Cannabidiol Targets Colorectal Cancer Cells via Cannabinoid Receptor 2, Independent of Common Mutations

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“Cannabidiol (CBD) is a non-neurotoxic, phytocannabinoid from cannabis with reported medicinal properties, including antiepileptic and anti-inflammatory activity.

Several in vitro and in vivo studies have shown that CBD has antitumor potential against colorectal cancer (CRC), the third deadliest cancer in the world. However, as different mutations influence the antitumor effects and CBD can bind a variety of receptors, it is yet to be determined whether specific CRC mutations affect CBD’s efficacy in treatment of CRC.

To investigate this, we selected four CRC cell lines, including HCT116, HT-29, LS174T, and LS153, which harbor distinct mutations. Cells were treated with a range of concentrations of CBD to evaluate its cytotoxic effects and impact on cell proliferation, migration, and invasion by using a live-cell imaging system. IC50 values were then calculated for each parameter. The level of endoplasmic reticulum (ER) stress pathway markers was also measured using qRTPCR. The requirements for CB1 or CB2 receptor-medicated signaling were investigated using the selective inhibitors AM251 and SR144528, respectively.

Our results demonstrate that CBD induces apoptosis and halts proliferation, migration, and invasion of CRC cell lines in a concentration-dependent manner.

CBD showed potent antitumor effects in the tested cell lines with no obvious effect from different mutations such as KRAS, BRAF, APC, PTEN, etc. CBD also induced ER stress in CRC cells but not in healthy intestinal organoids. Cotreatment with SR144528 inhibited the effects of indicating involvement of CB2 receptor activation in the anticancer effects of CBD.

Together, these results demonstrated that CBD could be effective for CRC regardless of the underlying mutation through CB2 receptor activation.”

https://pubmed.ncbi.nlm.nih.gov/39974647/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00644

Medical Cannabis for Patients Over Age 50: A Multi-site, Prospective Study of Patterns of Use and Health Outcomes

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“Objective: Cannabis is being used as a therapeutic option by patients around the globe, and older patients represent a rapidly growing subset of this population. This study aims to assess the patterns of medical cannabis use in patients over 50 years of age and its effect on health outcomes such as pain, sleep, quality of life, and co-medication.

Method: The Medical Cannabis in Older Patients Study (MCOPS) is a multi-site, prospective observational study examining the real-world impact of medical cannabis use on patients over age 50 under the guidance of a health care provider. The study included validated instruments, with treating physicians collecting detailed data on participant characteristics, medical cannabis and co-medication use, and associated impacts on pain, sleep, quality of life, as well as adverse events.

Results: Inclusion criteria were met by 299 participants. Average age of participants was 66.7 years, and 66.2% of respondents identified as female. Approximately 90% of patients used medical cannabis to treat pain-related conditions such as chronic pain and arthritis. Almost all patients reported a preference for oral cannabis products (e.g., extracts, edibles) rather than inhalation products (e.g., flower, vapes), and most preferred oral formulations high in cannabidiol and low in tetrahydrocannabinol.

Over the six-month study period, significant improvements were noted in pain, sleep, and quality of life measures, with 45% experiencing a clinically meaningful improvement in pain interference and in sleep quality scores. Additionally, nearly 50% of patients taking co-medications at baseline had reduced their use by the end of the study period, and quality of life improved significantly from baseline to M3 and from baseline to M6, with an incremental cost per quality-adjusted life-year (QALY) of $25,357.20. No serious adverse events (SAEs) were reported.

Conclusions: In this cohort of older patients, most of whom suffered from pain-related conditions, medical cannabis seemed to be a safe and effective treatment. Most patients experienced clinically significant improvements in pain, sleep, and quality of life and reductions in co-medication. The cost per QALY was well below the standard for traditional pharmaceuticals, and no SAEs were reported, suggesting that cannabis is a relatively safe and cost-effective therapeutic option for adults dealing with age-related health conditions.”

https://pubmed.ncbi.nlm.nih.gov/39968489/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/239

Weight Loss and Therapeutic Metabolic Effects of Tetrahydrocannabivarin (THCV)-Infused Mucoadhesive Strips

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“Objective: Metabolic syndrome is due to dysregulation that starts with fat accumulation, causing inflammatory response, insulin resistance, dyslipidemia, hypertension, and fatty liver disease. The endocannabinoid system, via cannabinoid receptor type 1 (CB1), has been shown to be involved with energy homeostasis and regulation of appetitive behavior via activity in the hypothalamus, limbic forebrain and amygdala and in the peripheral tissues including adipose, liver and muscle. Therefore, two phytocannabinoids, tetrahydrocannabivarin (THCV), a CB1 neutral antagonist, and cannabidiol (CBD), a negative allosteric modulator of CB1, are expected to have therapeutic metabolic benefits, including weight loss.

Method: A placebo-controlled study was conducted on 44 subjects (31 females and 13 males) with an average age of 51.75. The study evaluated the efficacy of two different doses of THCV and CBD (8 mg THCV/10 mg CBD in the lower dose and 16 mg THCV/20 mg CBD in the higher dose), taken once daily for 90 days via mucoadhesive oral strips, for weight loss and improvement of certain metabolic markers.

Results: Use of the THCV/CBD strip was associated with statistically significant weight loss, decreases in abdominal girth, systolic blood pressure, and total and LDL cholesterol. The study was limited by small sample sizes in both the high dose and placebo groups.

Conclusions: The 16 mg/20 mg daily dose was superior for weight loss compared to the 8 mg/10 mg daily dose; both sets of results differed from placebo in a way that was statistically significant. The results of this study were congruent with the prior unpublished studies of a hemp extract containing significant percentages of THCV, CBDV and CBD.”

https://pubmed.ncbi.nlm.nih.gov/39968488/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/206

Recreational Cannabis Laws and Fills of Pain Prescriptions in the Privately Insured

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“Objective: Almost half of U.S. states have passed recreational cannabis laws as of May 2024. While considerable evidence to date indicates cannabis may be a substitute for prescription opioids in the treatment of pain, it remains unclear if patients are treating pain with cannabis alone or concomitantly with other medications.

Method: Using data from a national sample of commercially insured adults, we examine the effect of recreational cannabis legalization (through two sequential policies) on prescribing of opioids, NSAIDS, and other pain medications by implementing synthetic control estimations and constructing case-study level counterfactuals for the years 2007-2020.

Results: Overall, we find recreational cannabis legalization is associated with a decrease in opioid fills among commercially insured adults in the U.S., and we find evidence of a compositional change in prescriptions of pain medications more broadly. Specifically, we find marginally significant increases in prescribing of non-opioid pain medications after recreational cannabis becomes legal in some states. Once recreational cannabis dispensaries open, we find statistically significant decreases in the rate of opioid prescriptions (13% reduction from baseline, p < .05) and marginally significant decreases in the average daily supply of opioids (6.3% decrease, p < .10) and number of opioid prescriptions per patient (3.5% decrease, p < .10).

Conclusions: These results suggest that substitution of cannabis for traditional pain medications increases as the availability of recreational cannabis increases. There appears to be a small shift once recreational cannabis becomes legal, but we see stronger results once users can purchase cannabis at recreational dispensaries. The decrease in opioids and marginal increase in non-opioid pain medication may reflect patients substituting opioids with cannabis and non-opioid pain medications, either separately or concomitantly. Reductions in opioid prescription fills stemming from recreational cannabis legalization may prevent exposure to opioids in patients with pain and lead to decreases in the number of new opioid users, rates of opioid use disorder, and related harms.”

https://pubmed.ncbi.nlm.nih.gov/39968486/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/268

Motherhood and medicinal cannabis

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“Introduction: Women are emerging as a key demographic for medicinal cannabis (MC) use in countries that have implemented MC reforms. However, research on mothers’ experiences of consuming MC remains limited beyond studies on perinatal outcomes. This study explores mothers’ diverse experiences of consuming MC in New Zealand under the legal MC scheme.

Methods: Interviews with 15 mothers using MC via prescriptions, the illegal market or both in the last 12 months. Thematic analysis focused on MC use in parenting, MC conversations with children, societal stigma and risks.

Results: Mothers reported MC as an important facilitator of their ability to positively parent their children, enabling them to manage their own health needs (i.e., anxiety, endometriosis and arthritis). High costs of legal products hindered access to MC. Participants expressed unique risks that mothers face accessing the unregulated market for MC like being deemed a ‘bad mother’ and losing custody of children. Stigma was countered with narratives of empowerment through proactive MC conversations with children and agency by self-medicating with MC despite the judgement they may face for being a parent that uses cannabis.

Discussion and conclusions: Mothers felt managing their health with MC allowed them to be more present parents and better tolerate the stressors of motherhood. In-depth exploration of discussing MC with children and anticipating these conversations was a novel finding. Most mothers tried to destigmatise MC in conversations by classifying it in the same category as other medications and discussing its therapeutic benefits. Few were cautious about having these conversations too early.”

https://pubmed.ncbi.nlm.nih.gov/39967064/

“This study has provided insights into MC use among mothers, highlighting perceived therapeutic benefits for managing the unique stressors of motherhood and health and wellbeing in general. The findings illustrate the global legalisation of MC as a possible catalyst for shifting attitudes towards cannabis use in parenting, and a trend of women exercising agency in their health using complementary alternative therapies.”

https://onlinelibrary.wiley.com/doi/10.1111/dar.14027

Purified cannabidiol leads to improvement of severe treatment-resistant behavioral symptoms in children with autism spectrum disorder

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“Objective: The aim of our study was to evaluate the efficacy and safety of purified cannabidiol as an add-on medication in pediatric patients with autism spectrum disorder (ASD) associated with treatment resistant repetitive behaviors, behavior disorders, and intellectual disability and unresponsive to conventional medications and behavioral interventions.

Material and methods: A prospective, observational, before-and-after study was conducted including 20 patients with severe ASD who initiated treatment with purified CBD. Patients were evaluated using different scales at baseline and at three-month intervals during followup.

Results: The median total CBD dose was 363.5 mg (range, 100-700), and the median follow-up was 11 months (range, 6-12). As to the primary outcome evaluating symptoms reported by parents, improvement in at least one was observed after CBD initiation in 18 patients (90 %) and no improvement in two (10 %) (1 worsening, 1 no response). In the responders, 83.5 % (n = 76) of all reported symptoms improved. Regarding the secondary outcomes based on the assessment with different scales, improvement of around 30 % was found in irritability, social withdrawal, hyperactivity. Restricted and repetitive behavior improved in nine (50 %), while no changes were seen in seven (38.8 %). Sleep patterns were found to be slightly improved. Adverse effects were reported in 13 patients (65 %), mainly consisting of increased irritability and decreased appetite, but were mild or moderate and transient in all. In 40 % of the children, concomitant medication could be reduced or partially discontinued.

Conclusion: Our results suggest that treatment with purified CBD is effective and safe and could benefit patients with severe ASD by improving some of the core symptoms, including repetitive behaviors and social interaction, as well as associated comorbidities. The families considered the quality of life to have improved.”

https://pubmed.ncbi.nlm.nih.gov/39965749/

“Treatment with cannabidiol improved the quality of life of patients and their families.”

https://www.sciencedirect.com/science/article/abs/pii/S0091305725000188?via%3Dihub

Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice

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“Cannabidiol (CBD), a nonpsychoactive compound from Cannabis, has various bioactive functions in humans and animals.

Evidence suggests that CBD promotes muscle injury recovery in athletes, but whether and how CBD improves endurance performance remains unclear.

Here we investigated the effects of CBD treatment on exercise performance in mice and assessed whether this effect involves the gut microbiome.

CBD administration significantly increased treadmill running performance in mice, accompanied by an increase in oxidative myofiber composition. CBD also increased mitochondrial biogenesis and the expression of associated genes such as PGC-1α, phosphorylated CREB and AMPK in muscle tissue. Interestingly, CBD altered the composition of the gut microbiome, and antibiotic treatment reduced the muscle endurance-enhancing effects of CBD and mitochondrial biogenesis.

We isolated Bifidobacterium animalis, a microbe increased by CBD administration, and named it KBP-1. Treatment with B. animalis KBP-1 in mice resulted in improved running performance. Whole-genome analysis revealed that B. animalis KBP-1 presented high expression of genes involved in branched-chain amino acid biosynthesis, expression of branched-chain amino acid release pumps and metabolism of lactic acid.

In summary, our study identified CBD and B. animalis KBP-1 as potential endurance exercise-promoting agents.”

https://pubmed.ncbi.nlm.nih.gov/39966566/

“In summary, we propose that both CBD and the gut bacteria B. animalis KBP-1, which is increased by CBD treatment, could be used in strategies to promote endurance exercise performance.”

https://www.nature.com/articles/s12276-025-01404-5

The role of cannabinoid-mediated signaling pathways and mechanisms in brain disorders

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“Cannabinoids play significant roles in the central nervous system (CNS), but cannabinoid-mediated physiopathological functions are not elaborated. Cannabinoid receptors (CBRs) mediate functions that include the regulation of neuroinflammation, oxidative stress, apoptosis, autophagy, and neurogenesis.

Microglia are the primary immune cells responsible for mediating neuroinflammation in the CNS. Therefore, this article primarily focuses on microglia to summarize the inflammatory pathways mediated by cannabinoids in the CNS, including nuclear factor-κB (NF-κB), NOD-like receptor protein 3 (NLRP3) inflammasome, mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and cAMP-dependent protein kinase (PKA) signaling pathways. Additionally, we provide a table summarizing the role of cannabinoids in various brain diseases.

Medical use of cannabinoids has protective effects in preventing and treating brain diseases; however, excessive and repeated use can be detrimental to the CNS. We propose that cannabinoids hold significant potential for preventing and treating brain diseases, including ferroptosis, lactate metabolism, and mitophagy, providing new insights for further research on cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39952540/

“Cannabis plants were historically used by pharmacologists as drugs to treat diseases in ancient India and China. Cannabinoids are natural compounds extracted from the cannabis plant. The most well-known component of cannabis is delta-9-tetrahydrocannabinol (delta9-THC)”

“This article reviews the role of cannabinoids in signaling pathways, including NF-κB, the NLRP3 inflammasome, MAPK, and AKT. Cannabinoids primarily combat neuroinflammation through CB2R-mediated signaling. Additionally, we discuss the effects of cannabinoids on oxidative stress, apoptosis, autophagy, and neurogenesis. Numerous studies demonstrate the neuroprotective effects of cannabinoids”

https://www.sciencedirect.com/science/article/abs/pii/S089865682500066X?via%3Dihub

The Endocannabinoid System as a Target for Ischemic Stroke Therapy

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“Introduction: Cannabinoids are increasingly being explored as a potential treatment for neurodegenerative diseases. This article aims to provide a narrative review of available data on the treatment of neurological disorders with cannabis constituents, focusing on ischemic stroke. 

Methods: Selected articles are summarized to describe design, results, limitations, conclusions, and implications about this theme. 

Results: The growing understanding of the endocannabinoid system and the cannabinoid receptors distribution in all human body systems and organs and particularly in brain structures importantly involved in myelination processes, suggests potential benefits for stroke symptoms and overall patient improvement. However, the variety of studied compounds, the different administration routes, dosages, and timing complicates data comparison, especially due to limited studies about these compounds, peculiarly in stroke patients. Thereat, this review to showcase disparities in findings and to summarize current advancements in cannabinoid use for potential future treatments. 

Conclusion: This article offers a review of the current literature in the field and discuss a pragmatic approach to the clinical use of cannabinoids in patients with ischemic stroke.”

https://pubmed.ncbi.nlm.nih.gov/39951358/

THC shows activity against cultured Plasmodium falciparum

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“The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites.

The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa.

Traditional use of cannabis for malaria fever was reported in the world’s oldest pharmacopoeia, dating to around 5000 years ago.

In this research we report that THC inhibits β-haematin (synthetic haemozoin) and malaria parasite growth.

Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited β-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action.

For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.”

https://pubmed.ncbi.nlm.nih.gov/34763083/

https://www.sciencedirect.com/science/article/abs/pii/S0960894X21006697?via%3Dihub