[Impact of dronabinol shortage on a population of chronic pain patients: A retrospective observational study]

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“Objective: A supply shortage of dronabinol occurred between December 2023 and February 2024, forcing chronic pain patients to discontinue this treatment. We assessed the impact of this shortage on patients in our hospital.

Method: A retrospective observational study of patients treated with dronabinol was conducted. Collected data included socio-demographic, pharmacological and clinical data. Pain intensity and its interference, the intensity of other pain dimensions (mood, relationship with others, etc.) and quality of sleep were collected before discontinuation (dronabinol dosage balanced, M0) and at the end of discontinuation (dronabinol stopped for several weeks, M3). The patient’s perception of his state of health evolution was collected at the end of the shortage.

Results: Health deterioration was reported by 86% of patients after 3 months of rupture. Pain intensity and its interference with patients’ daily lives increased significantly. Patients’ sleep deteriorated significantly. The number of patients with permanent pain increased 5-fold (n=2 at M0 and n=10 at M3). The number of patients with more than 20 painful attacks per 24hours increased 2-fold (n=2 at M0 and n=4 at M3).

Conclusion: Although data on the efficiency of dronabinol are currently limited, this supply disruption has had negative clinical consequences for our patients. With drug shortages multiplying in recent years, the marketing of new specialties and therefore the availability of therapeutic alternatives could help reduce the clinical impact of a possible new dronabinol shortage in these refractory chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/39824703/

https://www.sciencedirect.com/science/article/abs/pii/S0040595724002191?via%3Dihub

“Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns”

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

Cannabis use in Crohn’s disease: a systematic review and meta-analysis of randomized controlled trials (RCTs)

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“Objective: This meta-analysis aims to systematically evaluate the efficacy and safety of cannabis in the management of Crohn’s disease (CD) by synthesizing evidence from randomized controlled trials (RCTs). By adhering to the 2020 PRISMA guidelines and registering the study protocol with PROSPERO, this research intends to offer robust, evidence-based recommendations for healthcare practitioners on the therapeutic potential and clinical implications of cannabis use in CD management.

Methods: A literature search encompassing PubMed, Google Scholar, and the Cochrane Library was conducted to identify relevant RCTs comparing cannabis to placebo or standard therapy in CD patients. Inclusion criteria focused on outcomes such as remission rates, C-reactive protein (CRP) levels, quality of life (QoL), and adverse events (AEs). Statistical analysis using RevMan 5.3 involved weighted mean differences (MD) and 95% confidence intervals to compare outcomes between the cannabis and control groups.

Results: The meta-analysis revealed significant findings regarding the impact of cannabis on CD management. The cannabis group exhibited significantly higher clinical remission rates at 8 weeks compared to the control group, with low heterogeneity [MD = – 67.98; 95% CI: (- 100.68, – 35.29)]. However, a statistically significant improvement in QoL was observed in the placebo group compared to the cannabis-treated group [MD = 19.62; 95% CI (14.24 to 25.00)]. There was a non-significant lowering in serum CRP levels compared to the placebo group [MD: – 0.51; 95% CI: (- 1.05, 0.02)].

Conclusion: The study concludes that cannabis shows promise as a therapeutic option for CD, demonstrating higher remission rates and potential benefits for disease management. However, it also highlights the need for larger, standardized research studies to solidify conclusions regarding efficacy, safety, and biomarker responses in CD patients.”

https://pubmed.ncbi.nlm.nih.gov/39821383/

https://link.springer.com/article/10.1007/s11845-024-03844-w

Evaluation of the Antibacterial Potential of Ethanolic Cannabis sativa L. (Hang Kra Rog Phu Phan ST1) Extracts Against Human Pathogenic Bacteria

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“Background and Objective: Amid the escalating challenge of antibiotic resistance, the exploration of new sources has become essential, with plants serving as a promising reservoir of bioactive compounds.

Cannabis sativa has attracted significant research interest for its antimicrobial properties and broad applications in medicine, industry and nutrition.

This study aimed to investigate the antibacterial activity of ethanolic extracts from the stems and leaves of the Hang Kra Rog Phu Phan ST1 strain against twelve human pathogenic bacteria.

Materials and Methods: Stems and leaves from the Hang Kra Rog Phu Phan ST1 strain were subjected to ethanol extraction. The primary antibacterial activity of ethanolic extracts from Tanao Si Kan Dang RD1 was assessed using the disc diffusion method, while the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined via the broth microdilution method. The inhibition zone diameter (mm) was analyzed using Duncan’s Multiple Range Test (DMRT) with the SAS software.

Results: The findings revealed that the ethanolic extract from the leaves of Hang Kra Rog Phu Phan ST1 produced the largest inhibition zone diameter of 10.00 mm against <i>Bacillus subtilis</i> TISTR 008. The MIC and MBC of the leaf extract showed the lowest values of 0.09 and 0.19 mg/mL, respectively, recorded against <i>Staphylococcus aureus</i> TISTR 1466.

Conclusion: This is the first report on the antibacterial activity of the ethanolic extracts from the leaves and stems of Hang Kra Rog Phu Phan ST1, which offers potential benefits for developing natural antibiotic drugs to combat infections caused by the tested pathogenic bacteria.”

https://pubmed.ncbi.nlm.nih.gov/39820562/

https://scialert.net/abstract/?doi=pjbs.2025.1.7

Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis

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“Background: Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent.

Objective: The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.

Methods: Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured.

Results: Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone.

Conclusion: Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/39819647/

“In conclusion, our results corroborated previous findings but on kidney podocytes. We strongly suggest that the Lebanese Cannabis oil extract may be of significant therapeutic benefits against the renal complications of cisplatin. Thus, Lebanese COE produces its renoprotective effects partly through activating antiinflammatory and antiapoptoric mechanisms in podocytes.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00260-4

Cannabinoid-based Pharmacology for the Management of Substance Use Disorders

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“In the last two decades, the endocannabinoid system has emerged as a crucial modulator of motivation and emotional processing. Due to its widespread neuroanatomical distribution and characteristic retrograde signaling nature, cannabinoid type I receptors and their endogenous ligands finely orchestrate somatic and axon terminal activity of dopamine neurons.

Owing to these unique features, this signaling system is a promising pharmacological target to ameliorate dopamine-mediated drug-seeking behaviors while circumventing the adverse side effects of, for instance, dopaminergic antagonists.

Despite considerable preclinical efforts, an agreement on the efficacy of endocannabinoid-targeting compounds for treating drug substance use disorders in humans has not been reached. In the following chapter, we will summarize preclinical and clinical evidence addressing the therapeutic potential of cannabinoids and endocannabinoid-targeting compounds in substance use disorders.

To bridge the gap between animal and clinical research, we capitalize on studies evaluating the impact of endocannabinoid-targeting compounds in relevant settings, such as the management of drug relapse.

Finally, we discuss the therapeutic potential of novel cannabinoid compounds that hold promise for treating substance use disorders.”

https://pubmed.ncbi.nlm.nih.gov/39813001/

https://link.springer.com/chapter/10.1007/7854_2024_551

Plant-Derived Compounds in Hemp Seeds (Cannabis sativa L.): Extraction, Identification and Bioactivity-A Review

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“The growing demand for plant-based protein and natural food ingredients has further fueled interest in exploring hemp seeds (Cannabis sativa L.) as a sustainable source of and nutrition.

In addition to the content of proteins and healthy fats (linoleic acid and alpha-linolenic acid), hemp seeds are rich in phytochemical compounds, especially terpenoids, polyphenols, and phytosterols, which contribute to their bioactive properties.

Scientific studies have shown that these compounds possess significant antioxidant, antimicrobial, and anti-inflammatory effects, making hemp seeds a promising ingredient for promoting health. Since THC (tetrahydrocannabinol) and CBD (cannabidiol) are found only in traces, hemp seeds can be used in food applications because the psychoactive effects associated with cannabis are avoided.

Therefore, the present article reviews the scientific literature on traditional and modern extraction methods for obtaining active substances that meet food safety standards, enabling the transformation of conventional foods into functional foods that provide additional health benefits and promote a balanced and sustainable diet.

Also, the identification methods of biologically active compounds extracted from hemp seeds and their bioactivity were evaluated. Mechanical pressing extraction, steam distillation, solvent-based methods (Soxhlet, maceration), and advanced techniques such as microwave-assisted and supercritical fluid extraction were evaluated. Identification methods such as high-performance liquid chromatography (HPLC) and mass spectrometry (MS) allowed for detailed chemical profiling of cannabinoids, terpenes, and phenolic substances.

Optimizing extraction parameters, including solvent type, temperature, and time, is crucial for maximizing yield and purity, offering the potential for developing value-added foods with health benefits.”

https://pubmed.ncbi.nlm.nih.gov/39795183/

https://www.mdpi.com/1420-3049/30/1/124

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

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

Genotoxicity study of Cannabis sativa L. extract

Toxicology Reports

“Cannabis sativa L., a member of the Cannabaceae family, has been thoroughly investigated for its diverse therapeutic properties, primarily attributed to cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Secondary, metabolites like terpenes also exhibit pharmacological effects.

This study examined the genotoxicity of a whole Cannabis sativa flower extract 160.32 mg/mL using three OECD-recommended protocols: the Ames test, micronucleus test, and comet assay. Five groups of six Wistar rats were used. Three doses of the extract (500, 1000, and 2000 mg/kgbw) or negative control (placebo) were administered orally, while cyclophosphamide monohydrate (20 mg/kgbw) was used as a positive control via intraperitoneal injection. Blood was collected for the comet test, and the animals were euthanized for bone marrow collection for the micronucleus test.

The Cannabis extract did not increase the number of revertant bacterial colonies at (375, 250, 125, and 62.5 μg/plate) in TA100 or TA98, nor did it affect the number of micronucleated polychromatic erythrocytes (MNPCEs) or the ratio of polychromatic to normochromatic erythrocytes (PCEs/NCEs). It also did not alter the index or frequency of DNA damage in hematopoietic cells.

These results suggest no genotoxic effects, supporting its potential therapeutic use.”

“Cannabis sativa extract shows no significant genotoxic effects in tested models.”

“Study supports therapeutic use of whole Cannabis sativa extract.”

https://www.sciencedirect.com/science/article/pii/S2214750024002476

https://pubmed.ncbi.nlm.nih.gov/39816045/

https://www.forbes.com/sites/emilyearlenbaugh/2024/12/30/cannabis-study-finds-no-genotoxic-effects/

Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study

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“Background: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP.

Methods: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analysed.

Results: Among 826 eligible patients ≥18 years old, 529 (64%) were included for data analysis at first follow-up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60 ± 15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<0.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intention-to-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis.

Conclusion: Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids.

Significance: The findings in this retrospective study conducted in a real-world clinical setting suggest a favourable safety profile of cannabinoids. Moreover, one-sixth (intention-to-treat) and one-third (per-protocol) of patients with chronic pain refractory to conventional analgesics, or experiencing intolerable adverse effects, benefited significantly from therapy with oral cannabinoid regimens. Combination of THC and CBD seems overall more effective than cannabinoid monotherapy. Conduction of randomized controlled trials investigating safety and efficacy of cannabinoid therapy to diagnosis specific patient subgroups with comparable clinical and pathophysiological chronic pain characteristics is warranted, hence contributing further to the process of clinical evidence clarification currently in progress.”

https://pubmed.ncbi.nlm.nih.gov/36394124/

“In conclusion, oral cannabinoid therapy in general appears to be safe and effective for relief of chronic pain in some patients, including a subset of patients with cancer-related pain (9%), not responding adequately to conventional treatment regimens or experiencing intolerable AEs. Moreover, beneficial effects on sleep and QoL were reported by the patients receiving oral cannabinoid therapy, although the assessment was not performed in a validated manner. Hence, our study confirms previously reported findings related to patients with chronic pain receiving oral cannabinoid therapy and in that way the study contributes further to the evidence pyramid at the level of observational studies. “

https://onlinelibrary.wiley.com/doi/10.1002/ejp.2054