Indeterminacy of cannabis impairment and ∆ 9-tetrahydrocannabinol (∆ 9-THC) levels in blood and breath

Scientific Reports

“Previous investigators have found no clear relationship between specific blood concentrations of ∆9-tetrahydrocannabinol (∆9-THC) and impairment, and thus no scientific justification for use of legal “per se” ∆9-THC blood concentration limits. Analyzing blood from 30 subjects showed ∆9-THC concentrations that exceeded 5 ng/mL in 16 of the 30 subjects following a 12-h period of abstinence in the absence of any impairment. In blood and exhaled breath samples collected from a group of 34 subjects at baseline prior to smoking, increasing breath ∆9-THC levels were correlated with increasing blood levels (P < 0.0001) in the absence of impairment, suggesting that single measurements of ∆9-THC in breath, as in blood, are not related to impairment. When post-smoking duration of impairment was compared to baseline ∆9-THC blood concentrations, subjects with the highest baseline ∆9-THC levels tended to have the shortest duration of impairment. It was further shown that subjects with the shortest duration of impairment also had the lowest incidence of horizontal gaze nystagmus at 3 h post-smoking compared to subjects with the longest duration of impairment (P < 0.05). Finally, analysis of breath samples from a group of 44 subjects revealed the presence of transient cannabinoids such as cannabigerol, cannabichromene, and ∆9-tetrahydrocannabivarin during the peak impairment window, suggesting that these compounds may be key indicators of recent cannabis use through inhalation. In conclusion, these results provide further evidence that single measurements of ∆9-THC in blood, and now in exhaled breath, do not correlate with impairment following inhalation, and that other cannabinoids may be key indicators of recent cannabis inhalation.”

https://pubmed.ncbi.nlm.nih.gov/35585089/

“In conclusion, we present further evidence that single measurements of ∆9-THC in blood cannot establish impairment, that single measurements of ∆9-THC in exhaled breath likewise do not correlate with impairment, and that ∆9-THCV and CBC may be key indicators of recent cannabis use through inhalation within the impairment window.”

https://www.nature.com/articles/s41598-022-11481-5

A Review of Hemp as Food and Nutritional Supplement

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“The term “hemp” refers to Cannabis sativa cultivars grown for industrial purposes that are characterized by lower levels of tetrahydrocannabinol (THC), the active principle responsible for Cannabis psychotropic effects. Hemp is an extraordinary crop, with enormous social and economic value, since it can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil.

Various parts of the hemp plant represent a valuable source of food and ingredients for nutritional supplements. While hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, hempseed has a pleasant nutty taste and represents a valuable source of essential amino acids and fatty acids, minerals, vitamins, and fibers. In addition, hempseed oil is a source of healthy polyunsaturated fatty acids, and hemp sprouts are rich in antioxidants.

This review article aims to provide a comprehensive outlook from a multidisciplinary perspective on the scientific evidence supporting hemp beneficial properties when consumed as food or supplement. Marketing of hemp-derived products is subjected to diversified and complex regulations worldwide for several reasons, including the fact that CBD is also the active principal of pharmaceutical agents and that regulatory bodies in some cases ban Cannabis inflorescence regardless of its THC content. Some key regulatory aspects of such a complex scenario are also analyzed and discussed in this review article.”

https://pubmed.ncbi.nlm.nih.gov/33614949/

https://www.liebertpub.com/doi/10.1089/can.2020.0001

Hemp Seeds of the Polish ‘Bialobrzeskie’ and ‘Henola’ Varieties ( Cannabis sativa L. var. sativa) as Prospective Plant Sources for Food Production

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“This publication characterizes the nutritional value of the Polish hemp seeds of the ‘Bialobrzeskie’ and ‘Henola’ varieties, including the profile/content of fatty acids and amino acids. Hemp seeds were found to be rich in protein, fat, and dietary fiber. Polyunsaturated fatty acids (PUFA) dominated the unsaturated fatty acids (UFA) profile. Their average share within the total fatty acids (FA) was as high as 75%. Linoleic acid belonging to this group accounted for 55% of the total FA. Lipid profile indices (Σ n – 6/Σ n – 3, Σ PUFA/Σ SFA, the thrombogenicity index, the atherogenicity index and the hypocholesterolemic/hypercholesterolemic ratio) proved the high nutritional value of hemp oil. Considering the tyrosine + phenylalanine and histidine contents, hemp protein exhibited a great degree of similarity to egg protein, which is known and valued for its high biological value.”

https://pubmed.ncbi.nlm.nih.gov/35209234/

https://www.mdpi.com/1420-3049/27/4/1448


Cannabis sativa CBD Extract Shows Promising Antibacterial Activity against Salmonella typhimurium and S. newington

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“Products derived from Cannabis sativa L. have gained increased interest and popularity. As these products become common amongst the public, the health and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in the literature, the antibacterial properties of cannabidiol (CBD) have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Styphimurium. In this study, we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Styphimurium and Snewington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.”

https://pubmed.ncbi.nlm.nih.gov/35566019/

https://www.mdpi.com/1420-3049/27/9/2669


CBD formulation improves energetic homeostasis in dermal fibroblasts from Gulf War Illness patients

“Gulf War Illness (GWI) corresponds to an array of symptoms that includes chronic fatigue, musculoskeletal pain, cognitive dysfunction, sleep disturbance, gastrointestinal, respiratory, and dermatological symptoms that affect ~250,000 U.S. military veterans that served in Operation Desert Storm/Desert Shield (1990-1991). Mitochondrial function impairments have been shown in GWI patients. GWI patients report partial amelioration of chronic fatigue and brain fog after medicinal marijuana and CBD oils. Interestingly, cannabidiol (CBD) modulates mitochondrial physiology though this has not been characterized in detail. We hypothesize that GWI mitochondrial pathology can be recapitulated in dermal fibroblasts (DF) from subjects to help define and develop a cell-based model to study GWI and CBD treatment of DF promotes energy production by improving mitochondrial physiology. GWI patients (gender/age matched to healthy controls) were recruited to collect skin punch biopsy explants that were processed and cultured in DMEM FBS 10% for 30-days to obtain dermal fibroblasts. DF were treated with serial dilutions of Verséa™ CBD (50mg/mL) lipid formulation (VESIsorb® that increases 4.4-fold Cmax ). Using real time mitochondrial analysis by Seahorse, energy phenotype and mitochondrial function was analyzed in control and GWI DF. Mitochondrial networks and ultrastructure were studied by live-imaging using MitoTracker™ and transmission electron microscopy, respectively. Energy phenotype studies suggest that GWI DF present with lower mitochondrial metabolism and higher glycolytic activity, compared with controls. Additionally, mitochondrial stress suggests a significant reduction in mitochondrial maximal capacity. Such data establish GWI derived DF as a personalized model system to study mitochondrial pathology in GWI. After 18h treatment with Verséa™ CBD, GWI DF show a significant improvement in mitochondrial and glycolytic metabolism; control patients show no increases in mitochondrial metabolism but improved glycolysis. Verséa™ CBD treatment induced mitochondrial networks re-organization in DF. These findings suggest that CBD improves GWI DF mitochondrial physiology, thus improving energy homeostasis. Our data provide new evidence that will validate the potential of cannabinoids as a therapeutic strategy to mitigate energy imbalance that may contribute to detrimental symptomatology (i.e., chronic fatigue, brain fog, cognitive dysfunction, etc.) in GWI patients.”

https://pubmed.ncbi.nlm.nih.gov/35560565/

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.0R790

Cannabis for Medical Use: Versatile Plant Rather Than a Single Drug

Frontiers in Pharmacology welcomes new Field Chief Editor – Science &  research news | Frontiers

“Medical Cannabis and its major cannabinoids (-)-trans9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are gaining momentum for various medical purposes as their therapeutic qualities are becoming better established. However, studies regarding their efficacy are oftentimes inconclusive. This is chiefly because Cannabis is a versatile plant rather than a single drug and its effects do not depend only on the amount of THC and CBD. Hundreds of Cannabis cultivars and hybrids exist worldwide, each with a unique and distinct chemical profile. Most studies focus on THC and CBD, but these are just two of over 140 phytocannabinoids found in the plant in addition to a milieu of terpenoids, flavonoids and other compounds with potential therapeutic activities. Different plants contain a very different array of these metabolites in varying relative ratios, and it is the interplay between these molecules from the plant and the endocannabinoid system in the body that determines the ultimate therapeutic response and associated adverse effects. Here, we discuss how phytocannabinoid profiles differ between plants depending on the chemovar types, review the major factors that affect secondary metabolite accumulation in the plant including the genotype, growth conditions, processing, storage and the delivery route; and highlight how these factors make Cannabis treatment highly complex.”

https://pubmed.ncbi.nlm.nih.gov/35548332/

“The use of medical Cannabis is ever increasing in the treatment of numerous conditions as it has been proven to be both effective and safe, but the Cannabis plant contains more than 500 different components, each with potential therapeutic qualities. The components of Cannabis act together, hitting several targets at once and mutually enhancing each other’s activity so that the overall outcome is greater than that of their additive effect.

Cannabis can treat a multitude of very different conditions as it exerts its effects via the ECS, which is involved in many physiological processes. Cannabis treatment can be personalized to both the condition and the person to improve treatment outcomes while also reducing the drug load and minimizing the adverse effects. “

https://www.frontiersin.org/articles/10.3389/fphar.2022.894960/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/

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


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



“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

Frontiers in Pharmacology welcomes new Field Chief Editor – Science &  research news | Frontiers

“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