Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Hexahydrocannabinol (HHC) and Δ9-tetrahydrocannabinol (Δ9-THC) driven activation of cannabinoid receptor 1 results in biased intracellular signaling

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“The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders.

In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the treatment of other health conditions. Using an evidence-based approach, pharmacological investigation of CB1R agonists is timely, with the aim to provide chronically ill patients relief using well-defined and characterized compounds from cannabis.

Hexahydrocannabinol (HHC), currently available over the counter in many countries to adults and even children, is of great interests to policy makers, legal administrators, and healthcare regulators, as well as pharmacologists. Herein, we studied the pharmacodynamics of HHC epimers, which activate CB1R. We compared their key CB1R-mediated signaling pathway activities and compared them to the pathways activated by Δ9-tetrahydrocannabinol (Δ9-THC). We provide evidence that activation of CB1R by HHC ligands is only broadly comparable to those mediated by Δ9-THC, and that both HHC epimers have unique properties.

Together with the greater chemical stability of HHC compared to Δ9-THC, these molecules have a potential to become a part of modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/38649680/

https://www.nature.com/articles/s41598-024-58845-7

In vitro Antibacterial Activity of Ethanolic Tanao Si Kan Dang RD1 (Cannabis sativa L.) Extracts Against Human Antibiotic-Resistant Bacteria

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“Background and Objective: A new strain of cannabis, Cannabis sativa L. Tanao Si Kan Dang RD1, has been approved and registered by the Rajamangala University of Technology Isan, Thailand. The C. sativa is acknowledged for its medicinal properties which demonstrated various therapeutic properties, such as anti-cancer and antibacterial activities. This study aimed to investigate the antibacterial activity of ethanolic extracts from the stems and leaves of the Tanao Si Kan Dang RD1 strain against seven antibiotic-resistant bacteria. 

Materials and Methods: The primary antibacterial activity of ethanolic Tanao Si Kan Dang RD1 extracts were determined using the disc diffusion method, while the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using the broth microdilution method. 

Results: The largest inhibition zone, measuring 12 mm, was observed in leaf extracts against Pseudomonas aeruginosa 101. The lowest MIC, at 0.78 mg/mL, was obtained from stem extracts against Stenotrophomonas maltophilia. The lowest MBCs, at 12.5 mg/mL, were observed in leaf extracts against Enterococcus faecalis, Acinetobacter baumannii, multidrug-resistant Klebsiellapneumoniae, Stenotrophomonas maltophilia and Pseudomonas aeruginosa 101 and stem extracts against Acinetobacter baumannii, multidrug-resistant Klebsiella pneumoniae, Stenotrophomonas maltophilia and Pseudomonas aeruginosa 101. 

Conclusion: This study presents a novel finding regarding the antibacterial activity of ethanolic extracts from the leaves and stems of Tanao Si Kan Dang RD1 against antibiotic-resistant bacteria. The potential application of these cannabis plant extracts in the development of antibiotics capable of combating antibiotic-resistant pathogenic bacteria represents a promising strategy to address a significant global health concern.”

https://pubmed.ncbi.nlm.nih.gov/38686733/

https://scialert.net/abstract/?doi=pjbs.2024.119.124

Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

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“Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials.

Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain.

Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, “responders” (≥30% reduction in weekly pain at any time point) were identified.

Results: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (F(3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were “responders” but could not be identified by baseline parameters. “Responders” exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious.

Conclusion: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.”

https://pubmed.ncbi.nlm.nih.gov/38680212/

“In conclusion, this structured, prospective cohort study demonstrated modest improvements in pain, associated symptoms, functioning, and quality of life, and a reduction in opioid use. The reduction in “disease burden” was more pronounced in nearly a quarter of the patients, but no predictors for treatment success could be identified before treatment initiation. The doses of THC and CBD in the oil extracts were modest and considerably lower than those required to achieve similar magnitude of effect by cannabis inflorescence. Although medical cannabis treatment appears to be generally safe for most patients, some still experience SAEs.”

https://journals.lww.com/painrpts/fulltext/2024/04000/cannabis_oil_extracts_for_chronic_pain__what_else.12.aspx

Exploring Cannabinoids with Enhanced Binding Affinity for Targeting the Expanded Endocannabinoid System: A Promising Therapeutic Strategy for Alzheimer’s Disease Treatment

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“Despite decades of rigorous research and numerous clinical trials, Alzheimer’s disease (AD) stands as a notable healthcare challenge of this century, with effective therapeutic solutions remaining elusive.

Recently, the endocannabinoid system (ECS) has emerged as an essential therapeutic target due to its regulatory role in different physiological processes, such as neuroprotection, modulation of inflammation, and synaptic plasticity. This aligns with previous research showing that cannabinoid receptor ligands have the potential to trigger the functional structure of neuronal and brain networks, potentially impacting memory processing.

Therefore, our study aims to assess the effects of prolonged, intermittent exposure (over 90 days) to JWH-133 (0.2 mg/kg) and an EU-GMP certified Cannabis sativa L. (Cannabixir® Medium Flos, 2.5 mg/kg) on recognition memory, as well as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed the cognitive deficits. Additionally, a reduction was observed in both the number and size of Aβ plaque deposits, along with decreased cerebral glucose metabolism, as well as a decline in the expression of mTOR and CB2 receptors. Furthermore, the study revealed enlarged astrocytes and enhanced expression of M1 mAChR in mice subjected to cannabinoid treatment.

Our findings highlight the pivotal involvement of the extended endocannabinoid system in cognitive decline and pathological aspects associated with AD, presenting essential preclinical evidence to support the continued exploration and assessment of cannabinoid receptor ligands for AD treatment.”

https://www.mdpi.com/1424-8247/17/4/530

“In conclusion, our current findings suggest that pharmacological activation of the expanded ECS via the selective CB2 agonist JWH-133 or Cannabixir® Medium Flos—15.6% THC and <1% CBD ameliorates the Alzheimer-like phenotype in APP/PS1 mice by mitigating neuroinflammation and accumulation of Aβ plaque deposits, reducing cerebral glucose metabolism, and increasing glial reactivity. These results support the notion that targeting the ECS using cannabinoid receptor ligands, which lack psychoactive side effects, is a promising target for the development of novel therapeutic approaches against AD.”

https://pubmed.ncbi.nlm.nih.gov/38675490/

“Prevention of Alzheimer’s Disease Pathology by Cannabinoids. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.”

https://www.jneurosci.org/content/25/8/1904

Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems

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“The compounds present in hemp show multidirectional biological activity. It is related to the presence of secondary metabolites, mainly cannabinoids, terpenes, and flavonoids, and the synergy of their biological activity. The aim of this study was to assess the activity of the Henola Cannabis sativae extract and its combinations with selected carriers (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, magnesium aluminometasilicate, and hydroxypropyl-β-cyclodextrin) in terms of antimicrobial, probiotic, and immunobiological effects.

As a result of the conducted research, the antimicrobial activity of the extract was confirmed in relation to the following microorganisms: Clostridium difficile, Listeria monocytogenes, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus pyrogenes, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aereuginosa, and Candida albicans (microorganism count was reduced from ~102 CFU mL-1 to <10 CFU mL-1 in most cases). Additionally, for the system with hydroxypropyl-β-cyclodextrin, a significant probiotic potential against bacterial strains was established for strains Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus reuteri, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus fermentum, and Streptococcus thermophilus (microorganism count was increased from ~102 to 104-107). In terms of immunomodulatory properties, it was determined that the tested extract and the systems caused changes in IL-6, IL-8, and TNF-α levels.”

https://pubmed.ncbi.nlm.nih.gov/38667045/

“This study investigated the antimicrobial potential of Cannabis sativa extract, Henola variety, and systems with carriers. The extract showed antimicrobial activity against pathogenic microorganisms, suggesting its possible application as support in combating infections. Additionally, the system with hydroxypropyl-β-cyclodextrin may possess prebiotic properties, stimulating the growth of probiotic microorganisms. Furthermore, the investigated systems exhibit immunomodulatory and immunostimulatory effects, with potential therapeutic implications for modulating inflammatory responses. Overall, these findings underscore the multifaceted therapeutic potential of Cannabis sativa extracts. The delivery systems might be used as powder-based food additives, but they might also be subjected to formulation studies for the development of an oral dietary supplement.”

https://www.mdpi.com/2079-6382/13/4/369

Phytocannabinoids: Exploring Pharmacological Profiles and Their Impact on Therapeutical Use

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“Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses.

This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids.

CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions.

THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential.

In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN).

The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways.

The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/38673788/

“Phytocannabinoids offer diverse therapeutic applications, ranging from pain management to neurological disorders and inflammatory diseases. Their antimicrobial and anti-inflammatory properties make them valuable candidates for combating antibiotic resistance and modulating inflammatory pathways. By leveraging the synergistic effects of combination therapies and targeting multiple disease pathways, phytocannabinoids hold immense potential to revolutionize the future of pharmacotherapy and improve human health outcomes. “

https://www.mdpi.com/1422-0067/25/8/4204

Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines

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“In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines’ viability compared to cells treated with a vehicle.

The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids.

We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 μM to 50 μM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD.

The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG.

Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.”

https://pubmed.ncbi.nlm.nih.gov/38672512/

“Our study demonstrated a significant moderate inhibitory effect of CBD, THC, and WIN on canine and human NHL cell viability. Our results also revealed that CBD, THC, and WIN decreased lymphoma cell viability because they increased oxidative stress, leading to downstream apoptosis.”

https://www.mdpi.com/2218-273X/14/4/495

Targeting Colorectal Cancer: Unravelling the Transcriptomic Impact of Cisplatin and High-THC Cannabis Extract

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“Cisplatin and other platinum-derived chemotherapy drugs have been used for the treatment of cancer for a long time and are often combined with other medications. Unfortunately, tumours often develop resistance to cisplatin, forcing scientists to look for alternatives or synergistic combinations with other drugs.

In this work, we attempted to find a potential synergistic effect between cisplatin and cannabinoid delta-9-THC, as well as the high-THC Cannabis sativa extract, for the treatment of HT-29, HCT-116, and LS-174T colorectal cancer cell lines. However, we found that combinations of the high-THC cannabis extract with cisplatin worked antagonistically on the tested colorectal cancer cell lines. To elucidate the mechanisms of drug interactions and the distinct impacts of individual treatments, we conducted a comprehensive transcriptomic analysis of affected pathways within the colorectal cancer cell line HT-29.

Our primary objective was to gain a deeper understanding of the underlying molecular mechanisms associated with each treatment modality and their potential interactions. Our findings revealed an antagonistic interaction between cisplatin and high-THC cannabis extract, which could be linked to alterations in gene transcription associated with cell death (BCL2, BAD, caspase 10), DNA repair pathways (Rad52), and cancer pathways related to drug resistance.”

https://pubmed.ncbi.nlm.nih.gov/38674023/

“There is a need for new and better ways to prevent and treat it, possibly by combining different drugs. Recent research suggests that cannabinoids could be promising in this regard.”

https://www.mdpi.com/1422-0067/25/8/4439

The Use of Tetrahydrocannabinol Is Associated with an Increase in Survival Time in Palliative Cancer Patients: A Retrospective Multicenter Cohort Study

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“Introduction: Tetrahydrocannabinol (THC) is often prescribed for ambulatory palliative patients to improve sleep quality and appetite and to reduce anxiety, stress, and pain. However, it is not known if THC has also an effect on the mortality of these patients.

Method: The objective was the impact of THC on mortality of ambulatory palliative patients. For this purpose, data from the palliative treatment documentation from 5 ambulatory palliative care teams in Brandenburg, Germany were used for this analysis. Survival time was calculated for 3 groups of patients: (1) without THC; (2) with THC in a low dosage (≤4.7 mg per day); and (3) THC in higher doses (≥4.7 mg per day). The analysis was done for 2 cohorts of patients. Cohort 1: all patients with a survival time of at least 7 days after inclusion in specialized ambulatory palliative care (SAPC) and cohort 2: a subgroup of patients with a survival time between 7 and 100 days. Kaplan-Meier curves were created, and multivariate analysis was done to investigate the impact of THC on mortality.

Results: A total of 9,419 patients with a survival time of at least 7 days after inclusion in SAPC were included in the analysis (cohort 1). 7,085 among them had a survival time between 7 and 100 days (cohort 2). In both cohorts, survival time was significantly prolonged by THC, but only when the daily THC dose was above the median of 4.7 mg. Survival time was 15 days longer in cohort 2 (40 vs. 25 days), when more than 4.7 mg THC were prescribed per day.

Conclusion: Use of THC is associated with a significant increase in survival time in ambulatory palliative patients which survive longer than 7 days the initiation of THC prescription and which use of THC >4.7 mg/day.”

https://pubmed.ncbi.nlm.nih.gov/38655402/

“Thus, in view of its significant prolongation of patient survival time, THC therapy should be included as part of the first-line therapy for ambulatory palliative patients.”

https://karger.com/mca/article/7/1/59/896816/The-Use-of-Tetrahydrocannabinol-Is-Associated-with

Medicinal Cannabis oil improves anxiety-like and depressive-like behaviors in CCS mice via the BDNF/TRPC6 signaling pathway

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“Background: Post-traumatic stress disorder (PTSD) refers to a chronic impairing psychiatric disorder occurring after exposure to the severe traumatic event. Studies have demonstrated that medicinal cannabis oil plays an important role in neuroprotection, but the mechanism by which it exerts anti-PTSD effects remains unclear.

Methods: The chronic complex stress (CCS) simulating the conditions of long voyage stress for 4 weeks was used to establish the PTSD mice model. After that, behavioral tests were used to evaluate PTSD-like behaviors in mice. Mouse brain tissue index was detected and hematoxylin-eosin staining was used to assess pathological changes in the hippocampus. The indicators of cell apoptosis and the BDNF/TRPC6 signaling activation in the mice hippocampus were detected by western blotting or real-time quantitative reverse transcription PCR experiments.

Results: We established the PTSD mice model induced by CCS, which exhibited significant PTSD-like phenotypes, including increased anxiety-like and depression-like behaviors. Medicinal cannabis oil treatment significantly ameliorated PTSD-like behaviors and improved brain histomorphological abnormalities in CCS mice. Mechanistically, medicinal cannabis oil reduced CCS-induced cell apoptosis and enhanced the activation of BDNF/TRPC6 signaling pathway.

Conclusions: We constructed a PTSD model with CCS and medicinal cannabis oil that significantly improved anxiety-like and depressive-like behaviors in CCS mice, which may play an anti-PTSD role by stimulating the BDNF/TRPC6 signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/38641178/

https://www.sciencedirect.com/science/article/abs/pii/S016643282400161X?via%3Dihub