Monthly Archives: May 2022

Cannabis, cannabinoids, and cannabis-based medicines: future research directions for analgesia

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“The use of cannabis spans thousands of years and encompasses almost all dimensions of the human experience, including consumption for recreational, religious, social, and medicinal purposes. Its use in the management of pain has been anecdotally described for millennia. However, an evidence base has only developed over the last 100 years, with an explosion in research occurring in the last 20-30 years, as more states in the USA as well as countries worldwide have legalized and encouraged its use in pain management. Pain remains one of the most common reasons for individuals deciding to use cannabis medicinally. However, cannabis remains illegal at the federal level in the USA and in most countries of the world, making it difficult to advance quality research on its efficacy for pain treatment. Nonetheless, new products derived both from the cannabis plant and the chemistry laboratory are being developed for use as analgesics. This review examines the current landscape of cannabinoids research and future research directions in the management of pain.”

https://pubmed.ncbi.nlm.nih.gov/35534020/

https://rapm.bmj.com/content/early/2022/05/08/rapm-2021-103109


Efficacy of Δ9 -Tetrahydrocannabinol (THC) Alone or in Combination With a 1:1 Ratio of Cannabidiol (CBD) in Reversing the Spatial Learning Deficits in Old Mice

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“Decline in cognitive performance, an aspect of the normal aging process, is influenced by the endocannabinoid system (ECS). Cannabinoid receptor 1 (CB1) signaling diminishes with advancing age in specific brain regions that regulate learning and memory and abolishing CB1 receptor signaling accelerates cognitive aging in mice. We recently demonstrated that prolonged exposure to low dose (3 mg/kg/day) Δ9-tetrahydrocannabinol (THC) improved the cognitive performances in old mice on par with young untreated mice. Here we investigated the potential influence of cannabidiol (CBD) on this THC effect, because preclinical and clinical studies indicate that the combination of THC and CBD often exhibits an enhanced therapeutic effect compared to THC alone. We first tested the effectiveness of a lower dose (1 mg/kg/day) THC, and then the efficacy of the combination of THC and CBD in 1:1 ratio, same as in the clinically approved medicine Sativex®. Our findings reveal that a 1 mg/kg/day THC dose still effectively improved spatial learning in aged mice. However, a 1:1 combination of THC and CBD failed to do so. The presence of CBD induced temporal changes in THC metabolism ensuing in a transient elevation of blood THC levels. However, as CBD metabolizes, the inhibitory effect on THC metabolism was alleviated, causing a rapid clearance of THC. Thus, the beneficial effects of THC seemed to wane off more swiftly in the presence of CBD, due to these metabolic effects. The findings indicate that THC-treatment alone is more efficient to improve spatial learning in aged mice than the 1:1 combination of THC and CBD.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435893/

“In conclusion, our observations indicate that 1 mg/kg/day THC dose is still effective in improving the spatial learning in aged mice. With regard to the efficacy, THC-alone has proved to be more efficient in improving spatial learning in aged mice than its 1:1 combination with CBD. However, the possibility of THC/CBD being efficient in other ratios or at the earliest time-points, like immediately after the treatment cease, cannot be negated. Possibly, reducing the dose of CBD may improve the efficacy of the THC/CBD combination.”

https://www.frontiersin.org/articles/10.3389/fnagi.2021.718850/full

Positive Effect of Cannabis sativa L. Herb Extracts on Skin Cells and Assessment of Cannabinoid-Based Hydrogels Properties

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“The skin is an organ that is constantly exposed to many external factors that can affect its structure and function. Due to the presence of different cannabinoid receptors on many types of skin cells, cannabinoids can interact directly with them. Therefore, as part of this work, the impact of two types of Cannabis sativa L. herb extracts on keratinocytes and fibroblasts was assessed. The content of biologically active compounds such as phenols, flavonoids, chlorophylls and cannabinoids was evaluated. The antioxidant capacity of prepared extracts using the DPPH radical, H2DCFDA probe and measurement of superoxide dismutase activity was also assessed. The cytotoxicity of hemp extracts was determined using the Alamar Blue, Neutral Red and LDH assays. The ability of the extracts to inhibit the activity of matrix metalloproteinases, collagenase and elastase, was assessed. Preparations of model hydrogels were also prepared and their effect on transepidermal water loss and skin hydration was measured.

The obtained results indicate that hemp extracts can be a valuable source of biologically active substances that reduce oxidative stress, inhibit skin aging processes and positively affect the viability of skin cells. The analysis also showed that hydrogels based on cannabis extracts have a positive effect on skin hydration.”

“In addition to the previously known antioxidant properties of the tested extracts, which can have a positive effect on the structure and condition of skin cells, this work also shows other benefits of hemp extracts.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913911/

Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids

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“The use of Cannabis sativa is currently recognized to ease certain types of chronic pain, reduce chemotherapy-induced nausea, and improve anxiety. Nevertheless, few studies highlighted the therapeutic potential of C. sativa extracts and related phytocannabinoids for a variety of widespread skin disorders including acne, atopic dermatitis, psoriasis, pruritus, and pain. This review summarized the current evidence on the effects of phytocannabinoids at the cutaneous level through the collection of in vitro, in vivo, and clinical studies published on PubMed, Scopus, Embase, and Web of Science until October 2020.

Phytocannabinoids have demonstrated potential anti-inflammatory, antioxidant, anti-aging, and anti-acne properties by various mechanisms involving either CB1/2-dependent and independent pathways.

Not only classical immune cells, but also several skin-specific actors, such as keratinocytes, fibroblasts, melanocytes, and sebocytes, may represent a target for phytocannabinoids. Cannabidiol, the most investigated compound, revealed photoprotective, antioxidant, and anti-inflammatory mechanisms at the cutaneous level, while the possible impact on cell differentiation, especially in the case of psoriasis, would require further investigation. Animal models and pilot clinical studies supported the application of cannabidiol in inflammatory-based skin diseases. Also, one of the most promising applications of non-psychotropic phytocannabinoids is the treatment of seborrheic disorders, especially acne. In conclusion, the incomplete knowledge of the role of the endocannabinoid system in skin disorders emerged as an important limit for pharmacological investigations. Moreover, the limited studies conducted on C. sativa extracts suggested a higher potency than single phytocannabinoids, thus stimulating new research on phytocannabinoid interaction.”

https://pubmed.ncbi.nlm.nih.gov/33851375/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1420-5780


In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

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“Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1β, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG’s broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.”

https://pubmed.ncbi.nlm.nih.gov/35056807/

https://www.mdpi.com/1420-3049/27/2/491


Cutaneous Squamous Cell Carcinoma and Lichen Simplex Chronicus Successfully Treated with Topical Cannabinoid Oil: A Case Report and Summary of Cannabinoids in Dermatology

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“Cannabidiol is a member of the cannabinoids, consisting of a diverse class of compounds derived from Cannabis sativa. There are three types of cannabinoids based on origin: endocannabinoids (endogenous), phytocannabinoids (plant-derived), and synthetic cannabinoids (synthesized). The endocannabinoid system plays a key role in skin homeostasis, such as proliferation, differentiation, and inflammatory signaling. A 64-year-old woman with a history of multiple squamous cell carcinomas who presented with skin lesions on her bilateral dorsal hands is reported. Her skin biopsies showed lichen simplex chronicus on her left hand and squamous cell carcinoma on her right hand; both lesions resolved with topical application of 20% cannabidiol. Cutaneous adverse events associated with cannabinoid use and potential therapeutic uses of cannabinoids in inflammatory skin diseases and skin cancer are also summarized.”

https://pubmed.ncbi.nlm.nih.gov/35530920/

“Cannabinoids are a class of drugs that are found in animals, humans, and plants; they are also synthesized. They are useful in the management of several systemic diseases. Indeed, cannabinoids have also been observed to be potentially effective in the treatment of cosmetic skin conditions and cutaneous diseases. In addition, they may be therapeutic in the management of not only non-melanoma skin cancer, such as squamous cell carcinoma, but also melanoma and Kaposi sarcoma. Our patient had successful treatment of a benign skin condition (lichen simplex chronicus); in addition, she had complete regression of several biopsy-confirmed squamous cell carcinomas. Therefore, the possibility of treating non-melanoma skin cancer, such as squamous cell carcinoma, with topical cannabinoids may warrant further investigation.”

https://www.cureus.com/articles/91630-cutaneous-squamous-cell-carcinoma-and-lichen-simplex-chronicus-successfully-treated-with-topical-cannabinoid-oil-a-case-report-and-summary-of-cannabinoids-in-dermatology


Patterns of Use and Self-reported Effectiveness of Cannabis for Hyperemesis Gravidarum

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“Introduction There is limited research on effective treatment of Hyperemesis Gravidarum (HG), the most extreme version of nausea and vomiting during pregnancy (NVP). This paper examines current patterns of use and self-reported effectiveness of cannabis/cannabis-based products (CBP) to treat HG. Results Of the 550 survey respondents, 84% experienced weight loss during pregnancy; 96% reported using prescription antiemetics and 14% reported cannabis use for HG. Most respondents reported using cannabis/CBPs (71%) because their prescribed antiemetics were self-reported to be ineffective. More than half of cannabis/CBP users reported using products daily or multiple times per day (53%), primarily via smoke inhalation (59%), and mainly either delta-9-tetrahydrocannabinol (THC) only or THC dominant preparations (57%). Eighty-two percent of cannabis/CBP users reported symptom relief, compared to 60% of prescription antiemetic users. Among patients who reported weight loss during pregnancy, 56% of cannabis users reported gaining weight within two weeks of treatment, compared to 25% of prescription antiemetic users. Conclusions Respondents reported using cannabis primarily because prescribed medications were self-reported to be ineffective. Although the survey approach has inherent limitations so results should be interpreted with caution, in this sample, cannabis was self-reported to be more effective than prescription medications in alleviating HG symptoms and enabling pregnancy weight gain. Therefore, depending on the safety profiles, randomized, double-blinded, placebo-controlled trials of cannabis compared to other antiemetics are warranted to determine whether cannabinoids may provide an effective alternative treatment for HG.”

https://pubmed.ncbi.nlm.nih.gov/35528189/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1749-5391

Medicinal Cannabis and Central Nervous System Disorders

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“Cannabinoids, including those found in cannabis, have shown promise as potential therapeutics for numerous health issues, including pathological pain and diseases that produce an impact on neurological processing and function. Thus, cannabis use for medicinal purposes has become accepted by a growing majority. However, clinical trials yielding satisfactory endpoints and unequivocal proof that medicinal cannabis should be considered a frontline therapeutic for most examined central nervous system indications remains largely elusive. Although cannabis contains over 100 + compounds, most preclinical and clinical research with well-controlled dosing and delivery methods utilize the various formulations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the two most abundant compounds in cannabis. These controlled dosing and delivery methods are in stark contrast to most clinical studies using whole plant cannabis products, as few clinical studies using whole plant cannabis profile the exact composition, including percentages of all compounds present within the studied product. This review will examine both preclinical and clinical evidence that supports or refutes the therapeutic utility of medicinal cannabis for the treatment of pathological pain, neurodegeneration, substance use disorders, as well as anxiety-related disorders. We will predominately focus on purified THC and CBD, as well as other compounds isolated from cannabis for the aforementioned reasons but will also include discussion over those studies where whole plant cannabis has been used. In this review we also consider the current challenges associated with the advancement of medicinal cannabis and its derived potential therapeutics into clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/35529444/

“This review of current and past studies finds that preclinical research indicates therapeutic potential for cannabis, THC, and CBD mediated through either CB1R, CB2R, 5-HT1A, or a variable combination of these receptors. Clinical research utilizing cannabinoids within instances of neurodegenerative disease, pain, addiction, and anxiety suggest both tolerability and therapeutic potential either alone or in combination with current therapeutics.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.881810/full

Cannabinoids as Emergent Therapy Against COVID-19

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“The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-Cov-2), was identified for the first time in late 2019 in China, resulting in a global pandemic of massive impact. Despite a fast development and implementation of vaccination strategies, and the scouting of several pharmacological treatments, alternative effective treatments are still needed. In this regard, cannabinoids represent a promising approach because they have been proven to exhibit several immunomodulatory, anti-inflammatory, and antiviral properties in COVID-19 disease models and related pathological conditions. This mini-review aims at providing a practical brief overview of the potential applications of cannabinoids so far identified for the treatment and prevention of COVID-19, finally considering key aspects related to their technological and clinical implementation.”

https://pubmed.ncbi.nlm.nih.gov/35512732/

“Overall, cannabinoids offer a great pharmacological potential in the management of COVID-19. It is to be hoped that the scientific evidence so far reported on cannabinoids effects along with the possibilities offered by drug delivery systems will entice the development of valuable therapies in this area.”

https://www.liebertpub.com/doi/10.1089/can.2022.0018

Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration

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Scientific Reports

“The endocannabinoid system has been postulated to help restrict cancer progression and maintain osteoblastic function during bone metastasis. Herein, the effects of cannabinoid receptor (CB) type 1 and 2 activation on breast cancer cell and osteoblast interaction were investigated by using ACEA and GW405833 as CB1 and CB2 agonists, respectively. Our results showed that breast cancer cell (MDA-MB-231)-derived conditioned media markedly decreased osteoblast-like UMR-106 cell viability. In contrast, media from MDA-MB-231 cells pre-treated with GW405833 improved UMR-106 cell viability. MDA-MB-231 cells were apparently more susceptible to both CB agonists than UMR-106 cells. Thereafter, we sought to answer the question as to how CB agonists reduced MDA-MB-231 cell virulence. Present data showed that co-activation of CB1 and CB2 exerted cytotoxic effects on MDA-MB-231 cells by increasing apoptotic cell death through suppression of the NF-κB signaling pathway in an ROS-independent mechanism. ACEA or GW405833 alone or in combination also inhibited MDA-MB-231 cell migration. Thus, it can be concluded that the endocannabinoid system is able to provide protection during breast cancer bone metastasis by interfering cancer and bone cell interaction as well as by the direct suppression of cancer cell growth and migration.”

https://pubmed.ncbi.nlm.nih.gov/35513484/

“In conclusions, we have demonstrated that the ECS—which was present in bone microenvironment—provided a protection against breast cancer bone metastasis and its negative consequence on bone cell survival. Specifically, CB agonists, especially CB2 agonist, was able to prevent breast cancer-induced osteoblast suppression. Each of the two CB agonists or a combination of both could reduce breast cancer cell survival and migration through the NF-κB-dependent pathway. “

https://www.nature.com/articles/s41598-022-11116-9