Author Archives: David

Cannabis oil in treating Parkinson’s disease: improvement of motor and non-motor symptoms: a case report

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“Parkinson’s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to a reduction in the production of dopamine. Medication with levodopa becomes less effective as the disease progresses. Despite the excellent results observed in clinical practice with the medicinal use of Cannabis in the treatment of PD, the level of scientific evidence is still limited due to the small number of studies published in this field.

We present the case of a 77-year-old man diagnosed 22 years ago with PD in an advanced stage, with significant bradykinesia, tremor, and rigidity along with the inability to maintain an upright position and walk, exacerbated by a femur fracture. He also had advanced dysphagia, resulting in a gastrostomy. Although lucid, he showed no interest in conversation and tended to become depressed and isolated. He used Prolopa® with no satisfactory therapeutic response.

After starting treatment with Cannabis sativa oil, he is now able to walk around the house frequently and eat pasty food regularly without choking or broncho-aspiration episodes. There has also been a significant improvement in non-motor symptoms; he is more active, cheerful, communicative, and attentive to his surroundings.

Further studies are needed to elucidate these results and the mechanisms of action of cannabinoids through which they exert possible neuroprotective and neuroreparative effects.

These compelling results suggest that cannabis oil may offer a valuable and effective therapeutic option for individuals with Parkinson’s disease.”

https://pubmed.ncbi.nlm.nih.gov/39841751/

“Considering Parkinson’s disease a neurodegenerative process, in this report we present a unique case where, in addition to slowing the progression of the disease, there was recovery of motor and cognitive functions in a patient with advanced stage Parkinson’s disease, after starting treatment with full-spectrum cannabis oil.”

https://www.scielo.br/j/bjb/a/nqQFzz3NtnydWM8KWdfYyWz/?lang=en

The proof is in the pudding: patient engagement in studying cannabidiol in mild cognitive impairment

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“Background: Patient engagement (PE) in clinical trials has gained importance yet remains uncommon, particularly in patients with mild cognitive impairment (MCI), a critical precursor to Alzheimer’s disease (AD). Cannabidiol (CBD) shows potential in slowing MCI progression due to its neuroprotective and anti-inflammatory properties. In CBD research, PE is underutilized too. To design a study on CBD for MCI, we administered an online survey to individuals with MCI to better understand their preferences for trial setup and outcomes.

Methods: We asked 209 individuals with MCI to complete an online survey assessing (i) willingness to participate in a trial using CBD; (ii) importance of improvements in various domains; (iii) acceptance of adverse events (AEs); (iv) reasons for AE-related dropout; (v) willingness to undergo blood sampling and lumbar puncture to assess AD pathology; and (vi) willingness to participate in a trial with a 50% chance of receiving a placebo. Data were analyzed with descriptive statistics.

Results: N = 118 agreed to participate and N = 88 completed the survey. Participants prioritized improvement in cognitive abilities (87.5%), followed by quality of life (63.6%), daily activities (55.7%), sleep (55.7%), pain (52.3%), mood (52.3%), behavior (48.9%), and anxiety (43.2%). Headache (55.7%) was the least accepted AE followed by nausea (46.6%), fatigue (35.2%), and diarrhea (35.2%). Persistent diarrhea (90.9%) and severe fatigue (84.1%) were the main reasons for potential dropout. While most would undergo blood sampling (67.0%), only a minority (21.6%) would accept lumbar puncture. One-third were ready to participate (34.1%), while 54.5% were interested pending details. Among those in favor of participation, 71.6% would participate even with a 50% chance of placebo.

Conclusions: Our study identified cognitive improvement as highly relevant for patients, indicating cognitive assessment tools as primary endpoints in MCI research. Given concerns about AEs, dose titration should be carefully considered to enhance acceptance and prevent AEs. Blood sampling seems well-accepted for AD biomarker assessment. Despite potential AEs, participation in a trial using CBD for MCI is seen as attractive, even under placebo-controlled conditions. This cross-sectional study emphasizes the importance of patient engagement in designing high-quality trials for using CBD to treat MCI.”

https://pubmed.ncbi.nlm.nih.gov/39844123/

“In summary, this study is the first to incorporate PE into a trial on the use of CBD for MCI, as there are currently no existing PE activities in this area. It provides valuable insights into the concerns, aims, and needs of people with MCI and offers initial implications for planning and conducting future studies involving this population. Our main message is to encourage the incorporation of PE activities in the drug research process, not only to reflect the goals and needs of patients but also to improve the quality of research.”

https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-04753-w

Mechanisms and strategic prospects of cannabinoids use: Potential applications in antimicrobial food packaging-A review

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“This review focuses on antimicrobial packaging for food safety, critically examining the activity and efficacy of cannabinoids against commonly found microorganisms and exploring their antimicrobial mechanisms.

Specifically, the review considers cannabinoids derived from industrial hemp plants, which are characterized by low levels of psychoactive components. It also outlines viable strategies to control the sustained release of cannabinoids from the packaging, enabling extended storage and enhanced safety of food products.

Research demonstrates that cannabinoids are effective against both foodborne bacteria and fungi, with their antimicrobial action primarily attributed to microbial membrane instability.

Cannabinoids can be utilized to prepare effective antimicrobial films and edible coatings; however, the number of studies in this area remains limited.

The potential of cannabinoids to contribute to intelligent packaging systems is also discussed, with an emphasis on the regulatory aspects and challenges associated with incorporating cannabinoids into food packaging. Finally, the review identifies future research directions to address current limitations and advance hemp-based antimicrobial food packaging solutions.”

https://pubmed.ncbi.nlm.nih.gov/39840610/

https://ift.onlinelibrary.wiley.com/doi/10.1111/1541-4337.70113

Treatment With Full-Spectrum Cannabidiol Oil Improved the Pathological Findings of Dystrophic Mutant Mice

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“Introduction/aims: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene, making muscle fibers susceptible to contraction-induced membrane damage. Given the potential beneficial action of cannabidiol (CBD), we evaluated the in vitro effect of full-spectrum CBD oil on the viability of dystrophic muscle fibers and the in vivo effect on myopathy of the mdx mouse, a DMD model.

Methods: In vitro, dystrophic cells from the mdx mouse were treated with full-spectrum CBD oil and assessed with cell viability and cytotoxic analyses. In vivo, fourteen-day-old mdx mice received 10 mg/kg/day of the full-spectrum CBD oil for 14 days. We analyzed creatine kinase (CK) levels, liver damage markers, and histopathology of the diaphragm (DIA) and quadriceps (QUA [myonecrotic fibers with positive IgG staining, regenerated fibers/central nuclei, the minimum Feret’s diameter, the fibrosis area, the inflammatory area, the presence of macrophages, and NF-kappa B content]).

Results: In vitro treatment with full-spectrum CBD oil showed a dose-dependent cytotoxic effect; however, in vivo 10 mg/kg treatment was safe and effectively improved DMD histopathological assessment parameters in DIA and QUA: reduction of central nuclei: 1.7% ± 2.0% versus 22.4% ± 5.3% and 11.1% ± 10.7% versus 32.3% ± 4.6%; reduction of IgG+ myofibers: 0.6% ± 0.7% versus 8.4% ± 1.6% and 0.9% ± 0.3% versus 7.5% ± 1.0%; increase in myofiber size: 85.2 ± 3.2 versus 64.3 ± 4.0 μm and 106.5 ± 8.6 versus 81.2 ± 4.8 μm; decrease in inflammatory area: 6.2% ± 2.7% versus 15.1% ± 2.6% and 5.3 ± 4.1 versus 17.3% ± 2.8%; reduced macrophage area: 0.05% ± 0.1% versus 10.8% ± 4.3% and 1.0% ± 0.7% versus 10.3% ± 4.9%; NF-κB levels: 0.6% ± 0.1% versus 1.7% ± 0.2% and 1.7% ± 0.1% versus 5.2% ± 2.1%; and fibrosis: 5.6% ± 1.8% versus 12.0% ± 3.7% and 1.3% ± 0.5% versus 4.7% ± 1.5%. It also reduced serum CK.

Discussion: Full-spectrum CBD oil may represent a promising new approach to treating DMD, but its potential toxicity must be considered.”

https://pubmed.ncbi.nlm.nih.gov/39840534/

https://onlinelibrary.wiley.com/doi/10.1002/mus.28337

Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders

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“Cannabidiol (CBD), the primary non-intoxicating compound in cannabis, is currently approved for treating rare, treatment-resistant seizures.

Recent preclinical research suggests that CBD’s multifaceted mechanisms of action in the brain, which involve multiple molecular targets, underlie its neuroprotective, anti-inflammatory, anxiolytic, and antipsychotic effects. Clinical trials are also exploring CBD’s therapeutic potential beyond its current uses.

This review focuses on CBD’s polypharmacological profile and discusses the latest preclinical and clinical findings regarding its efficacy in neuropsychiatric disorders.

Existing evidence suggests that CBD’s ability to modulate multiple signaling pathways may benefit neuropsychiatric disorders, and we propose further research areas to clarify its mechanisms, address data gaps, and refine its therapeutic indications.”

https://pubmed.ncbi.nlm.nih.gov/39837749/

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(24)00271-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614724002712%3Fshowall%3Dtrue

First case report of effective and safe application of cannabidiol to treat concurrent ALG3-CDG and Lennox-Gastaut Syndrome

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“This study presents the first reported case of a Korean patient with Alpha-1,3-Mannosyltransferase-Congenital Disorder of Glycosylation (ALG3-CDG), characterized by a novel maternally inherited missense mutation and a previously reported paternally inherited nonsense mutation. The patient exhibited typical ALG3-CDG manifestations, including developmental delays, epilepsy, and multisystem involvement, alongside a diagnosis of Lennox-Gastaut Syndrome (LGS).

Cannabidiol therapy, combined with dietary management, led to seizure freedom for over 13 months, significant EEG improvement, and enhanced developmental outcomes.

This case underscores the potential of cannabidiol as a promising treatment strategy for patients with ALG3-CDG and refractory epilepsy, broadening therapeutic perspectives for this rare disorder.”

https://pubmed.ncbi.nlm.nih.gov/39831946/

https://link.springer.com/article/10.1007/s10072-025-08004-1

Exploring the antifungal potential of Cannabis sativa-derived stilbenoids and cannabinoids against novel targets through in silico protein interaction profiling

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“Cannabinoid and stilbenoid compounds derived from Cannabis sativa were screened against eight specific fungal protein targets to identify potential antifungal agents.

The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity.

This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations. The ligands with the highest binding affinities were identified, and their pharmacokinetic profiles were analyzed using ADMET analysis. The results indicate that GMP synthase exhibited the highest binding affinity with Cannabistilbene I (-9.1 kcal/mol), suggesting hydrophobic solid interactions and multiple hydrogen bonds. Similarly, Chitin Synthase 2 demonstrated significant binding with Cannabistilbene I (-9.1 kcal/mol). In contrast, ligands such as Cannabinolic acid and 8-hydroxycannabinolic acid exhibited moderate binding affinities, underscoring the variability in interaction strengths among different proteins.

Despite promising in silico results, experimental validation is necessary to confirm therapeutic potential. This research lays a crucial foundation for future studies, emphasizing the importance of evaluating binding affinities, pharmacokinetic properties, and multi-target interactions to identify promising antifungal agents.”

https://pubmed.ncbi.nlm.nih.gov/39834844/

“This study provides a comprehensive assessment of how selected cannabinoid and stilbenoid compounds interact with eight different fungal proteins, highlighting the promising potential of these compounds as antifungal agents. In conclusion, this study highlights the therapeutic potential of cannabinoids and stilbenoids and provides a solid foundation for the development of new antifungal therapies.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1515424/full

Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids

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“Pain impacts billions of people worldwide, but treatment options are limited and have a spectrum of adverse effects. The search for safe and nonaddictive pain treatments has led to a focus on key mediators of nociceptor excitability.

Voltage-gated sodium (Nav) channels in the peripheral nervous system-Nav1.7, Nav1.8, and Nav1.9-play crucial roles in pain signaling. Among these, Nav1.8 has shown promise due to its rapid recovery from inactivation and role in repetitive firing, with recent clinical studies providing proof-of-principal that block of Nav1.8 can reduce pain in humans.

We report here that three nonpsychotomimetic cannabinoids-cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN)-effectively inhibit Nav1.8, suggesting their potential as analgesic compounds.

In particular, CBG shows significant promise due to its ability to effectively inhibit excitability of peripheral sensory neurons. These findings highlight the therapeutic potential of cannabinoids, particularly CBG, as agents that may attenuate pain via block of Nav1.8, warranting further in vivo studies.”

https://pubmed.ncbi.nlm.nih.gov/39835903/

“Chronic pain is a major health problem worldwide; however, treatment options remain limited and often involve adverse side-effects or addiction risk. Targeting voltage-gated sodium (Nav) channels in sensory neurons, particularly Nav1.8, represents a promising therapeutic approach. Our work demonstrates that nonpsychotomimetic cannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), effectively inhibit Nav1.8. CBG, in particular, exhibits a potent inhibition of dorsal root ganglion neuron excitability, suggesting its potential as a nonaddictive analgesic. Our findings open different avenues for the development of cannabinoid-based treatments for pain therapy, with a focus on Nav1.8 inhibition as a therapeutic target.”

https://www.pnas.org/doi/10.1073/pnas.2416886122

Investigation of Cannabidiol’s Protective Effects on Cadmium-Induced Toxicity in Mice

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“Current chelation treatments used for cadmium poisoning may cause some serious side effects. Thus, safer novel treatments could be promising for clinical use.

This study evaluated the effects of cannabidiol on Cd toxicity.

Four groups of 10 mice were formed: Groups I and III were cadmium-free, while groups II and IV received 50 mg/L cadmium in drinking water. Groups III and IV received daily cannabidiol (25 mg/kg) via intragastric gavage. After 30 days, the animals were killed, and blood and tissue samples were collected. Oxidative stress and inflammation markers, including glutathione, catalase, myeloperoxidase, TNF-α, IL-1β and IL-6, were analysed using ELISA. Additionally, histological evaluations of the liver, kidney and testis were performed. Cadmium exposure reduced glutathione and catalase levels in the blood, liver, kidney and testis, while increasing myeloperoxidase.

Cannabidiol mitigated these effects on oxidative stress markers. Cannabidiol also reduced the increase in proinflammatory cytokines. Histopathological analysis revealed reduced liver and kidney damage in cannabidiol-treated groups compared to cadmium-only groups. In addition, histopathological evaluation showed CBD had no protective effect on the testicular tissue against Cd toxicity.

Our results indicate that cannabidiol protects against some toxic effects of cadmium. If confirmed by future studies, cannabidiol may be proposed as a novel treatment for cadmium toxicity.”

https://pubmed.ncbi.nlm.nih.gov/39832793/

“Cadmium (Cd) is a heavy metal that can have toxic effects on multiple organs. Chelation treatments that are used for treating Cd toxicity can have serious side effects, which limit their use. This study aimed to investigate cannabidiol (CBD), a non-psychoactive compound derived from hemp, for its potential to reduce Cd toxicity.

Our experiments on mice showed CBD had significant protective effects against Cd-induced tissue damage in the liver and the kidneys by reducing oxidative stress and inflammation. These findings suggest that CBD can be explored as a safer treatment option for Cd toxicity in a clinical setting.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.14131

Cannabinoid receptor 1 ligands: Biased signaling mechanisms driving functionally selective drug discovery

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“G protein-coupled receptors (GPCRs) adopt conformational states that activate or inhibit distinct signaling pathways, including those mediated by G proteins or β-arrestins. Biased signaling through GPCRs may offer a promising strategy to enhance therapeutic efficacy while reducing adverse effects.

Cannabinoid receptor 1 (CB1), a key GPCR in the endocannabinoid system, presents therapeutic potential for conditions such as pain, anxiety, cognitive impairment, psychiatric disorders, and metabolic diseases.

This review examines the structural conformations of CB1 coupling to different signaling pathways and explores the mechanisms underlying biased signaling, which are critical for the design of functionally selective ligands. We discuss the structure-function relationships of endogenous cannabinoids (eCBs), phytocannabinoids, and synthetic cannabinoid ligands with biased properties. Challenges such as the complexity of ligand bias screening, the limited availability of distinctly biased ligands, and the variability in receptor signaling profiles in vivo have hindered clinical progress.

Although the therapeutic potential of biased ligands in various clinical conditions remains in its infancy, retrospective identification of such molecules provides a strong foundation for further development. Recent advances in CB1 crystallography, particularly insights into its conformations with G proteins and β-arrestins, now offer a framework for structure-based drug design. While there is still a long way to go before biased CB1 ligands can be widely used in clinical practice, ongoing multidisciplinary research shows promise for achieving functional selectivity in targeting specific pathways.

These progresses could lead to the development of safer and more effective cannabinoid-based therapies in the future.”

https://pubmed.ncbi.nlm.nih.gov/39828030/

https://www.sciencedirect.com/science/article/abs/pii/S0163725825000075?via%3Dihub