Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Selective Cytotoxicity of Medical Cannabis ( Cannabis sativa L.) Extracts Across the Whole Vegetation Cycle Under Various Hydroponic and Nutritional Treatments

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“Introduction: The use of Cannabis sativa L. in health care requires stringent care for the optimal production of the bioactive compounds. However, plant phenotypes and the content of secondary metabolites, such as phytocannabinoids, are strongly influenced by external factors, such as nutrient availability. It has been shown that phytocannabinoids can exhibit selective cytotoxicity against various cancer cell lines while protecting healthy tissue from apoptosis. 

Research Aim: This study aimed to clarify the cytotoxic effect of cannabis extracts on colorectal cell lines by identifying the main active compounds and determining their abundance and activity across all developmental stages of medical cannabis plants cultivated under hydroponic conditions. 

Materials and Methods: Dimethyl sulfoxide extracts of medical cannabis plants bearing the genotype classified as chemotype I were analyzed by high-performance liquid chromatography, and their cytotoxic activity was determined by measuring cell viability by methylthiazolyldiphenyl-tetrazolium bromide assay on the human colon cancer cell lines, Caco-2 and HT-29, and the normal human epithelial cell line, CCD 841 CoN. 

Results: The most abundant phytocannabinoid in cannabis extracts was tetrahydrocannabinolic acid (THCA). Its maximum concentrations were reached from the 7th to the 13th plant vegetation week, depending on the nutritional cycle and treatment. Almost all extracts were cytotoxic to the human colorectal cancer (CRC) cell line HT-29 at lower concentrations than the other cell lines. The phytocannabinoids that most affected the cytotoxicity of individual extracts on HT-29 were cannabigerol, Δ9-tetrahydrocannabinol, cannabidiol, cannabigerolic acid, and THCA. The tested model showed almost 70% influence of these cannabinoids. However, THCA alone influenced the cytotoxicity of individual extracts by nearly 65%. 

Conclusions: Phytocannabinoid extracts from plants of the THCA-dominant chemotype interacted synergistically and showed selective cytotoxicity against the CRC cell line, HT-29. This positive extract response indicates possible therapeutic value.”

https://pubmed.ncbi.nlm.nih.gov/36459627/

https://www.liebertpub.com/doi/10.1089/can.2022.0243


Receptor-mediated effects of Δ9 -THC & CBD on the inflammatory response of alveolar macrophages

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“Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD) are cannabinoids found in Cannabis sativa. While research supports cannabinoids reduce inflammation, the consensus surrounding receptor(s) mediated effects has yet to be established.

Here, we investigated the receptor-mediated properties of Δ9 -THC and CBD on alveolar macrophages, an important pulmonary immune cell in direct contact with cannabinoids inhaled by cannabis smokers.

MH-S cells, a mouse alveolar macrophage cell line, were exposed to Δ9 -THC and CBD, with and without lipopolysaccharide (LPS). Outcomes included RNA-sequencing and cytokine analysis. Δ9 -THC and CBD alone did not affect the basal transcriptional response of MH-S cells.

In response to LPS, Δ9 -THC and CBD significantly reduced the expression of numerous pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, an effect that was dependent on CB2 . The anti-inflammatory effects of CBD- but not Δ9 -THC- were mediated through a reduction in signaling through NF-κB and ERK1/2.

These results suggest that CBD and Δ9 -THC have potent immunomodulatory properties in alveolar macrophages, a cell type important in immune homeostasis in the lungs. Further investigation into the effects of cannabinoids on lung immune cells could lead to the identification of therapies that may ameliorate conditions characterized by inflammation.”

https://pubmed.ncbi.nlm.nih.gov/36510483/

https://onlinelibrary.wiley.com/doi/10.1111/imcb.12614


Cannabis sativa Cannabinoids as Functional Ingredients in Snack Foods-Historical and Developmental Aspects

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“The published health benefits of Cannabis sativa has caught the attention of health-conscious consumers and the food industry. Historically, seeds have long been utilized as a food source and currently there is an increasing number of edibles on the market that contain cannabis. Cannabinoids include the psychoactive constituent, delta-9-tetrahydrocannabinol (THC), and the non-psychoactive cannabidiol (CBD) that are both compounds of interest in Cannabis sativa.

This paper looks at the distribution of nutrients and phytocannabinoids in low-THC Cannabis sativa, the historical uses of hemp, cannabis edibles, and the possible side-effects and concerns related to cannabis edibles. Several authors have pointed out that even though the use of cannabis edibles is considered safe, it is important to mention their possible side-effects and any concerns related to its consumption that negatively influence consumer acceptance of cannabis edibles. Such risks include unintentional overdose by adults and accidental ingestion by children and adolescents resulting in serious adverse effects. Therefore, cannabis edibles should be specifically packaged and labelled to differentiate them from known similar non-cannabis edibles so that, together with tamperproof packaging, these measures reduce the appeal of these products to children.”

https://pubmed.ncbi.nlm.nih.gov/36501366/

“Cannabis sativa possesses many health-promoting qualities and so it has played an effective role as a traditional medicine to treat a variety of ailments from pain, anxiety and weight gain through to conditions such as cardiovascular disease and diabetes, as well as infectious diseases such as malaria, and cancer.

Opinion regarding cannabis edibles is changing amongst consumers and most countries around the world are shifting towards the legalization of the recreational and medicinal use of cannabis leading to a rapid increase in the global acceptance and availability of cannabis edibles. “

https://www.mdpi.com/2223-7747/11/23/3330


Antibacterial, antioxidant, and haemolytic potential of silver nanoparticles biosynthesized using roots extract of Cannabis sativa plant

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“In this study, Cannabis sativa roots extract has been employed for the biosynthesis of silver nanoparticles (AgNPs). The appearance of reddish-brown colour followed by absorption peak of AgNPs at 408 nm through UV-vis spectrophotometry suggested biosynthesis of AgNPs. The size of the particles ranged from 90-113 nm, confirmed using DLS and TEM along with zeta potential of -25.3 mV. The FTIR provided information regarding the phytochemical capping. The study was further elaborated for determining AgNPs antibacterial, antioxidant, and cellular toxicity using MIC, DPPH, MTT, and haemolytic assays, respectively. The AgNPs were significantly effective against Staphylococcus aureus (Gram-positive), as compared to that of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli (Gram-negative). AgNPs also exhibited remarkable antioxidant potential wherein 58.01 ± 0.09% free radical scavenging was observed at a concentration of 100 µg/ml. AgNPs revealed lower cytotoxicity where cell viability was observed to be 52.38 ± 0.6% at a very high concentration of 500 µg/ml in HEK 293 cells. Further, very low toxicity was seen in RBCs i.e. 6.47 ± 0.04% at a high concentration of 200 µg/ml. Thus, the current study beholds anticipation that Cannabis sativa ethanolic root extract-mediated AgNPs may play a vital role in therapeutic.”

https://pubmed.ncbi.nlm.nih.gov/36519372/

“The study demonstrates the efficient biosynthesis of silver nanoparticles using Cannabis sativa ethanolic root extract. The potency of the plant extract and phytochemically fabricated silver nanoparticles were analysed over certain parameters such as antimicrobial, antioxidant and cellular toxicity tests. The study concludes the significant effectiveness of silver nanoparticles, thus prognosticating theirs use henceforth.”

https://www.tandfonline.com/doi/full/10.1080/21691401.2022.2149543

Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts

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“In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation.

Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity.

Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts.

Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk.

Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36497198/

“THC and CBD stimulated fibroblasts’ ability to close damaged wounds, while THC induced wound healing better than common nutrient signaling regulators,”

https://www.mdpi.com/2073-4409/11/23/3939

In Silico Binding Analysis of Cannabinoids with Eph Receptors for Therapeutic Use in Gliomas

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“Background: Accumulating evidence suggests overexpression of Eph receptors is associated with malignant human gliomas. Inhibiting interactions of Eph receptors with their ephrin ligands may improve clinical outcomes in glioma patients. The present study investigated the potential of cannabinoids to bind Eph receptors and block Eph/ephrin interactions.

Methods: Twelve major cannabinoids were computationally docked with ligand binding domains from six glioma-associated Eph receptors through Auto Dock Vina to measure their potential binding affinities. The molecular structures and residue interactions of the most favorable poses for each receptor binding domain were further visually examined.

Results: Cannabichromene (CBC) exhibited the most favorable binding with EphA2, EphA3, and EphB4 receptor ligand binding domains while tetrahydrocannabinol (THC) was predicted to bind favorably with EphB2 and EphB3 receptor ligand binding domains. EphA4 showed the best potential binding affinity with cannabidivarin (CBDV). Further analysis revealed that these cannabinoids bind to specific locations on Eph receptors required for Eph/ephrin interactions.

Conclusion: The findings suggest that certain cannabinoids can effectively bind to hydrophobic pockets required for ephrin binding and thereby be used to block subsequent Eph/ephrin interactions.”

https://pubmed.ncbi.nlm.nih.gov/36468933/

Cannabinoids inhibit ethanol-induced activation of liver toxicity in rats through JNK/ERK/MAPK signaling pathways

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“Cannabinoids (CBs) are psychoactive compounds, with reported anticancer, anti-inflammatory, and anti-neoplastic properties. The study was aimed at assessing the hepatoprotective effects of CB against ethanol (EtOH)-induced liver toxicity in rats. The animals were divided into seven groups: control (Group I) and Group II were treated with 50% ethanol (EtOH 5 mg/kg). Groups III, IV, and VI were treated with (EtOH + CB 10 mg/kg), (EtOH + CB 20 mg/kg), and (EtOH + CB 30 mg/kg), respectively. Groups V and VII consisted of animals treated with 20 and 30 mg/kg, of CB, respectively. Biochemical analysis revealed that Group IV (EtOH + CB 20 mg/kg) had reduced levels of ALT-alanine transferase, AST-aspartate aminotransferase, ALP-alanine peroxidase, MDA-malondialdehyde and increased levels of GSH-reduced glutathione. Histopathological analysis of liver and kidney tissues showed that EtOH + CB (20 and 30 mg/kg) treated animal groups exhibited normal tissue architecture similar to that of the control group. ELISA revealed that the inflammatory markers were reduced in the animal groups that were treated with EtOH + CB 20 mg/kg, in comparison to the animals treated only with EtOH. The mRNA expression levels of COX-2, CD-14, and MIP-2 showed a remarkable decrease in EtOH + CB treated animal groups to control groups. Western blot analysis revealed that CB downregulated p38/JNK/ERK thereby exhibiting its hepatoprotective property by inhibiting mitogen-activated protein kinase pathways. Thus, our findings suggest that CB is a potential candidate for the treatment of alcohol-induced hepatotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/36453646/

https://onlinelibrary.wiley.com/doi/10.1002/jbt.23260

Antitumor Effects of Delta (9)-Tetrahydrocannabinol and Cannabinol on Cholangiocarcinoma Cells and Xenograft Mouse Models

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“Cholangiocarcinoma (CCA) is a very aggressive tumor. The development of a new therapeutic drug for CCA is required.

This study aims to evaluate the antitumor effect of ∆9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), and cannabinol (CBN), a minor, low-psychoactive cannabinoid, on CCA cells and xenograft mice.

THC and CBN were isolated, and their identities were confirmed by comparing 1H- and 13C-NMR spectra and mass spectra with a database. Cell proliferation, cell migration, and cell apoptosis assays were performed in HuCCT1 human CCA cells treated with THC or CBN. The phosphorylation of signaling molecules in HuCCT1 cells was detected. To determine the effects of THC and CBN in an animal model, HuCCT1 cells were inoculated subcutaneously into nude mice. After the tumors reached an appropriate size, the mice were treated with THC or CBN for 21 days. Tumor volumes were monitored and calculated. The 1H- and 13C-NMR data of THC and CBN were almost identical to those reported in the literature.

THC and CBN significantly inhibited cell proliferation and migration and induced apoptosis in HuCCT1 cells. The phosphorylation of AKT, GSK-3α/β, and ERK1/2 decreased in HuCCT1 cells treated with THC or CBN. CCA xenograft mice treated with THC showed significantly slower tumor progression and smaller tumor volumes than control mice. THC and CBN induced apoptosis in CCA by inhibiting the AKT and MAPK pathways.

These findings provide a strong rationale for THC and CBN as therapeutic options for CCA.”

https://pubmed.ncbi.nlm.nih.gov/36452140/

“THC and CBN induced apoptosis in CCA by inhibiting the AKT and MAPK pathways, leading to a decrease in cell proliferation in vitro and tumor volume in vivo. In addition, in this animal model, THC appeared to be superior in potency to CBN. These findings provide a strong rationale for THC and CBN as therapeutic options for CCA.”

https://www.hindawi.com/journals/ecam/2022/6477132/

A Systemic Review of Medical Cannabinoids Dosing in Human

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“Purpose: This systemic review assesses currently available clinical information on which cannabinoids and what range of doses have been used to achieve positive effects in a diversity of medical context.

Methods: The data were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol guidelines. Inclusion criteria were articles that assessed administration of any cannabinoid to any clinical population, reported in the ClinicalTrials.gov or PubMed databases, that involved a comparison with other treatment or placebo and a result measurement to assess the effectiveness or ineffectiveness of the cannabinoid. Exclusion criteria were review or letter; articles not in the English language; not full-text articles; not a clinical trial, case report, case series, open-label trial, or pilot study; administration in animals, in vitro, or in healthy participants; cannabinoids administered in combination with other cannabinoids (except for cannabidiol [CBD] or tetrahydrocannabinol [THC]) or as whole cannabis extracts; no stated concentration; inhalation or smoke as a route of administration; and no results described. The articles were assessed by the risk of bias.

Finding: In total, 1668 articles were recovered, of which 55 studies met the inclusion criteria for 21 diseases. Positive effects were reported in clinical studies: 52% with THC (range, 0.01-0.5 mg/kg/d [0.62-31 mg/d]), 74% with CBD (range, 1-50 mg/kg/d [62-3100 mg/d]), 64% with THC-CBD (mean, 1:1.3 mg/kg/d [ratio, 1:1]), and 100% with tetrahydrocannabivarin (THCV) (0.2 mg/kg/d).

Implications: THC, CBD, and THCV can regulate activity in several pathologies. New studies of cannabinoids are highly encouraged because each patient is unique and requires a unique cannabinoid medication.”

https://pubmed.ncbi.nlm.nih.gov/36411116/

https://www.clinicaltherapeutics.com/article/S0149-2918(22)00349-6/fulltext

Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies

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Drug and Alcohol Dependence

“Background: While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.

Methods: We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.

Results: Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.

Conclusions: Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/36434879/

https://www.sciencedirect.com/science/article/abs/pii/S0376871622004392?via%3Dihub