Author Archives: David Worrell

Effects of Cannabidiol in a Caenorhabditis Elegans Amyotrophic Lateral Sclerosis Model

Posted on by

“Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by the progressive death of motor neurons. Cannabidiol, the second most prevalent cannabinoid in the Cannabis sativa plant, is a potential therapeutic tool for ALS due to its antioxidant, anti-inflammatory, and anti-spasticity effects, as well as its complementary role in treating other neurodegenerative diseases. In SOD1-G93A murine ALS models, cannabinoids have been shown to slow disease progression, extending lifespan and increasing motor function. However, the effects of specific cannabinoids-including cannabidiol-are yet undefined and their functions slowing disease progression are unknown. To advance this understanding we aim to study the effects of cannabidiol treatment in a Caenorhabditis elegans ALS model: a SOD-1 mutant transgenic strain with SOD-1 aggregation in muscular cells. We will use a death assay to measure the lifespan of SOD-1 mutant C. elegans and cannabidiol-treated SOD-1 mutant C. elegans to investigate whether treatment with cannabidiol impacts the lifespan of SOD-1 mutants. To assess mechanosensation, we will touch C. elegans with sutures of various sizes, based on the Von Frey filaments touch response assay in humans. We will develop a novel computational analysis system to measure C. elegans movement in response to touch. We will then compare the motor response of the SOD-1 mutant transgenic strain to wild type and study if cannabidiol modulates a possible change in motor response. This study will evaluate the functions of cannabidiol as a potential therapeutic tool in ALS using a SOD-1 mutant C. elegans model.”

https://pubmed.ncbi.nlm.nih.gov/35555765/

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.0R317

Acute Cannabigerol Administration Lowers Blood Pressure in Mice

Posted on by

“Cannabigerol (CBG) is a cannabinoid compound that is synthesized from Cannabis sativa L. and acts as a substrate for both Δ9-tetraydrocannabinol (Δ9-THC) and cannabidiol (CBD) formation. Given that it does not exhibit psychoactive effects, emerging research has focused on CBG as a potential therapeutic for health conditions including algesia, epilepsy, anxiety, and cancer. While CBG can bind to cannabinoid receptors CB1 and CB2, it has also been described as an agonist at α2-adrenoreceptors (A2-AR), which when activated inhibit the release of norepinephrine from α-adrenergic neurons. This raises the concern that CBG could act at A2-AR to reduce norepinephrine release to cardiovascular end organs, such as the heart and kidneys, causing a reduction in blood pressure. Despite this possibility, there are no reports examining cardiovascular effects of CBG. In this study, we tested the hypothesis that acute CBG administration can lower blood pressure. To test this, six male C57BL/6J mice underwent surgery at 8-10 weeks of age to implant a radiotelemetry probe, which allows for continuous measurement of blood pressure, heart rate and locomotor activity in conscious, freely moving mice. Following 10 days of recovery, baseline measurements were obtained and then mice were randomized to receive intraperitoneal injections of CBG (3.3, 5.6, and 10 mg/kg) and vehicle in a crossover design, with at least one-week washout between treatments. Changes in blood pressure, heart rate, and locomotor activity were measured for two hours post-injection. We found that acute CBG significantly lowered blood pressure compared with vehicle (-12±5 mmHg vehicle vs. -28±2 mmHg at 10 mg/kg CBG; p=0.018), with no apparent dose responsiveness at the doses used in this study (-22±2 mmHg at 3.3 mg/kg CBG; -28±4 at 5.6 mg/kg CBG). The greatest blood pressure reduction was seen at 90-minutes post-CBG administration, which is consistent with reports for peak plasma concentrations of this compound in rodents. The blood pressure lowering effects of CBG occurred in the absence of changes in heart rate or locomotor activity. These overall findings suggest acute CBG may lower blood pressure in phenotypically normal young adult male mice, which may provide caution for the potential of hypotension as an adverse effect of CBG administration. Additional studies are needed to determine if the blood pressure lowering effects of CBG are via an A2-AR mechanism.”

https://pubmed.ncbi.nlm.nih.gov/35555999/

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.0R576

The Effects of ß-caryophyllene on Pain-Evoked and Pain-Depressed Behaviors in Rats with Chronic Inflammatory Pain

Posted on by

“The antinociceptive effects of major cannabinoids such as ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have been extensively studied in rats. These studies have led to formulations of THC and CBD for human use; however, humans use different strains of Cannabis that contain several hundred different compounds. The contribution of these compounds to pain relief produced by Cannabis is unclear. ß-caryophyllene (BCP) is one compound found in the essential oils of Cannabis. Despite some early studies, the extent to which these compounds produce pain relief in assays of pain-evoked behaviors (i.e., von Frey and Hargreaves tests) and pain-depressed behaviors (i.e., home cage wheel running) is unclear. We hypothesized that BCP would inhibit mechanical allodynia and thermal hyperalgesia as well as restore depressed wheel running activity in male Sprague-Dawley rats with inflammatory pain. Three different doses of BCP (10, 30, and 100 mg/kg) or vehicle were administered to rats via an intraperitoneal injection after hindpaw inflammation induced by an intraplantar injection of Complete Freund’s Adjuvant (CFA). Neither the low dose (10 mg/kg) nor the medium dose (30 mg/kg) of BCP reversed mechanical allodynia of the inflamed hindpaw after intraperitoneal injection. However, a high dose of BCP (100 mg/kg) reversed mechanical allodynia on the von Frey test; however, this dose did not reverse thermal hyperalgesia. A hindpaw injection of 0.1 mL CFA decreased wheel running activity as is consistent with a painful stimulus. However, neither 30 mg/kg BCP nor 100 mg/kg BCP restored pain-depressed wheel running in injured rats. These same doses of BCP did not affect wheel running in uninjured control rats. Therefore, a high dose BCP produces pain relief, although it only does so against mechanical allodynia. BCP does not restore normal activity. This suggests that although pain may be eliminated following BCP administration, a return to normal levels of activity may not be possible which raises questions about the utility of BCP to treat pain. Future studies of the pain-relieving effects of Cannabis constituents must include tests of many pain-related behaviors to understand dose-response relationships and their therapeutic potential.”

https://pubmed.ncbi.nlm.nih.gov/35556755/

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.R3008

Cannabinoids as Potential Molecules for Addiction Disorders

Posted on by
Generic placeholder image


“Addictions are a group of chronic and recurrent diseases of the brain characterized by a pathological search for reward or relief through the use of a substance or other action. This situation implies an inability to control behavior, difficulty in permanent abstinence, a compelling desire to consume, decreased recognition of significant problems caused by behavior and interpersonal relationships, and a dysfunctional emotional response. The result is a decrease in the quality of life of the affected person, generating problems in their work, academic activities, social relationships, or family or partner relationships. Unfortunately, there are not enough pharmacotherapeutic solutions to treat addictions due to the complexity of their physiopathology and signaling pathways. Therefore, it is an imperative search for new pharmacological alternatives which may be used for this purpose.

This review summarizes the main recent findings of the potential therapeutic effects of different cannabinoids on treating several addictions, including alcohol, opioids, methamphetamine, cocaine, and nicotine use disorders.

Highlights Standpoints: It has been demonstrated that many phyto, synthetic, and endogenous cannabinoids may act as therapeutic molecules in this psychiatric pathology through their action on multiple cannabinoid receptors. To highlight, cannabinoid receptors, types 1 and 2 (CB1 and CB2) have a crucial role in modulating the anti-addictive properties of these compounds.”

https://pubmed.ncbi.nlm.nih.gov/35538819/

https://www.eurekaselect.com/article/123316

The Anti-Inflammatory Effects of Cannabidiol (CBD) on Acne

Posted on by


“Acne is the most common skin condition in the United States and affects approximately 85% of people ages 12-24. As a multifactorial disease, the pathogenesis of acne involves overproduction of sebum, irregular shedding of the cutaneous cells, accretion of Cutibacterium acnes at the pilosebaceous unit, and inflammation. To date, conventional therapies for acne include topical retinoids, over-the-counter bactericidal agents, and systematic treatments, such as oral antibiotics and isotretinoin. However, the potential for significant side effects and risk of antibiotic resistance remain limitations in these therapies, in turn reducing patient compliance and adherence to acne treatment regimens. Therefore, the use of natural plant-derived treatments or phytotherapeutics as an alternative or adjuvant to conventional treatments is attractive to patients due to their safety and minimal risk for side effects. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid of the Cannabis sativa (hemp) plant. The therapeutic use of CBD has been implicated in many diseases with an inflammatory aspect, including cancers, neurodegeneration, immunological disorders, and dermatological diseases. However, the use of CBD for acne treatment remains a novel window of opportunity. Herein, we summarize the available and relevant data, highlighting the potential use of CBD in acne for its anti-inflammatory properties. To that extent, CBD and other cannabis constituents such as cannabis seeds were found to reduce inflammation and expression of inflammatory cytokines including TNF-α and IL-1β when evaluated in acne-like conditions. Treatment with these cannabis extracts was also found to be safe and well tolerated, further strengthening the prospect of CBD as an anti-inflammatory therapeutic for acne.”

https://pubmed.ncbi.nlm.nih.gov/35535052/

https://www.dovepress.com/the-anti-inflammatory-effects-of-cannabidiol-cbd-on-acne-peer-reviewed-fulltext-article-JIR


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

Posted on by

“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

Posted on by
Logo of frontagineuro

“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

Posted on by
Logo of molecules

“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

Posted on by

“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

Posted on by
molecules-logo

“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