Real-world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies

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“Objective: Highly purified cannabidiol (CBD) is approved as adjunctive therapy for seizures associated with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC), although its role in other developmental and epileptic encephalopathies (DEEs) remains unexplored. The aim of this study was to assess the real-world use, efficacy, and safety of CBD across a broad cohort of patients with DEEs, including off-label indications.

Methods: In this retrospective study, we evaluated 107 patients with DEEs treated with CBD for ≥3 months between 2020 and 2024. Data on seizure frequency, tolerability, retention, and non-seizure outcomes were collected. Efficacy was defined as ≥50% or ≥75% seizure reduction. Statistical analyses explored predictors of response.

Results: Patients had LGS (55.1%), DS (16.8%), TSC (8.4%), or other DEEs (19.6%), with a genetic etiology in 56.1%. At a median follow-up of 20 months, 69% achieved ≥50% seizure reduction, and 21% achieved ≥75% reduction. Patients with LGS, TSC, and other DEEs showed higher efficacy and retention rates compared to DS. Genetic or unknown etiology was associated with better outcomes (p = 0.011). Combination with valproate was associated with reduced efficacy (p = 0.006), while combination with clobazam had no significant effect on efficacy nor safety. Non-seizure improvements included increased alertness (56%), improved sleep quality (25%), and enhanced motor performance (14%). Adverse events occurred in 33.6%, mostly mild and transient; 9% discontinued due to side effects.

Significances: This study confirms the effectiveness and good tolerability of CBD in a real-world DEE population, including off-label use. These findings support expanding CBD indications and underscore the need for prospective studies targeting both seizure and developmental outcomes.

Plain language summary: This study looked at the use of cannabidiol (CBD), a cannabis-based medicine, in 107 people with severe forms of epilepsy called developmental and epileptic encephalopathies (DEEs). With CBD add-on, about two-thirds of patients had fewer seizures, and some caregivers noticed improvements in alertness, sleep, or movement. Most patients tolerated the treatment well, but some experienced side effects, and a few had to stop taking it. While the results are promising, more research is needed to confirm how effective and safe CBD is for different types of DEEs, especially those not currently approved for treatment with CBD.”

https://pubmed.ncbi.nlm.nih.gov/41165013/

“After a median follow-up of 20 months, CBD was globally effective and safe in 107 patients with LGS, DS, TSC, and other DEEs.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70149

The Therapeutic Potential of Cannabidiol in Skin Conditions

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“Background: Dermatological disorders can have a negative impact on quality of life. Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis sativa L. plant. It has multiple molecular targets, many of which are expressed in the skin, and may have therapeutic potential in several skin conditions.

Aims: This review aims to provide an overview of preclinical and clinical studies of CBD in dermatological disorders.

Methods: Literature searches were conducted using databases including PubMed and Google Scholar using the search terms: (‘cannabidiol’ OR ‘CBD’) AND ‘skin’, ‘acne’, ‘psoriasis’, ‘dermatitis’, and ‘wound healing’. Studies were included if they were original research articles focused on CBD and skin conditions.

Results: Preclinical evidence suggests that CBD may have therapeutic potential for the treatment of a variety of skin conditions, while evidence for skin moisturizing properties suggests possible cosmetic benefits. To date, there is limited clinical evidence that CBD may be beneficial in the treatment of acne, dermatitis, and psoriasis, as well as for cosmetic purposes including improving skin hydration, elasticity, and protection against skin aging.

Conclusions: There is some evidence indicating the therapeutic potential of CBD for a variety of skin conditions, including acne, dermatitis, and psoriasis, and possible utility for cosmetic purposes. Several clinical trials involving the topical application of CBD for skin conditions are currently ongoing, and the results of these trials will be important in determining the therapeutic potential of CBD.”

https://pubmed.ncbi.nlm.nih.gov/41178006/

“CBD may have therapeutic potential for the treatment of a variety of skin conditions such as acne, psoriasis, and dermatitis, with its anti-inflammatory, antimicrobial and potential anti-pruritic effects.”

https://onlinelibrary.wiley.com/doi/10.1111/jocd.70527

Selective activation of cannabinoid receptors by cannabis terpenes

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“Terpenes are aromatic compounds abundantly present in plants, including cannabis. Emerging preclinical and clinical evidence indicates that certain terpenes exhibit pharmacological effects in various physiological and psychological conditions. Yet, their molecular mechanisms of action, particularly in cannabis preparations, remain poorly understood.

We have previously reported results of activating cannabinoid receptor type 1 (CB1R) by several terpenes that are most common in cannabis. Here we employed the same Xenopus oocytes functional heterologous expression system to complement the CB1R data and to study the activation of the cannabinoid receptor type 2 (CB2R) by sixteen individual cannabis terpenes and by terpene mixtures.

Employing receptor- induced GIRK currents as a measure for receptor activation, dose-dependent responses were found for many of these terpenes, reaching a maximal response of about 10-60 % the activation elicited by THC. Terpenes’ apparent EC50 at CB1R and CB2R were similar to, or lower than those obtained for THC at the same apparatus, suggesting lower efficacy but equivalent or even improved potency. At CB2R, multiple terpenes reach ‘clinical effect level’ at concentration equivalent or lower than those of THC (≥ 0.1 µM). Per a given receptor, terpenes differ in their activation level. Additionally, terpenes act differently at the two receptors, giving room for receptor selectivity.

Our results support the role of cannabis terpenes as partial agonists at CB1R and CB2R and provide the basis for selecting terpenes or terpene mixture for affecting physiological functions involving these receptors. These results may further contribute to our understanding of terpenes’ medicinal effects.”

https://pubmed.ncbi.nlm.nih.gov/41173057/

“Terpenes, a vast and chemically diverse class of organic compounds, are widely recognized for imparting characteristic aromas and flavors to plants, including Cannabis sativa. More than 200 terpenes have been identified in the cannabis plant, with approximately 20 being the most prevalent, including myrcene, limonene, pinene, linalool, terpinolene, β-caryophyllene, and humulene.”

“Collectively, these findings suggest a pharmacological basis for incorporating specific terpenes into ECS-focused product design and warrant further research into their tissue-specific activity, and synergistic potential when used in combination with cannabinoids or other therapeutic agents. The broad availability and favorable safety profiles of many terpenes further support their potential as accessible, scalable, and customizable tools in the modulation of endocannabinoid signaling.”

https://www.sciencedirect.com/science/article/pii/S0006295225007634?via%3Dihub

Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice

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“The pharmacological potential of industrial hemp (Cannabis sativa) has been widely studied. However, the majority of studies have focused on cannabidiol, isolated from the inflorescence and leaf of the plant.

In the present study, we evaluated the anti-diabetic potential of hemp root water (HWE) and ethanol extracts (HEE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice.

The administration of HWE and HEE ameliorated hyperglycemia and improved glucose homeostasis and islet function in STZ-treated mice (p < 0.05). HWE and HEE suppressed β-cell apoptosis and cytokine-induced inflammatory signaling in the pancreas (p < 0.05). Moreover, HWE and HEE normalized insulin-signaling defects in skeletal muscles and apoptotic response in the liver and kidney induced by STZ (p < 0.05).

Gas chromatography-mass spectrometry analysis of HWE and HEE showed possible active compounds which might be responsible for the observed anti-diabetic potential.

These findings indicate the possible mechanisms by which hemp root extracts protect mice against insulin-deficient diabetes, and support the need for further studies geared towards the application of hemp root as a novel bioactive material.”

https://pubmed.ncbi.nlm.nih.gov/37175224/

“In conclusion, the present study demonstrated that HWE and HEE counteracted STZ-induced hyperglycemia and islet dysfunction via the inhibition of β-cell apoptosis in mice. The inhibition of β-cell apoptosis by HWE and HEE was associated with the suppression of cytokine-induced inflammatory signaling. In addition, HWE and HEE attenuated apoptosis in the liver and kidney and improved insulin signaling in skeletal muscle. These findings provide novel scientific evidence for the pharmaceutical application of hemp root, which has been considered a minor part of the plant in Cannabis-based medicinal and functional food studies.”

https://www.mdpi.com/1420-3049/28/9/3814

Hemp seed protein exerts its hypoglycemic and hypolipidemic effects through degradation into short peptides

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“This study aimed to investigate the effects of hemp seed protein (HSP) on glucose and lipid metabolism and its possible mechanisms.

In a high-fat-induced mouse obesity model, HSP supplementation significantly reduced serum TC (Total cholesterol), TG (Triglycerides), and LDL-C (Low-density lipoprotein cholesterol) levels by 28 % (P < 0.001), 34 % (P < 0.001), and 40 % (P < 0.001) respectively, compared to the model group, while HDL-C (High-density lipoprotein cholesterol) increased by 77 % (P < 0.001).

Hepatic lipid accumulation was alleviated, and glucose tolerance and insulin sensitivity improved. In vitro, HSP hydrolysates exhibited stronger inhibitory activity against pancreatic α-amylase and lipase than HSP itself. Network pharmacology and molecular docking identified three hemp seed peptides from HSP hydrolysates, which interacted with AKT1, PPARG, and HMGCR.

These findings suggest that the metabolic regulatory effects of HSP are mediated by bioactive peptides that inhibit digestive enzymes and regulate AMPK-AKT1/PPARG/HMGCR metabolism pathway, providing insights into its potential as a functional health food.”

https://pubmed.ncbi.nlm.nih.gov/40279904/

https://www.sciencedirect.com/science/article/pii/S0308814625016577?via%3Dihub

A randomized clinical trial of low-dose cannabis extract in Alzheimer’s disease

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“Preclinical and clinical evidence suggest that low-dose cannabinoids could ameliorate Alzheimer’s disease (AD) signs and symptoms.

We designed this trial to evaluate the safety and efficacy of low-dose THC-CBD balanced cannabinoid extract in the treatment of patients with AD-associated dementia.

The objective of this phase 2 trial was to evaluate the safety and efficacy of a balanced THC-CBD cannabinoid extract for symptomatic patients with AD.

A Phase 2, randomized, double-blind, placebo-controlled, clinical trial including patients between 60 and 80 years-old diagnosed with AD-associated dementia. For 26 weeks, participants orally received either placebo or THC-CBD extract (0.350 mg/THC and 0.245 mg/CBD), daily.

At week 26, Mini-Mental State Exam total score was significantly higher in cannabis- when compared to placebo-treated patients, which was assessed using the mixed model analysis. No significant difference was detected between placebo and cannabis groups in terms of secondary outcomes and adverse events incidence.

To this date, this is the longest clinical trial evaluating cannabinoids effects on AD patients. We initially demonstrate that low-dose THC-CBD potentially can be an effective and safe therapeutic option for AD-related dementia. Nonetheless, larger and longer trials are necessary to confirm this finding and establish cannabinoid administration as therapy for AD dementia.”

https://pubmed.ncbi.nlm.nih.gov/41160460/

https://journals.sagepub.com/doi/10.1177/13872877251389608

Measuring the Effects of Cannabis on Anxiety and Depression Among Cancer Patients

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“Introduction: Cancer patients are increasingly turning to cannabis products to modulate physical and psychological symptoms despite limited evidence supporting their efficacy. We aimed to explore cancer patients’ self-reported anxiety and depression symptoms in response to cannabis use.

Methods: This longitudinal study examined how patient-reported anxiety and depression symptoms varied according to the dose, ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD), and route of administration of cannabis products among cancer patients. Change in self-reported anxiety and depression symptoms was evaluated in 1962 cancer patients after 30 days of enrollment in the Minnesota Medical Cannabis Program.

Results: Anxiety scores improved more in patients taking higher doses of CBD (> 14.3 mg/day) compared to those taking lower doses (< 4.6 mg/day) and among patients using enteral cannabis products. Depression scores also improved more for patients taking enteral products.

Discussion: Anxiety scores varied according to the dose of cannabis, the ratio of THC to CBD, and the route of administration of cannabis products. In contrast, depression scores only varied according to the route of administration.

Conclusions: This study of cancer patients in Minnesota suggests that patterns of cannabis use that include relatively higher doses of CBD taken enterally may improve the quality of life of cancer survivors who report anxiety and depression. This study constructs a foundation for future research to improve the tailoring of cannabis-related educational materials to patients’ needs and inform the training of healthcare professionals on how to recommend cannabis products for cancer survivors.”

https://pubmed.ncbi.nlm.nih.gov/41163433/

“Given the high prevalence of anxiety and depression symptoms among cancer patients, along with the potential for cannabis products to alleviate these serious psychological symptoms, this study suggests specific patterns of use that may improve the quality of life of cancer survivors.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.71342

Phytochemical Profile, Extraction and Characterization of Bioactive Compounds from Industrial Hemp (Cannabis sativa L.) Felina 32 Variety

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“An efficient method for the simultaneous extraction of cannabinoids and terpenes from the leaves and flowers of Cannabis sativa L. (var. Felina 32) was developed.

Extraction parameters, including solvent type, temperature, and pressure, were optimized, revealing that hexane enables high-yield cannabinoid recovery. Moreover, terpene composition was influenced by the extraction temperature. Two extracts with the highest cannabinoid content were selected for further study, Feli1 (64.76%) and Feli2 (61.32%), both obtained using hexane. Feli1, extracted at -55 °C, had a monoterpene-to-sesquiterpene ratio of 16.7% to 83.3%, while Feli2, extracted at 25 °C, showed a higher monoterpene content (25.2%) and lower sesquiterpene content (74.8%).

Both extracts demonstrated selective antiproliferative activity against cancer cell lines, with reduced toxicity toward normal breast epithelial cells (MCF-10A). Feli2 showed slightly stronger antiproliferative effects, likely due to its higher monoterpene content. At low concentrations, both extracts stimulated the growth of MV4-11 leukemia and MDA-MB-468 triple-negative breast cancer (TNBC) cells, while higher concentrations led to growth inhibition. These stimulatory effects were weaker than those observed for pure Δ9-THC or CBD.”

https://pubmed.ncbi.nlm.nih.gov/41157165/

https://www.mdpi.com/1420-3049/30/20/4148

Cannabidiol and Parkinson’s disease: Investigating receptor interactions and their therapeutic implications

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“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.”

https://pubmed.ncbi.nlm.nih.gov/41161354/

“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.”

https://www.sciencedirect.com/science/article/abs/pii/S016372582500155X?via%3Dihub

Venous Thromboembolism and Coagulation Biomarker Changes in Trauma Patients Using Cannabis

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“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.”

https://pubmed.ncbi.nlm.nih.gov/41160914/

https://journals.sagepub.com/doi/10.1177/00031348251393925