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The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

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“Maintaining specific and reproducible cannabinoid compositions (type and quantity) is essential for the production of cannabis-based remedies that are therapeutically effective.

The current study investigates factors that determine the plant’s cannabinoid profile and examines interrelationships between plant features (growth rate, phenology and biomass), inflorescence morphology (size, shape and distribution) and cannabinoid content. An examination of differences in cannabinoid profile within genotypes revealed that across the cultivation facility, cannabinoids’ qualitative traits (ratios between cannabinoid quantities) remain fairly stable, while quantitative traits (the absolute amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV)) can significantly vary.

The calculated broad-sense heritability values imply that cannabinoid composition will have a strong response to selection in comparison to the morphological and phenological traits of the plant and its inflorescences. Moreover, it is proposed that selection in favour of a vigorous growth rate, high-stature plants and wide inflorescences is expected to increase overall cannabinoid production. Finally, a range of physiological and phenological features was utilised for generating a successful model for the prediction of cannabinoid production.

The holistic approach presented in the current study provides a better understanding of the interaction between the key features of the cannabis plant and facilitates the production of advanced plant-based medicinal substances.”

https://pubmed.ncbi.nlm.nih.gov/36771577/

“These findings will have a significant impact on the breeding and cultivation of the chemotypically stable and reproducible cannabis genotypes that will facilitate the production of novel medicinal applications.”

https://www.mdpi.com/2223-7747/12/3/493

Cannabinoids in the Modulation of Oxidative Signaling

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“Cannabis sativa-derived compounds, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and components of the endocannabinoids system, such as N-arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), are extensively studied to investigate their numerous biological effects, including powerful antioxidant effects. Indeed, a series of recent studies have indicated that many disorders are characterized by alterations in the intracellular antioxidant system, which lead to biological macromolecule damage. These pathological conditions are characterized by an unbalanced, and most often increased, reactive oxygen species (ROS) production.

For this study, it was of interest to investigate and recapitulate the antioxidant properties of these natural compounds, for the most part CBD and THC, on the production of ROS and the modulation of the intracellular redox state, with an emphasis on their use in various pathological conditions in which the reduction of ROS can be clinically useful, such as neurodegenerative disorders, inflammatory conditions, autoimmunity, and cancers. The further development of ROS-based fundamental research focused on cannabis sativa-derived compounds could be beneficial for future clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/36768835/

“In conclusion, it has been reported that cannabinoids modulate oxidative stress in inflammation and autoimmunity, which makes them a potential therapeutic approach for different kinds of pathologies.”

https://www.mdpi.com/1422-0067/24/3/2513

Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota

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“Cannabidiol (CBD) and cannabigerol (CBG) are two pharmacologically active phytocannabinoids of Cannabis sativa L. Their antimicrobial activity needs further elucidation, particularly for CBG, as reports on this cannabinoid are scarce. We investigated CBD and CBG’s antimicrobial potential, including their ability to inhibit the formation and cause the removal of biofilms.

Our results demonstrate that both molecules present activity against planktonic bacteria and biofilms, with both cannabinoids removing mature biofilms at concentrations below the determined minimum inhibitory concentrations. We report for the first time minimum inhibitory and lethal concentrations for Pseudomonas aeruginosa and Escherichia coli (ranging from 400 to 3180 µM), as well as the ability of cannabinoids to inhibit Staphylococci adhesion to keratinocytes, with CBG demonstrating higher activity than CBD. The value of these molecules as preservative ingredients for cosmetics was also assayed, with CBG meeting the USP 51 challenge test criteria for antimicrobial effectiveness. Further, the exact formulation showed no negative impact on skin microbiota.

Our results suggest that phytocannabinoids can be promising topical antimicrobial agents when searching for novel therapeutic candidates for different skin conditions. Additional research is needed to clarify phytocannabinoids’ mechanisms of action, aiming to develop practical applications in dermatological use.”

https://pubmed.ncbi.nlm.nih.gov/36768709/

“This report compares CBD and CBG’s antimicrobial effectiveness and further cements phytocannabinoids’ potential to be used as antimicrobial agents. Both molecules’ antimicrobial capacity strongly depends on the target microorganism, namely whether it is Gram-negative or Gram-positive. Nonetheless, we were able to determine MICs for all tested strains, including S. pyogenes, E. coli, and P. aeruginosa. It is of note that CBG revealed a stronger antimicrobial effect than CBD, particularly in the challenge test and in the antibiofilm assay. Further studies are needed to understand these discrepancies, as they may be connected to structural differences, receptor-binding affinity, or another mechanism other than a receptor-mediated one. Since no significant impact on the skin microbiota was observed and given its current widespread use, both CBD and CBG might be considered safe. Thus, we can assume that the development of topical formulations with active concentrations of CBG and/or CBD might represent a promising approach to tackle skin conditions where microorganisms and inflammation play a fundamental role, including psoriasis, atopic dermatitis, and acne.”

https://www.mdpi.com/1422-0067/24/3/2389

Cannabidiol mediates epidermal terminal differentiation and redox homeostasis through aryl hydrocarbon receptor (AhR)-dependent signaling

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Home Page: Journal of Dermatological Science

“Background: Cannabidiol, a non-psychoactive phytocannabinoid, has antioxidant and anti-inflammatory activity in keratinocytes. However, the signaling pathway through which cannabidiol exerts its effect on keratinocytes or whether it can modulate keratinocyte differentiation has not been fully elucidated yet.

Objective: We investigated whether cannabidiol modulates epidermal differentiation and scavenges reactive oxygen species through the aryl hydrocarbon receptor (AhR) in keratinocytes and epidermal equivalents.

Methods: We investigated the cannabidiol-induced activation of AhR using AhR luciferase reporter assay, qRT-PCR, western blot, and immunofluorescence assays. We also analyzed whether keratinocyte differentiation and antioxidant activity are regulated by cannabidiol-induced AhR activation.

Results: In both keratinocytes and epidermal equivalents, cannabidiol increased both the mRNA and protein expression of filaggrin, involucrin, NRF2, and NQO1 and the mRNA expression of the AhR target genes, including CYP1A1 and aryl hydrocarbon receptor repressor. Additionally, cannabidiol showed antioxidant activity that was attenuated by AhR knockdown or co-administration with an AhR antagonist. Moreover, cannabidiol increased the ratio of OVOL1/OVOL2 mRNA expression, which is a downstream regulator of AhR that mediates epidermal differentiation. In addition to increased expression of barrier-related proteins, cannabidiol-treated epidermal equivalent showed a more prominent granular layer than the control epidermis. The increased granular layer by cannabidiol was suppressed by the AhR antagonist.

Conclusion: Cannabidiol can be a modulator of the AhR-OVOL1-filaggrin axis and AhR-NRF2-NQO1 signaling, thus indicating a potential use of cannabidiol in skin barrier enhancement and reducing oxidative stress.”

https://pubmed.ncbi.nlm.nih.gov/36725458/

https://www.jdsjournal.com/article/S0923-1811(23)00024-5/fulltext

Do tobacco and cannabis use and co-use predict lung function: A longitudinal study

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Respiratory Medicine | Journal | ScienceDirect.com by Elsevier

“Background: Use of tobacco and cannabis is common and has been reported to predict lung function. Less is known about co-use of tobacco and cannabis and their impact on changes in lung function to early adulthood.

Research question: The study examines whether cigarette smoking or cannabis use and co-use are each associated with lung function in a population sample of young adults.

Study design and methods: Data are from a prospective cohort study of cigarette smoking, cannabis use and co-use at 21 and 30 years of age and lung function (FVC, FEV1, FEV1/FVC) measured at 30 years. Lung function results are transformed using Global Lung Function Formulae. Subjects are the children of pregnant women who were recruited into the cohort study over the period 1981-3. Respondents were administered a spirometry assessment at 21 and 30 years of age. These respondents completed a smoking and cannabis use questionnaire at 21- and 30-year follow-ups.

Results: Cigarette smoking (with or without cannabis use) is associated with reduced airflow. There is no consistent association between cannabis use and measures of lung function. The co-use of tobacco and cannabis appears to entail no additional risk to lung function beyond the risks associated with tobacco use alone.

Interpretation: Persistent cigarette smoking is associated with reduced airflow even in young adults. Cannabis use does not appear to be related to lung function even after years of use.”

https://pubmed.ncbi.nlm.nih.gov/36682602/

“•Cigarette smoking and cannabis use and co-use are risk factors for impaired lung function.

•By 30 years, those who have smoked cigarettes since adolescence already show evidence of impairment of lung function.

•By 30 years, those who used cannabis since the adolescent period do not appear to have evidence of impaired lung function.

•Co-use of tobacco and cannabis does not appear to predict lung function beyond the effects of tobacco use alone.”

https://www.resmedjournal.com/article/S0954-6111(23)00012-4/fulltext

“Smoking Cannabis Not Associated With Impaired Lung Functioning In Latest Study”

https://www.forbes.com/sites/emilyearlenbaugh/2023/02/01/smoking-cannabis-not-associated-with-impaired-lung-functioning-in-latest-study/?sh=5f2e60c6a630

Hemp seeds: Nutritional value, associated bioactivities and the potential food applications in the Colombian context

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Frontiers - Crunchbase Company Profile & Funding

“For many years, Colombia was one of the countries with the largest illegal cultivation of cannabis around the world. Currently, it is going through a period of transition with a new government law that recently allows the cultivation, transformation, and commercialization of such plant species. In this sense, the identification of strategies for the valorization of products or by-products from Cannabis sativa represent a great opportunity to improve the value chain of this crop.

One of these products is hemp seeds, which are exceptionally nutritious and rich in healthy lipids (with high content of three polyunsaturated fatty acids: linoleic acid, alpha-linolenic acid, and gamma-linolenic acid), good quality protein, and several minerals. In addition, hemp seeds contain THC (tetrahydrocannabinol) or CBD (cannabidiol) in traces, molecules that are responsible for the psychoactive and therapeutic properties of cannabis. These low terpenophenolic contents make it more attractive for food applications.

This fact, together with the constant search for proteins of vegetable origin and natural food ingredients, have aroused an important interest in the study of this biomass. Some bioactivities of phytochemical compounds (polyphenols and terpenoids, mainly) present in hemp seeds have provided antioxidant, antimicrobial, and anti-inflammatory properties. This review summarizes and discusses the context of hemp use in Latin-American and the new opportunities for hemp seeds culture in Colombia considering the valuable nutritional value, main functional bioactivities, and recent advances in food market applications of hemp seeds.”

https://pubmed.ncbi.nlm.nih.gov/36712539/

“As a future trend, a holistic approach by the use of hemp seed could be employed as a food ingredient, in Colombia and those Latin American countries where the legislation has been relaxed. This is in the line with the increasing awareness about nutritional dietary patterns as well as the therapeutic application of plant-based food for improving the human health population, aiding to decrease nutrition-related diseases, and ensuring the physical and mental wellbeing of the population.”

https://www.frontiersin.org/articles/10.3389/fnut.2022.1039180/full

State Cannabis Legalization and Psychosis-Related Health Care Utilization

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JAMA editors name the journal's best articles of the decade | American Medical Association

“Importance: Psychosis is a hypothesized consequence of cannabis use. Legalization of cannabis could therefore be associated with an increase in rates of health care utilization for psychosis.

Objective: To evaluate the association of state medical and recreational cannabis laws and commercialization with rates of psychosis-related health care utilization.

Design, setting, and participants: Retrospective cohort design using state-level panel fixed effects to model within-state changes in monthly rates of psychosis-related health care claims as a function of state cannabis policy level, adjusting for time-varying state-level characteristics and state, year, and month fixed effects. Commercial and Medicare Advantage claims data for beneficiaries aged 16 years and older in all 50 US states and the District of Columbia, 2003 to 2017 were used. Data were analyzed from April 2021 to October 2022.

Exposure: State cannabis legalization policies were measured for each state and month based on law type (medical or recreational) and degree of commercialization (presence or absence of retail outlets).

Main outcomes and measures: Outcomes were rates of psychosis-related diagnoses and prescribed antipsychotics.

Results: This study included 63 680 589 beneficiaries followed for 2 015 189 706 person-months. Women accounted for 51.8% of follow-up time with the majority of person-months recorded for those aged 65 years and older (77.3%) and among White beneficiaries (64.6%). Results from fully-adjusted models showed that, compared with no legalization policy, states with legalization policies experienced no statistically significant increase in rates of psychosis-related diagnoses (medical, no retail outlets: rate ratio [RR], 1.13; 95% CI, 0.97-1.36; medical, retail outlets: RR, 1.24; 95% CI, 0.96-1.61; recreational, no retail outlets: RR, 1.38; 95% CI, 0.93-2.04; recreational, retail outlets: RR, 1.39; 95% CI, 0.98-1.97) or prescribed antipsychotics (medical, no retail outlets RR, 1.00; 95% CI, 0.88-1.13; medical, retail outlets: RR, 1.01; 95% CI, 0.87-1.19; recreational, no retail outlets: RR, 1.13; 95% CI, 0.84-1.51; recreational, retail outlets: RR, 1.14; 95% CI, 0.89-1.45). In exploratory secondary analyses, rates of psychosis-related diagnoses increased significantly among men, people aged 55 to 64 years, and Asian beneficiaries in states with recreational policies compared with no policy.

Conclusions and relevance: In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes. As states continue to introduce new cannabis policies, continued evaluation of psychosis as a potential consequence of state cannabis legalization may be informative.”

https://pubmed.ncbi.nlm.nih.gov/36696111/

“In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800728

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review

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Journal of Traditional and Complementary Medicine

“Background and aim: Cannabis sativa L. is a medicinal plant with a long history. Phyto-cannabinoids are a class of compounds from C. sativa L. with varieties of structures. Endocannabinoids exist in the human body. This article provides an overview of natural cannabinoids (phyto-cannabinoids and endocannabinoids) with an emphasis on their pharmacology activities.

Experimental procedure: The keywords “Cannabis sativa L″, “cannabinoids”, and “central nervous system (CNS) diseases” were used for searching and collecting pieces of literature from PubMed, ScienceDirect, Web of Science, and Google Scholar. The data were extracted and analyzed to explore the effects of cannabinoids on CNS diseases.

Result and conclusion: In this paper, schematic diagrams are used to intuitively show the phyto-cannabinoids skeletons’ mutual conversion and pharmacological activities, with special emphasis on their relevant pharmacological activities on central nervous system (CNS) diseases. It was found that the endocannabinoid system and microglia play a crucial role in the treatment of CNS diseases. In the past few years, pharmacological studies focused on Δ9-THC, CBD, and the endocannabinoids system. It is expected to encourage new studies on a more deep exploration of other types of cannabinoids and the mechanism of their pharmacological activities in the future.”

https://pubmed.ncbi.nlm.nih.gov/36685079/

https://www.sciencedirect.com/science/article/pii/S2225411022000761?via%3Dihub

The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury

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“The endocannabinoid (EC) system is a complex cell-signaling system that participates in a vast number of biological processes since the prenatal period, including the development of the nervous system, brain plasticity, and circuit repair. This neuromodulatory system is also involved in the response to endogenous and environmental insults, being of special relevance in the prevention and/or treatment of vascular disorders, such as stroke and neuroprotection after neonatal brain injury. Perinatal hypoxia-ischemia leading to neonatal encephalopathy is a devastating condition with no therapeutic approach apart from moderate hypothermia, which is effective only in some cases. This overview, therefore, gives a current description of the main components of the EC system (including cannabinoid receptors, ligands, and related enzymes), to later analyze the EC system as a target for neonatal neuroprotection with a special focus on its neurogenic potential after hypoxic-ischemic brain injury.”

https://pubmed.ncbi.nlm.nih.gov/36672536/

“The ubiquitous lipid signaling-based EC system is involved in outstanding regulatory functions throughout the human body, including neural development under physiological conditions and neuroprotection, and repair after pathophysiological processes.In the context of neonatal brain injury, the administration of endogenous or exogenous CBs, or the blockage of EC degradation, has revealed a strong neuroprotective response in different preclinical models after HI. Similarly, the possibility of tissue repair in the developing brain by enhancing the proliferative potential of the SVZ and SGZ neurogenic niches is currently under active investigation. Selective modulation of the EC system in the sites of damage by targeting the enzymes responsible for EC degradation may represent an important therapeutic approach in order to avoid non-desired widespread effects.Despite the clinical use of CB-related drugs that must be taken with caution, the modulation of the EC system to ameliorate the neurological consequences after neonatal HI is currently an exciting field of research with enormous possibilities for clinical translation.”

https://www.mdpi.com/2227-9059/11/1/28

Hemp Protein Hydrolysates Modulate Inflammasome-Related Genes in Microglial Cells

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“A prolonged inflammatory response can lead to the development of neurodegenerative diseases such as Alzheimer’s disease. Enzymatic hydrolysis is a sustainable way to increase the value of protein sources by obtaining peptides that can exert bioactivity.

Hemp (Cannabis sativa L.) protein hydrolysates have been proven to exert anti-inflammatory activity.

In this study, two hemp protein hydrolysate (HPHs), obtained with Alcalase as sole catalyst, or with Alcalase followed by Flavourzyme, were evaluated as inflammatory mediators (TNFα, IL-1β, IL-6, and IL-10), microglial polarization markers (Ccr7, iNos, Arg1, and Ym1), and genes related to inflammasome activation (Nlrp3, Asc, Casp1, and Il18), employing the lipopolysaccharide (LPS)-induced neuroinflammation model in murine BV-2 microglial cells.

A significant decrease of the expression of proinflammatory genes (e.g., Tnfα, Ccr7, inos, and Nlrp3, among others) and increase of the expression anti-inflammatory cytokines in microglial cells was observed after treatment with the test HPHs. This result in the cell model suggests a polarization toward an anti-inflammatory M2 phenotype. Our results show that the evaluated HPHs show potential neuroprotective activity in microglial cells via the inflammasome.”

https://pubmed.ncbi.nlm.nih.gov/36671742/

“Neuroinflammation can lead to the development of neurodegenerative diseases. Food-derived peptides released by the action of enzymes have been proven to modulate several physiological processes. In this study, peptides obtained from hemp protein were evaluated as anti-inflammatory agents employing a cell model, measuring the responses of inflammatory mediators, microglial polarization markers, and genes related to inflammasome activation, as markers of inflammation and the potential counteraction exerted by the peptides, related to neurodegenerative processes. Results showed a neuroprotective effect based on anti-inflammatory activity of the peptides, via the inflammasome. The use of these peptides in the diet could help to prevent inflammation and promote a healthy aging of humans.”

https://www.mdpi.com/2079-7737/12/1/49