Monthly Archives: February 2023

The evolution of cannabinoid receptors in cancer

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“Cannabis sativa (cannabis) has been used as a therapeutic treatment for centuries treating various diseases and disorders. However, racial propaganda led to the criminalization of cannabis in the 1930s preventing opportunities to explore marijuana in therapeutic development. The increase in recreational use of cannabis further grew concern about abuse, and lead to further restrictions and distribution of cannabis in the 1970s when it was declared to be a Schedule I drug in the USA. In the late 1990s in some states, legislation assisted in legalizing the use of cannabis for medical purposes under physician supervision.

As it has been proven that cannabinoids and their receptors play an essential role in the regulation of the physiological and biological processes in our bodies. The endocannabinoid system (ECS) is the complex that regulates the cell-signaling system consisting of endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of the endocannabinoids. The ECS along with phytocannabinoids and synthetic cannabinoids serves to be a beneficial therapeutic target in treating diseases as they play roles in cell homeostasis, cell motility, inflammation, pain-sensation, mood, and memory.

Cannabinoids have been shown to inhibit proliferation, metastasis, and angiogenesis and even restore homeostasis in a variety of models of cancer in vitro and in vivo. Cannabis and its receptors have evolved into a therapeutic treatment for cancers.”

https://pubmed.ncbi.nlm.nih.gov/36750231/

https://wires.onlinelibrary.wiley.com/doi/10.1002/wsbm.1602

Medical cannabis for treatment-resistant combat PTSD

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“Targeting the endocannabinoid system may have a role in the treatment of post-traumatic stress disorder (PTSD). However, few studies have examined the effectiveness of cannabis on symptoms of PTSD, and more research is needed to ascertain cannabis’ effectiveness.

In this retrospective naturalistic study, we followed 14 relatively mature (32-68 years of age), treatment-resistant, chronic combat post-traumatic patients who remained severely symptomatic despite treatment with many lines of conventional treatment prior to receiving medicinal cannabis.

Our findings show that total sleep score, subjective sleep quality, and sleep duration significantly improved (p < 0.01). Total PTSD symptom score and its subdomains (intrusiveness, avoidance, and alertness) showed improvement (p < 0.05). However, there was no improvement in the frequency of nightmares (p = 0.27). The mean follow-up time was 1.1 ± 0.8 years (range of 0.5 to 3 years).”

https://pubmed.ncbi.nlm.nih.gov/36741572/

“To the best of our knowledge, this is the first published study examining long-term cannabis efficacy in chronic combat treatment-resistant PTSD patients. The study we conducted is consistent with existing literature which indicates a decrease in PTSD symptoms under medical cannabis treatment.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1014630/full

The Endocannabinoid System as a Potential Therapeutic Target for HIV-1-Associated Neurocognitive Disorder

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“Background: Despite the successful introduction of combined antiretroviral therapy, the prevalence of mild to moderate forms of HIV-associated neurocognitive disorders (HAND) remains high. It has been demonstrated that neuronal injury caused by HIV is excitotoxic and inflammatory, and it correlates with neurocognitive decline in HAND. Endocannabinoid system (ECS) protects the body from excitotoxicity and neuroinflammation on demand and presents a promising therapeutic target for treating HAND. Here, we firstly discuss the potential pathogenesis of HAND. We secondly discuss the structural and functional changes in the ECS that are currently known among HAND patients. We thirdly discuss current clinical and preclinical findings concerning the neuroprotective and anti-inflammatory properties of the ECS among HAND patients. Fourth, we will discuss the interactions between the ECS and neuroendocrine systems, including the hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes under the HAND conditions. 

Materials and Methods: We have carried out a review of the literature using PubMed to summarize the current state of knowledge on the association between ECS and HAND. 

Results: The ECS may be ideally suited for modulation of HAND pathophysiology. Direct activation of presynaptic cannabinoid receptor 1 or reduction of cannabinoid metabolism attenuates HAND excitotoxicity. Chronic neuroinflammation associated with HAND can be reduced by activating cannabinoid receptor 2 on immune cells. The sensitivity of the ECS to HIV may be enhanced by increased cannabinoid receptor expression in HAND. In addition, indirect regulation of the ECS through modulation of hormone-related receptors may be a potential strategy to influence the ECS and also alleviate the progression of HAND due to the reciprocal inhibition of the ECS by the HPA and HPG axes. 

Conclusions: Taken together, targeting the ECS may be a promising strategy to alleviate the inflammation and neurodegeneration caused by HIV-1 infection. Further studies are required to clarify the role of endocannabinoid signaling in HIV neurotoxicity. Strategies promoting endocannabinoid signaling may slow down cognitive decline of HAND are proposed.”

https://pubmed.ncbi.nlm.nih.gov/36745405/

https://www.liebertpub.com/doi/10.1089/can.2022.0267

Association between cannabis use and blood pressure levels according to comorbidities and socioeconomic status

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Scientific Reports

“The associations between blood pressure and cannabis use remain inconsistent. The purpose of our study was to examine gender stratified associations of cannabis use and blood pressure [systolic, diastolic blood pressure (BP), pulse pressure (PP)] levels among the general UK Biobank population based study. Among 91,161 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low and never users. Associations between cannabis use and BP were estimated using multiple gender linear regressions.

In adjusted covariates models, lifetime heavy cannabis use was associated with decrease in both SBP, DBP and PP in both genders, but with a higher effect among women (for SBP in men, b = − 1.09 (0.27), p < 0.001; in women, b = − 1.85 (0.36), p < 0.001; for DBP in men, b = − 0.50 (0.15), p < 0.001; in women, b = − 0.87 (0.17), p < 0.001; and for PP in men, b = − 0.60 (0.20), p < 0.001; in women, b = − 0.97 (0.27), p < 0.001. Among men, lower SBP and DBP levels were observed with participants without dyslipidemia and lower PP in participants with high income levels. Among women, lower SBP, DBP and PP were observed with current smokers, moderate/low alcohol levels and participants without dyslipidemia.

Current cannabis use was associated with lower SBP levels in men (b = − 0.63 (0.25), p = 0.012) and in women (b = − 1.17 (0.31), p < 0.001). Same results were observed for DBP and PP. Negative association between BP in men was found but not in women. The small association in BP differences between heavy users and never users remains too small to adopt cannabis-blood pressure public policy in clinical practice.”

https://www.nature.com/articles/s41598-022-22841-6

Inhalant cannabidiol impedes tumor growth through decreased tumor stemness and impaired angiogenic switch in NCI-H1437-induced human lung cancer model

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SpringerLink

“Lung cancer remains the most chronic form of cancer and the leading cause of cancer mortality in the world. Despite significant improvements in the treatment of lung cancer, the current therapeutic interventions are only partially effective, necessitating the continued search for better, novel alternative treatments. Angiogenesis and cancer stem cells play a central role in the initiation and propagation of cancers. Tumor angiogenesis is triggered by an angiogenic switch when pro-angiogenic factors exceed anti-angiogenic components. Although many anti-angiogenic agents are used in cancer treatment, there are therapeutic limitations with significant side effects.

In recent years, cannabinoids have been investigated extensively for their potential anti-neoplastic effects. Our previous findings showed that cannabidiol (CBD) could impede tumor growth in mouse models of melanoma and glioblastoma.

Importantly, CBD has been suggested to possess anti-angiogenic activity.

In this study, we tested, for the first time, inhalant CBD in the treatment of heterotopic lung cancer and whether such potential effects could reduce cancer stem cell numbers and inhibit tumor angiogenesis.

We implanted NCI H1437 human lung cancer cells in nude mice and treated the mice with inhalant CBD or placebo. The outcomes were measured by tumor size and imaging, as well as by immunohistochemistry and flow cytometric analysis for CD44, VEGF, and P-selectin.

Our findings showed that CBD decreased tumor growth rate and suppressed expression of CD44 and the angiogenic factors VEGF and P-selectin.

These results suggest, for the first time, that inhalant CBD can impede lung cancer growth by suppressing CD44 and angiogenesis.”

https://pubmed.ncbi.nlm.nih.gov/36737540/

https://link.springer.com/article/10.1007/s13577-023-00869-8

Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer

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Pharmacological Research

“In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood.

Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signalling.

Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signalling pathways.

The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.”

https://pubmed.ncbi.nlm.nih.gov/36736415/

https://www.sciencedirect.com/science/article/pii/S1043661823000397?via%3Dihub

Cannabidiol mediates epidermal terminal differentiation and redox homeostasis through aryl hydrocarbon receptor (AhR)-dependent signaling

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Home Page: Journal of Dermatological Science

“Background: Cannabidiol, a non-psychoactive phytocannabinoid, has antioxidant and anti-inflammatory activity in keratinocytes. However, the signaling pathway through which cannabidiol exerts its effect on keratinocytes or whether it can modulate keratinocyte differentiation has not been fully elucidated yet.

Objective: We investigated whether cannabidiol modulates epidermal differentiation and scavenges reactive oxygen species through the aryl hydrocarbon receptor (AhR) in keratinocytes and epidermal equivalents.

Methods: We investigated the cannabidiol-induced activation of AhR using AhR luciferase reporter assay, qRT-PCR, western blot, and immunofluorescence assays. We also analyzed whether keratinocyte differentiation and antioxidant activity are regulated by cannabidiol-induced AhR activation.

Results: In both keratinocytes and epidermal equivalents, cannabidiol increased both the mRNA and protein expression of filaggrin, involucrin, NRF2, and NQO1 and the mRNA expression of the AhR target genes, including CYP1A1 and aryl hydrocarbon receptor repressor. Additionally, cannabidiol showed antioxidant activity that was attenuated by AhR knockdown or co-administration with an AhR antagonist. Moreover, cannabidiol increased the ratio of OVOL1/OVOL2 mRNA expression, which is a downstream regulator of AhR that mediates epidermal differentiation. In addition to increased expression of barrier-related proteins, cannabidiol-treated epidermal equivalent showed a more prominent granular layer than the control epidermis. The increased granular layer by cannabidiol was suppressed by the AhR antagonist.

Conclusion: Cannabidiol can be a modulator of the AhR-OVOL1-filaggrin axis and AhR-NRF2-NQO1 signaling, thus indicating a potential use of cannabidiol in skin barrier enhancement and reducing oxidative stress.”

https://pubmed.ncbi.nlm.nih.gov/36725458/

https://www.jdsjournal.com/article/S0923-1811(23)00024-5/fulltext

Do tobacco and cannabis use and co-use predict lung function: A longitudinal study

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Respiratory Medicine | Journal | ScienceDirect.com by Elsevier

“Background: Use of tobacco and cannabis is common and has been reported to predict lung function. Less is known about co-use of tobacco and cannabis and their impact on changes in lung function to early adulthood.

Research question: The study examines whether cigarette smoking or cannabis use and co-use are each associated with lung function in a population sample of young adults.

Study design and methods: Data are from a prospective cohort study of cigarette smoking, cannabis use and co-use at 21 and 30 years of age and lung function (FVC, FEV1, FEV1/FVC) measured at 30 years. Lung function results are transformed using Global Lung Function Formulae. Subjects are the children of pregnant women who were recruited into the cohort study over the period 1981-3. Respondents were administered a spirometry assessment at 21 and 30 years of age. These respondents completed a smoking and cannabis use questionnaire at 21- and 30-year follow-ups.

Results: Cigarette smoking (with or without cannabis use) is associated with reduced airflow. There is no consistent association between cannabis use and measures of lung function. The co-use of tobacco and cannabis appears to entail no additional risk to lung function beyond the risks associated with tobacco use alone.

Interpretation: Persistent cigarette smoking is associated with reduced airflow even in young adults. Cannabis use does not appear to be related to lung function even after years of use.”

https://pubmed.ncbi.nlm.nih.gov/36682602/

“•Cigarette smoking and cannabis use and co-use are risk factors for impaired lung function.

•By 30 years, those who have smoked cigarettes since adolescence already show evidence of impairment of lung function.

•By 30 years, those who used cannabis since the adolescent period do not appear to have evidence of impaired lung function.

•Co-use of tobacco and cannabis does not appear to predict lung function beyond the effects of tobacco use alone.”

https://www.resmedjournal.com/article/S0954-6111(23)00012-4/fulltext

“Smoking Cannabis Not Associated With Impaired Lung Functioning In Latest Study”

https://www.forbes.com/sites/emilyearlenbaugh/2023/02/01/smoking-cannabis-not-associated-with-impaired-lung-functioning-in-latest-study/?sh=5f2e60c6a630

Hemp seeds: Nutritional value, associated bioactivities and the potential food applications in the Colombian context

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Frontiers - Crunchbase Company Profile & Funding

“For many years, Colombia was one of the countries with the largest illegal cultivation of cannabis around the world. Currently, it is going through a period of transition with a new government law that recently allows the cultivation, transformation, and commercialization of such plant species. In this sense, the identification of strategies for the valorization of products or by-products from Cannabis sativa represent a great opportunity to improve the value chain of this crop.

One of these products is hemp seeds, which are exceptionally nutritious and rich in healthy lipids (with high content of three polyunsaturated fatty acids: linoleic acid, alpha-linolenic acid, and gamma-linolenic acid), good quality protein, and several minerals. In addition, hemp seeds contain THC (tetrahydrocannabinol) or CBD (cannabidiol) in traces, molecules that are responsible for the psychoactive and therapeutic properties of cannabis. These low terpenophenolic contents make it more attractive for food applications.

This fact, together with the constant search for proteins of vegetable origin and natural food ingredients, have aroused an important interest in the study of this biomass. Some bioactivities of phytochemical compounds (polyphenols and terpenoids, mainly) present in hemp seeds have provided antioxidant, antimicrobial, and anti-inflammatory properties. This review summarizes and discusses the context of hemp use in Latin-American and the new opportunities for hemp seeds culture in Colombia considering the valuable nutritional value, main functional bioactivities, and recent advances in food market applications of hemp seeds.”

https://pubmed.ncbi.nlm.nih.gov/36712539/

“As a future trend, a holistic approach by the use of hemp seed could be employed as a food ingredient, in Colombia and those Latin American countries where the legislation has been relaxed. This is in the line with the increasing awareness about nutritional dietary patterns as well as the therapeutic application of plant-based food for improving the human health population, aiding to decrease nutrition-related diseases, and ensuring the physical and mental wellbeing of the population.”

https://www.frontiersin.org/articles/10.3389/fnut.2022.1039180/full

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

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Brain and Development | Journal | ScienceDirect.com by Elsevier

“Background: Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy.

Case report: A previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively.

Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery.

At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit.

Conclusions: To our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.”

https://pubmed.ncbi.nlm.nih.gov/36725381/

https://www.brainanddevelopment.com/article/S0387-7604(23)00004-9/fulltext