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Medical Cannabis Activity Against Inflammation: Active Compounds and Modes of Action

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

“Inflammation often develops from acute, chronic, or auto-inflammatory disorders that can lead to compromised organ function. Cannabis (Cannabis sativa) has been used to treat inflammation for millennia, but its use in modern medicine is hampered by a lack of scientific knowledge. Previous studies report that cannabis extracts and inflorescence inhibit inflammatory responses in vitro and in pre-clinical and clinical trials. The endocannabinoid system (ECS) is a modulator of immune system activity, and dysregulation of this system is involved in various chronic inflammations. This system includes cannabinoid receptor types 1 and 2 (CB1 and CB2), arachidonic acid-derived endocannabinoids, and enzymes involved in endocannabinoid metabolism. Cannabis produces a large number of phytocannabinoids and numerous other biomolecules such as terpenes and flavonoids. In multiple experimental models, both in vitro and in vivo, several phytocannabinoids, including Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabigerol (CBG), exhibit activity against inflammation. These phytocannabinoids may bind to ECS and/or other receptors and ameliorate various inflammatory-related diseases by activating several signaling pathways. Synergy between phytocannabinoids, as well as between phytocannabinoids and terpenes, has been demonstrated. Cannabis activity can be improved by selecting the most active plant ingredients (API) while eliminating parts of the whole extract. Moreover, in the future cannabis components might be combined with pharmaceutical drugs to reduce inflammation.”

https://pubmed.ncbi.nlm.nih.gov/35614947/

“Cannabis compounds, in some cases via the endocannabinoids system, were shown to affect some of the cornerstones of chronic inflammation. However, in light of the large number of active molecules produced by cannabis and their sometimes-synergistic interactions, there is a need to better specify cannabis-based treatments and the active compounds, while utilizing the synergy identified between cannabis phytomolecules. Thus, even if CBD or THC are considered potentially leading molecules, additional cannabis-derived compounds may be selected for improved activity.

Future approaches for improved usage of cannabis demand the development, transformation and formulation of full-spectrum cannabis extracts into active plant ingredients (APIs) to achieve higher effectivity.

Importantly, once the mode of action of phytocannabinoids and that of their combination is known, APIs might be targeted towards specific mechanisms involved with inflammation.

Moreover, it might be that cannabis components can be combined with other pharmaceutical drugs to reduce inflammation. “

https://www.frontiersin.org/articles/10.3389/fphar.2022.908198/full


Antioxidant Activity of Hemp ( Cannabis sativa L.) Seed Oil in Drosophila melanogaster Larvae under Non-Stress and H 2 O 2-Induced Oxidative Stress Conditions

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“The oil extracted from hemp seeds has significant nutritional and biological properties due to the unique composition of polyunsaturated fatty acids and various antioxidant compounds. The potential of this oil for the prevention of oxidative stress and for the treatment of oxidative-stress-induced ailments is of increasing interest. Most studies of hemp seed oil were conducted in-vitro, meaning we lack information about effects and activity in vivo. In the present study, we evaluated the hypothesis that hemp seed oil at different concentrations improves the oxidative state of D. melanogaster, under non-stress as well as hydrogen-peroxide-induced stress. We analyzed the effects of hemp seed oil on oxidative stress markers and on the life cycle of D.melanogaster under non-stress and hydrogen-peroxide-induced stress conditions. D.melanogaster larvae were exposed to hemp seed oil concentrations ranging from 12.5 to 125 μL/mL. The results revealed that under non-stress conditions, oil concentrations up to 62.5 µL/mL did not induce negative effects on the life cycle of D. melanogaster and maintained the redox status of the larval cells at similar levels to the control level. Under oxidative stress conditions, biochemical parameters were significantly affected and only two oil concentrations, 18.7 and 31.2 µL/mL, provided protection against hydrogen peroxide stress effects. A higher oil concentration (125 μL/mL) exerted negative effects on the oxidative status and increased larval mortality. The tested oil was characterized chemically by NMR, transesterification, and silylation, followed by GC-MS analyses, and was shown to contain polyunsaturated fatty acid triglycerides and low levels of tocopherols. The high levels of linoleic and linolenic acids in the oil are suggested to be responsible for the observed in vivo antioxidant effects. Taken together, the results show that hemp seed oil is effective for reducing oxidative stress at the cellular level, thus supporting the hypothesis. The obtained results point to the potential of hemp seed oil for the prevention and treatment of conditions caused by the action of reactive oxygen species.”

https://pubmed.ncbi.nlm.nih.gov/34067432/

https://www.mdpi.com/2076-3921/10/6/830

A review on the techno-functional, biological, and health-promoting properties of hempseed-derived proteins and peptides

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Journal of Food Biochemistry

“Protein-energy malnutrition is a global challenge that demands urgent attention, especially with the increasing population growth and unmatched food security plans. One strategy is to expand the list of protein sources, such as neglected and underutilized crops, with high protein content. A good number of plant proteins, in addition to their nutritional benefits, exert therapeutic properties as seen in seeds derived from legumes and emerging sources such as hemp. In this review, the transepithelial transport, functional, and biological properties of hempseed proteins (HSPs) and peptides were discussed. The review also described the potential safety issues of incorporating hempseeds in food products. Due to the multitargeted effects of hempseed-derived proteins and their peptides against many chronic diseases, and their functional properties, current knowledge shows that hempseed has tremendous potential for functional food and nutraceutical applications.

PRACTICAL APPLICATIONS: The alarming rate of malnutrition and the attendant health consequences demand that underexploited nutrient-rich crops should be incorporated as part of our common dietary sources. Among these crops, hempseed is gaining attention as an emerging source of proteins and peptides with promising potential in prevention and management of chronic diseases such as diabetes, hypertension, cancer, hypercholesterolemia, obesity, and diseases whose etiology involves oxidative stress and inflammation. Fortunately, a growing body of research evidence is demonstrating that hempseed is a reservoir of proteins and peptides with nutraceutical potentials for curbing life-threatening diseases.”

https://pubmed.ncbi.nlm.nih.gov/35312074/

https://onlinelibrary.wiley.com/doi/10.1111/jfbc.14127


Tobacco, but Neither Cannabis Smoking Nor Co-Drug Use, Is Associated With Hearing Loss in the National Health and Nutrition Examination Survey, 2011 to 2012 and 2015 to 2016

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“Introduction: A relationship between tobacco smoking and hearing loss has been reported; associations with cannabis smoking are unknown. In this cross-sectional population-based study, we examined relationships between hearing loss and smoking (tobacco, cannabis, or co-drug use).

Methods: We explored the relationship between hearing loss and smoking among 2705 participants [mean age = 39.41 (SE: 0.36) years] in the National Health and Nutrition Examination Survey (2011 to 12; 2015 to 16). Smoking status was obtained via questionnaire; four mutually exclusive groups were defined: nonsmokers, current regular cannabis smokers, current regular tobacco smokers, and co-drug users. Hearing sensitivity (0.5 to 8 kHz) was assessed, and two puretone averages (PTAs) computed: low- (PTA0.5,1,2) and high-frequency (PTA3,4,6,8). We defined hearing loss as threshold >15 dB HL. Multivariable logistic regression was used to examine sex-specific associations between smoking and hearing loss in the poorer ear (selected based on PTA0.5,1,2) adjusting for age, sex, race/ethnicity, hypertension, diabetes, education, and noise exposure with sample weights applied.

Results: In the age-sex adjusted model, tobacco smokers had increased odds of low- and high-frequency hearing loss compared with non-smokers [odds ratio (OR) = 1.58, 95% confidence ratio (CI): 1.05 to 2.37 and OR = 1.97, 95% CI: 1.58 to 2.45, respectively]. Co-drug users also had greater odds of low- and high-frequency hearing loss [OR = 2.07, 95% CI: 1.10 to 3.91 and OR = 2.24, 95% CI: 1.27 to 3.96, respectively]. In the fully adjusted multivariable model, compared with non-smokers, tobacco smokers had greater odds of high-frequency hearing loss [multivariable adjusted odds ratio = 1.64, 95% CI: 1.28-2.09]. However, in the fully adjusted model, there were no statistically significant relationships between hearing loss (PTA0.5,1,2 or PTA3,4,6,8) and cannabis smoking or co-drug use.

Discussion: Cannabis smoking without concomitant tobacco consumption is not associated with hearing loss. However, sole use of cannabis was relatively rare and the prevalence of hearing loss in this population was low, limiting generalizability of the results. This study suggests that tobacco smoking may be a risk factor for hearing loss but does not support an association between hearing loss and cannabis smoking. More definitive evidence could be derived using physiological measures of auditory function in smokers and from longitudinal studies.”

https://pubmed.ncbi.nlm.nih.gov/35383601/

https://journals.lww.com/ear-hearing/Abstract/9900/Tobacco,_but_Neither_Cannabis_Smoking_Nor_Co_Drug.3.aspx

Heavy and Chronic Cannabis Addiction does not Impact Motor Function: BOLD-fMRI Study

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“Objective: The aim of this paper is to demonstrate the impact of heavy and chronic cannabis use on brain potential functional control, reorganization, and plasticity in the cortical area.

Methods: 23 cannabis users were convened in 3 user’s groups. The first group included 11 volunteers with an average of 15 joins/day; the second group included 6 volunteers with an average of 1.5 joins/day; the third group included 6 volunteers with an average of 2.8 joins/week. Besides, a 6 healthy volunteers (control group). All healthy and cannabis users underwent identical brain BOLD-fMRI assessment of the motor function. Besides, neuropsychological and full biological assessments were achieved.

Results: BOLD-fMRI maps of motor areas were obtained, including quantitative evaluation of the activations in the motor area. Besides, statistical analysis of various groups was achieved.

Conclusion: Chronic cannabis addiction of varying use strength by groups of heavy, moderate, low dose, and zero doses are shown to have systematically equivalent effects on the control of brain motor function. Indeed, the BOLD-fMRI shows a remarkable sensitivity to minimal brain plasticity and reorganization of the functional motor control of the studied cortical area, and such varionation was not shown. Specific elucidation of the cannabis effect mechanisms in this unique function should clarify further protective pharmacological effects. This might illuminate the use of neuronal resources to prepare processes for pharmacological use and pharmaceutical forms. This suggests exploring any potential cannabis pharmaceutical form in diseases involving motor impairments.”

https://pubmed.ncbi.nlm.nih.gov/35578884/

https://www.eurekaselect.com/article/123583

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

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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 S. typhimurium. 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 S. typhimurium and S. newington 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

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“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