Exosomal delivery of cannabinoids against cancer

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“Exosomes are extracellular vesicles (EVs) originating from endosomes that play a role in cellular communication. These vesicles which mimic the parental cells that release them are promising candidates for targeted drug delivery and therapeutic applications against cancer because of their favorable biocompatibility, specific targeting, low toxicity, and immunogenicity.

Currently, Delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and other cannabinoids (e.g., CBG, THCV, CBC), are being explored for their anticancer and anti-proliferative properties. Several mechanisms, including cell cycle arrest, proliferation inhibition, activation of autophagy and apoptosis, inhibition of adhesion, metastasis, and angiogenesis have been proposed for their anticancer activity. EVs could be engineered as cannabinoid delivery systems for tumor-specificity leading to superior anticancer effects.

This review discusses current techniques for EV isolation from various sources, characterization and strategies to load them with cannabinoids. More extensively, we culminate information available on different sources of EVs that have anticancer activity, mechanism of action of cannabinoids against various wild type and resistant tumors and role of CBD in histone modifications and cancer epigenetics. We have also enumerated the role of EVs containing cannabinoids against various tumors and in chemotherapy induced neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/37257632/

https://www.sciencedirect.com/science/article/abs/pii/S0304383523001945?via%3Dihub

The Cannabis sativa genetics and therapeutics relationship network: automatically associating cannabis-related genes to therapeutic properties through chemicals from cannabis literature

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“Background: Understanding the genome of Cannabis sativa holds significant scientific value due to the multi-faceted therapeutic nature of the plant. Links from cannabis gene to therapeutic property are important to establish gene targets for the optimization of specific therapeutic properties through selective breeding of cannabis strains. Our work establishes a resource for quickly obtaining a complete set of therapeutic properties and genes associated with any known cannabis chemical constituent, as well as relevant literature.

Methods: State-of-the-art natural language processing (NLP) was used to automatically extract information from many cannabis-related publications, thus producing an undirected multipartite weighted-edge paragraph co-occurrence relationship network composed of two relationship types, gene-chemical and chemical property. We also developed an interactive application to visualize sub-graphs of manageable size.

Results: Two hundred thirty-four cannabis constituent chemicals, 352 therapeutic properties, and 124 genes from the Cannabis sativa genome form a multipartite network graph which transforms 29,817 cannabis-related research documents from PubMed Central into an easy to visualize and explore network format.

Conclusion: Use of our network replaces time-consuming and labor intensive manual extraction of information from the large amount of available cannabis literature. This streamlined information retrieval process will enhance the activities of cannabis breeders, cannabis researchers, organic biochemists, pharmaceutical researchers and scientists in many other disciplines.”

https://pubmed.ncbi.nlm.nih.gov/37254213/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-023-00182-z

Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population

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“Background: Patients diagnosed as having multiple sclerosis (MS) experience a wide range of symptoms requiring pharmacologic management, and many do not achieve adequate symptom control. The purpose of this study was to evaluate the role of medical cannabis (MC) as part of a comprehensive treatment plan for patients with MS.

Methods: A retrospective medical record review of 141 patients with MS receiving MC for symptom management was conducted. Data were collected for up to 4 follow-up appointments after initiation of MC. Outcomes included changes in MS symptoms, medication changes, adverse events, and changes in cognition and mobility.

Results: Patients experienced extensive MS symptom improvement after initiation of MC, with alleviation of pain (72% of patients) and spasticity (48% of patients) and improvement in sleep (40% of patients) the most common. There was a significant reduction in concomitant opioid use after initiating MC as evidenced by a significant decrease in daily morphine milligram equivalents among patients prescribed opioid analgesics (P = .01). Decreases in muscle relaxant use and benzodiazepine use did not reach significance (P > .05). The most common adverse reaction to MC was fatigue (11% of patients).

Conclusions: In many patients with MS, MC was well tolerated, eased pain and spasticity, improved sleep and other symptoms, and reduced use of concomitant opioid analgesics. Prospective studies are needed to further investigate the role of MC in the treatment of patients with MS.”

https://pubmed.ncbi.nlm.nih.gov/37250194/

https://meridian.allenpress.com/ijmsc/article/25/3/111/489178/Multiple-Sclerosis-and-Use-of-Medical-Cannabis-A

Use of Medical Cannabis by Patients with Cancer: Attitudes, Knowledge, and Practice

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“Objectives: The study sought to assess factors contributing to the demand for MC among patients with cancer.

Methods: Patients applying for a permit to receive MC at a pain and palliative clinic of a university-affiliated cancer center in Israel in 2020-2021 were asked to complete self-report questionnaires assessing attitudes, knowledge, and expectations regarding MC use. Findings were compared between first-time and repeat applicants. Repeat applicants were asked to report their indications for requesting MC, patterns of use, and treatment effect.

Results: The cohort included 146 patients: 63 first-time applicants and 83 repeat applicants. First-time applicants were more likely to consult sources other than their oncologist for MC-related information (p <.01) and expressed more concern about addiction (p <.001) and side effects (p <.05). They often erroneously assumed the treatment was subsidized (p <.001). Repeat applicants were younger (p <.05) and included more smokers (p <.05) and recreational cannabis users (p <.05); 56.6% were cancer survivors and 78% used high-potency MC. Most patients believed to some degree that MC is more effective than conventional medications for symptom control, and over half thought that MC helps to cure cancer.

Conclusion: Misconceptions regarding the effectiveness of MC for symptom management and treatment may explain the motivation of patients with cancer to apply for a permit. There seems to be an association of young age, cigarette smoking, and recreational cannabis use with ongoing use of MC among cancer survivors.”

https://pubmed.ncbi.nlm.nih.gov/37244526/

https://www.jpsmjournal.com/article/S0885-3924(23)00514-6/fulltext

Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment-resistant epilepsies in the expanded access program

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“Cannabidiol (CBD) Expanded Access Program (EAP), initiated in 2014, provided CBD (Epidiolex®) to patients with treatment-resistant epilepsy (TRE). In the final pooled analysis of 892 patients treated through January 2019 (median exposure 694 days), CBD treatment was associated with a 46%-66% reduction in median monthly total (convulsive plus nonconvulsive) seizure frequency. CBD was well tolerated, and adverse events were consistent with previous findings. We used pooled EAP data to investigate the effectiveness of add-on CBD therapy for individual convulsive seizure types (clonic, tonic, tonic-clonic, atonic, focal to bilateral tonic-clonic) and nonconvulsive seizure types (focal with and without impaired consciousness, absence [typical and atypical], myoclonic, myoclonic-absence) and epileptic spasms. CBD treatment was associated with a reduction in the frequency of convulsive seizure types (median percentage reduction, 47%-100%) and nonconvulsive seizure types and epileptic spasms (median percentage reduction, 50%-100%) across visit intervals through 144 weeks of treatment. Approximately 50% of patients had ≥50% reduction in convulsive and nonconvulsive seizure types and epileptic spasms at nearly all intervals. These results show a favorable effect of long-term CBD use in patients with TRE who may experience various convulsive and nonconvulsive seizure types. Future controlled trials are needed to confirm these findings.”

https://pubmed.ncbi.nlm.nih.gov/37243404/

https://onlinelibrary.wiley.com/doi/10.1111/epi.17665