“Cannabidiol (CBD) is one of the major active constituents among the several hundreds of compounds found in the cannabis plant. It is a non-psychoactive compound known for its anti-inflammatory, neuroprotective, antidepressant and anxiolytic effects.
In preclinical studies it has shown to be effective, safe, and well-tolerated in mitigating the symptoms associated with Parkinson’s disease (PD) and other neurodegenerative diseases. However, the mechanism of action is not fully characterised.
CBD is postulated to exert its therapeutic effects through its interaction with the endocannabinoid system (ECS), and via interaction with a large array of non-cannabinoid receptors, neurotransmitters, and enzymes. These interactions are complex and are influenced by cell type, concentration and exposure time.
The lack of specificity for a single receptor system makes CBD an intriguing therapeutic compound and enables it to influence multiple pathways. This broad interaction goes beyond its beneficial therapeutic effects and could lead to potential adverse effects. Detailed understanding of the versatility and complexity of how CBD exerts its effect is required so that the true potential as a therapeutic option can be realised.”
“Most of the available preclinical studies investigating the effects of CBD in PD have demonstrated predominantly positive outcomes, with only a few reporting mild adverse effects such as diarrhea. The positive therapeutic effects include significant reductions in tremor and rigidity, along with improvements in sleep and overall quality of life.”
“Prior studies showed contradictory results regarding the impact of cannabinoids on thromboembolic events in trauma patients. The goal of the study was to investigate the association of cannabinoids to venous thromboembolism (VTE).
Records for all trauma patients admitted to the level one trauma center aged 14 years and above between October 18, 2019 and December 29, 2023 with urine drug screening (UDS) and blood alcohol concentration (BAC) results were included for collection. Patients testing positive for cannabinoids and patients testing negative for cannabinoids that were also negative for other illicit drugs and for alcohol were included in the final analysis primarily examining VTE occurrence, along with secondary outcomes in mortality, hospital length of stay, discharge disposition, and coagulation-related biomarkers. One-to-one propensity score matching analysis was performed.
Patient population was mostly white (78.8%), mostly male (71.5%), had a median age of 46, and a median ISS of 17. Out of 302 patients, 226 tested negative and 76 tested positive for cannabinoids. In the matched analysis, no difference was observed in rates of VTE (7.4% vs 4.4%, P = .683) or in platelet count (median [IQR], 260 [215-304] vs 260 [211-306], P = .790). No significant differences were found between the groups on coagulation profiles, complications, or other outcomes.
This study failed to identify significant differences between coagulation-related biomarkers and VTE incidence of adolescent and adult, trauma patients who tested positive for cannabinoids vs those that tested negative for cannabinoids.”
“Background/Objectives: Hemp (Cannabis sativa L. subsp. sativa) is a plant within the Cannabis sativa species and utilized for several applications, including antioxidation, antihypertension, and anti-inflammation. To our knowledge, no prior study has assessed the acute and sub-chronic oral safety of hemp leaf oil in Sprague-Dawley rats under Thailand-compliant THC levels. This study investigates the acute and sub-chronic effects of Hemp leaf oil (HLO) on the heart, liver, and kidneys of male and female Sprague-Dawley rats.
Methods: Six-week-old male and female Sprague-Dawley rats were administered HLO (1.5 mL/kg) intragastrically, either as a single dose or a repeat dose over 28 days.
Results: No changes in body or organ weights were observed following acute and sub-chronic HLO administration in sex-matched groups. Moreover, blood pressure and heart rate remained comparable across groups after acute and sub-chronic HLO treatment. Both acute and sub-chronic administration of HLO did not influence electrolyte balance, liver enzymes, total protein, albumin, blood urea nitrogen, or creatinine levels. Hematoxylin and eosin staining revealed the normal morphology of the heart, liver, and kidneys in rats subjected to HLO, during both acute and sub-chronic treatment.
Conclusions: In conclusion, our data suggested that both acute and sub-chronic administration of HLO at 1.5 mL/kg could be safe for the vital organs. These findings support the potential use of HLO in therapeutic applications, particularly in scenarios when the safety of essential organs is at stake.”
“These results support the safety effect of HLO treatment and the prospective application of HLO in preclinical research or clinical settings. This safety profile supports the extension of research into many domains, including dose-escalation studies and extended chronic toxicity assessments. This will strengthen the evidence base for any future clinical development of HLO.”
“Background/Objectives: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evidence suggests that cannabis, acting via the endocannabinoid system, may provide analgesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. Inhaled cannabis exhibits rapid onset pharmacokinetics (within minutes, lasting 2-4 h) due to pulmonary absorption, targeting CB1 and CB2 receptors to modulate pain and inflammation.
Methods: In this prospective, observational study, 52 patients with confirmed painful DN, unresponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, <1% CBD), titrated individually. Assessments occurred at baseline and annually for 5 years, including the Brief Pain Inventory (BPI) for pain severity and interference; the degree of pain relief; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score; HbA1c; and medication usage. Statistical analyses used repeated-measures ANOVA, Kruskal-Wallis tests, Welch’s t-tests, and Pearson’s correlations via Analyze-it for Excel.
Results: Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p < 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p < 0.001), LANSS score (19.4 ± 3.8 to 10.2 ± 6.4, p < 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p < 0.001). Analgesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r = 0.74, p < 0.001) and negatively with narcotic use (r = -0.43, p < 0.001) and pain interference (r = -0.43, p < 0.001). No serious adverse events were reported; mild side effects (e.g., dry mouth or euphoria) occurred in 15.4% of patients.
Conclusions: Inhaled cannabis showed sustained pain relief, improved glycemic control, and opioid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings are associative due to the observational design, and randomized controlled trials (RCTs) are needed to confirm efficacy and determine optimal usage, addressing limitations such as single-center bias and small sample size (n = 52). Future studies incorporating biomarker analysis (e.g., endocannabinoid levels) could elucidate mechanisms and enhance precision in cannabis therapy.”
“Inhaled cannabis add-on therapy mitigated symptoms of diabetic neuropathy over the course of a five-year observation period. Some reduction in glycosylated hemoglobin is observed as well as major reduction in the need for other prescription medications, including opiates and opioids. It is possible to state the following: (1). Inhaled cannabis significantly reduced pain and neuropathic symptoms over 5 years. (2). It decreased opioid use, supporting an opioid-sparing effect. (3). HbA1c improvements suggest a metabolic benefit, though causality is unproven. (4). No serious adverse events occurred, with mild effects in 15.4% of patients. (5). RCTs are needed to confirm efficacy and address accessibility barriers. Integration of objective pain assessment tools, such as salivary biomarker devices, could enhance the precision and reproducibility of cannabis therapy outcomes in DN.”
“Background/objectives: Parents of autistic children often face behavioral and participation challenges of their children, leading them to make accommodations to maintain a stable daily family routine. These family accommodations (FA) involve adapting family routines, actively engaging with the child’s support needs and symptoms, and avoiding specific situations.
Methods: This open-label, mixed-methods study investigated the impact of CBD-rich cannabis treatment on FA. In the quantitative phase, analyses included 44 parents (from 87 initially recruited) who had complete FAS-RRB data at baseline, 3 months, and 6 months. In the following qualitative phase, 15 parents from the full sample participated in semi-structured interviews.
Results: Quantitative results showed reductions in FA frequency and parental distress at 3 and 6 months. Qualitative findings revealed positive changes in family routines, enhanced well-being, and improved parental engagement in meaningful activities and social interactions.
Conclusions: This study provides preliminary evidence that CBD-rich cannabis treatment may reduce family accommodation (FA) and parental distress, while improving family routines and well-being. However, given the open-label design and observed adverse events and withdrawals, the findings should be interpreted with caution.”
CBD-rich cannabis treatment over 6 months was associated with reduced family accommodation (FA) and parental distress in families of autistic children.
Qualitative findings showed improved family routines, parental well-being, and greater engagement in meaningful activities and social interactions.
What are the main findings?
Implications
CBD-rich cannabis treatment may reduce FA and parental distress, while improving family routines and well-being.
These results provide preliminary support for CBD-rich cannabis treatment in autistic children, though further controlled studies are needed.”
“Background: Perioperative tobacco use has been identified as an independent risk factor for adverse events after total hip arthroplasty (THA). It is unknown if perioperative cannabis users share similar levels of risk for adverse events after THA.
Methods: Patients undergoing THA were identified from the 2010 to 2021 PearlDiver M151 administrative data set. Patient subcohorts were categorized based on presence or absence of cannabis and/or tobacco use, as determined by coding. These subcohorts were equally matched based on patient age, sex, and Elixhauser Comorbidity Index scores to form groups of nonusers, tobacco users, tobacco and cannabis users, as well as cannabis users. The incidences of adverse events within 90 days postoperatively were obtained and compared using univariate and multivariate analyses that controlled for age, sex, and Elixhauser Comorbidity Index. Bonferroni correction was applied.
Results: Of 494,431 THA patients, nonusers were 442,000 (89.40%), tobacco users 46,925 (9.50%), tobacco and cannabis users 3,390 (0.69%), and cannabis users 2,116 (0.43%). After matching, there were 1,897 in each group. By multivariate analyses, tobacco-only users were at significantly greater risk of severe adverse events, sepsis, and pneumonia (P < 0.001 for each). Tobacco and cannabis users were at significantly greater risk of severe adverse events, myocardial infarction, pneumonia, and readmission (P < 0.001 for each). Conversely, cannabis-only users were not at significantly greater risk for any of the combined or individual adverse events assessed.
Discussion: This study confirmed that THA patients with tobacco-only use were at greater risk of perioperative adverse events and that these were relatively similar to those with concurrent tobacco and cannabis use. However, cannabis-only users were not at greater risk, a finding that is of clinical interest given the evolving access and increasing use of this agent.”
“Cannabidiol (CBD) is a non-psychotropic compound found in plants of the Cannabis genus, extensively studied for its therapeutic potential. Research has shown that CBD possesses anti-inflammatory, antioxidant, and regenerative properties, and may contribute to the recovery of neural and bone tissues.
In light of the aging population and the resulting rise in neurodegenerative and osteodegenerative conditions, exploring novel therapeutic strategies that promote cellular regeneration is increasingly important.
This review aims to compile and critically analyze key studies published in recent decades regarding the effects of CBD on the regeneration of the central and peripheral nervous systems, as well as bone tissue.
Findings from in vivo studies indicate that CBD can attenuate inflammatory responses, inhibit oxidative stress, and modulate cellular pathways involved in tissue repair, thereby supporting neuronal and bone regeneration. Moreover, evidence suggests that CBD may protect cells from structural damage, enhancing the functional recovery of affected tissues.
Despite scientific advances highlighting cannabidiol as a promising agent for bone and nerve regeneration, its therapeutic application still faces significant limitations. The primary challenge lies in the lack of robust clinical trials in humans, as most existing evidence is derived from in vitro and in vivo studies, making it difficult to confirm its efficacy and safety in clinical contexts. Additionally, CBD’s low bioavailability-due to first-pass hepatic metabolism-hinders dose standardization and reduces the predictability of therapeutic outcomes.
Compounding these issues are regulatory constraints and the persistent social stigma surrounding cannabis-derived compounds, which further impede their integration and acceptance in regenerative medicine. Therefore, future research is essential to validate the therapeutic benefits of CBD and to establish its clinical applicability in treating neurological and bone disorders.”
“Collectively, these effects underscore the potential of CBD as a regenerative agent in pathological conditions related to aging, trauma, and neurodegenerative or musculoskeletal disorders. This review offers a comprehensive synthesis of current findings, emphasizing the innovative potential of cannabidiol (CBD) as a minimally invasive and multifunctional therapeutic strategy for the regeneration of nerve and bone tissues.”
“Background/Objectives: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effects against the SARS-CoV-2 virus.
Methods: Compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues, were evaluated in vitro against SARS-CoV-2 to a antiviral activity and inhibitory effect against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect affecting the interaction between the receptor-binding domain (RBD) protein and/or ACE2 was evaluated using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of the compounds after 3 days of treatment.
Results: Compounds PQM-243 and PQM-249 exhibited IC50 values of 0.0648 ± 0.041 µM and 0.2860 ± 0.057 µM against SARS-CoV-2 with a selective index of >1543.21 and 349.65, respectively, and IC50 values of 12.1 nM and 13.3 nM, respectively, against ACE2. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational studies suggest that these new compounds are potent direct anti-SARS-CoV-2 agents, capable of reducing both virus viability and its invasive ability in the host cells by reducing the interaction between RBD and ACE2. It was also demonstrated that even when administered by the oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Our data suggests that both compounds can act as potent direct anti-SARS-CoV-2 agents, reducing both viral viability and host cell entry. In addition, they exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally.
Conclusions: Overall, these findings support further investigation of PQM-243 and PQM-249 as promising antiviral and anti-inflammatory multi-target prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases.”
“Taken together, our data suggests that PQM-243 and PQM-249—two newly synthesized, easily accessible, and structurally simplified CBD-based compounds—can act as potent direct anti-SARS-CoV-2 agents, capable of reducing both viral viability and host cell entry by inhibiting the interaction between the viral receptor-binding domain (RBD) and the ACE2 receptor. Notably, both compounds exhibited a significant multi-target-directed pharmacological profile, demonstrating not only virucidal activity but also the ability to reduce SARS-CoV-2-induced lung inflammation when administered orally.”
“As a psychoactive drug, marijuana is used for recreational purposes. Given its addictive nature and the serious damage it causes to both individual health and social stability, marijuana has been banned in most countries worldwide. In recent years, with the continuous improvement of basic research, researchers have discovered the vital role of cannabinoids, the primary active ingredient in marijuana, in multiple human systems.
Research found that cannabinoids play roles in regulating immune system function and have therapeutic potential in immune system-related diseases.
However, the use of cannabinoids still poses certain hazards. For instance, the abuse of cannabinoids by pregnant women can exert certain impacts on fetal nervous system development; cannabinoids use can lead to adverse reactions such as dizziness, nausea, and dry mouth. Moreover, there are still numerous contradictions in current research on the effects of cannabinoids, and the mechanisms by which cannabinoids exert protective effects in certain diseases remain unelucidated.
In this review, we systematically discuss the endocannabinoid system and summarize the molecular and cellular bases of cannabinoid function in the immune system, and elucidate the effects of cannabinoids on immune system-related diseases.”
“These findings collectively demonstrate the protective roles of CB1 agonists in immune system-related diseases.”
“These findings underscore the broad therapeutic efficacy of CB2 agonists in immune system-related diseases.”
“Cannabinoids exert immunoregulatory effects by inducing the apoptosis of immune cells, inhibiting immune cell proliferation, suppressing the production of proinflammatory cytokines, and regulating the functions of immune cells such as B cells, NK cells, and Treg cells.”
“Immunosuppression within the tumor microenvironment (TME) is a major obstacle for effective cancer immunotherapy. This is largely driven by myeloid suppressor cells, specifically Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs), which create an environment that inhibits the immune response. The presence of these cells is strongly correlated with poor patient outcomes and resistance to treatment, highlighting the need for new strategies to mitigate their effects.
In this study, we investigated the therapeutic potential of Cannabidivarin (CBDV), a less-studied non-psychoactive cannabinoid, to reprogram these immunosuppressive cells.
We found that CBDV directly targets myeloid suppressor cells, significantly impairing their immunosuppressive function both in vitro and in vivo. Mechanistically, CBDV reduces the key immunosuppressive markers inducible, Nitric Oxide Synthase (iNOS) and Arginase-1 (Arg-1) in murine MDSCs and promotes the differentiation of TAMs into M1-like macrophages.
This shift in myeloid cell function leads to restored CD8 + T-cell proliferation and activation. Furthermore, our results show that CBDV treatment in tumor-bearing mice reduces tumor progression and improves the anti-tumor immune response within the TME. We also confirmed the clinical relevance of our findings, demonstrating that CBDV effectively reduces the immunosuppressive phenotype of human-derived myeloid cells.
Altogether, these results establish CBDV as a new immunotherapeutic agent that directly neutralizes myeloid suppressor cells, thereby enhancing the immune system’s response against cancer.”
