analysis was collected from a cross-sectional questionnaire administered to people who concurrently use cannabis and unregulated stimulants in Vancouver, Canada. We used logistic regression models to analyze the association between cannabis use to manage stimulant cravings and self-reported changes in the frequency of stimulant use.

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Anti-Inflammatory Effects of Minor Cannabinoids CBC, THCV, and CBN in Human Macrophages

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Inflammation is a natural response of the body to signals of tissue damage or infection caused by pathogens. However, when it becomes imbalanced, it can lead to various disorders such as cancer, obesity, cardiovascular problems, neurological conditions, and diabetes. The endocannabinoid system, which is present throughout the body, plays a regulatory role in different organs and influences functions such as food intake, pain perception, stress response, glucose tolerance, inflammation, cell growth and specialization, and metabolism. Phytocannabinoids derived from Cannabis sativa can interact with this system and affect its functioning. In this study, we investigate the mechanisms underlying the anti-inflammatory effects of three minor phytocannabinoids including tetrahydrocannabivarin (THCV), cannabichromene (CBC), and cannabinol (CBN) using an in vitro system. We pre-treated THP-1 macrophages with different doses of phytocannabinoids or vehicle for one hour, followed by treating the cells with 500 ng/mL of LPS or leaving them untreated for three hours.

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Cannabinoid modulations of pain and stress related circuits

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In the past decade, significant advancements have been made in understanding the brain regions and neuronal circuits regulating neurological behaviors. The endocannabinoid (eCB) system, which is ubiquitously distributed in the brain and extensively involved in synaptic modulation, has been believed to play potential roles in neuronal circuit processes and related disorders. Although eCB-based pharmacological studies have made some clinical achievements, they still often encounter conflicting reports or undesired effects due to global manipulation of manifold brain regions and neuronal circuits, which impede the therapeutic application of eCB-based medications. In this review, we are devoted to discussing the versatile forms of eCB-mediated synaptic plasticity and dissecting currently well-studied specific cannabinoid circuits involved in behavioral domains which are closely linked to the organism’s survival and life quality, such as pain perception and stress-related emotion disorders. By gaining new insights into selective cannabinoid control in circuits, we can potentially mitigate the drawbacks of traditional pharmacology and facilitate the development of precision medicine with novel therapeutic strategies and drug discoveries.

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Cannabis Use Frequency and Cannabis-Related Consequences in High-Risk Young Adults Across Cannabis Legalization

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A key concern about recreational cannabis legalization is increases in use and adverse consequences, particularly among young adults (aged 18-29 years) who have the highest prevalence of cannabis use, and especially in higher-risk, more vulnerable young adults. However, few longitudinal studies have examined patterns of cannabis consumption in high-risk young adults over the course of legalization. To examine changes in cannabis use frequency and cannabis-related consequences over recreational cannabis legalization in Canada in a longitudinal sample of high-risk young adults.

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Association between marijuana use and kidney stone: a cross-sectional study of NHANES 2009 to 2018

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The purpose of this investigation is to determine whether regular marijuana use is related to history of kidney stones in the US population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Kidney stone and marijuana use data were collected from self-report questionnaires. Multivariate logistic regression and multiple sensitivity analyses were applied to examine the relationship between marijuana usage and kidney stones.

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Labour and premature delivery differentially affect the expression of the endocannabinoid system in the human placenta

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Plasma concentrations of N-arachidonyletholamine (AEA), N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA) increase at term and can predict when a woman is likely to go into labour. We hypothesised that increased plasma AEA concentrations in women in preterm and term labour might also be increased and have a function in the placenta at the end of pregnancy. Here we examined the expression of the N-acylethanolamine-modulating enzymes fatty acid amide hydrolase (FAAH) and N-acyl-phosphatidylethanolamine-specific phospholipase-D (NAPE-PLD) and of the cannabinoid receptors (CB1 and CB2) in the placenta and their activation in an in vitro model of the third-trimester placenta to determine if those expressions change with labour and have functional significance. Expression of CB1, CB2, FAAH and NAPE-PLD was examined by immunohistochemistry (IHC) and RT-qPCR in placental samples obtained from four patient groups: preterm not in labour (PTNL), term not in labour (TNL), preterm in labour (PTL) and term in labour (TL). Additionally, the effects of AEA on a third-trimester human cell line (TCL-1) were evaluated. All ECS components were present in the third-trimester placenta, with NAPE-PLD and CB2 being the key modulated proteins in terms of expression. Functionally, AEA reduced TCL-1 cell numbers through the actions of the CB2 receptor whilst CB1 maintained placental integrity through the expression of the transcription regulators histone deacetylase 3, thyroid hormone receptor β 1 and the modulation of 5α reductase type 1. The placenta in the third trimester and at term is different from the placenta in the first trimester with respect to the expression of CB1, CB2, FAAH and NAPE-PLD, and the expression of these proteins is affected by labour. These data suggest that early perturbation of some ECS components in the placenta may cause AEA-induced PTL and thus PTB.

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Cannabis constituents for chronic neuropathic pain; reconciling the clinical and animal evidence

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Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined can- nabinoids which contain the psychoactive constituent delta-9-tetrahydrocannabinol (THC). While there have been some positive findings, meta-analyses of this clinical work indicates that this effectiveness is limited and hampered by side-effects. This review focuses on how recent preclinical studies have predicted the clinical limita- tions of THC-containing cannabis extracts, and importantly, point to how they might be improved. This work highlights the importance of targeting channels and recep- tors other than cannabinoid CB1 receptors which mediate many of the side-effects of cannabis.

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