Author Archives: David Worrell

Observational Analysis of the Influence of Medical Marijuana Use on Quality of Life in Patients

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“Introduction: A significant gap exists in the understanding and utilization of medical marijuana and its effects on a patient’s quality of life. This is largely attributed to Cannabis’ sp. Schedule 1 classification, which has impeded the scientific investigation of its effects on the endocannabinoid system (ECS) and quality of life. Additionally, conflicting results from previous studies highlight the need for more research to provide guidance to both patients and clinicians regarding the therapeutic potential of medical marijuana.

Methods: Patients over 18 years of age who were members of the Pennsylvania Medical Marijuana Program (PAMMP) were recruited from regulated Pennsylvania medical marijuana dispensaries. Eligible patients were enrolled through informed consent, following a study design that received approval from the LECOM Institutional Review Board (IRB). Over 90 days, participants were remotely administered an electronic survey every 30 days to collect medical marijuana use patterns and assess changes in quality of life.

Results: Of the 103 participants who completed the study, significant improvements were observed in physical and social functioning, emotional well-being, and energy levels within the first 30 days. Participants reported significant decreases in emotional limitations, fatigue, and pain levels. Notably, participants who used inhaled or vaped products (defined as vape cartridges and concentrates) were younger and exhibited a significantly higher increase in emotional well-being scores compared to those who used flower products (defined as dry leaf only). Participants who consumed medical marijuana for opioid use demonstrated significantly higher THC consumption compared to those seeking treatment for anxiety, chronic pain, or inflammatory bowel disease (IBD). Improvements in the first 30 days also remained constant for the remainder of the study.

Discussion: This study contributed valuable insights into the effects of medical marijuana on quality of life and highlighted potential benefits associated with its use. Moreover, ongoing research aims to assess the observed sustained improvements beyond 90 days, investigating potential long-term trends. While further research is needed to explore the underlying mechanisms of action and long-term effects of medical marijuana, clinicians and patients can gain a better understanding of medical marijuana’s therapeutic potential, enabling more informed decisions regarding its use in clinical settings.”

https://pubmed.ncbi.nlm.nih.gov/38500669/

“This research looks at the effects of medical marijuana on a patient’s quality of life. The study involved 103 participants from Pennsylvania who were using medical marijuana for various health conditions. They answered four surveys over 90 days, reporting on their experiences with marijuana and their well-being.

The results showed that many participants experienced improvements in their physical and social functioning, energy levels, and emotional well-being within the first 30–60 days of using medical marijuana.

Interestingly, the study found that how often someone used medical marijuana could affect their overall health. Those who used it once a day tended to have better general health scores compared to those who used it more frequently. Alcohol use seemed to have an impact too. People who used both alcohol and medical marijuana had lower energy levels and emotional well-being, suggesting that the combination might not be ideal. The study also looked at how people consumed medical marijuana, whether by inhaling it or using it as a flower, and found differences in THC consumption and emotional well-being. However, the study had some limitations, like relying on self-reported data and having a small sample size. Still, it provides valuable insights into how medical marijuana can affect people’s lives and highlights the need for personalized approaches to its use.”

https://karger.com/mca/article/7/1/44/895874/Observational-Analysis-of-the-Influence-of-Medical

The efficacy and safety of cannabidiol (CBD) in pediatric patients with Dravet Syndrome: a narrative review of clinical trials

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“Background: Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials.

Methods: A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to “Cannabidiol,” “Dravet Syndrome,” and “pediatric patients.”

Results: The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD’s efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable.

Conclusion: This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD’s efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.”

https://pubmed.ncbi.nlm.nih.gov/38500226/

“This review offers a comprehensive and in-depth analysis of the existing evidence on the efficacy and safety of CBD in pediatric patients diagnosed with DS. The findings, compiled from ten distinct clinical trials, consistently point to the potential of CBD as a valuable therapeutic option for managing DS. Notably, CBD remarkably reduces seizure frequency and enhances the overall quality of life for affected patients.”

https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01788-6

Exploring the Possible Role of Cannabinoids in Managing Post-Cardiac Surgery Complications: A Narrative Review of Preclinical Evidence and a Call for Future Research Directions

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“Open-heart surgery with cardiopulmonary bypass (CPB) often leads to complications including pain, systemic inflammation, and organ damage. Traditionally managed with opioids, these pain relief methods bring potential long-term risks, prompting the exploration of alternative treatments.

The legalization of cannabis in various regions has reignited interest in cannabinoids, such as CBD, known for their anti-inflammatory, analgesic, and neuroprotective properties. Historical and ongoing research acknowledges the endocannabinoid system’s crucial role in managing physiological processes, suggesting cannabinoids could offer therapeutic benefits in post-surgical recovery.

Specifically, CBD has shown promise in managing pain, moderating immune responses, and mitigating ischemia/reperfusion injury, underscoring its potential in postoperative care. However, the translation of these findings into clinical practice faces challenges, highlighting the need for extensive research to establish effective, safe cannabinoid-based therapies for patients undergoing open-heart surgery.

This narrative review advocates for a balanced approach, considering both the therapeutic potential of cannabinoids and the complexities of their integration into clinical settings.”

https://pubmed.ncbi.nlm.nih.gov/38498618/

https://journals.lww.com/cardiovascularpharm/abstract/9900/exploring_the_possible_role_of_cannabinoids_in.298.aspx

Anti-proliferative and apoptotic effect of cannabinoids on human pancreatic ductal adenocarcinoma xenograft in BALB/c nude mice model

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“Human pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal tumor of the exocrine pancreas.

Cannabinoids extracted from the hemp plant Cannabis sativa have been suggested as a potential therapeutic agent in several human tumors. However, the anti-tumor effect of cannabinoids on human PDAC is not entirely clarified. In this study, the anti-proliferative and apoptotic effect of cannabinoid solution (THC:CBD at 1:6) at a dose of 1, 5, and 10 mg/kg body weight compared to the negative control (sesame oil) and positive control (5-fluorouracil) was investigated in human PDAC xenograft nude mice model.

The findings showed that cannabinoids significantly decreased the mitotic cells and mitotic/apoptotic ratio, meanwhile dramatically increased the apoptotic cells. Parallelly, cannabinoids significantly downregulated Ki-67 and PCNA expression levels. Interestingly, cannabinoids upregulated BAX, BAX/BCL-2 ratio, and Caspase-3, meanwhile, downregulated BCL-2 expression level and could not change Caspase-8 expression level.

These findings suggest that cannabinoid solution (THC:CBD at 1:6) could inhibit proliferation and induce apoptosis in human PDAC xenograft models. Cannabinoids, including THC:CBD, should be further studied for use as the potent PDCA therapeutic agent in humans.”

https://pubmed.ncbi.nlm.nih.gov/38499634/

“Herbal medicinal plants and their derivatives have been discovered and used as potential sources for the treatment of human cancers for decades. Of these, cannabinoids extracted from the hemp plant Cannabis sativa have been remarkably noted as a potential therapy for the treatment of several human tumors.”

“In summary, this study revealed that cannabinoids (THC:CBD) (1:6) could inhibit the proliferation and induce apoptosis in human PDAC xenograft nude mice models.”

https://www.nature.com/articles/s41598-024-55307-y

Medical cannabis use in oncology and associated outcomes: A scoping review

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“Background: Natural and synthetic cannabinoids are being used worldwide to treat various symptoms in cancer patients. This study aims to map the therapeutic benefits and adverse effects associated with the use of cannabis-based drugs in these outcomes.

Methods: Following Joanna Briggs Institute guidelines a scoping review was conducted. The study protocol was available in the Open Science Framework public repository. An extensive search strategy involving databases like Cochrane Library, Embase, CINAHL, Medline/PubMed, Lilacs, Google Scholar, and Open Gray for gray literature analysis was executed by a skilled librarian. The inclusion criteria were primary studies (observational and randomized) that evaluated the efficacy and safety of cannabinoids in cancer patients. The review encompassed studies of diverse designs, publication years, and types, as long as they addressed cannabinoids’ impact in oncology.

Results: Twenty-nine (82.86%) out of total of 35 were randomized and 6 (14.14%) were non-randomized. About 57.1% of studies utilized registered products as interventions, with THC being the most natural cannabinoid cited in variable doses and administration routes. Moreover, 62.85% of studies specified the cancer types (breast, lung, sarcomas, hematological and reproductive system), while only one study detailed cancer staging. The evaluated outcomes encompassed nausea and vomiting (77.14%), appetite (11.43%), pain (8.57%), and tumor regression (2.86%) across different proportions of studies.

Conclusion: Cannabinoids show promise in managing pain, emesis, and anorexia/cachexia linked to cancer progression. New randomized clinical trials with a larger number of participants and observational studies on long-term safety are crucial to affirm their medicinal utility for cancer patients unresponsive to conventional drugs.”

https://pubmed.ncbi.nlm.nih.gov/38477532/

https://journals.sagepub.com/doi/10.1177/10781552241239006

Platinum (IV) drugs with cannabidiol inducing mitochondrial dysfunction and synergistically enhancing anti-tumor effects

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“Chemotherapy resistance is an insurmountable problem in clinical anticancer therapy. Although Oxaliplatin is an effective chemotherapeutic agent for the treatment of colorectal cancer (CRC), it still suffers from serious toxicities as well as drug resistance. In this work, three Oxaliplatin tetravalent platinum prodrugs(O1-O3) and three novel mixed ammine/amine analogs(C1-C3) were constructed, introducing cannabidiol with anti-tumor activity in their axial position.

All Pt(IV) prodrugs exhibited potent antitumor effects in a variety of tumor cell lines, especially in HCT-116 cells, where complex O3 showed strong inhibitory effects with the half maximal inhibitory concentrations (IC50) value of 6.02 ± 0.69 μM and about 2.6 times higher than that of Oxaliplatin. Further studies revealed that complex O3 decreased cellular mitochondrial membrane potential in a concentration-dependent manner and enhanced reactive oxygen species (ROS) accumulation by decreasing the expression of catalase, superoxide dismutase 2 (SOD2) and superoxide dismutase 3 (SOD3). Complex O3 induces mitochondrial dysfunction and upregulates the pro-apoptotic protein Noxa, ultimately leading to severe DNA damage. The upregulation of Phosphorylated histone protein H2AX (γ-H2AX) expression is clear evidence. In addition, O3 inhibits the expression of RAD51 protein and prevents DNA damage repair, thus overcoming drug resistance.

This strategy of combining bioactive molecules cannabidiol with platinum drugs to improve therapeutic efficacy and overcome drug resistance has been proven to be very effective and deserves further investigation.”

https://pubmed.ncbi.nlm.nih.gov/38490045/


“The cannabidiol was introduced into the platinum antitumor drugs, and the Pt(IV) complexes O1-O3 and C1- C3 were synthesized.

•Complex O3 is highly cytotoxic to all cancer cells and cannabidiol exerts a synergistic antitumor effect with Oxaliplatin.”

https://www.sciencedirect.com/science/article/abs/pii/S0162013424000382?via%3Dihub


Canonical DDR activation by EMT inducing agent 5-Fluorouracil is modulated by a cannabinoid based combinatorial approach via inducing autophagy and suppression of vimentin expression

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“Anastasis cascade including induction of Epithelial to Mesenchymal Transition (EMT), DNA repair, and stimulation of pro-survival mediators collectively exaggerate therapy resistance in cancer prognosis. The extensive implications of DNA-damaging agents are clinically proven futile for the rapid development of disease recurrence during treatment regime.

Herein we report a glycosidic derivative of Δ9-tetrahydrocannabinol (THC-9-OG) abrogates sub-toxic doses of 5-Fluorouracil (5FU) induced EMT in colon cancer cells nullifying DNA repairing mechanism. Our in vitro and in vivo data strongly proclaims that THC-9-OG could not only abrogated 5FU mediated background EMT activation through stalling matrix degradation as well as murine 4T1 lung metastasis but also strongly diminished Rad-51 repairing mediator along with stimulation of γ-H2AX foci formation.

The combinatorial treatment (5FU + THC-9-OG) in Apc knockout colorectal carcinoma model conferred remission of the crypt progenitor phenotype which was prominently identified in 5FU treatment. Mechanistically, we demonstrated that 5FU plus THC-9-OG significantly attenuated major EMT inducer Vimentin via extensive ROS generation along with autophagy induction via LC3B I-II conversion and p62 degradation in a p-ATM dependent manner. Additionally, Cannabinoid receptor CB1 was responsible for abrogation of Vimentin since we found increase in the expression of γH2AX and decrease in vimentin expression in CB1 agonist (ACEA) plus 5FU treated cells.

Nutshell, our results unveil a new direction of Cannabinoid based combinatorial approach to control background EMT along with robust enhancing of DNA damage potential of sub-toxic concentration of 5FU resulting immense inhibition of distant metastasis coupled with triggering cell death in vitro and in vivo.”

https://pubmed.ncbi.nlm.nih.gov/38490521/

https://www.sciencedirect.com/science/article/abs/pii/S0006295224001096?via%3Dihub

Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models

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“Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear.

This study substantiated CBD’s interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied.

Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 μM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD’s anxiolytic-like effects. Additionally, CBD’s effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus.

These findings offer novel insights for advancing the exploration of CBD’s anxiolytic-like and antipsychotic-like effects.”

https://pubmed.ncbi.nlm.nih.gov/38467272/

https://www.sciencedirect.com/science/article/abs/pii/S0304394024001009?via%3Dihub

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson’s disease and in comorbidity with psychiatric disorders

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“Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson’s diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson’s disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.”

https://pubmed.ncbi.nlm.nih.gov/38477419/

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13997

Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions

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“Background: Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB.

Methods: Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo.

Results: We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-mediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition.

Conclusions: WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.”

https://pubmed.ncbi.nlm.nih.gov/38461169/

“Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns. Our study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.”

https://pubmed.ncbi.nlm.nih.gov/26775260/