Monthly Archives: January 2025

Chronic oral dosing of cannabidiol and cannabidiolic acid full-spectrum hemp oil extracts has no adverse effects in horses: a pharmacokinetic and safety study

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“Objective: To compare the pharmacokinetics of cannabidiol (CBD) and cannabidiolic acid (CBDA) in horses and to evaluate the safety of their chronic administration.

Methods: CBD- and CBDA-rich oil (1 mg/kg) were administered orally twice daily to 7 adult horses over 6 weeks in a randomized, crossover design with a 2-week washout period. A 12-hour pharmacokinetic analysis was conducted on day 1 of each 6-week trial, followed by the measurement of peak and trough concentrations at weeks 1, 2, 4, and 6. The cannabinoids safety was assessed via daily physical examination, periodic bloodwork, and liver biopsy at the beginning and end of the study.

Results: 12-hour pharmacokinetics revealed a higher maximum serum concentration (103 vs 12 ng/mL) and greater area under the curve (259 vs 62 ng·h/mL) for CBDA when compared to CBD. Cannabidiolic acid nadir and peak serum levels over time ranged from 46 to 122 ng/mL, which was higher than CBD (12 to 38 ng/mL). Complete blood count and serum chemistry revealed no clinically relevant changes with either CBD or CBDA. No significant abnormalities were detected on liver ultrasonographic and histopathologic evaluation on day 0 and after both phases of the study.

Conclusions: A dose of either 1 mg/kg of CBD or CBDA administered long term appears safe; however, CBDA serum concentrations suggest superior absorption/retention.

Clinical relevance: Chronic cannabinoid supplementation in horses is safe. Considering the higher absorption of CBDA, its use is recommended to evaluate the therapeutic efficacy of this common hemp derived cannabinoid.”

https://pubmed.ncbi.nlm.nih.gov/39787699/

https://avmajournals.avma.org/view/journals/ajvr/aop/ajvr.24.08.0235/ajvr.24.08.0235.xml

Cannabidiol Alleviates Intestinal Fibrosis in Mice with Ulcerative Colitis by Regulating Transforming Growth Factor Signaling Pathway

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“Objective: The aim of this study is to investigate the protective effect of Cannabidiol (CBD) on DSS-induced colitis in C57BL/6 mice and its related pathways.

Methods: A mouse model of ulcerative colitis (US) was induced by DSS. Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase-chain reaction (qRT-PCR), Western blot (WB) and immunofluorescence (IF) were used to identify the key factors involved in inflammatory response, oxidative stress and intestinal fibrosis. In addition, we transfected si-RNA into CCD-18Co cells.

Results: The research suggests that CBD significantly improves intestinal inflammation by up-regulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression, inhibiting the classical Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κb) pathway, and inhibiting the release of IL-6 (Interleukin), IL-1β, Tumor Necrosis Factor-α (TNF-α) and other factors. At the same time, CBD plays an antioxidant role by regulating Nrf2/ HO-1 (Heme Oxygenase-1) pathway and activating HO-1 activity. On the other hand, CBD may regulate Transforming growth factor beta (TGF-β)/SMADs signaling pathway by inhibiting the expression of TGF-β1, thereby inhibiting the expression of α-SMA, Collagen1, TIMP1 and other factors, thus playing an anti-fibrotic role. Notably, when Nrf2 is inhibited or lacking, CBD loses the above protective effect against DSS-induced colon injury.

Conclusion: CBD affects the classical NF-κb pathway, Nrf2/ Heme Oxygenase-1 (HO-1) pathway, and Transforming growth factor beta (TGF-β)/SMAD pathway by regulating Nrf2, thereby reducing colonic inflammation and oxidative stress and improving the progression of colonic fibrosis.”

https://pubmed.ncbi.nlm.nih.gov/39802511/

“Taken together, our study demonstrated that CBD affected the classical NF-κb pathway, Nrf2/HO-1 pathway, and TGF-β1/SMAD pathway by regulating Nrf2, thereby reducing intestinal inflammation, oxidative stress and intestinal fibrosis, improving intestinal function and pathological symptoms, and thereby protecting against DSS-induced colon injury. These findings provide new ideas and directions for the treatment of UC.”

https://www.dovepress.com/cannabidiol-alleviates-intestinal-fibrosis-in-mice-with-ulcerative-col-peer-reviewed-fulltext-article-JIR

CBD and the 5-HT1A receptor: A medicinal and pharmacological review

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“Cannabidiol (CBD), a phytocannabinoid, has emerged as a promising candidate for addressing a wide array of symptoms.

It has the ability to bind multiple proteins and receptors, including 5-HT1AR, transient receptor potential vanilloid 1 (TRPV1), and cannabinoid receptors. However, CBD’s pharmacodynamic interaction with 5-HT1AR and its medicinal outcomes are still debated.

This review explores recent literature to elucidate these questions, highlighting the neurotherapeutic outcomes of this pharmacodynamic interaction and proposing a signaling pathway underlying the mechanism by which CBD desensitizes 5-HT1AR signaling.

A comprehensive survey of the literature underscores CBD’s multifaceted neurotherapeutic effects, encompassing antidepressant, anxiolytic, neuroprotective, antipsychotic, antiemetic, anti-allodynic, anti-epileptic, anti-degenerative, and addiction-treating properties, attributable in part to its interactions with 5-HT1AR.

Furthermore, evidence suggests that the pharmacodynamic interaction between CBD and 5-HT1AR is contingent upon dosage. Moreover, we propose that CBD can induce desensitization of 5-HT1AR via both homologous and heterologous mechanisms. Homologous desensitization involves the recruitment of G protein-coupled receptor kinase 2 (GRK2) and β-arrestin, leading to receptor endocytosis. In contrast, heterologous desensitization is mediated by an elevated intracellular calcium level or activation of protein kinases, such as c-Jun N-terminal kinase (JNK), through the activity of other receptors.”

https://pubmed.ncbi.nlm.nih.gov/39778776/

“Cannabis was one of the first inhaled drugs utilized by humans, with evidence of use for gout, rheumatism, and malaria dating to 2737 BCE”

“The concurrent literature revealed that CBD produces several therapeutic effects through its complex pharmacodynamic interactions with 5-HT1AR. Therapeutic applications of CBD, including its anxiolytic, antidepressant, antipsychotic, anti-degenerative, neuroprotective, anti-epileptic, and anti-addictive properties were mediated, at least in part, by its binding to 5-HT1AR.”

https://www.sciencedirect.com/science/article/abs/pii/S0006295225000048?via%3Dihub

Medicinal Cannabis and the Intestinal Microbiome

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“Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries.

The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea.

It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut-microbiota-brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems.

An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity.

This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota.

We advance an exogenous cannabinoid-intestinal microbiota-endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis.”

https://pubmed.ncbi.nlm.nih.gov/39770543/

“Furthermore, other modes of delivery of medicinal cannabis, such as oro-buccal, sublingual and inhaled/smoked alternatives, provide cannabinoids that have rapid access to the systemic circulation, bypassing the intestinal tract.”

https://www.mdpi.com/1424-8247/17/12/1702

The Role of Cannabinoids and the Endocannabinoid System in the Treatment and Regulation of Nausea and Vomiting

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“Despite using the recommended anti-emetic treatments, control of nausea and vomiting is still an unmet need for cancer patients undergoing chemotherapy treatment. Few properly controlled clinical trials have evaluated the potential of exogenously administered cannabinoids or manipulations of the endogenous cannabinoid (eCB) system to treat nausea and vomiting. In this chapter, we explore the pre-clinical and human clinical trial evidence for the potential of exogenous cannabinoids and manipulations of the eCB system to reduce nausea and vomiting. Although there are limited high-quality human clinical trials, pre-clinical evidence suggests that cannabinoids and manipulations of the eCB system have anti-nausea/anti-emetic potential. The pre-clinical anti-nausea/anti-emetic evidence highlights the need for further evaluation of cannabinoids and manipulations of eCBs and other fatty acid amides in clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/39739175/

https://link.springer.com/chapter/10.1007/7854_2024_554

Protective Action of Cannabidiol on Tiamulin Toxicity in Humans-In Vitro Study

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“The growing awareness and need to protect public health, including food safety, require a thorough study of the mechanism of action of veterinary drugs in consumers to reduce their negative impact on humans. Inappropriate use of veterinary drugs in animal husbandry, such as tiamulin, leads to the appearance of residues in edible animal tissues.

The use of natural substances of plant origin, extracted from hemp (Cannabis sativa L.), such as cannabidiol (CBD), is one of the solutions to minimize the negative effects of tiamulin.

This study aimed to determine the effect of CBD on the cytotoxicity of tiamulin in humans.

The cytotoxic activity of tiamulin and the effect of its mixtures with CBD were tested after 72 h exposure to three human cell lines: SH-SY5Y, HepG2 and HEK-293. Cytotoxic concentrations (IC50) of the tested drug and in combination with CBD were assessed using five biochemical endpoints: mitochondrial and lysosomal activity, proliferation, cell membrane integrity and effects on DNA synthesis. Oxidative stress, cell death and cellular morphology were also assessed. The nature of the interaction between the veterinary drug and CBD was assessed using the combination index. The long-term effect of tiamulin inhibited lysosomal (SH-SY5SY) and mitochondrial (HepG2) activity and DNA synthesis (HEK-293). IC50 values for tiamulin ranged from 2.1 to >200 µg/mL (SH-SY5SY), 13.9 to 39.5 µg/mL (HepG2) and 8.5 to 76.9 µg/mL (HEK-293). IC50 values for the drug/CBD mixtures were higher.

Reduced levels of oxidative stress, apoptosis and changes in cell morphology were demonstrated after exposure to the mixtures. Interactions between the veterinary drug and CBD showed a concentration-dependent nature of tiamulin in cell culture, ranging from antagonistic (low concentrations) to synergistic effects at high drug concentrations.

The increased risk to human health associated with the presence of the veterinary drug in food products and the protective nature of CBD use underline the importance of these studies in food toxicology and require further investigation.”

https://pubmed.ncbi.nlm.nih.gov/39769305/

https://www.mdpi.com/1422-0067/25/24/13542

Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models

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“Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits.

To date, CBC’s known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg).

The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05).

These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response.”

https://pubmed.ncbi.nlm.nih.gov/39769302/

https://www.mdpi.com/1422-0067/25/24/13539

Exploring Natural Analgesics for Chronic Pain Management: Cannabinoids and Other Phytoconstituents

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“Chronic pain lasting more than three months or persisting after normal healing is a significant global health issue. In a healthcare system, it is crucial to ensure proper chronic pain management. Traditional pharmacological and non-pharmacological pain management techniques may not fully meet the requirements of physicians regarding effectiveness and safety. Therefore, researchers are exploring natural analgesics.

Plant-based phytoconstituents show promise in relieving chronic pain associated with various diseases.

This study aims to review the latest advances in discovering natural bioactive compounds that can help alleviate chronic pain. It discusses the pathways of chronic pain and a multifactorial treatment strategy. It also organizes data on using plant- derived substances, such as cannabinoids, terpenoids, phenolics, and crude extracts. Additionally, it delves into the pharmacodynamics of cannabinoids, including their route of administration and elimination.

The review presents the results of 22 clinical trials on various cannabinoids for pain relief. It is important to note that opioids and other alkaloids from plants are not covered in this article due to their primary use in controlling acute rather than chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/39779559/

https://www.eurekaselect.com/article/145464

Synergistic Pain-Reducing Effects of Bixa orellana (Chronic® and Chronic In®) and Cannabidiol-Rich Cannabis sativa Extracts in Experimental Pain Models

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“Background: The present study aimed to evaluate the potential synergy between pharmaceutical formulations containing Bixa orellana L. (granulated-CHR OR and injectable nanodispersion-CHR IN) in conjunction with a cannabidiol (CBD)-rich extract of Cannabis sativa L. (CSE) on experimental pain models in Wistar rats. 

Methods: Chemical analysis was performed using gas chromatography (GC-MS). The pain tests employed were acetic acid-induced writhing (injection i.p. of 0.9% acetic acid), formalin (solution 1%), hot plate (55 ± 0.5 °C), and cold-water tail withdrawal tests. 

Results: Chemical analyses by chromatography confirmed that the oil from B. orellana is rich in δ-tocotrienol (72.0 ± 1.0%), while the oil from Cannabis sativa highlighted the presence of cannabidiol (CBD). The results from the experimental pain tests indicated that the combined administration of formulations containing Bixa orellana and C. sativa, such as the granulated CHR OR (400 mg/kg, orally) with CSE (40 mg/kg, orally) or the nanodispersion CHR IN (10 mg/kg, intramuscularly) with CSE (40 mg/kg, orally), demonstrated significant results (p < 0.001) in pain reduction. Although the formulations containing Bixa orellana extract showed statistical significance in the tests when used in isolation, their effects were inferior compared to the combined use with CSE or the isolated use of CSE. These findings suggest that combining formulations containing extracts of these plant species may represent a viable therapeutic option, considering the synergistic action in reducing pain under the experimental conditions employed. 

Conclusions: these results imply that combining the phytocomplexes present in B. orellana and C. sativa may be a promising approach for pain treatment.”

https://pubmed.ncbi.nlm.nih.gov/39770552/

https://www.mdpi.com/1424-8247/17/12/1710

Hemp Extract (Extractum Cannabis) in the Treatment of Gastrointestinal Distress and Dyspepsia: Historical Insights from Barcelona, Spain

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“This study explores the trajectory of interest in and use of Extractum Cannabis (hemp extract, i.e., extract of Cannabis sativa L.) for the symptomatic treatment of minor gastrointestinal distress and dyspepsia in nineteenth- and early twentieth-century Barcelona (Catalonia, Spain) prior to 1939, through a review of primary sources.

The objective of this paper is to present a historical pharmaceutical and applied review of the medical use of the hemp genus (Cannabis L.) prior to its prohibition, thereby contributing to its recognition as a medicinal product.

The information provided demonstrates evidence of the medicinal use of cannabis within the historical context studied. The interactions between this legacy medical use and the contemporary body of pharmacological and toxicological knowledge (on hemp, its constituents, and the endocannabinoid system in gastrointestinal and stomach disorders) are discussed, providing new possible clinical perspectives.

Within its limitations-including the scope, limited accessibility to, and varying quality of archives-this research contributes to a more granular understanding of the historical embeddedness of psychoactive hemp medicines in northeastern Spain, suggesting that medical and pharmaceutical traditions could play a role in informing contemporary approaches to “medical marijuana”.”

https://pubmed.ncbi.nlm.nih.gov/39770428/

https://www.mdpi.com/1424-8247/17/12/1585