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Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.

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Cannabis sativa Terpenes are Cannabimimetic and Provide Support for the Entourage Effect Hypothesis

10.1101/2020.10.22.350868 ◽

2020 ◽

Author(s):

Justin E. LaVigne ◽

Ryan Hecksel ◽

Attila Keresztes ◽

John M. Streicher

Keyword(s):

Cannabis Sativa ◽

Behavioral Effects ◽

Limited Evidence ◽

Improved Outcomes ◽

Therapeutic Properties ◽

Effect Hypothesis ◽

Cannabinoid Agonist ◽

Mixed Mechanism

AbstractLimited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were additive with WIN55,212, providing support for a terpene “entourage effect.” In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.

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Scientific Evaluation of Dhuma Yoga (An Ayurvedic Fumigation Medicine) as Preventive and Curative on Symptoms of Covid-19 Disease

International Journal of Ayurveda and Pharma Research ◽

10.47070/ijapr.v9i6.1969 ◽

2021 ◽

pp. 49-61

Author(s):

Siva Ram

Keyword(s):

Scientific Explanation ◽

Cannabis Sativa ◽

Symptomatic Treatment ◽

In Vivo Studies ◽

Scientific Evaluation ◽

Systematic Effects ◽

Novel Coronavirus ◽

Fast Acting

Covid-19, an infectious disease caused by a novel coronavirus SARS-CoV-2 spreads primarily through droplets of saliva or discharge from the nose when an infected person talks, coughs or sneezes where the viruses are active in the environment within the suspended micro droplets. Sanitization of environment to weaken/terminate the virus and halting the replication of virus inside the host along with symptomatic treatment is the primary approach to end the pandemic. In Ayurveda, Dhupana (medicated fumigation of vicinity) and Dhumapana (medicated smoking) therapies done by drugs of herbal/animal/mineral origin are a swift way to decontaminate the environment and Respiratory system. Dhuma (medicated fumes) is a unique drug delivery system acting directly on respiratory tissues which can deliver quick results in this Covid-19 pandemic by its local and systematic effects recommended by AYUSH ministry in the guidelines for Covid-19. We intend to put forward the scientific explanation of powerful Ayurvedic Cannabis based polyherbal dhumapana (medicated smoking) medication named Dhuma Yoga available in the market as an alternate remedy for Covid-19 whose four out of five herbal ingredients are in the list of WHO manual of traditional medicine. We emphasized on Vijaya (Cannabis sativa Linn.) as the centre of formulation because it is a Rasayana (rejuvenative) herb having Vyavayi (fast acting) and Yogavahi (synergetic) properties. Phytochemicals of all the herbal ingredients of Dhuma Yoga formulation are studied through in silico, In vitro and In vivo studies for Covid-19 with favourable outcomes.

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Cannabidiol Signaling in the Eye and Its Potential as an Ocular Therapeutic Agent

Cellular Physiology and Biochemistry ◽

10.33594/000000371 ◽

2021 ◽

Vol 55 (S5) ◽

pp. 1-14

Keyword(s):

Cannabis Sativa ◽

Therapeutic Potential ◽

In Vivo Studies ◽

Future Directions ◽

Clinical Drug Development ◽

Therapeutic Uses ◽

The 1960S ◽

Clinical Drug

Cannabidiol (CBD), the major non-intoxicating constituent of Cannabis sativa, has gained recent attention due to its putative therapeutic uses for a wide variety of diseases. CBD was discovered in the 1940s and its structure fully characterized in the 1960s. However, for many years most research efforts related to cannabis derived chemicals have focused on D9-tetrahydrocannabinol (THC). In contrast to THC, the lack of intoxicating psychoactivity associated with CBD highlights the potential of this cannabinoid for clinical drug development. This review details in vitro and in vivo studies of CBD related to the eye, the therapeutic potential of cannabidiol for various ocular conditions, and molecular targets and mechanisms for CBD-induced ocular effects. In addition, challenges of CBD applications for clinical ocular therapeutics and future directions are discussed.

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Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature

Toxics ◽

10.3390/toxics8020041 ◽

2020 ◽

Vol 8 (2) ◽

pp. 41 ◽

Cited By ~ 3

Author(s):

Patricia Golombek ◽

Marco Müller ◽

Ines Barthlott ◽

Constanze Sproll ◽

Dirk W. Lachenmeier

Keyword(s):

Cannabis Sativa ◽

Current Knowledge ◽

In Vivo Studies ◽

Food Ingredient ◽

Over The Counter ◽

Scientific Debate ◽

Consumer Safety ◽

Psychotropic Effects

Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient. Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse. While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.

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Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids

Planta Medica ◽

10.1055/a-1420-5780 ◽

2021 ◽

Author(s):

Giulia Martinelli ◽

Andrea Magnavacca ◽

Marco Fumagalli ◽

Mario DellʼAgli ◽

Stefano Piazza ◽

...

Keyword(s):

Clinical Studies ◽

Skin Diseases ◽

Cannabis Sativa ◽

Therapeutic Potential ◽

Current Evidence ◽

Skin Disorders ◽

Anti Inflammatory

AbstractThe 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.

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Cancer Initiation, Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Molecules ◽

10.3390/molecules26092668 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2668

Author(s):

Ersilia Nigro ◽

Marialuisa Formato ◽

Giuseppina Crescente ◽

Aurora Daniele

Keyword(s):

Molecular Mechanisms ◽

Cannabinoid Receptors ◽

Cannabis Sativa ◽

Current Knowledge ◽

Endocannabinoid System ◽

Peripheral Tissues ◽

Positive Effects ◽

Cancer Initiation

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.

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Striking lung cancer response to self-administration of cannabidiol: A case report and literature review

SAGE Open Medical Case Reports ◽

10.1177/2050313x19832160 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1983216 ◽

Cited By ~ 3

Author(s):

Josep Sulé-Suso ◽

Nick A Watson ◽

Daniel G van Pittius ◽

Apurna Jegannathen

Keyword(s):

Lung Cancer ◽

Cannabis Sativa ◽

Tumour Response ◽

Drug Repurposing ◽

New Drugs ◽

Self Administration ◽

Immune Response To Cancer

In spite of new drugs, lung cancer is associated with a very poor prognosis. While targeted therapies are improving outcomes, it is not uncommon for many patients to have only a partial response, and relapse during follow-up. Thus, new drugs or re-evaluation of existing therapies used to treat other non-malignant diseases (drug repurposing) are still needed. While this research both in vitro and in vivo is being carried out, it is important to be attentive to patients where the disease responds to treatments not considered standard in clinical practice. We report here a patient with adenocarcinoma of the lung who, after declining chemotherapy and radiotherapy, presented with tumour response following self-administration of cannabidiol, a non-psychoactive compound present in Cannabis sativa. Prior work has shown that cannabidiol may have anti-neoplastic properties and enhance the immune response to cancer. The data presented here indicate that cannabidiol might have led to a striking response in a patient with lung cancer.

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Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity

Scientific Reports ◽

10.1038/s41598-021-87740-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Justin E. LaVigne ◽

Ryan Hecksel ◽

Attila Keresztes ◽

John M. Streicher

Keyword(s):

Cannabis Sativa ◽

Behavioral Effects ◽

Limited Evidence ◽

Improved Outcomes ◽

Therapeutic Properties ◽

Effect Hypothesis ◽

Cannabinoid Agonist ◽

Mixed Mechanism

AbstractLimited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.

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Pathogenicity and Mefenoxam Sensitivity of Pythium, Globisporangium, and Fusarium Isolates From Coconut Coir and Rockwool in Marijuana (Cannabis sativa L.) Production

Frontiers in Agronomy ◽

10.3389/fagro.2021.706138 ◽

2021 ◽

Vol 3 ◽

Author(s):

Cora S. McGehee ◽

Rosa E. Raudales

Keyword(s):

Root Rot ◽

Cannabis Sativa ◽

Disease Incidence ◽

Elongation Factor ◽

Pythium Myriotylum ◽

Internal Transcribed Spacer Region ◽

Pythium Irregulare ◽

Coconut Coir

Oomycetes and fungi were recovered from coconut coir and rockwool substrates where marijuana (Cannabis sativa L. cv. Silver and Citron) plants with root rot and wilt symptoms were grown in a commercial growing facility in Connecticut. The objectives of this study were to identify the isolates collected from these substrates, determine the pathogenicity of the isolates on hemp seedlings in vitro and in vivo, and evaluate the pathogens' sensitivity to mefenoxam. Pythium and Globisporangium isolates were identified by sequencing the mitochondrially-encoded cytochrome oxidase genes (COI and COII) and Fusarium sp. with the translation elongation factor (EF-1α) region and internal transcribed spacer region (ITS4 and ITS5) genes. Three isolates were identified as Globisporangium irregulare (formerly Pythium irregulare), 21 isolates were Pythium myriotylum, and one was Fusarium oxysporum. All the isolates tested were pathogenic to hemp plants in vitro and in vivo, with disease incidence between 6.7 and 100%. Inoculated plants were smaller by 32% or more compared with the non-inoculated control. On average, hemp plants infected with Pythium myriotylum produced the lowest biomass and relative greenness values. None of the Pythium and Globisporangium isolates were resistant to mefenoxam—all were sensitive to ≥5 μg·mL−1 mefenoxam. This is the first report of G. irregulare causing root rot on marijuana and hemp plants. The results of this study provide information about the characteristics of pathogens that can be found potentially in soilless substrates in controlled environment agriculture.

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