Monthly Archives: May 2022

Safety and Efficacy of the Therapeutic Use of Cannabis-Based Products in the Treatment of Dogs: An Integrative Review

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“The use of cannabis-based products for therapeutic purposes is a reality in the field of animal health. However, although cannabis is considered safe when appropriately used by human patients, cannabis-based products can pose a risk to companion animals such as dogs, depending on their composition or route of administration. Thus, this article discusses aspects of the safety and efficacy of different cannabis-based products in dogs’ treatment through an integrative review. The review was systematically performed in Medline (via Pubmed®) and Latin American and Caribbean Health Sciences Literature (LILACS) databases, with period restriction (between 1990 and 2021). The qualified articles (n=19), which met the previously established inclusion criteria, were critically evaluated. Based on the literature review, it is possible to infer safety in the administration of cannabis-based products for the treatment of dogs, especially products rich in cannabidiol (CBD), free or with low concentrations of tetrahydrocannabinol, under the conditions evaluated. In addition, CBD products potentially promote improved quality of life and reduce pain perception in animals affected by canine osteoarthritis. Finally, owing to the lack of large-scale and robust clinical research studies, the performance of clinical trials, considering the individual characteristics of each cannabis-based product (composition, concentration, nature of adjuvants, dosage form, route of administration), is strongly encouraged.”

https://pubmed.ncbi.nlm.nih.gov/35512739/

https://www.liebertpub.com/doi/10.1089/can.2021.0172

Nanoencapsulation of essential oils from industrial hemp (Cannabis sativa L.) by-products into alfalfa protein nanoparticles

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“Essential oils of industrial hemp (Cannabis sativa L.) by-products (HBEO) were characterized by gas chromatography-mass spectrometry (GC-MS); then, encapsulated in alfalfa protein isolate nanoparticles (API-NPs) as a novel nanocarrier. A desirable retention (45.5-63.4%) of HBEO within API-NPs was confirmed. These nanoparticles exhibited a shrunk and globular shape with a size range of 156.9-325.9 nm as indicated by dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Furthermore, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and thermal analyses corroborated that HBEO was successfully encapsulated within API NPs in an amorphous form without specific chemical interaction with the carrier matrix. The antioxidant activity of loaded HBEO into API-NPs was higher than free HBEO implying that encapsulation of HBEO in API-NPs was an efficient strategy for improving its stability and functionality. HBEO-loaded API-NPs is a promising candidate to be used in future foods and supplements for novel applications.”

https://pubmed.ncbi.nlm.nih.gov/35509161/

https://www.sciencedirect.com/science/article/abs/pii/S0308814622007270?via%3Dihub


A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing

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Materials Science and Engineering: C

“In addition to preventing infection and promoting angiogenesis, novel hydrogel dressings are highly expected to possess the potential to scavenge reactive oxygen species (ROS) and reduce inflammatory responses during the wound healing process. In this study, we designed and fabricated a hydrogel dressing (CBD/Alg@Zn) containing cannabidiol (CBD) based on the ion crosslinked interaction between Zn2+ ions and the alginate polymer (Alg). The as-fabricated hydrogel exhibited a suitable swelling ratio, sufficient thermal stability, and stable rheological property. In vitro biological activity experiments indicated that the hydrogel has good biocompatibility, antibacterial activity, and angiogenesis properties. Moreover, it could significantly scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals and reduce the inflammatory response. In vivo studies revealed that the CBD/Alg@Zn hydrogel significantly facilitated the wound healing process by controlling the inflammatory infiltration, promoting collagen deposition and the granulation tissue, and benefiting the formation of blood vessels. We, therefore, suggested that CBD/Alg@Zn hydrogel should be a potential candidate material for wound dressing and skin tissue engineering.”

https://pubmed.ncbi.nlm.nih.gov/35523648/

“A cannabidiol-containing alginate based hydrogel (CBD/Alg@Zn) was developed as novel multifunctional wound dressing.•

The Alg@Zn hydrogel not only acts as a drug carrier but also shows significantly anti-bacterial and angiogenic activities.•

The introduction of cannabidiol (CBD) endowed the hydrogels with antioxidant and anti-inflammatory effects.•

The CBD/Alg@Zn hydrogel showed accelerated wound healing effect in vivo.”

https://www.sciencedirect.com/science/article/abs/pii/S0928493121007001?via%3Dihub


Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies

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“Industrial hemp (Cannabis sativa) is traditionally cultivated as a valuable source of fibers and nutrients. Multiple studies also demonstrated antimicrobial, anti-proliferative, phytotoxic and insecticide effects of the essential oil from hemp female inflorescences. On the other side, only a few studies explored the potential pharmacological application of polar extracts from inflorescences. In the present study, we investigated the water extract from inflorescences of industrial hemp Futura 75 variety, from phytochemical and pharmacological point of view. The water extract was assayed for phenolic compound content, radical scavenger/reducing, chelating and anti-tyrosinase effects. Through an ex vivo model of toxicity induced by lipopolysaccharide (LPS) on isolated rat colon and liver, we explored the extract effects on serotonin, dopamine and kynurenine pathways and the production of prostaglandin (PG)E2. Anti-proliferative effects were also evaluated against human colon cancer HCT116 cell line. Additionally, antimycotic effects were investigated against Trichophyton rubrum, Trichophyton interdigitale, Microsporum gypseum. Finally, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted in order to predict the putative targets underlying the observed pharmacological and microbiological effects. Futura 75 water extract was able to blunt LPS-induced reduction of serotonin and increase of dopamine and kynurenine turnover, in rat colon. Additionally, the reduction of PGE2 levels was observed in both colon and liver specimens, as well. The extract inhibited the HCT116 cell viability, the growth of T. rubrum and T. interdigitale and the activity of tyrosinase, in vitro, whereas in silico studies highlighting the inhibitions of cyclooxygenase-1 (induced by carvacrol), carbonic anhydrase IX (induced by chlorogenic acid and gallic acid) and lanosterol 14-α-demethylase (induced by rutin) further support the observed pharmacological and antimycotic effects. The present findings suggest female inflorescences from industrial hemp as high quality by-products, thus representing promising sources of nutraceuticals and cosmeceuticals against inflammatory and infectious diseases.”

https://pubmed.ncbi.nlm.nih.gov/32429587/

“Concluding, the present findings highlight the potential of water extracts from industrial hemp inflorescences as sources of natural compounds that, besides the intrinsic antiradical activity, possess discrete mechanisms related to anti-inflammatory, anti-proliferative and antimycotic effects. In this context, and also in view of a more sustainable circular economy, it is desirable an improvement of industrial hemp chain production, taking into consideration the female inflorescences as high quality by-products with putative nutraceutical and cosmeceutical applications.”

https://www.mdpi.com/2076-3921/9/5/437/htm

Anti-Inflammatory, Antioxidative, and Hepatoprotective Effects of Trans Δ9-Tetrahydrocannabinol/Sesame Oil on Adjuvant-Induced Arthritis in Rats

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“Rheumatoid arthritis (RA) is a painful chronic autoimmune disease affecting the joints. Its first-line therapy, Methotrexate (MTX), although effective in ameliorating the progress of the disease, induces hepatotoxicity over long-term usage. Thus, seeking natural compounds with fewer side effects could be an alternative therapeutic approach. This study aimed to investigate the anti-inflammatory, antiarthritic, and antioxidative effects of synthetic trans-Δ9-tetrahydrocannabinol (Δ9-THC) dissolved in sesame oil (Dronabinol) against MTX in adjuvant-induced arthritis (AIA) rat model. Daily oral administration of Δ9-THC/sesame oil, over a period of 21 days, was well tolerated in arthritic rats with no particular psychoactive side effects. It markedly attenuated the severity of clinical manifestations, recovered the histopathological changes in tibiotarsal joints, and repressed the splenomegaly in arthritic rats. Δ9-THC/sesame oil therapy showed similar effects to MTX in neutralizing the inflammatory process of AIA, through attenuating erythrocyte sedimentation rate (ESR) scores and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and interleukin-6 (IL-6) levels, to normal values. As opposed to MTX, this natural combination markedly protected the liver of arthritic rats and downregulated the induced oxidative stress by increasing the antioxidant defense system such as activities of catalase and superoxide dismutase (SOD) and levels of glutathione (GSH). These results suggest promising effects for the clinical use of Δ9-THC/sesame oil therapy in alleviating arthritic clinical signs as well as arthritis-induced liver injury.”

https://pubmed.ncbi.nlm.nih.gov/30046349/

“Dronabinol (Δ9-THC in sesame oil) is usually used to treat nausea and vomiting caused by chemotherapy or weight loss and loss of appetite in AIDS patients, yet, to the best of our knowledge, this is the first study that proves the antiarthritic and antioxidative effects of this combination in an experimental model of RA with a hepatoprotective effect against arthritis-induced liver injury compared to commonly used antirheumatic drug (MTX).”

https://www.hindawi.com/journals/ecam/2018/9365464/


Impact of smoking cannabidiol (CBD)-rich marijuana on driving ability

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“To investigate effects of smoking cannabidiol (CBD)-rich marijuana on driving ability and determine free CBD and Δ9-tetrahydrocannabinol (THC) concentrations in capillary blood samples, a randomised, double-blind, placebo-controlled, two-way crossover pilot study was conducted with 33 participants. Participants smoked a joint containing 500 mg of tobacco and either 500 mg of CBD-rich marijuana (16.6% total CBD; 0.9% total THC) or 500 mg of a placebo substance, then performed three different dimensions of the Vienna Test System TRAFFIC examining reaction time, behaviour under stress, and concentration performance. For further assessment of participants’ fitness to drive, three tests of balance and coordination were evaluated and vital signs (blood pressure and pulse) were measured. Dried blood spot samples of capillary blood were taken after smoking and after completion of the tests to determine the cannabinoid concentrations (CBD, THC and THC-metabolites). The results revealed no significant differences between the effects of smoking CBD-rich marijuana and placebo on reaction time, motor time, behaviour under stress, or concentration performance. Maximum free CBD and THC concentrations in capillary blood were detected shortly after smoking, ranging between 2.6-440.0 ng/mL and 6.7-102.0 ng/mL, respectively. After 45 min, capillary blood concentrations had already declined and were in the range of 1.9-135.0 ng/mL (free CBD) and 0.9-38.0 ng/mL (free THC). Although the observed levels of free THC concentrations have been reported to cause symptoms of impairment in previous studies in which THC-rich marijuana was smoked, no signs of impairment were found in the current study. This finding suggests that higher CBD concentrations cause a negative allosteric effect in the endocannabinoid system, preventing the formation of such symptoms. Nevertheless, it is recommended that consumers refrain from driving for several hours after smoking CBD-rich marijuana, as legal THC concentration limits may be exceeded.”

https://pubmed.ncbi.nlm.nih.gov/34868711/

  • “No significant impact on driving ability was found after smoking CBD-rich marijuana.”

https://www.tandfonline.com/doi/full/10.1080/20961790.2021.1946924

Cannabidiol Inhibits In Vitro Human Liver Microsomal Metabolism of Remdesivir: A Promising Adjuvant for COVID-19 Treatment

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“Introduction: The year 2020 began with the world being flounced with a wave of novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) disease, named COVID-19. Based on promising pre-clinical and clinical data, remdesivir (RDV) was the first drug to receive FDA approval and so far, it is the most common therapy for treatment of SARS-CoV-2/MERS-CoV. However, following intravenous administration, RDV metabolizes majorly by human liver carboxylesterase 1 (CES1) and marginally by the CYP3A4 enzyme in merely less than an hour. Its resultant active metabolite is a hydrophilic nucleoside with very limited accumulation within lung tissues. Therefore, there is a need to investigate strategies to overcome such premature metabolism issues and improve the antiviral efficacy of RDV at the target site. Objective: Considering the major CES1-mediated metabolism of RDV on systemic administration, we intend to explore the remarkable CES1 plus CYP3A4 inhibitory activity of cannabidiol (CBD) against in vitro microsomal metabolism of RDV to indicate its therapeutic potential as an adjuvant to RDV in the treatment and management of COVID-19. Methods: We investigated the in vitro human liver microsomal metabolism of RDV in the presence of two potential CES1 inhibitors-CBD and nelfinavir, and two standard CYP3A4 inhibitors-ritonavir (RITO) and cyclosporin A. The microsomal metabolism assay was further validated by using a well-characterized CYP3A4-selective substrate, midazolam (MDZ), in the presence of CBD and RITO. Results: Our findings depicted that RDV was rapidly and completely metabolized by human liver microsomes within 60 min. Coincubation with CBD substantially reduced microsomal metabolism of RDV and prolonged its in vitro half-life from 8.93 to 31.07 min. CBD showed significantly higher inhibition of RDV compared with known CES1 and CYP3A4 inhibitors. Inhibition of MDZ metabolism by CBD and RITO further validated the assay. Conclusions: The current study strongly suggests that CBD significantly inhibits human liver microsomal metabolism of RDV and extends its in vitro half-life. Thus, concomitant administration of CBD with RDV intravenous injection could be a promising strategy to prevent premature metabolism in COVID-19 patients.”

https://pubmed.ncbi.nlm.nih.gov/34918945/

https://www.liebertpub.com/doi/10.1089/can.2021.0109


Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment

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“Despite the importance of pain as a warning physiological system, chronic neuropathic pain is frequently caused by damage in the nervous system, followed by persistence over a long period, even in the absence of dangerous stimuli or after healing of injuries. Chronic neuropathic pain affects hundreds of millions of adults worldwide, creating a direct impact on quality of life. This pathology has been extensively characterized concerning its cellular and molecular mechanisms, and the endocannabinoid system (eCS) is widely recognized as pivotal in the development of chronic neuropathic pain. Scientific evidence has supported that phyto-, synthetic and endocannabinoids are efficient for pain management, while strong data arise from the therapeutic use of Cannabis-derived products. The use of medicinal Cannabis products is directed toward not only relieving symptoms of chronic pain, but also improving several aspects of patients’ welfare. Here, we review the involvement of eCS, along with other cellular and molecular elements, in chronic neuropathic pain pathology and how this system can be targeted for pain management.”

https://pubmed.ncbi.nlm.nih.gov/34916962/

“The role of eCS as a pharmacological target and the advantages of using medicinal Cannabis sp. to treat pain is remarkable, as described in this review.”

https://www.frontiersin.org/articles/10.3389/fphys.2021.785176/full


Cannabidiol Inhibits Tau Aggregation In Vitro

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“A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), and atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking, and job’s plot, we further demonstrated that one molecule of CBD interacts with one molecule of tau protein through a spontaneous binding. Experiments performed by quenching assay, docking, and Thioflavin T assay further established that the main forces are hydrogen Van der Waals and some non-negligible hydrophobic forces, affecting the lag phase of tau protein kinetics. Taken together, this study provides new insights about a natural substance, CBD, for tau therapy which may offer new hope for the treatment of AD.”

https://pubmed.ncbi.nlm.nih.gov/34944028/

https://www.mdpi.com/2073-4409/10/12/3521


Applications of Cannabis Sativa L. in Food and Its Therapeutic Potential: From a Prohibited Drug to a Nutritional Supplement

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“Hemp (Cannabis sativa L.) is a herbaceous anemophilous plant that belongs to the Cannabinaceae family. The cannabis seed (hemp) has long been utilized as a food source and is commercially important as an edible oil source. In this review, the positive and negative health effects of cannabis, the relationship between cannabis and various diseases, and the use of cannabis in various food products have been discussed. In addition, the scientific literature on the potential use of cannabis and its derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic degenerative diseases in animals and humans has been reviewed. Cannabis is being developed as a key ingredient in a variety of food items, including bakery, confectionery, beverages, dairy, fruits, vegetables, and meat. Hemp seeds are high in readily digestible proteins, lipids, polyunsaturated fatty acids (PUFA), insoluble fiber, carbs, and favorable omega-6 PUFA acid to omega-3 PUFA ratio and have high nutritional value. The antioxidants of cannabis, such as polyphenols, help with anxiety, oxidative stress, and the risk of chronic illnesses, including cancer, neurological disorders, digestive problems, and skin diseases. Overall, the purpose of this research is to stimulate more in-depth research on cannabis’s adaptation in various foods and for the treatment of chronic illnesses.”

https://pubmed.ncbi.nlm.nih.gov/34946779/

https://www.mdpi.com/1420-3049/26/24/7699