Monthly Archives: October 2022

Association of Cannabis Use During Pregnancy with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Retrospective Cohort Study

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“Background and aims: Cannabis use is increasingly common among pregnant individuals and might be a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to test whether prenatal cannabis use is associated with increased risk of SARS-CoV-2 infection during pregnancy.

Design: Retrospective cohort study.

Setting: California USA.

Participants: 58,114 pregnancies (with outcomes from 3/5/2020 to 9/30/2021) among 57,287 unique pregnant women aged 14-54 years who were screened for prenatal substance use, enrolled in Kaiser Permanente Northern California (KPNC) (a healthcare system), and had not tested positive for COVID-19 prior to pregnancy onset.

Measurements: We utilized data from the KPNC electronic health record. Cannabis use status (current, recently quit, non-user) was based on universal screenings during prenatal care (including ≥1 urine toxicology test and self-reported use on a self-administered questionnaire). SARS-CoV-2 infection (based on polymerase chain reaction (PCR) tests) was estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined differences in a) SARS-CoV-2 positivity testing rates and b) SARS-CoV-2 infection rates among those tested.

Findings: We observed 348,810 person-months of follow-up time in our cohort with 41,064 SARS-CoV-2 PCR tests, and 6% (n=2,414) of tests being positive. At the start of follow-up, 7% of pregnant individuals had current use, 12% had recently quit, and 81% did not use cannabis. Adjusting for covariates, current use was associated with lower rates of SARS-CoV-2 infection (adjusted hazard ratio [aHR]=0.60,95% confidence interval [CI]:0.49-0.74) than non-use. Those who had recently quit did not differ from non-cannabis users in infection rates (aHR=0.96,95%CI:0.86-1.08). Sensitivity analyses among patients who received a SARS-CoV-2 test also found lower odds of infection associated with current versus no cannabis use (aOR=0.76,CI:0.61-0.93).

Conclusions: Current cannabis use appears to be associated with a reduced risk of severe acute respiratory syndrome coronavirus 2 infection among pregnant individuals.”

https://pubmed.ncbi.nlm.nih.gov/36189777/

https://onlinelibrary.wiley.com/doi/10.1111/add.16056

Lipid nano-carriers loaded with Cannabis sativa extract for epilepsy treatment – in vitro characterization and in vivo efficacy studies

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Journal of Pharmaceutical Sciences

“Taking into consideration the latest reported beneficial anticolvusant effects of cannabidiol (CBD) and cannabiodiolic acid (CBDA) for clinical applications and the advantages of lipid nano-systems as carriers for targeted brain delivery, the aim of this study was set in direction of in vitro physico-chemical and biopharmaceutical characterization and in vivo evaluation of nanoliposomes and nanostructured lipid carriers loaded with Cannabis sativa extract intended for safe and efficient transport via blood-brain barrier and treatment of epilepsy. These nanoliposomes and nanostructured lipid formulations were characterized with z-average diameter <200 nm, following unimodal particle size distribution, negative values for Z-potential, high drug encapsulation efficiency and prolonged release during 24h (38.84-60.91 %). Prepared formulations showed statistically significant higher antioxidant capacity compared to the extract. The results from in vivo studies of the anticonvulsant activity demonstrated that all formulations significantly elevated the latencies for myoclonic, clonic and tonic seizures and, therefore, could be used in preventing different types of seizures. A distinction in the potential of the nano-systems was noted, which was probably anticipated by the type and the characteristics of the prepared formulations.”

https://pubmed.ncbi.nlm.nih.gov/36189477/

https://jpharmsci.org/article/S0022-3549(22)00417-8/fulltext

Will tetrahydrocannabinol be formed from cannabidiol in gastric fluid? An in vivo experiment

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SpringerLink

“Cannabidiol (CBD) products have ascribed an uprising trend for their health-promoting effects worldwide. In contrast to Δ9-tetrahydrocannabinol (THC), CBD exhibits no state of euphoria. Since conversion of CBD into THC in an acidic environment has been reported, it has not been proved whether this degradation will also occur in human gastric fluid.

A total of 9 subjects ingested 400 mg CBD as a water-soluble liquid together with lecithin as an emulsifier and ethanol as a solubilizer. Blood samples were taken up to 4 h, and urine samples were submitted up to 48 h. THC, 11-hydroxy-Δ9-THC (THC-OH), 11-nor-9-carboxy-Δ9-THC (THC-COOH), CBD, 7-hydroxy cannabidiol (7-OH-CBD), and 7-carboxy cannabidiol (7-CBD-COOH) were determined in blood and THC-COOH and 7-CBD-COOH in urine by LC-MS/MS. Neither THC, THC-OH, nor THC-COOH were detectable in any serum specimen. Only two urine samples revealed THC-COOH values slightly above the threshold of 10 ng/ml, which could also be caused by trace amounts of THC being present in the CBD liquid.

It can be concluded that negative consequences for participants of a drug testing program due to a conversion of CBD into THC in human gastric fluid appear unlikely, especially considering a single intake of dosages of less than 400 mg.

Nevertheless, there is a reasonable risk for consumers of CBD products being tested positive for THC or THC metabolites. However, this is probably not caused by CBD cyclization into THC in human gastric fluid but is most likely due to THC being present as an impurity of CBD products.”

https://pubmed.ncbi.nlm.nih.gov/36190564/

https://link.springer.com/article/10.1007/s00414-022-02896-w

Cannabidiol as a personalized treatment for anxiety: clinical cases in Mexico

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Drugs in Context

“Anxiety-related disorders are one of the most common mental health issues worldwide. Mexico has reported an increase in the prevalence of these ailments secondary to the confinement derived from the COVID-19 pandemic. Given the limitations of commonly used treatments for these disorders, a need arises to develop new pharmacological treatments for these patients. This paper has the primary objective of evaluating the efficacy and safety of cannabidiol isolate in drug compounding used as a personalized treatment in patients with anxiety disorders through the presentation of four clinical cases.”

https://pubmed.ncbi.nlm.nih.gov/36188636/

Cannabidiol as a personalized treatment for anxiety: clinical cases in Mexico

Effects of Cannabidiol on Appetite and Body Weight: A Systematic Review

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SpringerLink

“Background and objective: Cannabidiol, one of the main components of the Cannabis sativa plant, is a non-psychotropic cannabinoid that has recently drawn the attention of researchers and clinicians for its potential therapeutic applications. In this systematic review, we aim to describe the possible effects of cannabidiol in appetite and body weight.

Methods: Both authors independently ran a thorough search in both PubMed and Cochrane databases up to 31 July, 2022 and included every peer-reviewed, original randomized controlled clinical trial that reported data on either of the said outcomes. Risk of assessment bias was performed with Cochrane’s risk of bias tool and results were summarized in tables.

Results: A total of 11 trials were included in this review. Of these, the majority reported on cannabidiol reducing appetite and/or body weight whilst some have found no significant changes and one trial described an increase in appetite.

Conclusions: This systematic review suggests that cannabidiol has an anorexigenic effect, correlated with a decrease in body weight. However, most of the studies included in the present review raised some concerns in terms of risk of bias. We believe further research is needed in order to clarify potential mechanisms involved in the effect of cannabidiol on feeding/appetite.”

https://pubmed.ncbi.nlm.nih.gov/36180814/

“In light of the available evidence, CBD appears to have an anorexigenic effect that may be more substantial in individuals with a higher BMI. Cannabinoids are known to have an orexigenic effect mediated by CB1 and CB2 receptors, but distinctly from Δ9-THC, which possesses an orexigenic effect, CBD appears to decrease food intake. This observation is very interesting and clearly relevant in the context of obesity, a disease whose prevalence is increasing worldwide and which constitutes a risk factor for the development of comorbid conditions such as hyperinsulinemia, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, gallbladder disease, and certain malignancies [45, 46]. Therefore, the evidence presented in the present work points to the need for additional primary research in order to unveil and clarify mechanisms of not only appetite modulation by CBD, but also on other metabolic effects of CBD that may contribute to changes in body weight.”

https://link.springer.com/article/10.1007/s40261-022-01205-y

A Cannabinoid Hairy-Tale: Hair Loss or Hair Gain?

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Journal of Cosmetic Dermatology

“Background: Few studies have reported on the use of cannabinoid products to treat hair loss.

Aim: This article aims to reconcile cannabinoids’ impact on hair growth.

Method: A comprehensive and structured search was conducted in PubMed and Google Scholar on 23 June 2022.

Result: While cannabidiol (CBD), a phytocannabinoid, may cause hair growth, several other phytocannabinoids may lead to hair loss. Additionally, the effect of CBD on hair growth may be concentration-dependent. CBD may cause hair loss at high concentrations (≥10 μM). Therefore, the concentration of CBD needs to be adjusted so that it is optimal for hair growth. One trial found that once-daily application of CBD-rich topical cannabis extract for six months increased nonvellus hair count by approximately 93.5% in 35 Caucasian AGA patients: 28 males aged 28-72 years [average 43 years] and 7 females aged 46-76 years [average 61 years]. Each application contained 3-4 mg of CBD. The CBD-rich topical cannabis extract was prepared by ultra-pulverizing Cannabis sativa [hemp] flower into a green chalk-like powder [10.78% CBD and 0.21% tetrahydrocannabinol] and then infusing the powder into a lanolin paste and Emu oil carrier.

Conclusion: Topical CBD preparations require further studies to establish their safety and efficacy profile. An ideal topical cannabinoid preparation should contain CBD at the right concentration and lack phytocannabinoid adulterants.”

https://pubmed.ncbi.nlm.nih.gov/36181341/

https://onlinelibrary.wiley.com/doi/10.1111/jocd.15427


Cannabinoid receptors in the inflammatory cells of canine atopic dermatitis

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Frontiers in Veterinary Science accepted into PubMed Central - Science & research news | Frontiers

“Background: Atopic dermatitis (AD) is one of the most common cutaneous inflammatory and pruritic diseases in dogs. Considering its multifactorial nature, AD can be a challenging disease to manage, and the therapeutic strategy must often be multimodal. In recent years, research has been moving toward the use of natural products which have beneficial effects on inflammation and itching, and no side effects. Cannabinoid receptors have been demonstrated to be expressed in healthy and diseased skin; therefore, one of the potential alternative therapeutic targets for investigating AD is the endocannabinoid system (ECS).

Objective: To immunohistochemically investigate the expression of the cannabinoid receptor type 2 (CB2R), and the cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in mast cells (MCs), macrophages, dendritic cells (DCs), T cells, and neutrophils of the skin of dogs with AD.

Animals: Samples of skin tissues were collected from eight dogs with AD (AD-dogs).

Materials and methods: The immunofluorescent stained cryosections of the skins of 8 dogs with AD having antibodies against CB2R, GPR55, TRPV1, TRPA1 were semiquantitatively evaluated. The inflammatory cells were identified using antibodies against tryptase (mast cells), ionized calcium binding adaptor molecule 1 (IBA1) (macrophages/DCs), CD3 (T cells), and calprotectin (neutrophils). The proportions of MCs, macrophages/DCs, T cells, and neutrophils expressing CB2R, GPR55, TRPV1 and TRPA1 were evaluated.

Results: The cells of the inflammatory infiltrate showed immunoreactivity (IR) for all or for some of the cannabinoid and cannabinoid-related receptors studied. In particular, MCs and macrophages/DCs showed CB2R-, GPR55-, TRPA1-, and TRPV1-IR; T cells showed CB2R-, GPR55- and TRPA1-IR, and neutrophils expressed GPR55-IR. Co-localization studies indicated that CB2R-IR was co-expressed with TRPV1-, TRPA1-, and GPR55-IR in different cellular elements of the dermis of the AD-dogs.

Conclusions and clinical importance: Cannabinoid receptor 2, and cannabinoid-related receptors GPR55, TRPV1 and TRPA1 were widely expressed in the inflammatory infiltrate of the AD-dogs. Based on the present findings, the ECS could be considered to be a potential therapeutic target for dogs with AD, and may mitigate itch and inflammation.”

https://pubmed.ncbi.nlm.nih.gov/36187821/

“The evidence regarding the effect of cannabinoid and cannabinoid-related receptors on MCs, macrophages and DCs (CB2R, GPR55, TRPV1, TRPA1), T-cells (CB2R, GPR55, TRPA1), and on neutrophils (GPR55) suggests the possibility that the manipulation of the inflammatory cell functions with endocannabinoids and cannabinoids could result in a novel approach to the treatment of AD. Phytocannabinoids could potentially modulate inflammatory responses by regulating more than one underlying mechanism (inflammatory cells, keratinocytes, sensory nerves, fibroblasts, etc.).”

https://www.frontiersin.org/articles/10.3389/fvets.2022.987132/full

Investigation on the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract in an in vitro model of excitotoxicity

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Fitoterapia

“The purpose of this study was to evaluate the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract (CSE) and its main constituents, cannabidiol and β-caryophyllene. An in vitro model of glutamate-induced neuronal excitotoxicity using SH-SY5Y cells was optimized. The impact of CSE on glutamate-impaired cell viability, brain-derived neurotrophic factor release, CB1 protein expression, and ERK levels was evaluated. The involvement of CB1 modulation was verified by the cotreatment with the CB1 antagonist AM4113. CSE was able to significantly protect SH-SY5Y from glutamate-impaired cell viability, and to counteract the changes in brain-derived neurotrophic factor levels, with a mechanism of action involving ERK modulation. Moreover, CSE completely reversed the reduction of CB1 receptor expression induced by glutamate, and the presence of the CB1 antagonist AM4113 reduced CSE effectiveness, suggesting that CBr play a role in the modulation of neuronal excitotoxicity. This work demonstrated the in vitro effectiveness of CSE as a neuroprotective agent, proposing the whole cannabis phytocomplex as a more effective strategy, compared to its main constituents alone, and suggested further investigations by using more complex cell models before moving to in vivo studies.”

https://pubmed.ncbi.nlm.nih.gov/36179898/

https://www.sciencedirect.com/science/article/abs/pii/S0367326X22001939?via%3Dihub

Changes in the expression of endocannabinoid system components in an experimental model of chemotherapy-induced peripheral neuropathic pain: Evaluation of sex-related differences

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Experimental Neurology

“Chemotherapy-induced neuropathic pain is a serious clinical problem and one of the major side effects in cancer treatment. The endocannabinoid system (ECS) plays a crucial role in regulating pain neurotransmission, and changes in the expression of different components of the ECS have been reported in experimental models of persistent pain. In addition, sex differences have been observed in ECS regulation and function. The aim of our study was to evaluate whether administration of oxaliplatin, a neurotoxic antineoplastic agent, induced changes in the expression of ECS components in peripheral and central stations of the pain pathway, and if those changes exhibited sexual dimorphism. Adult male and female rats were injected with oxaliplatin or saline, and mechanical and cold hypersensitivity and allodynia were evaluated using Von Frey and Choi Tests. The mRNA levels corresponding to cannabinoid receptors (CB1, CB2), cannabinoid-related receptors (GPR55, 5HT1A, TRPV1) and to the main enzymes involved in the synthesis (DAGL, DAGL, NAPE-PLD) and degradation (MGL, FAAH) of endocannabinoids were assessed in lumbar dorsal root ganglia (DRGs) and spinal cord by using real time RT-PCR. In addition, the levels of the main endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), were evaluated using commercial ELISA kits. Oxaliplatin administration induced the development of mechanical and cold hypersensitivity and allodynia in male and female animals. Oxaliplatin also induced early and robust changes in the expression of several components of the ECS in DRGs. A marked upregulation of CB1, CB2, 5HT1A and TRPV1 was detected in both sexes. Interestingly, while DAGL mRNA levels remained unchanged, DAGL was downregulated in male and upregulated in female rats. Finally, MGL and NAPE-PLD showed increased levels only in male animals, while FAAH resulted upregulated in both sexes. In parallel, reduced 2-AG and AEA levels were detected in DRGs from male or female rats, respectively. In the lumbar spinal cord, only TRPV1 mRNA levels were found to be upregulated in both sexes. Our results reveal previously unreported changes in the expression of cannabinoid receptors, ligands and enzymes occurring mainly in the peripheral nervous system and displaying certain sexual dimorphism. These changes may contribute to the physiopathology of oxaliplatin-induced neuropathic pain in male and female rats. A better understanding of these dynamic changes will facilitate the development of mechanism- and sex-specific approaches to optimize the use of cannabinoid-based medicines for the treatment of chemotherapy-induced pain.”

https://pubmed.ncbi.nlm.nih.gov/36179876/

https://www.sciencedirect.com/science/article/abs/pii/S0014488622002576?via%3Dihub

Expression of cannabinoid receptors CB1 and CB2 in canine cutaneous mast cell tumours

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Research in Veterinary Science

“Cannabinoid receptors (CB1 and CB2) belong to endocannabinoid system (ECS), which is also composed from endocannabinoids and the enzymatic systems involved in their biosynthesis and degradation. The expression of CB1 and CB2 have been previously identified in normal canine mast cell and in atopic dermatitis. Canine cutaneous mast cell tumours (cMCTs) are among the most common cutaneous neoplasms in dogs and have a highly variable clinical behaviour. Expression of CB1-CB2 was assessed by means of immunohistochemistry in thirty-seven dogs (from 2019 to 2021) with proven histological diagnosis of cMCT. Dogs were divided in two groups according to the Kiupel’s grading system: high-grade (HG) cMCT and low-grade (LG) cMCT. A semiquantitative (score 0-3) and quantitative assessment of immunoreactivity (IR) was performed for each case. Our results show that there CB1 and CB2 are highly expressed in LG- cMCT, in contrast to HG- cMCT.”

https://pubmed.ncbi.nlm.nih.gov/36179546/

https://www.sciencedirect.com/science/article/abs/pii/S0034528822002946?via%3Dihub