Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry

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“Rationale: Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety.

Objectives: This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs.

Methods: A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0.

Results: Improvements in anxiety, sleep quality and quality of life were observed at each time point (p < 0.001). Patients receiving CBMPs had improvements in GAD-7 at all time points (1 month: difference -5.3 (95% CI -4.6 to -6.1), 3 months: difference -5.5 (95% CI -4.7 to -6.4), 6 months: difference -4.5 (95% CI -3.2 to -5.7)). Thirty-nine participants (12.9%) reported 269 adverse events in the follow-up period.

Conclusions: Prescription of CBMPs in those with GAD is associated with clinically significant improvements in anxiety with an acceptable safety profile in a real-world setting. Randomised trials are required as a next step to investigate the efficacy of CBMPs.”

https://pubmed.ncbi.nlm.nih.gov/37314478/

https://link.springer.com/article/10.1007/s00213-023-06399-3

Cannabinoid Use in the Treatment of Laryngeal Dystonia and Vocal Tremor: A Pilot Investigation

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“Objectives/hypothesis: Laryngeal dystonia and vocal tremor can be debilitating conditions with suboptimal treatment options. Botulinum toxin chemodenervation is typically the first-line treatment and is considered the gold standard. However, patient response to botulinum toxin varies widely. There is anecdotal evidence for the use of cannabinoids in treating laryngeal dystonia with a scarcity of research investigating this potential treatment option. The primary objective of this study is to survey patients with laryngeal dystonia and vocal tremor to gauge how some people are using cannabinoids to treat their condition and to ascertain patient perceptions of cannabinoid effectiveness.

Study design: This is a cross-sectional survey study.

Methods: An eight-question anonymous survey was distributed to people with abductor spasmodic dysphonia adductor spasmodic dysphonia, vocal tremor, muscle tension dysphonia, and mixed laryngeal dystonia via the Dysphonia International (formerly National Spasmodic Dysphonia Association) email listserv.

Results: 158 responses: 25 males and 133 females, (mean [range] age, 64.9 [22-95] years). 53.8% of participants had tried cannabinoids for the purposes of treating their condition at some point, with 52.9% of this subset actively using cannabis as part of their treatment. Most participants who have used cannabinoids as a treatment rank their effectiveness as somewhat effective (42.4%) or ineffective (45.9%). Participants cited a reduction in voice strain and anxiety as reasons for cannabinoid effectiveness.

Conclusions: People with laryngeal dystonia and/or vocal tremor currently use or have tried using cannabinoids as a treatment for their condition. Cannabinoids were better received as a supplementary treatment than as a stand-alone treatment.”

https://pubmed.ncbi.nlm.nih.gov/37308367/

https://www.jvoice.org/article/S0892-1997(23)00158-3/fulltext

Cannabis and Cannabinoids in Multiple Sclerosis: From Experimental Models to Clinical Practice-A Review

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“Background: As far as 80% of people diagnosed with multiple sclerosis (MS) experience disabling symptoms in the course of the disease, such as spasticity and neuropathic pain. As first-line symptomatic therapy is associated with important adverse reactions, cannabinoids have become increasingly popular among patients with MS. This review intends to provide an overview of the evidence of the role of cannabinoids in treating symptoms related to MS and to encourage further research on this matter.

Areas of uncertainty: To date, the evidence supporting the role of cannabis and its derivatives in alleviating the MS-related symptoms comes only from studies on experimental models of demyelination. To the best of our knowledge, relatively few clinical trials inquired about the therapeutic effects of cannabinoids on patients with MS, with variable results.

Data sources: We conducted a literature search through PubMed and Google Scholar from the beginning until 2022. We included articles in English describing the latest findings regarding the endocannabinoid system, the pharmacology of cannabinoids, and their therapeutic purpose in MS.

Results: Evidence from preclinical studies showed that cannabinoids can limit the demyelination process, promote remyelination, and have anti-inflammatory properties by reducing immune cell infiltration of the central nervous system in mice with experimental autoimmune encephalomyelitis. Moreover, it has been established that experimental autoimmune encephalomyelitis mice treated with cannabinoids experienced a significant reduction of symptoms and slowing of the disease progression. Given the complexity of human immune and nervous systems, cannabinoids did not have the anticipated effects on human subjects. However, data obtained from clinical trials showed some beneficial results of cannabinoids as a single or as add-on therapy in reducing the spasticity and pain related to MS.

Conclusion: Considering their various mechanisms of action and good tolerability, cannabinoids remain an interesting therapy for spasticity and chronic pain related to MS.”

https://pubmed.ncbi.nlm.nih.gov/37278703/

https://journals.lww.com/americantherapeutics/Fulltext/2023/06000/Cannabis_and_Cannabinoids_in_Multiple_Sclerosis_.5.aspx

[Tetrahydrocannabinol (THC) in patients with fibromyalgia syndrome (FMS) : A retrospective study of changes in pain, psychometric variables, and analgesic consumption during inpatient interdisciplinary multimodal pain therapy (IMPT)]

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“Background: Since March 1, 2017, medical cannabis (MC) can be prescribed nationwide in Germany. To date, there have been a number of qualitatively different studies on the effectiveness of MC in fibromyalgia syndrome (FMS).

Objective: The aim of the study was to investigate the effectiveness of THC in the course of interdisciplinary multimodal pain therapy (IMPT) on pain and several psychometric variables.

Materials and methods: For the study, in the period 2017-2018, all patients in the pain ward of a clinic who were suffering from FMS and were treated in a multimodal interdisciplinary setting were selected based on inclusion criteria. The patients were examined separately according to groups with and without THC about pain intensity, various psychometric parameters and analgesic consumption during the stay.

Results: Of the 120 FMS patients included in the study, 62 patients (51.7%) were treated with THC. In the parameters of pain intensity, depression, and quality of life, there was a significant improvement in the entire group during the stay (p < 0.001), which was significantly greater through the use of THC. In five of the seven analgesic groups examined, the dose was reduced or the drug discontinued significantly more often in the patients treated with THC.

Conclusion: The results provide indications that THC can be considered as a medical alternative in addition to the substances previously recommended in various guidelines.”

https://pubmed.ncbi.nlm.nih.gov/37289246/

https://link.springer.com/article/10.1007/s00482-023-00727-4

Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

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“During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects. Conditioned media from cells treated with pure CBG or the high-CBG extract reduced the expansion and macrophage transition of the monocytic-MDSC subpopulation. Treated MO-MDSCs also expressed lower levels of iNOS, leading to restored CD8+ T-cell activation. Tumor-bearing mice treated with CBG presented reduced tumor progression, lower TAM frequencies and reduced TAM/M1 ratio. A combination of CBG and αPD-L1 was more effective in reducing tumor progression, enhancing survival and increasing the infiltration of activated cytotoxic T-cells than each treatment separately. We show a novel mechanism for CBG in modulating the TME and enhancing immune checkpoint blockade therapy, underlining its promising therapeutic potential for the treatment of a variety of tumors with elevated CSF-1 expression.”

https://pubmed.ncbi.nlm.nih.gov/37325437/

“Our findings have immediate practical implications; current treatment protocols that are already in combination with medical Cannabis as palliative care can select the CBG-rich chemovars in combination with immune checkpoint blockade therapy, making it more effective, and providing patients with antitumor properties in addition to the palliative ones.”

https://www.tandfonline.com/doi/full/10.1080/2162402X.2023.2219164

Anti-allodynic and medullary modulatory effects of a single dose of delta-9-tetrahydrocannabinol (THC) in neuropathic rats tolerant to morphine

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“Neuropathic pain (NP) is often treated with opioids, the prolonged use of which causes tolerance to their analgesic effect and can potentially cause death by overdose. The phytocannabinoid delta-9-tetrahydrocannabinol (THC) may be an effective alternative analgesic to treat NP in morphine-tolerant subjects. Male Wistar rats developed NP after spared nerve injury, and were then treated with increasing doses of THC (1, 1.5, 2, 2.5, and 5 mg/kg, intraperitoneally) which reduced mechanical allodynia at the dose of 2.5 and 5 mg/kg. Another group of NP rats were treated with morphine (5 mg/kg, twice daily for 7 days, subcutaneously), until tolerance developed, and on day 8 received a single dose of THC (2.5 mg/kg), which significantly reduced mechanical allodynia. To evaluate the modulation of THC in the descending pain pathway, in vivo electrophysiological recordings of pronociceptive ON cells and antinociceptive OFF cells in the rostroventral medulla (RVM) were recorded after intra-PAG microinjection of THC (10 μg/μl). NP rats with morphine tolerance, compared to the control one, showed a tonic reduction of the spontaneous firing rate of ON cells by 44%, but the THC was able to further decrease it (a hallmark of many analgesic drugs acting at supraspinal level). On the other hand, the firing rate, of the antinociceptive OFF cells was increased after morphine tolerance by 133%, but the THC failed to further activate it. Altogether, these findings indicate that a single dose of THC produces antiallodynic effect in individuals with NP who are tolerant to morphine, acting mostly on the ON cells of the descending pain pathways, but not on OFF cells.”

https://pubmed.ncbi.nlm.nih.gov/37257771/

https://www.sciencedirect.com/science/article/abs/pii/S027858462300091X?via%3Dihub

Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies

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“The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from Cannabis sativa, it lacks the psychoactive effects of Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD’s biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate that CBD interacts with other receptors and cellular signaling cascades, which further support CBD’s therapeutic potential beyond pain management. In this review, we take a closer look at the molecular mechanisms of CBD and its potential therapeutic application in the context of cancer, neurodegeneration, and autoimmune diseases.”

https://pubmed.ncbi.nlm.nih.gov/37259306/

https://www.mdpi.com/1424-8247/16/2/155

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