Author Archives: David Worrell

Supercritical CO2 extraction of hemp seeds: A multivariate perspective on the influence of processing parameters on oil composition, antioxidant activity, and enzyme inhibition

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“Hemp seeds are valued for their unique nutritional and health benefits.

This study examined the impact of supercritical (sc)CO2 extraction conditions on hemp seed oil yield, composition, antioxidant activity, and enzyme inhibition using a multivariate approach. While pressure (300-500 bar) had minimal effects, temperature (40-60 °C) and ethanol addition (0.6-1.5 %) significantly influenced oil yield.

The levels of fatty acids, tocopherols, carotenoids, chlorophylls, phenolics, and flavonoids varied independently of extraction pressure and temperature, but their extractability generally increased with ethanol concentration. The co-solvent addition also enhanced radical scavenging activity but diminished the metal-reducing and chelating properties.

Hemp seed oils inhibited enzymes linked to chronic diseases like diabetes, skin disorders, and Alzheimer’s.

Multivariate analysis grouped samples by fatty acid profile, pigment content, and bioactivity. This work provides novel insights into how scCO2 conditions affect the chemical and biological properties of hemp seed oils.”

https://pubmed.ncbi.nlm.nih.gov/41341704

“Cannabis sativa L. (hemp) seeds have been consumed as animal feed or for human nutrition for thousands of years. The whole hemp seeds are comprised of fiber, proteins, and contain more than 30 % oil.

Hemp seed oil is abundant in polyunsaturated fatty acids (PUFAs) and exhibits a favorable omega-6 to omega-3 fatty acid (ω6/ω3) ratio of 3:1. This ratio is regarded as optimal in human nutrition, as it can significantly reduce the incidence of cardiovascular pathologies.”

“This study highlighted that scCO2 extraction is a promising method for obtaining high-quality oil from de-hulled hemp seeds, with tunable parameters influencing both yield and bioactivity.”

https://www.sciencedirect.com/science/article/pii/S2590157525011435?via%3Dihub

A single dose of cannabidiol modulates the relationship between hippocampal glutamate and learning-related prefrontal activation in individuals at Clinical High Risk of Psychosis

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“Background: Cannabidiol (CBD) is being studied as a potential intervention for the people at clinical high risk for psychosis (CHR), though the mechanisms underlying its effects are not fully understood. Previous studies indicate that a single dose of CBD can normalize alterations in memory-related brain activation and modulate hippocampal glutamate levels in the early stages of psychosis. This study aimed to examine the acute effects of CBD on the relationship between hippocampal glutamate levels and brain activation during verbal memory in individuals at CHR.

Methods: A total of thirty-three participants (n = 33) at CHR were randomly assigned to receive a single 600 mg dose of CBD (CHR-CBD) or a placebo capsule (CHR-PLB). Age-matched healthy controls (HC) (n = 19) received no study drugs. Participants underwent MRI scanning while performing a verbal learning task, and proton magnetic resonance spectroscopy to measure hippocampal glutamate levels. Effect of group x hippocampal glutamate interactions on brain activation was tested.

Results: CHR-PLB showed positive correlation between hippocampal glutamate levels and dorsolateral prefrontal cortex (dlPFC) (Pcorr. = 0.0039) activation compared to HC during both verbal encoding and recall. Under a single dose of CBD, the glutamate-dlPFC activation relationship was negative and significantly different compared to placebo in CHR individuals (Pcorr. = 0.0001) during both verbal encoding and recall. The reversed correlation in CBD group was also observed in the parahippocampal gyrus (Pcorr. = 0.0022) and amygdala (Pcorr. = 0.0019) during verbal recall.

Conclusions: These findings suggest that CBD may normalise disrupted hippocampal-prefrontal glutamatergic coupling in CHR, highlighting its potential to target the neurochemical mechanisms underlying cognitive impairment.”

https://pubmed.ncbi.nlm.nih.gov/41337954

“To the best of our knowledge, this is the first study to demonstrate that a single dose of CBD may partially attenuate the altered relationship between hippocampal glutamate levels and activation in the prefrontal cortex, amygdala, and parahippocampal regions in individuals at CHR.”

“Single dose of CBD modulates hippocampal glutamate-prefrontal activation coupling in CHR.”

https://www.sciencedirect.com/science/article/abs/pii/S0925492725001507?via%3Dihub

Endocannabinoid system and mood responses to acute aerobic exercise in adult cancer patients versus healthy controls: a pilot study

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“Purpose: To investigate the endocannabinoid system (ECS) and affective state responses to acute aerobic exercise in adult cancer patients versus their healthy peers.

Methods: Participants engaged in 30 min of quiet rest followed by 30 min of exercise. Exercise involved 5-min warm-up/cool-down procedures and 20 min of moderate-intensity training (64-76% of age-predicted maximal heart rate) on a treadmill or cycle. Blood samples and 10 Visual Analog Scales (VAS) were collected before and after each condition. Participants were also asked after exercise: ‘Did you experience a Runner’s high’. Blood samples were analysed for endocannabinoids: N-arachidonoylethanolamine (AEA; anandamide), 2-arachidonoylglycerol (2-AG) and 1-arachidonoylglycerol (1-AG), and endocannabinoid-like lipid mediators: palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and stearoylethanolamide (SEA).

Results: Cancer patients had lower circulating AEA, OEA and log SEA versus controls across all timepoints (all p < 0.06). In the total cohort, exercise increased AEA, log 1-AG, OEA, PEA and log SEA (all p = 0.05) while log 2-AG did not change. Of 10 VAS, only Happiness increased with exercise in the total cohort (p = 0.02). There were no group x time effects or associations between ECS and VAS responses to exercise. Five patients per group (50%) reported experiencing a Runner’s high.

Conclusions: Exercise increased endocannabinoids and endocannabinoid-like lipid mediators in the total cohort. However, cancer patients exhibited lower AEA, OEA and SEA concentrations versus their peers, indicating potential ECS dysfunction.

Additional research is required to investigate the effect of various modalities and dosages of exercise on ECS markers and the clinical interpretation of these adaptations across a range of cancer populations.”

https://pubmed.ncbi.nlm.nih.gov/41331388

https://link.springer.com/article/10.1007/s00520-025-10221-5

“Exercise activates the endocannabinoid system”

https://pubmed.ncbi.nlm.nih.gov/14625449

“The Endocannabinoid System: A Target for Cancer Treatment.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC7037210

TRPA1 activation prompts lysosome-mediated Nrf2 degradation enhancing the killing of colorectal cancer cells

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“Redox homeostasis is crucial for cancer cell survival and resistance to therapy.

The transcription factor NRF2, a master regulator of antioxidant and metabolic genes, is often upregulated in tumors to mitigate oxidative stress. Although NRF2 stability is canonically governed by KEAP1-CUL3-proteasome degradation, emerging evidence implicates lysosomal and autophagic pathways in non-canonical NRF2 turnover. The mechanisms by which these alternative pathways are engaged during chronic oxidative signaling remain unclear.

We investigated whether sustained activation of the redox-sensitive ion channel TRPA1 by cannabidiol (CBD) disrupts redox homeostasis and promotes NRF2 degradation in colorectal cancer models.

Using five independent CRC cell lines (RKO, HCT116, HT29, SW480, and MC38), we assessed reactive oxygen species (ROS), mitochondrial function, autophagy, and NRF2 protein dynamics through biochemical assays, lysosomal fractionation, and imaging. Xenograft models were used for in vivo validation.

Chronic TRPA1 activation induced a biphasic ROS response, characterized by an early increase linked to mitochondrial Ca2+ influx and a delayed ROS surge associated with mitochondrial dysfunction. This oxidative trajectory initially stabilized but subsequently led to its degradation after 24 h via a KEAP1-independent, autophagy-lysosome pathway. Proteasome inhibition failed to rescue NRF2, whereas bafilomycin A1 restored its levels and blocked co-localization with lysosomal markers (e.g., LAMP2A).

Importantly, CBD-induced TRPA1 activation sensitized CRC cells to oxaliplatin, triggering apoptotic-not senescent-cell death. These effects were dose-dependent and consistent across all tested cell lines.

Our findings reveal a non-canonical bioelectric-lysosomal axis that links TRPA1 activity to NRF2 destabilization in colorectal cancer. This work expands the understanding of NRF2 proteostasis under sustained oxidative stress and highlights TRPA1 as a tractable redox-modulating target for overcoming chemoresistance.”

https://pubmed.ncbi.nlm.nih.gov/41330216

https://www.sciencedirect.com/science/article/pii/S2213231725004550?via%3Dihub

“In simple terms, this mechanism describes a way to disarm the cancer cells’ defense shield (Nrf2) by using TRPA1 activation, thereby making them easier to kill, potentially in combination with standard chemotherapies like oxaliplatin.”


Medicinal use of non-prescribed cannabis: a cross-sectional survey on patterns of use, motives for use, and treatment access in the Netherlands

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“Background: Despite the Netherlands having one of the world’s oldest medical cannabis programs, the majority of people who use cannabis for medicinal purposes continue to rely on non-prescribed sources. This study investigates patterns of use, motives for use, perceived effectiveness, and barriers to accessing prescribed cannabis among individuals self-medicating with non-prescribed cannabis.

Methods: A cross-sectional online survey was conducted between January and April 2023, using convenience sampling primarily via social media. Participants (N = 1059) were adults (18 years or older) residing in the Netherlands who self-reported current use of non-prescribed cannabis-based products to manage physical or mental health symptoms.

Results: Cannabis was used to manage a wide range of conditions, most commonly chronic pain, sleep disorders, depression, and ADHD/ADD, with three out of four participants reporting use for multiple conditions. Most participants obtained cannabis from coffeeshops, although one in four also reported home cultivation as a source. Participants typically smoked cannabis with tobacco, reported (near-)daily use for therapeutic purposes, and indicated a monthly expenditure of €100. The majority was not aware of the THC and CBD content of their products. Perceived effectiveness was rated as high, and more than half of those with a history of prescription medication use reported substituting cannabis for these medications. Only a minority of participants had ever used, or were currently using, prescribed cannabis. Commonly cited barriers included perceived lower quality, higher cost, and lower ease of access compared with non-prescribed cannabis.

Conclusions: The widespread use of non-prescribed cannabis for medicinal purposes in the Netherlands reflects both unmet health needs and barriers within the regulated medical cannabis system. Risky use practices – such as smoking cannabis with tobacco and using products without knowing their cannabinoid content – raise public health concerns. The findings highlight the need for harm reduction strategies and policies that better align medical cannabis regulation with patients’ real-world behaviours and care needs.”

https://pubmed.ncbi.nlm.nih.gov/41331499

https://link.springer.com/article/10.1186/s42238-025-00355-y

Hemp seed mitigates colonic inflammation through macrophage polarization and microbiota-barrier axis restoration

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“Hemp seed, historically considered a byproduct of the hemp fiber industry, has gained increasing attention for its nutritional and functional properties. Recent advances in hemp seed research have elucidated its benefits for gut health; however, its impact on colitis remains unclear.

In this study, we demonstrate that hemp seed consumption reduced colonic inflammation and mitigated tissue injury in an experimental colitis mouse model.

Notably, hemp seed reduced macrophage infiltration and promoted a phenotypic shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages. It also enhanced intestinal barrier function by restoring goblet cells, upregulating tight junction proteins, and reducing systemic lipopolysaccharide translocation. Furthermore, hemp seed optimized gut microbiota composition by enriching beneficial taxa, particularly Bifidobacterium, while suppressing colitis-associated genera.

Collectively, these findings indicate that hemp seed, as a whole-food dietary approach, confers protection against colitis by modulating immune responses, preserving barrier integrity, and reshaping gut microbiome.

These results underscore the potential of hemp seed as a sustainable nutritional strategy for promoting gut health.”

https://pubmed.ncbi.nlm.nih.gov/41328036

“The present study demonstrates that dietary hemp seed reduced colonic inflammation and alleviated tissue injury in the DSS-induced colitis mouse model.”

“Collectively, our study provides insights into the role of hemp seed in gut health and reinforces its potential as a promising and sustainable dietary intervention for IBD management.”

https://pubs.rsc.org/en/content/articlelanding/2026/fo/d5fo04119h

The endocannabinoid system as a therapeutic target in prodromal psychosis: From molecular mechanisms to clinical applications

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“This systematic review explores the role of the endocannabinoid system (ECS) in prodromal psychosis and its potential as a therapeutic target.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 22 studies published between 2000 and 2025 were analyzed, comprising preclinical research, genetic studies, neuroimaging investigations, and clinical trials.

Converging evidence suggests that ECS alterations precede and potentially contribute to the development of psychotic symptoms, with CB1 receptor modifications and endocannabinoid levels correlating with symptom severity and transition risk to full-blown psychosis.

Neuroimaging studies revealed reduced CB1 receptor availability in key brain regions in high-risk subjects, and intervention studies, particularly with cannabidiol-though its therapeutic mechanisms likely extend beyond ECS modulation to include dopaminergic and other neurotransmitter pathways-have shown promising results.

Proposed mechanisms of action include stress response attenuation, neuroinflammatory modulation, neurodevelopmental stabilization, and normalization of the dopamine-glutamate interface.

Despite limitations of existing studies, primarily small size and short duration, this review provides a solid foundation for developing ECS-targeted interventions as a promising approach to modify disease trajectory during the prodromal phase, potentially offering safer and more effective therapeutic options for individuals at clinical high risk for psychosis.”

https://pubmed.ncbi.nlm.nih.gov/41328544

https://journals.sagepub.com/doi/10.1177/02698811251389574

Predictors of Replacing Alcohol With Cannabis Among Adult Women

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“Background: Alcohol use among women varies by age, with younger women more likely to binge drink and older women more often engaging in consistent, long-term consumption. Both groups face health risks, including chronic disease, mental health conditions, and sleep disturbance. Cannabis has been proposed as a harm reduction substitute for alcohol because of its lower risks of dependency and health harms. The aims of this study are (a) to identify differences between younger and older women regarding their choices to use cannabis products as a substitute for alcohol and (b) to explore multiple drivers (sleep, stress, health state, post-traumatic stress disorder (PTSD), depression, and severity of alcohol use) behind the choice to replace alcohol with cannabis.

Methods: A cross-sectional online survey was conducted with 413 women aged 18 years and above who reported lifetime cannabis use. Participants were stratified into younger (<56 years) and older (≥56 years) groups. Measures included sociodemographics, cannabis substitution behaviors (cannabidiol (CBD), tetrahydrocannabinol (THC), or both), self-rated health, sleep and stress difficulties, and validated scales: Alcohol Use Disorders Identification Test (AUDIT), Primary Care PTSD Screen (PC-PTSD-4), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-8 (PHQ-8). Group differences were tested using chi-square and t-tests, and logistic regression identified predictors of substitution.

Results: Younger women (mean age 44.2 years) were significantly more likely than older women (mean age 62.9 years) to substitute THC for alcohol (14.0% vs. 7.8%, p = 0.019) and reported higher rates of sleep problems (52.5% vs. 39.1%, p = 0.007) and stress-coping difficulties (37% vs. 27%, p = 0.013). They also scored higher on AUDIT, PTSD, GAD, and PHQ instruments (all p < 0.01). Older women were more likely not to substitute cannabis for alcohol (83.5% vs. 71.0%, p = 0.002). Regression analyses showed that younger women with poorer health (OR = 1.76, 95% CI: 1.04-3.00) and higher AUDIT scores (OR = 1.07, 95% CI: 1.01-1.14) were more likely to substitute both CBD and THC. Sleep problems strongly predicted THC substitution in younger women (OR = 5.82, 95% CI: 1.58-21.45). Among older women, PTSD symptoms predicted substitution of both CBD and THC (OR = 1.60, 95% CI: 1.01-2.55), and sleep problems predicted THC substitution (OR = 3.05, 95% CI: 1.00-9.32).

Conclusions: Age-related differences emerged in women’s substitution of cannabis for alcohol. Younger women more frequently substituted THC and were influenced by alcohol severity, poor health, and sleep disturbance, whereas older women substituted less often, with PTSD and sleep difficulties as key predictors. These findings underscore cannabis substitution as a nuanced harm reduction strategy that requires age-specific approaches.”

https://pubmed.ncbi.nlm.nih.gov/41328136

“This study explored cannabis substitution as a potential harm reduction strategy, and its findings may inform prevention and intervention efforts aimed at reducing alcohol-related harms and improving women’s health outcomes.”

https://www.cureus.com/articles/418147-predictors-of-replacing-alcohol-with-cannabis-among-adult-women#!

The use of cannabis in supportive care and treatment of brain tumor

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“Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC.

Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive.

Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further.

Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.”

https://pubmed.ncbi.nlm.nih.gov/31385997

“For medicinal use, evidence goes back 5000 years to the Chinese emperor Chen Nung. Archeological findings suggest that palliative cancer treatment with cannabis was already in use 2500 years ago.”

“Cannabinoids Can be Used in Palliative Care for a Wide Range of Symptoms.”

“Cannabinoids Reduce Nausea and Vomiting.”

“Increase of Appetite and Weight is Only Seen with CB1 Agonists such as THC.”

“Cannabinoids Moderately but Consistently Improve Chronic Pain.”

“Cannabinoids Demonstrate Antitumor Effects on Glioma Cells.”

“Cannabinoids are Highly Effective in Animal Glioma Models.”

“Anticancer Effects of Cannabinoids may be able to Prolong Life.”

“Funded by the National Institutes of Health to find evidence that marijuana damages the immune system, the study found instead that THC slowed the growth of 3 kinds of cancer in mice—lung and breast cancer, and a virus-induced leukemia. The US Drug Enforcement Agency quickly shut down the Virginia study and all further cannabis/tumor research even though the researchers demonstrated remarkable antitumor effects.”

https://academic.oup.com/nop/article/4/3/151/2918616?login=false

RSM-Based Optimization of Dose Response and Antibacterial Potential of Cannabis sativa (L.) Leaves Using Computational Analysis

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“Background: In light of the growing problem of antibiotic resistance, it is imperative to investigate new sources, and plants offer a promising supply of bioactive chemicals. Because of its numerous uses in industry, health, and nutrition as well as its antibacterial qualities, Cannabis sativa (C.sativa) has garnered a lot of study interest. This study sought to determine whether ethanolic extracts from C.sativa leaves have antibacterial properties against six human pathogenic microorganisms.

Methodology: The antibacterial activity of C.sativa ethanolic extract was tested against six bacteria according to design of experiments made by Agar diffusion method accompanied by response surface method (RSM) of Minitab 17 software. The different combinations set were, concentration: 5.0, 7.5, and 10.0, pH: 5.0, 6.5, 8.0 and temperature: 35°C, 37.5°C, 40°C. By using RSM, maximum antibacterial activity has been checked for ethanolic extract of C.sativa against six bacteria by choosing three independent variables, temperature, pH, and concentration. In in-Silico studies, homology, threading approach, structure prediction, ligands designing and docking studies was performed against the antimicrobial target sequences for Beta-Lactamase, GABA Receptor, Lipoteichoic Acid, N-Acetylglucosamine (NAG), Peptidoglycan and Topoisomerase-IV through FASTA format from UniProt for structure prediction.

Results: The results indicated that the three concentrations were effective against tested bacteria. Moreover, effect of pH caused a significant variation in zone of inhibition. The graphs presented in this study indicate the highest zone of inhibition for plant extract; have been achieved at concentration of 10.0, pH 5.1 and temperature 37.5°C. It shows that by keeping the pH low, antibacterial activity will increase. Through the multiple regression analysis on the experimental data, the fitted regression model for the response variable and the test variable x1, x2, x3 are correlated by the second order polymeric equation.

Conclusion: It has been concluded that C.sativa can be considered as an effective drug in curing diseases caused by bacteria. Using the optimized values of temperature and pH analyzed in this experiment.”

https://pubmed.ncbi.nlm.nih.gov/41324030

“Humans have been employing C.sativa since ancient times, and numerous historians have recorded multiple uses of this plant abroad. This plant has been cultivated for religious and recreational purposes, as well as for food, fiber, and oil, according to recorded history. C.sativa is also used therapeutically to treat depression, inflammation, and chronic pain, according to numerous ethnobotanical surveys.”

“This study is the continuation of the research to examine the effectiveness of ethanolic extracts made from C. sativa leaves against harmful microorganisms in humans. The results show that this extract has strong antibacterial activity against a variety of pathogens, such as Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, Bacillus subtilis, Staphylococcus typhi, and Staphylococcus aureus which is affected more strongly by the pH and temperature variations rather than the concentrations of the extract. Moreover, it is confirmed by the application of the RSM model which indicates its activity. The zones of inhibition produced in the repetitive study has been concluded that C. sativa may be qualified as the drug of the future that can be efficacious for combating bacterial infections. The said plant is of high importance to synthesize a very high potency antibacterial drug by using the optimized ranges of temperature and pH.”

https://journals.sagepub.com/doi/10.1177/15593258251404067