UK Medical Cannabis Registry: A Clinical Outcomes Analysis for Complex Regional Pain Syndrome

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“Background: Complex regional pain syndrome is characterized by severe, persistent pain. Emerging evidence suggests that cannabis-based medicinal products may represent a new therapeutic option. However, to date, no clinical studies have evaluated the effects of cannabis-based medicinal products in individuals with complex regional pain syndrome. The aim of this study is to assess changes in patient-reported outcome measures and the prevalence of adverse events associated with cannabis-based medicinal products prescribed for complex regional pain syndrome.

Methods: This case series assessed changes in patient-reported outcome measures over 6 months in complex regional pain syndrome patients enrolled in the UK Medical Cannabis Registry. Adverse events were measured and graded using the Common Terminology Criteria for Adverse Events version 4.0.

Results: A total of 64 patients were identified for inclusion. At baseline, pain severity measured by the Brief Pain Inventory Short Form was 6.69 ± 1.42. This improved at 1 (5.85 ± 1.73), 3 (5.91 ± 1.82), and 6 months (6.05 ± 1.72; p < 0.050). Participants also reported improvements in severity as measured by the Short Form-McGill Pain Questionnaire-2 and pain visual analogue scale at the same time points (p < 0.050). Participants also reported improvements in anxiety symptoms, sleep quality, and general health-related quality of life (p < 0.050), as measured by validated measures. Five patients (7.81%) reported 50 (78.13%) adverse events.

Discussion: This study represents the outcomes in individuals with complex regional pain syndrome prescribed cannabis-based medicinal products. These suggest initiation of cannabis-based medicinal products is associated with improvements in patient-reported outcome measures. While these findings are consistent with the literature, they must be interpreted with caution, considering the limitations of this study.

Conclusion: Cannabis-based medicinal products were associated with improvements in pain severity and interference. Participants also reported improvements in important metrics of health-related quality of life. This supports further research through high-quality randomized controlled trials to ascertain the efficacy of cannabis-based medicinal products in improving complex regional pain syndrome symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40898690/

“In conclusion, the results imply that initiation of CBMPs was associated with improved pain relief and health-related quality of life in complex regional pain syndrome patients.”

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70823

Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines

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“Despite effective antiretroviral therapy (ART), people with HIV (PWH) experience persistent inflammation and metabolic dysfunction, increasing their risk for non-AIDS comorbidities. Accordingly, we evaluated the effects of long-term/low-dose Δ9-tetrahydrocannabinol (THC) supplementation in simian immunodeficiency virus (SIV)-infected, ART-treated rhesus macaques (RMs).

THC significantly increased plasma/jejunum serotonin and indole-3-propionate, enhancing gut-brain communication through up-regulation of serotonin receptors (HTR4/HTR7) and aryl hydrocarbon receptor (Ahr) signaling via a cannabinoid receptor (CBR)-2-mediated mechanism. Furthermore, THC enriched cholesterol-metabolizing Oscillibacter and reduced plasma cholesterol and toxic secondary bile acids (SBAs), thus improving cholesterol and SBA homeostasis.

Furthermore, THC increased β-hydroxybutyrate (BHB) levels via a CBR1-mediated mechanism, suggesting enhanced hepatic fatty acid oxidation for metabolic and cardiovascular health. THC restored ART/SIV-induced elevation of pro-inflammatory and cardiotoxic long-chain acylcholines to preinfection levels. THC-treated RMs maintained viral suppression despite reduced plasma ART levels, suggesting diminished ART-related toxicity.

Our findings demonstrate phytocannabinoids to be a safe adjunct therapy alongside ART to mitigate chronic inflammation and metabolic dysfunction in PWH.”

https://pubmed.ncbi.nlm.nih.gov/40901952/

“Taken as a whole, our findings uncover numerous hitherto unknown mechanisms of cannabinoid action and provide multiple lines of evidence for its utility as an effective and relatively safe adjunct therapy to ART.”

https://www.science.org/doi/10.1126/sciadv.adw4021

Case Report: Effect of medicinal cannabis on fitness to drive in a patient with Tourette Syndrome and ADHD

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“Background: Tourette Syndrome (TS) is a childhood onset chronic disorder in which motor and vocal tics co-occur. Cannabinoids are a potential therapeutic option for otherwise treatment resistant patients. However, there is an ongoing debate regarding potential side effects. This is particularly important in relation to activities being necessary for daily life such as driving a car.

Case presentation: We present the case of a 28-year-old male with TS and comorbid attention-deficit/hyperactivity disorder (ADHD) who was medicated by his treating physician with an extremely high dose of inhaled medicinal cannabis (MC) of up to 10 g/d. We were interested in the effects of MC on patient’s fitness to drive as well as corresponding serum levels of tetrahydrocannabinol (THC) and its metabolites. Therefore, clinical assessments and computer-based tests (Vienna Test System) were performed at different time points at two consecutive days before and after intake of MC at a dose that was determined by the patient according to clinical need. On day 1, he inhaled a total dose of 3.3 g and 4.1 g MC, respectively, before driving tests were performed. Until the end of the day, he used a total dose of 8.8 g. On day 2, he took no MC before all tests were completed.

Remarkably, according to the German Federal Highway Research Institute guidelines, the patient was considered fit to drive in all domains assessed at all time points at day 1 and 2. Higher doses of MC – and corresponding very high THC serum levels – resulted in best results with respect to patient’s driving ability. THC serum levels ranged from 19 ng/ml (at day 2 without MC intake at this day) to 364 ng/ml (at day 1 after intake of a total of 3.3 g MC at the same day). No clinically relevant side effects occurred.

Conclusions: This case study demonstrates that patients with TS plus comorbid ADHD may be fit to drive even after intake of high doses of MC. In any case, however, every driver, who uses MC, is obliged to check fitness to drive before driving a vehicle.”

https://pubmed.ncbi.nlm.nih.gov/40901261/

“We present the case of a patient with TS using extremely high doses of MC (up to 10 g/d) for several years, who reported marked reductions of his tics and comorbid ADHD symptoms after use of MC. According to driving tests performed, he can be considered as fit to drive both on a day when using 3.3 g MC and 4.1 g MC, respectively, before testing as well as at the following day without additional prior MC use. Remarkably, his fitness to drive was even better on day 1 while taking MC and having THC serum levels of up to 364 ng/ml.”

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1595649/full

Pediococcus acidilactici KCTC 15831BP-fermented industrial hempseed (Cannabis sativa L.) supplementation corrects metabolite and gut microbiota dysbiosis, potentially mitigating Alzheimer’s disease-like symptoms induced by obesity in high-fat diet-fed mice

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“A long-term high-fat diet (HFD) intake causes obesity, disrupting the gut microbiota and body metabolite balance, and increasing the risk of Alzheimer’s disease (AD).

Fermented hempseed may restore microbiota balance, improve metabolism, and reduce neuroinflammation, potentially protecting against cognitive decline.

This study investigates the protective effects and mechanisms of action of Pediococcus acidilactici KCTC 15831BP-fermented hempseed (FHS) against AD-like symptoms induced by obesity in high-fat diet-fed mice.

Nine-week-old male C57BL/6 mice were fed an HFD and supplemented with either orlistat, raw hempseed, FHS, or live Pediococcus acidilactici KCTC 15831BP (PA) for 15 weeks. At the end of the experiment, the impacts of supplementation on obesity- and AD-related markers, brain and blood metabolites, and fecal microbiota were assessed.

HFD-fed mice exhibited obesity markers, such as increased body weight, altered serum lipids, insulin resistance, high leptin but low adiponectin levels, fatty liver, and enlarged adipose tissue. They also showed AD-related disorders, including cognitive decline, oxidative stress, neuroinflammation, and beta-amyloid accumulation. HFD feeding also led to gut microbiota dysbiosis and unfavorable changes in serum and brain metabolites.

FHS intervention reversed most adverse effects, restoring gut microbiome balance, improving the Firmicutes/Bacteroidetes ratio, and normalizing disrupted serum and brain metabolites, including increasing protective compounds like L-tryptophan and trans-cinnamic acid. The beneficial changes in the gut microbiota and metabolite profiles caused by FHS positively correlated with improvements in obesity and AD markers.

These findings highlight the interconnection between the diet, gut, and brain, emphasizing the role of the diet-microbiota-gut-brain axis in mitigating neurodegenerative diseases.”

https://pubmed.ncbi.nlm.nih.gov/40878211/

https://pubs.rsc.org/en/content/articlelanding/2025/fo/d5fo01921d

Isovitexin accelerates diabetic wound repair via coordinated angiogenesis and collagen remodeling: Mechanistic insights from cellular and streptozotocin-induced SD rat models

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“Chronic diabetic wounds pose significant clinical challenges due to persistent inflammation, vascular insufficiency, and impaired tissue remodeling, leading to poor healing outcomes. The PI3K/Akt/eNOS signaling pathway is critical for regulating angiogenesis, apoptosis, and extracellular matrix organization-key processes disrupted in diabetic wounds.

Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. However, its therapeutic potential and mechanistic action in diabetic wounds, particularly regarding multi-targeted regulation of angiogenesis, collagen deposition, and apoptosis within the complex wound microenvironment, remain unexplored.

This study demonstrates that isovitexin accelerates diabetic wound healing. Using streptozotocin-induced diabetic rodent models and cell culture, we found isovitexin significantly promoted angiogenesis and vascular maturation, reduced oxidative damage and apoptosis, and improved collagen organization versus controls. Crucially, these effects were entirely abolished by the eNOS inhibitor L-NAME, confirming PI3K/Akt/eNOS pathway specificity. Whereas previous studies have largely focused on single-pathway interventions for diabetic wounds, the concurrent modulation of angiogenesis, matrix remodeling, and apoptosis remains unexplored.

Our study uniquely demonstrates that isovitexin activates the PI3K/Akt/eNOS pathway to synchronously enhance angiogenesis, promote collagen maturation, and inhibit apoptosis. This tripartite mechanism-uncovered for the first time-provides a novel therapeutic strategy to address the multifactorial pathology of diabetic wounds. Future research should prioritize clinical translation of these findings.”

https://pubmed.ncbi.nlm.nih.gov/40882326/

“This study demonstrates the therapeutic potential of isovitexin in promoting diabetic wound healing and clarifies its underlying mechanisms. In vitro, isovitexin improved endothelial cell function under hyperglycemic conditions. In vivo, it activated the PI3K/Akt/eNOS pathway, enhancing angiogenesis while reducing oxidative stress, inflammatory responses, and apoptosis. These coordinated mechanisms collectively contribute to accelerated wound closure and suggest therapeutic potential”

“Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. “

“Isovitexin significantly accelerates diabetic wound healing through coordinated activation of the PI3K/Akt/eNOS signaling pathway. This natural compound synchronously enhances angiogenesis, promotes collagen matrix remodeling, and suppresses oxidative stress-mediated apoptosis, addressing multifactorial pathology in diabetic wounds.”

https://www.sciencedirect.com/science/article/abs/pii/S0040816625003829?via%3Dihub

Delta-9-tetrahydrocannabinol and Cannabidiol for Pain: Preclinical and Clinical Models

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“Cannabinoids are increasingly being used to manage pain resulting from a variety of conditions.

Both preclinical animal models and human studies have played a crucial role in advancing our knowledge of cannabinoids, their involvement in pain mechanisms, and their potential utility as novel analgesics.

This chapter first reviews basic pain neurobiology and the most common experimental pain paradigms, which provide a basis for our discussion of preclinical, human laboratory, and clinical research characterizing the effectiveness of cannabinoids for managing pain.

While a substantial body of literature exists describing these effects, findings are complex and largely mixed, dependent on the cannabinoid administered, route of administration, and pain modality/syndrome tested. Herein, we highlight the need for more rigorous, placebo-controlled research defining the therapeutic efficacy of cannabinoids.

The chapter concludes by emphasizing the need for further investigation of other cannabis constituents (e.g., minor cannabinoids and terpenes), potential interactions between cannabinoids and other analgesic medications, as well as other emerging issues in the intersection between cannabinoids and pain management.”

https://pubmed.ncbi.nlm.nih.gov/40877567/

https://link.springer.com/chapter/10.1007/7854_2025_604

Cannabigerol Attenuates Memory Impairments, Neurodegeneration, and Neuroinflammation Caused by Transient Global Cerebral Ischemia in Mice

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“Evidence supporting the clinical use of neuroprotective drugs for cerebral ischemia remains limited. Spatial and temporal disorientation, along with cognitive dysfunction, are among the most prominent long-term consequences of hippocampal neurodegeneration following cerebral ischemia.

Cannabigerol (CBG), a non-psychotomimetic constituent of Cannabis sativa, has demonstrated neuroprotective effects in experimental models of cerebral injury.

This study investigated the neuroprotective mechanisms of CBG in mitigating memory impairments caused by transient global cerebral ischemia in C57BL/6 mice using the bilateral common carotid artery occlusion (BCCAO) model.

Mice underwent sham or BCCAO surgeries and received intraperitoneal (i.p.) injections of either a vehicle or CBG (1, 5, or 10 mg/Kg), starting 1 h post-surgery and continuing daily for 7 days. Spatial memory performance and depression-like behaviors were assessed using the object location test (OLT) and tail suspension test (TST), respectively. Additional analyses examined neuronal degeneration, neuroinflammation, and neuronal plasticity markers in the hippocampus.

CBG attenuated ischemia-induced memory deficits, reduced neuronal loss in the hippocampus, and enhanced neuronal plasticity.

These findings suggest that CBG’s neuroprotective effects against BCCAO-induced memory impairments may be mediated by reductions in neuroinflammation and modifications in neuroplasticity within the hippocampus.”

https://pubmed.ncbi.nlm.nih.gov/40869376/

“CBG Improves Memory Impairment Induced by BCCAO in Mice.”

https://www.mdpi.com/1422-0067/26/16/8056

Cannabis Derivatives as Ingredients of Functional Foods to Combat the COVID-19 Pandemic

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“Lower respiratory infections predominantly affect children under five and the elderly, with influenza viruses and respiratory syncytial viruses (including SARS-CoV-2) being the most common pathogens. The COVID-19 pandemic has posed significant global public health challenges. While vaccination remains crucial, its efficacy is limited, highlighting the need for complementary approaches to mitigate immune hyperactivation in severe COVID-19 cases.

Medicinal plants like Cannabis sativa show therapeutic potential, with over 85% of SARS-CoV-2-infected patients in China receiving traditional herbal treatments. This review explores the antiviral applications of cannabis and its bioactive compounds, particularly against SARS-CoV-2, while evaluating their pharmacological and food industry potential.

Cannabis contains over 100 cannabinoids, terpenes, flavonoids, and fatty acids. Cannabinoids may block viral entry, modulate immune responses (e.g., suppressing pro-inflammatory cytokines via CB2/PPARγ activation), and alleviate COVID-19-related psychological stress.

There are several challenges with pharmacological and food applications of cannabinoids, including clinical validation of cannabinoids for COVID-19 treatment and optimizing cannabinoid solubility/bioavailability for functional foods. However, rising demand for health-focused products presents market opportunities. Genetic engineering to enhance cannabinoid yields and integrated pharmacological studies are needed to unlock cannabis’s full potential in drug discovery and nutraceuticals.

Cannabis-derived compounds hold promise for antiviral therapies and functional ingredients, though further research is essential to ensure safety and efficacy.”

https://pubmed.ncbi.nlm.nih.gov/40870742/

“Cannabis has been farmed for millennia as a source of traditional medicine and textile fiber, but it is now also being recognized as a source of a variety of secondary metabolites with value as medicines, flavoring compounds, and fragrances due to its unique composition and structure.”

“The cannabis food industry is poised for transformative growth as legalization expands globally and consumer acceptance increases.”

https://www.mdpi.com/2304-8158/14/16/2830

Cannabis Use Moderates Methamphetamine- and HIV-Related Inflammation: Evidence from Human Plasma Markers

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“Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions are limited. We examined potentially interacting associations of lifetime methamphetamine use disorder (MUD), recent cannabis use, and HIV with four plasma markers of immune and inflammatory functions.

Method: Participants with HIV (PWH, n = 86) and without HIV (PWoH, n = 148) provided urine and blood samples and completed neuromedical, psychiatric, and substance use assessments. Generalized linear models examined main and conditional associations of lifetime MUD, past-month cannabis use, and HIV with plasma concentrations of CXCL10/IP-10, CCL2/MCP-1, ICAM-1, and VCAM-1.

Results: PWH displayed higher CXCL10/IP-10 than PWoH. Past-month cannabis use was independently associated with lower CXCL10/IP-10 levels and conditionally lower CCL2/MCP-1, ICAM-1, and VCAM-1 levels among people with lifetime MUD, but only PWoH displayed cannabis-associated lower VCAM-1 levels.

Conclusions: Human plasma sample evidence suggests that cannabis use is associated with lower levels of immune and inflammatory molecules in the context of MUD or HIV. Cannabinoid pathways may be worthwhile clinical targets for treating sequelae of chronic inflammatory conditions.”

https://pubmed.ncbi.nlm.nih.gov/40872856/

“METH use disorder is highly prevalent in PWH, and both can have significant effects on immune function and pro-inflammatory processes that lead to significant central nervous system consequences, despite modern advances in anti-retroviral therapy effectiveness and tolerability. Results from this study support prior findings that METH and HIV disease confer risk for negative outcomes via their influence on chronic inflammatory processes, and we provide novel evidence from human plasma samples that cannabis use is associated with reduced levels of immune and inflammatory molecules in the context of chronic METH use or HIV infection (CCL2/MCP-1, VCAM-1, ICAM-1) and independent of METH use and HIV (CXCL10/IP-10). Associations between cannabis use and lower indices of inflammatory pathology from HIV and MUD point toward cannabinoid pathways as promising therapeutic targets that warrant further study.”

https://www.mdpi.com/1999-4915/17/8/1143

Phytocannabinoids as Novel SGLT2 Modulators for Renal Glucose Reabsorption in Type 2 Diabetes Management

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“Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids-bioactive compounds from Cannabis sativa-exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. 

Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. 

Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ9-Tetrahydrocannabinol or Δ9-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. 

Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC50 values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. 

Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. 

Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors.”

https://pubmed.ncbi.nlm.nih.gov/40872492/

“phytocannabinoids may complement or even extend the benefits of current SGLT2 inhibitors, offering a holistic, multi-mechanistic approach to complex metabolic disease management.”

https://www.mdpi.com/1424-8247/18/8/1101