Monthly Archives: August 2022

Oral cannabidiol for prevention of acute and transient chemotherapy-induced peripheral neuropathy

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SpringerLink

“Purpose: To assess the safety, dosing, and preventive effects of cannabidiol (CBD) on chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving oxaliplatin- or paclitaxel-based chemotherapy.

Methods: Patients with cancer scheduled to undergo treatment with carboplatin and paclitaxel (Carbo-Tax) or capecitabine and oxaliplatin (CAPOX) received 150 mg CBD oil twice daily (300 mg/daily) for 8 days beginning 1 day before initiation of chemotherapy. Ten CIPN-specific patient-reported outcome (PRO) measures were captured at baseline and each day after the first cycle of chemotherapy for 8 days. Multi-frequency vibrometry (MF-V) was captured at baseline and day 4 ± 1 after initiation of chemotherapy. Controls were obtained from a similar patient cohort that did not receive CBD. Adverse events were captured using the CTCAE ver. 4.03.

Results: From March to December 2021, 54 patients were recruited. CBD-treated patients were significantly older (p = 0.013/0.037, CAPOX/Carbo-Tax) compared to controls. Patients receiving CBD and CAPOX or Carbo-Tax showed significantly lower (better) change in Z-scores in high-frequency MF-V (125 and 250 Hz) compared to controls. This difference was most pronounced for patients receiving Carbo-Tax (- 1.76, CI-95 = [- 2.52; – 1.02] at 250 Hz). CAPOX patients treated with CBD had significantly lower peak baseline-adjusted difference in three PRO items on cold sensitivity to touch, discomfort swallowing cold liquids, and throat discomfort (- 2.08, – 2.06, and – 1.81, CI-95 = [- 3.89; – 0.12], NRS 0-10). No significant differences in PRO items were found for patients receiving Carbo-Tax. Possible side effects included stomach pain (grades 1-2) for patients receiving CAPOX.

Conclusion: CBD attenuated early symptoms of CIPN with no major safety concerns. Long-term follow-up is ongoing. Results should be confirmed in a larger, randomized study.”

https://pubmed.ncbi.nlm.nih.gov/35933415/

https://link.springer.com/article/10.1007/s00520-022-07312-y

Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis

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ISRCTN - Publish with BMC

“Background: While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users.

Methods: We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient’s social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users.

Results: Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users-CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 μg/L vs 622 μg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users.

Conclusions: This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients.”

https://pubmed.ncbi.nlm.nih.gov/35932069/

“In this retrospective review of 1831 COVID-19 patients requiring hospital admission, current cannabis use was associated with decreased disease severity. This was demonstrated in lower NIH severity scores as well as less need for oxygen supplementation, ICU admission and mechanical ventilation. While there was a trend toward improved survival in cannabis users”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00152-x

Protective effect and mechanism of cannabidiol on myocardial injury in exhaustive exercise training mice

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Chemico-Biological Interactions

“Cannabinoid diphenol (CBD) is a non-toxic main component extracted from cannabis, which has the effects of anti-inflammatory, anti-apoptosis and anti-oxidative stress.

In recent years, exercise-induced myocardial injury has become a research hotspot in the field of sports medicine and sports physiology. Exercise-induced myocardial injury is closely related to oxidative stress, inflammatory response and apoptosis. However, there is no clear evidence of the relationship between CBD and exercise-induced myocardial injury.

In this study, by establishing an animal model of exhaustive exercise training in mice, the protective effect of CBD on myocardial injury in mice was elaborated, and the possible molecular mechanism was discussed.

After CBD intervention, the arrangement and rupture of myocardial fiber tissue and the degree of inflammatory cell infiltration were reduced, the deposition of collagen fibers in myocardial tissue decreased. CBD can also significantly inhibit cardiac hypertrophy. Meanwhile, the expression of IL-6, IL-10, TNF-α, Bax, Caspase-3, Bcl-2, MDA-5, IRE-1α, NOX-2, SOD-1, Keap1, Nrf2, HO-1, NF-κB and COX-2 was recovered to normal.

In addition, after CBD intervention, the protein expression of Keap1 was down-regulated, the translocation of Nrf2 from the cytoplasm to the nucleus was significantly increased, then the transcriptional activity was increased, and the expression of the downstream HO-1 antioxidant protein was increased, indicating that CBD may improve the cardiac function of exhaustive exercise training mice by activating Keap1/Nrf2/HO-1 signaling pathway. Molecular docking results also confirmed that CBD had a good binding effect with Keap1/Nrf2/HO-1 signaling pathway proteins.

In conclusion, the protective mechanism of CBD on myocardial injury in exhaustive exercise training mice may be to activate Keap1/Nrf2/HO-1 signaling pathway, and then exert anti-inflammatory, anti-apoptosis and inhibition of oxidative stress.”

https://pubmed.ncbi.nlm.nih.gov/35926578/

https://www.sciencedirect.com/science/article/abs/pii/S0009279722002848?via%3Dihub

Cannabis Use and Sinonasal Symptoms in US Adults

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Medflixs - JAMA Otolaryngology Formation

“Importance: Cannabis is the most commonly used illicit substance in the US and worldwide. Understanding the association between cannabis use and sinonasal symptoms may help clinicians and patients better understand the symptomatology associated with cannabis use.

Objective: To assess the association between frequency of cannabis use and presence of sinonasal symptoms in a nationally representative sample of US adults.

Design, setting, and participants: This population-based, retrospective cross-sectional study included adults aged 20 to 69 years who had completed data on sinonasal symptoms and substance use for the 2013 to 2014 National Health and Nutrition Examination Survey. The data were analyzed in February 2022.

Exposures: Cannabis use frequency.

Main outcomes and measures: Presence of sinonasal symptoms, demographic information, and medical history were obtained from National Health and Nutrition Examination Survey questionnaires. Presence of any sinonasal symptoms was defined as responding yes to any of a series of questions assessing rhinologic symptoms. Regular cannabis users were defined as using cannabis 15 or more times within the last 30 days. Nonregular users were defined as using cannabis fewer than 15 times within the last 30 days. Multivariable models were used to examine the association between frequency of cannabis use and presence of sinonasal symptoms while adjusting for demographic characteristics and medical comorbidities.

Results: The study included 2269 adults with a mean (SD) age of 36.5 (12.4) years (1207 women [53.2%]; 330 Asian [14.5%], 739 Black [32.6%], 461 Hispanic [20.3%], and 656 White [28.9%] individuals). The prevalence of sinonasal symptoms among regular cannabis users (45.0%; 95% Cl, 38.9%-51.1%) was lower than the prevalence among never users (64.5%; 95% Cl, 58.3%-68.8%). Compared with adults who had never used cannabis, regular cannabis users were less likely to have sinonasal symptoms (odds ratio, 0.22, 95% CI, 0.10-0.50). Current tobacco smokers were more likely to have sinonasal symptoms (odds ratio, 1.96; 95% CI, 1.17-3.28). The most common sinonasal symptoms reported were nasal congestion (62.8%; 95% Cl, 60.2%-65.4%) and change in smell (17.8%; 95% Cl, 15.2%-20.9%).

Conclusions and relevance: This cross-sectional study found that the prevalence of sinonasal symptoms was lower among regular cannabis users. Further research is needed to elucidate the mechanisms underlying the association between cannabis use and sinonasal symptoms.”

https://pubmed.ncbi.nlm.nih.gov/35900733/

https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2794662

“SINONASAL SYMPTOMS LESS COMMON IN REGULAR CANNABIS USERS”

https://www.physiciansweekly.com/sinonasal-symptoms-less-common-in-regular-cannabis-users

Role of 5HT1A Receptors in the Neuroprotective and Behavioral Effects of Cannabidiol in Hypoxic-Ischemic Newborn Piglets

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Frontiers announces its first partnership with a leading Chinese University | STM Publishing News

“Background: Hypoxic-ischemic (HI) insults have important deleterious consequences in newborns, including short-term morbidity with neuromotor and cognitive disturbances. Cannabidiol (CBD) has demonstrated robust neuroprotective effects and shows anxiolytic/antidepressant effects as well. These effects are thought to be related to serotonin 5-HT1A receptor (5HT1AR) activation. We hereby aimed to study the role of 5HT1AR in the neuroprotective and behavioral effects of CBD in HI newborn piglets. 

Methods: 1-day-old piglets submitted to 30 min of hypoxia (FiO2 10%) and bilateral carotid occlusion were then treated daily with vehicle, CBD 1 mg/kg, or CBD with the 5HT1AR antagonist WAY 100635 1 mg/kg 72 h post-HI piglets were studied using amplitude-integrated EEG to detect seizures and a neurobehavioral test to detect neuromotor impairments. In addition, behavioral performance including social interaction, playful activity, hyperlocomotion, and motionless periods was assessed. Then, brain damage was assessed using histology (Nissl and TUNEL staining) and biochemistry (proton magnetic resonance spectroscopy studies. 

Results: HI led to brain damage as assessed by histologic and biochemistry studies, associated with neuromotor impairment and increased seizures. These effects were not observed in HI piglets treated with CBD. These beneficial effects of CBD were not reversed by the 5HT1AR antagonist, which is in contrast with previous studies demonstrating that 5HT1AR antagonists eliminated CBD neuroprotection as assessed 6 h after HI in piglets. HI led to mood disturbances, with decreased social interaction and playfulness and increased hyperlocomotion. Mood disturbances were not observed in piglets treated with CBD, but in this case, coadministration of the 5HT1AR antagonist eliminates the beneficial effects of CBD. 

Conclusion: CBD prevented HI-induced mood disturbances in newborn piglets by acting on 5HT1AR. However, 5HT1AR activation seems to be necessary for CBD neuroprotection only in the first hours after HI.”

https://pubmed.ncbi.nlm.nih.gov/35924056/

“Postinsult CBD administration prevented HI-induced brain damage, and neuromotor deficits and behavioral disturbances. These results indicate that, in addition to its robust neuroprotective effects, CBD could be an interesting candidate to be included in the treatment of HI newborns to mitigate the consequences of stress derived from brain damage and hypothermia treatment.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.925740/full

Cannabidiol: Influence on B Cells, Peripheral Blood Mononuclear Cells, and Peripheral Blood Mononuclear Cell/Rheumatoid Arthritis Synovial Fibroblast Cocultures

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“Background: Cannabidiol (CBD), one major nonintoxicating phytocannabinoid from Cannabis sativa demonstrated anti-inflammatory effects in animal models of several inflammatory conditions, including arthritis. However, it is still unknown which cell types mediate these anti-inflammatory effects of CBD, and, since CBD binds to a plethora of receptors and enzymes, it is complicated to pinpoint its mechanism of action. In this study, we elucidate the effects of CBD on B cells and peripheral blood mononuclear cells (PBMCs) in respect to survival, calcium mobilization, drug uptake, and cytokine (IL-6, IL-10, and TNF) and immunoglobulin production. 

Methods: Modulation of intracellular calcium and drug uptake in B cells was determined by using the fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin production was evaluated by enzyme-linked immunosorbent assay. PBMC composition and B cell survival after CBD treatment was assessed by flow cytometry. 

Results: B cells express two major target receptors for CBD, TRPV2 (transient receptor potential vanilloid 2) and TRPA1 (transient receptor potential ankyrin 1), which are not regulated by B cell activation. CBD increased intracellular calcium levels in mouse and human B cells, which was accompanied by enhanced uptake of PoPo3. These effects were not dependent on transient receptor potential channel activation. CBD increased the number of early apoptotic B cells at the expense of viable cells and diminished interleukin (IL)-10 and tumor necrosis factor (TNF) production when activated T cell independently. In PBMCs, CBD increased IL-10 production when B cells were activated T cell dependent, while decreasing TNF levels when activated T cell independently. In PBMC/rheumatoid synovial fibroblast cocultures, CBD reduced IL-10 production when B cells were activated T cell independently. Immunoglobulin M production was augmented by CBD when B cells were activated with CpG. 

Conclusion: CBD is able to provide pro- and anti-inflammatory effects in isolated B cells and PBMCs. This is dependent on the activating stimulus (T cell dependent or independent) and concentration of CBD. Therefore, CBD might be used to dampen B cell activity in autoimmune conditions such as rheumatoid arthritis, in which B cells are activated by specific autoantigens.”

https://pubmed.ncbi.nlm.nih.gov/35920857/

https://www.liebertpub.com/doi/10.1089/can.2021.0241

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury

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SpringerLink

“Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury.

Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression.

Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord.

The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments.

Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.”

https://pubmed.ncbi.nlm.nih.gov/21915768/

https://link.springer.com/article/10.1007/s12640-011-9273-8

Medical Cannabis Used as an Alternative Treatment for Chronic Pain Demonstrates Reduction in Chronic Opioid Use – A Prospective Study

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Pain Physician:::::

“Background: Chronic opioid therapy (COT) has been used to treat many chronic pain conditions even with poor evidence for its long-term effectiveness. Medical cannabis has emerged with certain pain-relieving properties, which has led to questions as to its’ potential application, especially in relation to its effect on opioid use.

Objectives: This study investigates a proposed clinical context in offering medical cannabis as a treatment for chronic pain for those already using chronic opioid therapy. It then details patients’ daily morphine milligram equivalent (MME) usage.

Study design: This single-center prospective study follows a group of patients trialing medical cannabis treatment for chronic pain that is already using COT in order to determine individual efficacy. Continued medical cannabis treatment was a decision made by the patient, after trialing medical cannabis, to either continue medical cannabis along with COT at a reduced daily MME, or to revert back to their previous COT regimen.

Setting: This study was performed at the Allegheny Health Network Institute for Pain Medicine in Pittsburgh, Pennsylvania. The state of Pennsylvania legalized medical cannabis in April of 2016, and it became available to patients in February of 2018 through medical dispensaries.

Methods: One hundred and fifteen patients met the inclusion criteria, with the majority of those excluded due to not being treated with COT. Of the 115 who chose to undergo a medical cannabis trial in addition to their COT, 75 chose to remain certified for medical cannabis as they had significant pain relief and subsequently weaned down on opioids. Additionally, of the 115 choosing to undergo a medical cannabis trial, 30 chose to be decertified due to ineffectiveness or side effects, and those were placed back on their COT regimen. The other 10 were not included for other denoted reasons. Compliance was monitored through urine drug screens (UDS).

Results: There was a 67.1% average decrease in daily MME/patient from 49.9 to 16.4 MME at the first follow-up. There was a 73.3% decrease in MME at second follow-up from 49.9 to 13.3 MME with an ANOVA analysis denoting a significant difference of P < 0.0001.

Limitations: The period of follow-up presented at this point includes their first 6 months of treatment with medical cannabis and COT concomitantly.

Conclusions: Presenting medical cannabis to chronic pain patients on COT should be done in the context of a patient choice between medical cannabis WITH decrement of COT or continued current dose of COT in order to maximize effectiveness in opioid reduction as well as to limit polypharmacy concerns regarding medical cannabis. Allowing for a temporary short-term period where patients may trial medical cannabis, while concomitantly gradually weaning their COT, is also essential in determining medical cannabis’ individual effectiveness for that patient’s specific type of chronic pain, which should serve to maximize long-term opioid reduction results and hence decrease opioid-related overdose deaths.”

https://pubmed.ncbi.nlm.nih.gov/35051158/

https://www.painphysicianjournal.com/linkout?issn=&vol=25&page=E113

Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study

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Plos One | Publons

“Gramicidin is a monomeric protein that is thought to non-selectively conduct cationic currents and water. Linear gramicidin is considered an antibiotic. This function is considered to be mediated by the formation of pores within the lipid membrane, thereby killing bacterial cells.

The main non-psychoactive active constituent of the cannabis plant, cannabidiol (CBD), has recently gained interest, and is proposed to possess various potential therapeutic properties, including being an antibiotic. We previously determined that CBD’s activity on ion channels could be, in part, mediated by altering membrane biophysical properties, including elasticity.

In this study, our goal was to determine the empirical effects of CBD on gramicidin currents in human embryonic kidney (HEK) cells, seeking to infer potential direct compound-protein interactions. Our results indicate that gramicidin, when applied to the extracellular HEK cell membrane, followed by CBD perfusion, increases the gramicidin current.”

https://pubmed.ncbi.nlm.nih.gov/35913948/

“One compound with amphiphilic properties is cannabidiol (CBD), the primary non-psychotropic constituent of Cannabis sativa. CBD is a clinically and experimentally substantiated therapeutic compound with efficacy against a variety of conditions, including seizure disorders (for which CBD is FDA-approved), pain, and muscle spasms. Furthermore, CBD has been suggested to have antibiotic properties.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271801

A polarized supercell produces specialized metabolites in cannabis trichomes

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Press – The Jensen Laboratory

“For centuries, humans have cultivated cannabis for the pharmacological properties that result from consuming its specialized metabolites, primarily cannabinoids and terpenoids. Today, cannabis is a multi-billion-dollar industry whose existence rests on the biological activity of tiny cell clusters, called glandular trichomes, found mainly on flowers. Cannabinoids are toxic to cannabis cells,1 and how the trichome cells can produce and secrete massive quantities of lipophilic metabolites is not known.1 To address this gap in knowledge, we investigated cannabis glandular trichomes using ultra-rapid cryofixation, quantitative electron microscopy, and immuno-gold labeling of cannabinoid pathway enzymes. We demonstrate that the metabolically active cells in cannabis form a “supercell,” with extensive cytoplasmic bridges across the cell walls and a polar distribution of organelles adjacent to the apical surface where metabolites are secreted. The predicted metabolic role of the non-photosynthetic plastids is supported by unusual membrane arrays in the plastids and the localization of the start of the cannabinoid/terpene pathway in the stroma of the plastids. Abundant membrane contact sites connected plastid paracrystalline cores with the plastid envelope, plastid with endoplasmic reticulum (ER), and ER with plasma membrane. The final step of cannabinoid biosynthesis, catalyzed by tetrahydrocannabinolic acid synthase (THCAS), was localized in the cell-surface wall facing the extracellular storage cavity. We propose a new model of how the cannabis cells can support abundant metabolite production, with emphasis on the key role of membrane contact sites and extracellular THCA biosynthesis. This new model can inform synthetic biology approaches for cannabinoid production in yeast or cell cultures.”

https://pubmed.ncbi.nlm.nih.gov/35917819/

https://www.cell.com/current-biology/fulltext/S0960-9822(22)01115-0?

“Study defines how cannabis cells make cannabinoids”

https://www.news-medical.net/news/20220803/Study-defines-how-cannabis-cells-make-cannabinoids.aspx