Monthly Archives: January 2023

Therapeutic and Supportive Effects of Cannabinoids in Patients with Brain Tumors (CBD Oil and Cannabis)

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“The potential medicinal properties of Cannabis continue to garner attention, especially in the brain tumor domain. This attention is centered on quality of life and symptom management; however, it is amplified by a significant lack of therapeutic choices for this specific patient population.

While the literature on this matter is young, published and anecdotal evidence imply that cannabis could be useful in treating chemotherapy-induced nausea and vomiting, stimulating appetite, reducing pain, and managing seizures. It may also decrease inflammation and cancer cell proliferation and survival, resulting in a benefit in overall patient survival.

Current literature poses the challenge that it does not provide standardized guidance on dosing for the above potential indications and cannabis use is dominated by recreational purposes. Furthermore, integrated and longitudinal studies are needed but these are a challenge due to arcane laws surrounding the legality of such substances. The increasing need for evidence-based arguments about potential harms and benefits of cannabis, not only in cancer patients but for other medical use and recreational purposes, is desperately needed.”

https://pubmed.ncbi.nlm.nih.gov/36633803/

https://link.springer.com/article/10.1007/s11864-022-01047-y

Cannabis as antivirals

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“Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries.

The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties.

Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication.

Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/36626776/

“Recently, scientists have discovered the potential medical roles of cannabis compounds in viral diseases. Cannabinoids such as CBD and Δ-9-THC, as well as essential oil such as terpenes extracted from the cannabis plants, were reported to have therapeutic effects in several virus infections such as SARS-CoV-2, HIV, HCV, and HSV.”

https://academic.oup.com/jambio/article/134/1/lxac036/6902073?login=false

Selected Seeds as Sources of Bioactive Compounds with Diverse Biological Activities

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“Seeds contain a variety of phytochemicals that exhibit a wide range of biological activities. Plant-derived compounds are often investigated for their antioxidant, anti-inflammatory, immunomodulatory, hypoglycemic, anti-hypercholesterolemic, anti-hypertensive, anti-platelet, anti-apoptotic, anti-nociceptive, antibacterial, antiviral, anticancer, hepatoprotective, or neuroprotective properties.

In this review, we have described the chemical content and biological activity of seeds from eight selected plant species-blackberry (Rubus fruticosus L.), black raspberry (Rubus coreanus Miq.), grape (Vitis vinifera L.), Moringa oleifera Lam., sea buckthorn (Hippophae rhamnoides L.), Gac (Momordica cochinchinensis Sprenger), hemp (Cannabis sativa L.), and sacha inchi (Plukenetia volubilis L). This review is based on studies identified in electronic databases, including PubMed, ScienceDirect, and SCOPUS.

Numerous preclinical, and some clinical studies have found that extracts, fractions, oil, flour, proteins, polysaccharides, or purified chemical compounds isolated from the seeds of these plants display promising, health-promoting effects, and could be utilized in drug development, or to make nutraceuticals and functional foods. Despite that, many of these properties have been studied only in vitro, and it’s unsure if their effects would be relevant in vivo as well, so there is a need for more animal studies and clinical trials that would help determine if they could be applied in disease prevention or treatment.”

https://pubmed.ncbi.nlm.nih.gov/36615843/

“In conclusion, seeds are a source of many promising compounds that have the potential to be implemented in the prevention or treatment of diseases in the future, but the process of introducing them in conventional medicine must be preceded by a thorough in vivo investigation of their effectiveness and safety.”

https://www.mdpi.com/2072-6643/15/1/187

Computer-Aided Screening for Potential Coronavirus 3-Chymotrypsin-like Protease (3CLpro) Inhibitory Peptides from Putative Hemp Seed Trypsinized Peptidome

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“To control the COVID-19 pandemic, antivirals that specifically target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently required. The 3-chymotrypsin-like protease (3CLpro) is a promising drug target since it functions as a catalytic dyad in hydrolyzing polyprotein during the viral life cycle. Bioactive peptides, especially food-derived peptides, have a variety of functional activities, including antiviral activity, and also have a potential therapeutic effect against COVID-19.

In this study, the hemp seed trypsinized peptidome was subjected to computer-aided screening against the 3CLpro of SARS-CoV-2. Using predictive trypsinized products of the five major proteins in hemp seed (i.e., edestin 1, edestin 2, edestin 3, albumin, and vicilin), the putative hydrolyzed peptidome was established and used as the input dataset.

To select the Cannabis sativa antiviral peptides (csAVPs), a predictive bioinformatic analysis was performed by three webserver screening programs: iAMPpred, AVPpred, and Meta-iAVP. The amino acid composition profile comparison was performed by COPid to screen for the non-toxic and non-allergenic candidates, ToxinPred and AllerTOP and AllergenFP, respectively. GalaxyPepDock and HPEPDOCK were employed to perform the molecular docking of all selected csAVPs to the 3CLpro of SARS-CoV-2. Only the top docking-scored candidate (csAVP4) was further analyzed by molecular dynamics simulation for 150 nanoseconds.

Molecular docking and molecular dynamics revealed the potential ability and stability of csAVP4 to inhibit the 3CLpro catalytic domain with hydrogen bond formation in domain 2 with short bonding distances. In addition, these top ten candidate bioactive peptides contained hydrophilic amino acid residues and exhibited a positive net charge.

We hope that our results may guide the future development of alternative therapeutics against COVID-19.”

https://pubmed.ncbi.nlm.nih.gov/36615263/

https://www.mdpi.com/1420-3049/28/1/50

Is marijuana a foe of male sexuality? Data from a large cohort of men with sexual dysfunction

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“Background: Although it has been assumed that chronic cannabis use may have an unfavorable impact on male sexual function and its metabolic correlates, evidence from clinical studies remains inconclusive.

Objective: To investigate the relationship between cannabis use and sexual behavior, anthropometrics and metabolic/vascular profiles in a large series of men evaluated for sexual dysfunction.

Methods: 4800 men (mean age 50.8 years) attending an andrology outpatient clinic for sexual dysfunction were studied. Sexual symptoms, hormonal, metabolic and instrumental (penile color Doppler ultrasound, PCDU) parameters were evaluated according to the reported habitual use of recreational substances (no use, 1-2 joints/week, >2 joints/week, and use of illicit drugs other than cannabis).

Results: When compared to nonusers, cannabis users were younger and exhibited a lower prevalence of comorbidities as well as better PCDU parameters, despite reporting higher alcohol and tobacco consumption. After adjustment for confounders, cannabis use was associated with a greater instability in the couple’s relationship and a higher frequency of masturbation. In addition, the group smoking >2 joints/week showed significantly lower body mass index (BMI) than both controls and users of substances other than cannabis. Men who reported using recreational drugs (either cannabis or other) exhibited significantly lower levels of both total and low-density lipoprotein cholesterol than nonusers. At the PCDU, smoking 1-2 joints/week was associated with significantly higher dynamic peak systolic velocity than both non-drug use and use of >2 joints/week. Prolactin levels were significantly higher in individuals smoking 1-2 joints/week and in those who used substances other than cannabis when compared to controls, whereas no difference in total testosterone levels was observed.

Discussion: In men with sexual dysfunction, mild cannabis consumption may be associated with a more favorable anthropometric and lipid profile and with a better penile arterial vascular response to intracavernous prostaglandin injection.”

https://pubmed.ncbi.nlm.nih.gov/36617843/

https://onlinelibrary.wiley.com/doi/10.1111/andr.13382

Cannabis Bioactive Compound-Based Formulations: New Perspectives for the Management of Orofacial Pain

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“The management of orofacial pain to alleviate the quality of life of affected patients is becoming increasingly challenging for scientific research and healthcare professionals. From this perspective, in addition to conventional therapies, new alternatives are being sought, increasingly looking at the use of both natural and synthetic products.

Cannabis sativa L. represents an interesting source of bioactive compounds, including non-psychoactive cannabinoids, flavonoids, and terpenes, many of which are effective in improving pain intensity.

Here, we aim to analyze the possible mechanisms of action of the bioactive natural and synthetic hemp-derived compounds responsible for the modulatory effects on pain-related pathways. The ability of these compounds to act on multiple mechanisms through a synergistic effect, reducing both the release of inflammatory mediators and regulating the response of the endocannabinoid system, makes them interesting agents for alternative formulations to be used in orofacial pain.”

https://pubmed.ncbi.nlm.nih.gov/36615298/

https://www.mdpi.com/1420-3049/28/1/106

Low-Dose Administration of Cannabigerol Attenuates Inflammation and Fibrosis Associated with Methionine/Choline Deficient Diet-Induced NASH Model via Modulation of Cannabinoid Receptor

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“Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD). NASH is distinguished by severe hepatic fibrosis and inflammation. The plant-derived, non-psychotropic compound cannabigerol (CBG) has potential anti-inflammatory effects similar to other cannabinoids. However, the impact of CBG on NASH pathology is still unknown. This study demonstrated the therapeutic potential of CBG in reducing hepatic steatosis, fibrosis, and inflammation.

Methods: 8-week-old C57BL/6 male mice were fed with methionine/choline deficient (MCD) diet or control (CTR) diets for five weeks. At the beginning of week 4, mice were divided into three sub-groups and injected with either a vehicle, a low or high dose of CBG for two weeks. Overall health of the mice, Hepatic steatosis, fibrosis, and inflammation were evaluated.

Results: Increased liver-to-body weight ratio was observed in mice fed with MCD diet, while a low dose of CBG treatment rescued the liver-to-body weight ratio. Hepatic ballooning and leukocyte infiltration were decreased in MCD mice with a low dose of CBG treatment, whereas the CBG treatment did not change the hepatic steatosis. The high dose CBG administration increased inflammation and fibrosis. Similarly, the expression of cannabinoid receptor (CB)1 and CB2 showed decreased expression with the low CBG dose but not with the high CBG dose intervention in the MCD group and were co-localized with mast cells. Additionally, the decreased mast cells were accompanied by decreased expression of transforming growth factor (TGF)-β1.

Conclusions: Collectively, the low dose of CBG alleviated hepatic fibrosis and inflammation in MCD-induced NASH, however, the high dose of CBG treatment showed enhanced liver damage when compared to MCD only group. These results will provide pre-clinical data to guide future intervention studies in humans addressing the potential uses of CBG for inflammatory liver pathologies, as well as open the door for further investigation into systemic inflammatory pathologies.”

https://pubmed.ncbi.nlm.nih.gov/36615835/

“In conclusion, this study provides initial findings and a foundation for future studies on the efficacy of CBG on NASH.”

https://www.mdpi.com/2072-6643/15/1/178

Effects of cannabinoids in Parkinson’s disease animal models: a systematic review and meta-analysis

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“Objectives: Cannabis has been proposed as a potential treatment for Parkinson’s disease (PD) due to its neuroprotective benefits. However, there has been no rigorous review of preclinical studies to evaluate any potential treatment effect. This systematic review was undertaken to provide evidence in support or against a treatment effect of cannabinoids in animal models of PD.

Methods: Databases were searched for any controlled comparative studies that assessed the effects of any cannabinoid, cannabinoid-based treatment or endocannabinoid transport blocker on behavioural symptoms in PD animal models.

Results: A total of 41 studies were identified to have met the criteria for this review. 14 of these studies were included in meta-analyses of rotarod, pole and open field tests. Meta-analysis of rotarod tests showed a weighted mean difference of 31.63 s for cannabinoid-treated group compared with control. Meta-analysis of pole tests also showed a positive treatment effect, evidenced by a weighted mean difference of -1.51 s for cannabinoid treat group compared with control. However, meta-analysis of open field test demonstrated a standardised mean difference of only 0.36 indicating no benefit.

Conclusion: This review demonstrates cannabinoid treatment effects in alleviating motor symptoms of PD animal models and supports the conduct of clinical trials of cannabis in PD population. However, there is no guarantee of successful clinical translation of this outcome because of the many variables that might have affected the results, such as the prevalent unclear and high risk of bias, the different study methods, PD animal models and cannabinoids used.”

https://pubmed.ncbi.nlm.nih.gov/36618606/

“Overall, this systematic review and meta-analysis provides evidence of the benefit of cannabinoid treatment in PD animal models, which warrants further investigations. This review supports clinical trial of cannabis or cannabis-based treatments in humans with PD.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812814/


Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats

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“Oxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as putative therapeutics for the treatment of the early toxic events in DR. Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 μL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. Immunohistochemical-histological, ELISA, and Evans-Blue analyses were performed to assess the neuroprotective and vasculoprotective properties of the pharmacological treatments on diabetes-induced retinal toxicity. Activation of CB2R or blockade of CB1R, as well as the dual treatment, attenuated the nitrative stress induced by diabetes. Both single treatments protected neural elements (e.g., RGC axons) and reduced vascular leakage. AM1710 alone reversed all toxic insults. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease.”

https://pubmed.ncbi.nlm.nih.gov/36613692/

“In closing, our findings suggest that topical administration of the three cannabinoid treatments, such as eye drops, provides protection to the diabetic retina in a differential manner against the four pathologies of ESDR. The actions of both CB2R activation and CB1R blockade in restoring ganglion cell axons (NFL-IR) in ESDR suggest that both agents may be effective in retarding RGC death. AM1710 is efficacious as an antioxidant, anti-inflammatory, neuroprotective and vasculoprotective agent and, thus, a promising new therapeutic for ESDR. Further advancement of retinal imaging to screen and identify the early events in DR, such as neurodegeneration in diabetic patients, is crucial for selecting neuroprotective drugs and implementing personalized treatments. As our findings clearly implicate the endocannabinoid system, the therapeutic benefits of this class of compounds should also extend to patients with diabetic nephropathy and cardiopathy/stroke since DR has been associated with the development of these diseases.”

https://www.mdpi.com/1422-0067/24/1/240

Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment

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“Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa‘s biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.”

https://pubmed.ncbi.nlm.nih.gov/36614303/

“In conclusion, there is a complex array of effects that polyphenolic and cannabinoid compounds elicit in relation to melanoma. Multiple biochemical and genetic cascades are regulated through the presence of these natural substances. Polyphenolic compounds emergingly demonstrate a significant capacity to mediate many of the impacts of cancer, including pain, inflammation and invasiveness. Combined administration of polyphenol compounds has shown existing promise for improvement of potency and bioactivity of these substances. To combat the complexity of cancer, new pharmacological perspectives are necessary. Accordingly, plant polyphenols, particularly those of cannabis provide a deep well of structural potential for the emergence of novel drugs with multi-applicability to the total sphere of cancer treatment. This is merely the budding tip of biocompounds available for exploration in plant-based medicine and is a substantive base for future research.”

https://www.mdpi.com/1422-0067/24/1/859