Entries by Michelle Smith

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Cannabidiol goes nuclear: The role of PPARγ

Cannabidiol (CBD) is one of the main phytocannabinoids found in Cannabis sativa. In contrast to Δ9-tetrahydrocannabinol, it has a low affinity for cannabinoid receptors CB1 and CB2, thereby it does not induce significant psychoactive effects. However, CBD may interact with other receptors, including peroxisome proliferator-activated receptor gamma (PPARγ). CBD is a PPARγ agonist and changes its expression. There is considerable evidence that CBD’s effects are mediated by its interaction with PPARγ. So, we reviewed studies related to the interaction of CBD and PPARγ.

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Cannabinoids and the placenta: Receptors, signaling and outcomes

In this article, we aim to summarize how phytocannabinoids can impact placental development and function. Specifically, the cannabinoids and their actions at the different receptors are described, with receptor localization throughout the human and murine placenta discussed. Findings from studies that included placental analysis and how cannabinoid signaling may modulate critical developmental processing including cell proliferation, angiogenesis and migration are described. Considering the current research, prenatal cannabinoid exposure may significantly impact placental development, and, as such, identifying windows of placental vulnerability for each cannabinoid will be critical to elucidate the etiology of fetal outcome studies.

Comparison of the Cannabinoid and Terpene Profiles in Commercial Cannabis from Natural and Artificial Cultivation

Interest in cultivating cannabis for medical and recreational purposes is increasing due to a dramatic shift in cannabis legislation worldwide. Therefore, a comprehensive understanding of the composition of secondary metabolites, cannabinoids, and terpenes grown in different environmental conditions is of primary importance for the medical and recreational use of cannabis. We compared the terpene and cannabinoid profiles using gas/liquid chromatography and mass spectrometry for commercial cannabis from genetically identical plants grown indoors using artificial light and artificially grown media or outdoors grown in living soil and natural sunlight. By analyzing the cannabinoids, we found significant variations in the metabolomic profile of cannabis for the different environments.

Risk of Motor Vehicle Collisions and Culpability among Older Drivers Using Cannabis: A Meta-Analysis

Limited studies have investigated the effects of cannabis use on driving among older adults, who represent the fastest growing segment of drivers globally. We conducted a systematic review and meta-analysis to evaluate the effects of delta-9-tetrahydrocannabinol (THC) exposure on risks of (1) motor vehicle collisions (MVC) and (2) culpability for MVCs among adults 50 years and older. Three reviewers screened 7022 studies identified through MEDLINE, EMBASE, CENTRAL, and PsycINFO. Odds Ratios (OR) were calculated using the Mantel-Haenszel method in Review Manager 5.4.1. Heterogeneity was assessed using I . The National Heart, Lung, and Blood Institute tool was used to assess the quality of each study. Seven cross-sectional studies were included. Three studies evaluated culpability while four evaluated MVC. The pooled risk of MVC was not signifi- cantly different between THC-positive and THC-negative older drivers (OR, 95% CI 1.15 [0.40, 3.31]; I2 = 72%). In culpability studies, THC exposure was not significantly associated with an increased risk of being culpable for MVC among adults over the age of 50 (OR, 95% CI 1.24 [0.95, 1.61]; I2 = 0%). Inspection of funnel plots did not indicate publication bias. Our review found that THC exposure was not associated with MVC involvement nor with culpability for MVCs.

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Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics

The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.

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Rare Phytocannabinoids Exert Anti-Inflammatory Effects on Human Keratinocytes via the Endocannabinoid System and MAPK Signaling Pathway

Increasing evidence supports the therapeutic potential of rare cannabis-derived phytocannabinoids (pCBs) in skin disorders such as atopic dermatitis, psoriasis, pruritus, and acne. However, the molecular mechanisms of the biological action of these pCBs remain poorly investigated. In this study, an experimental model of inflamed human keratinocytes (HaCaT cells) was set up by using lipopolysaccharide (LPS) in order to investigate the anti-inflammatory effects of the rare pCBs cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). To this aim, pro-inflammatory interleukins (IL)-1β, IL-8, IL-12, IL-31, tumor necrosis factor (TNF-β) and anti-inflammatory IL-10 levels were measured through ELISA quantification. In addition, IL-12 and IL-31 levels were measured after treatment of HaCaT cells with THCV and CBGA in the presence of selected modulators of endocannabinoid (eCB) signaling.

Cannabis and Public Health: A Study Assessing Regular Cannabis Users Through Health Indicators

An increasing number of countries are deciding to regulate the medicinal and/or recreational use of cannabis (Cannabis sativa L.). However, there is a lack of information on the impact of regular consumption of this substance on public health. In this study, for the first time, regular cannabis consumers in Spain were assessed using health indicators, comparing these data with the general population.

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Is it the Ideal Time to Start Prescribing Cannabis Derivatives to Treat Endometriosis-associated Pain?

Endometriosis affects 5%-10% of women of reproductive age and is often associated with painful symptoms like dysmenorrhea, dyschezia, dyspareunia, and even non cyclical pain. The disease is diagnosed in at least 20% of women with dysmenorrhea and/or non-menstrual pelvic pain, reaching a prevalence of 50% pain among adolescents. There is an alignment among international societies3,4 that the pre- sumed diagnosis of this disease is enough to start clinical treatment. Moreover, there seems to be a consensus that first-line treatment should be hormonal contraceptives since the efficacy is similar to that of surgery but with lower complication rates and costs. However, these drugs are
effective in only approximately two-thirds of patients, have limited long-term efficacy and may occasionally lead to undesirable side effects. Additionally, there are serious limitations in the interpretation of clinical trials.

Anticancer properties of cannabidiol and Δ9-tetrahydrocannabinol and synergistic effects with gemcitabine and cisplatin in bladder cancer cell lines

With the legalization of cannabis in multiple jurisdictions throughout the world, a larger proportion of the population consumes cannabis. Several studies have demonstrated anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of cannabinoids in bladder cancer, and how cannabinoids could potentially synergize with chemotherapeutic agents. Our study aims to identify whether a combination of cannabinoids, like cannabidiol and Δ9-tetrahydrocannabinol with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, is able to produce desirable synergistic effects. We also evaluated whether co-treatment of different cannabinoids also generated synergistic effects.

Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration

The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.

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Cannabinoids as a Potential Alternative to Opioids in the Management of Various Pain Subtypes: Benefits, Limitations, and Risks

Pain is a global phenomenon encompassing many subtypes that include neuropathic, musculoskeletal, acute postoperative, cancer, and geriatric pain. Traditionally, opioids have been a mainstay pharmacological agent for managing many types of pain. However, opioids have been a subject of controversy with increased addiction, fatality rates, and cost burden on the US healthcare system. Cannabinoids have emerged as a potentially favorable alternative or adjunctive treatment for various types of acute and chronic pain. This narrative review seeks to describe the efficacy, risks, and benefits of cannabinoids as an adjunct or even potential replacement for opioids in the treatment of various subtypes of pain.