Author Archives: David Worrell

The potential of Allium sativum and Cannabis sativa extracts for anti-tick activities against Rhipicephalus (Boophilus) microplus

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Ticks are major veterinary and agricultural pests, and growing resistance to conventional acaricides has increased interest in plant-based alternatives. In this study, extracts from Cannabis sativa and Allium sativum showed anti-tick activity against Rhipicephalus (Boophilus) microplus, a species that causes significant losses in cattle production. The findings support the potential use of cannabis-derived compounds, alone or in combination with other botanical extracts, as natural agents for tick control. This work adds to the growing evidence that Cannabis sativa may have practical applications in sustainable pest management as well as medicine and industry.

“The efficacy of Allium sativum and Cannabis sativa against Rhipicephalus microplus ticks was evaluated using the adult immersion and the larval packet test. In addition, an in silico approach was utilized by performing a docking study in order to identify the active ingredients from both plants.

Results showed a comparatively high lethal effect of A. sativum and C. sativa on egg laying (index of egg laying = 0.26 and 0.24, respectively), egg hatching (33.5 and 37.1, respectively), and total larval mortality (100%, both), at 40 mg/mL.

When applied to cattle which had been inoculated with larvae ticks, it was observed that a 45% solution of both herbal extracts significantly reduced the number of ticks by 96 h post treatment.

We analyzed in silico 27 known active molecules from both plants and identified in the PubChem database to explore the hypothesis that the effect found on ticks was based on inhibition of acetylcholinesterase (AChE).

Vitamin E and cannabidiol are the most potent AChE inhibitors with docking scores of -15.85 and -14.38, respectively.

Based on these findings, we conclude that A. sativum and C. sativa may potentially be used for the control of R. microplus, and should be further investigated as a potential supplement to or replacement of synthetic acaricides.”

https://pubmed.ncbi.nlm.nih.gov/32886258

https://link.springer.com/article/10.1007/s10493-020-00540-z

Cannabidiol-thiosemicarbazone exhibits dual tyrosinase inhibition and antioxidant activity in human skin-derived cells

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Cannabidiol-derived compounds are being explored for skin applications that go beyond inflammation and pain. In this study, a CBD-thiosemicarbazone derivative showed dual activity in human skin-derived cells by inhibiting tyrosinase, a key enzyme involved in melanin production, while also providing antioxidant protection. This combination suggests potential value in conditions associated with hyperpigmentation and oxidative skin damage. The findings highlight how modified cannabinoid compounds may expand the dermatological uses of cannabis-derived molecules.

“The search for modulators of melanogenesis with improved biological compatibility remains an active area of investigation, as existing tyrosinase (TYR) inhibitors are often limited by low potency, instability, or cytotoxicity.

Here, we investigated CBD-TSC1, a cannabidiol-based thiosemicarbazone derivative, as a TYR-targeting scaffold.

Structural characterization confirmed a single, stable E-isomer, and pKa profiling together with kinetic analyses indicated reversible mixed-type inhibition of human TYR, involving interactions with both free enzyme and enzyme-substrate complexes. CBD-TSC1 exhibited higher inhibitory activity than CBD and kojic acid under the tested conditions while maintaining low cytotoxicity in G361 melanoma and HaCaT keratinocyte cell lines. In addition, CBD-TSC1 reduced intracellular oxidative stress at low micromolar concentrations. In zebrafish larvae, treatment with CBD-TSC1 resulted in a dose-dependent reduction in melanin content, comparable to that of kojic acid under identical experimental conditions, supporting an association between thiosemicarbazone modification and the observed biological activity.

Overall, CBD-TSC1 demonstrated consistent activity across biochemical, cellular, and zebrafish-based assays under the tested conditions. Although the mechanistic relationship between TYR inhibition, redox modulation, and melanogenesis regulation remains to be fully clarified, the present findings support further investigation of cannabidiol-based thiosemicarbazone derivatives as modulators of TYR-related pathways.”

https://pubmed.ncbi.nlm.nih.gov/42235859

“CBD-TSC1 is a novel cannabidiol-thiosemicarbazone hybrid with dual anti-melanogenic activity.”

“Thiosemicarbazone modification is essential for superior enzymatic and redox performance.”

https://www.sciencedirect.com/science/article/abs/pii/S0960894X26001745?via%3Dihub

Cannabidiol attenuates tau hyperphosphorylation and cognitive deficits in an experimental model of Alzheimer’s disease and is associated with restoration of PP2A expression

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Abnormal tau phosphorylation is one of the major pathological features of Alzheimer’s disease and is closely linked to cognitive decline. In this experimental study, cannabidiol reduced tau hyperphosphorylation and improved cognitive deficits in an Alzheimer’s disease model. The effects were associated with restoration of PP2A expression, an important enzyme involved in regulating tau phosphorylation. The findings suggest that CBD may act on a core disease mechanism while also improving cognitive function, adding to evidence for its potential neuroprotective role in Alzheimer’s disease.

“Pathogenic tau hyperphosphorylation, together with reduced protein phosphatase 2 A (PP2A) expression, is associated with neurofibrillary tangle formation and cognitive deterioration in Alzheimer’s disease (AD).

Cannabidiol (CBD), a non-psychotropic phytocannabinoid, remains insufficiently studied for its potential to modulate the PP2A-tau axis in experimental AD.

This study evaluated whether CBD improves hippocampus-dependent spatial cognition in a D-galactose/AlCl₃ rat model of AD and whether these effects are associated with restoration of PP2A expression and attenuation of tau hyperphosphorylation.

AD-like pathology was induced in male Wistar rats by D-galactose (60 mg/kg i.p.) and AlCl₃ (200 mg/kg oral gavage) for 10 weeks, followed by CBD (20, 40 or 80 mg/kg) or donepezil (1 mg/kg) for three weeks. The Morris water maze, Jess Simple Western, and ELISA were used to assess cognition, PP2A expression, and p-tau levels, respectively.

CBD significantly improved spatial learning and memory. PP2A expression increased across all tested doses, with the highest mean level observed at 80 mg/kg. Hippocampal p-tau levels were significantly increased in the model group and significantly reduced by all CBD doses and donepezil (all p < 0.0001 vs. model). The inverse relationship between PP2A expression and p-tau levels suggests possible involvement of the PP2A-tau axis.

CBD attenuated cognitive deficits and tau hyperphosphorylation alongside restoration of PP2A expression, suggesting that the PP2A-tau axis may be a relevant therapeutic target in AD-related tauopathy.”

https://pubmed.ncbi.nlm.nih.gov/42240860

https://link.springer.com/article/10.1007/s11011-026-01894-w

Interplay between the HPA axis and inflammation as mechanisms therapeutic targets of Cannabis sativa in depression

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Depression is increasingly understood as a disorder involving not only brain chemistry, but also chronic inflammation and dysregulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. This review examines how Cannabis sativa and its cannabinoids may influence both systems, highlighting interactions with inflammatory signaling, stress hormones, and endocannabinoid pathways involved in mood regulation. The evidence suggests that cannabis-derived compounds may help restore balance across these interconnected biological systems, offering a broader therapeutic approach to depression than targeting a single neurotransmitter pathway alone.

“Major Depressive Disorder (MDD) is a highly prevalent and disabling psychiatric disorder, representing a major global health burden across all age groups.

Increasing evidence indicates that its pathophysiology involves a complex interplay between chronic stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, immune activation, and neuroinflammation. Persistent HPA axis hyperactivity, glucocorticoid resistance, and altered expression of key regulators such as FKBP51 contribute to sustained inflammatory signaling and impaired neural plasticity in brain regions involved in mood regulation. Epigenetic mechanisms, including DNA methylation and microRNA-mediated regulation, further modulate stress responsivity, inflammatory pathways, and vulnerability to major depressive disorder.

In this context, growing attention has been directed toward Cannabis sativa and its bioactive constituents as potential therapeutic agents.

Preclinical and clinical evidence suggest that cannabinoids may modulate the endocannabinoid system, attenuate HPA axis hyperactivity, reduce neuroinflammation, and influence monoaminergic and neuroplasticity-related pathways.

This review synthesizes the current literature on the mechanistic links among the HPA axis, inflammation, and MDD, highlighting the emerging role of Cannabis sativa-derived compounds in targeting these interconnected pathways.”

https://pubmed.ncbi.nlm.nih.gov/42239513

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1801474/full

Cannabis for tic control: a systematic review and meta-analysis of its efficacy in Tourette syndrome management

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Cannabis-based medicines are showing increasingly strong evidence for reducing tics in Tourette syndrome. In this systematic review and meta-analysis involving 306 adults, cannabinoid-based treatments significantly reduced tic severity on the Yale Global Tic Severity Scale and also significantly reduced premonitory urges—the uncomfortable sensations that often precede tics. The analysis found a mean YGTSS reduction of 13.29 points and a mean PUTS reduction of 4.09 points, providing quantitative evidence that cannabinoids can meaningfully improve two core features of Tourette syndrome.

“Background: Tourette syndrome (TS) involves motor and vocal tics, often with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). Cannabis-based medicines (CBMs) are a potential therapy due to their interaction with the endocannabinoid system, potentially reducing tics and associated symptoms. Compared to antipsychotics, CBMs may offer improved tolerability and fewer side effects. Although evidence is limited, emerging studies suggest their potential to improve quality of life in TS. This review was registered with PROSPERO (CRD420251088633).

Aim: To evaluate the effectiveness of CBMs in treating TS.

Methods: We systematically searched PubMed, Google Scholar, ScienceDirect, and the Cochrane Collaboration Database for cohort studies and randomized controlled trials (RCTs) up to July 2, 2025. Data extraction included study characteristics and efficacy outcomes measured by the Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). Meta-analysis using Review Manager 5.4 compared pre- and post-treatment scores using mean difference (MD) and 95% confidence intervals (CI).

Results: From 1,105 screened articles, eight studies met inclusion criteria for the review, and seven were included in the meta-analysis, involving 306 adult TS patients. CBMs significantly reduced YGTSS scores (MD = – 13.29, 95% CI [-21.67 to – 4.91], P = 0.002) and PUTS scores (MD = – 4.09, 95% CI [-7.24 to – 0.93], P = 0.01).

Conclusion: CBMs show promising potential in reducing tics and premonitory urges in TS. Larger, placebo-controlled trials are needed to confirm efficacy, ensure safety, and optimize dosing.”

https://pubmed.ncbi.nlm.nih.gov/42229830

“Cannabis-based medicines significantly reduced tic severity in Tourette syndrome.”

https://www.ibroneuroscience.org/article/S0306-4522(26)00367-2/abstract

Structural characterization and in vitro evaluation of the hypolipidemic activity of the HSP-Ia, a bioactive polysaccharide derived from hemp (Cannabis sativa L.) seeds

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Hemp seeds contain bioactive compounds that may contribute to metabolic health beyond their well-known nutritional value. In this study, researchers isolated and characterized a polysaccharide known as HSP-IA from Cannabis sativa seeds and found that it showed significant hypolipidemic activity in vitro. The compound helped reduce lipid accumulation and influenced pathways involved in fat metabolism, suggesting that hemp-seed polysaccharides may have potential for managing abnormal lipid levels. The findings expand the therapeutic interest in hemp beyond cannabinoids and highlight its polysaccharides as promising metabolic bioactives.

“A novel polysaccharide, HSP-Ia, with a molecular weight of 973.6 kDa, was isolated from hemp (Cannabis sativa L.) seed residues using sequential aqueous extraction, ethanol-induced precipitation, and chromatographic fractionation.

Its structural attributes were determined through methylation profiling and nuclear magnetic resonance spectroscopy. The physicochemical characteristics were examined using X-ray diffraction, atomic force microscopy, scanning electron microscopy, and circular dichroism spectroscopy. The hypolipidemic potential of HSP-Ia was assessed using oxidized low-density lipoprotein-induced RAW264.7 macrophages.

HSP-Ia was predominantly comprised of glucose, with minor proportions of arabinose and galactose. It had a backbone of →6)-α-D-Glcp-(1 → residues with side chains attached at the O-2 and O-3 positions. HSP-Ia possessed an amorphous, nonuniform, and discontinuous morphology, with height distributions ranging from 0.7 to 10.5 nm. It exhibited a zeta potential of -7.4 mV and retained a triple-helix conformation in aqueous media. Notably, HSP-Ia facilitated lipid efflux in foam cells in a dose-dependent manner, associated with the upregulation of Liver X receptor α/ATP-binding cassette transporter signaling pathway.

Overall, these findings enhance the current knowledge of the structural features of hemp seed-derived polysaccharides and underscore the potential application of HSP-Ia as a lipid-modulating agent in the development of functional food products and pharmaceutical formulations.”

https://pubmed.ncbi.nlm.nih.gov/42230038

“Hemp seed, the mature dried seed of Cannabis sativa L., is a prominent traditional medicinal and dietary crop in China, recognized as one of the “Dragon Nine Flavours” and often termed “longevity hemp”. According to traditional Chinese medicine theory, hemp seed is associated with the meridians of the spleen, stomach, and large intestine and is used to lubricate the intestines, alleviate constipation, tonify deficiency, and enhance circulation. Hemp seed is rich in proteins, lipids, vitamins, and carbohydrates and has extensive applications in the food and livestock feed sectors. Contemporary studies support these traditional uses, demonstrating that regular consumption of hemp seed can improve gastrointestinal function and reduce the risk of chronic diseases.”

“This study successfully isolated and characterized a novel polysaccharide, designated HSP-Ia, from hemp (C. sativa L.) seed residues.”

https://www.sciencedirect.com/science/article/abs/pii/S0144861726005564?via%3Dihub

UK Medical Cannabis Registry: an updated analysis of clinical outcomes of medicinal cannabis therapy for hypermobility-associated chronic pain

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Hypermobility-associated chronic pain can be persistent, widespread, and difficult to control with conventional treatment. In this updated UK Medical Cannabis Registry analysis, patients receiving medicinal cannabis reported significant improvements in pain, anxiety, sleep, and overall health-related quality of life. The benefits were observed across multiple follow-up points, adding real-world clinical evidence that cannabis-based medicines may help address both the pain itself and several of the symptoms that commonly accompany hypermobility disorders.


“Introduction/objective: The primary aim of this study was to evaluate changes in pain-specific and general health-related quality of life in individuals prescribed cannabis-based medicinal products (CBMPs) for hypermobility-associated chronic pain.

Methods: The case series utilised data from the UK Medical Cannabis Registry. Primary outcomes were changes in Brief Pain Inventory (BPI), Pain Visual Analogue Scale (VAS), Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), EQ-5D-5L index value, Generalised Anxiety Disorder-7 (GAD-7), and Single-item Sleep Quality Scale (SQS) over 24 months. Repeated measures analysis of variance was used to assess changes over time, with post hoc pairwise comparisons performed for significant findings.

Results: A total of 240 patients were analysed. Changes were observed across all patient-reported outcome measures (PROMs) on repeated measures analysis of variance (p < 0.001). Post hoc pairwise comparisons for the BPI subscales, SF-MPQ-2 and Pain VAS demonstrated improvement from baseline to all subsequent timepoints (p < 0.001). By 24 months, 56.67% (n = 136) and 61.25% (n = 147) of participants reported clinically significant improvements in BPI severity and interference respectively. Clinically significant improvements were also reported for SF-MPQ-2 (47.08%, n = 113) and Pain VAS scores (60.00%, n = 144).

Conclusion: In this real-world cohort, CBMP treatment was associated with sustained improvements in outcomes for individuals with hypermobility-associated chronic pain. These findings support the need for further controlled studies to determine causality.

Key Points • This 24-month real-world study demonstrates sustained improvements in pain, anxiety, and sleep outcomes for patients with hypermobility-associated chronic pain treated with cannabis-based medicinal products, with approximately 60% achieving clinically meaningful pain reductions.

• Cannabis-based medicinal products were associated with reductions in concomitant opioid prescriptions at 12, 18, and 24 months.

• This represents the largest and longest-duration observational study of medical cannabis therapy specifically in hypermobility spectrum disorders and Ehlers-Danlos syndrome, addressing a critical evidence gap in chronic pain management.

• Adverse events were predominantly mild-to-moderate in severity, with poor baseline sleep quality and current cannabis use identified as positive predictors of pain improvement, informing patient selection and treatment optimisation.”

https://pubmed.ncbi.nlm.nih.gov/42217098

“This study provides a 24-month real-world evaluation of CBMPs in patients with hypermobility-associated chronic pain. It demonstrates long-term sustained improvement in pain, anxiety and sleep-related outcomes, underpinning health-related quality of life. Despite its observational design, the study provides important insight into potentially addressing an area of significantly unmet therapeutic need.”

https://link.springer.com/article/10.1007/s10067-026-08166-z

Selective opioid-sparing effects of cannabidiol on opioid analgesia in rats

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Reducing opioid exposure while preserving pain relief is a major goal in pain management, and cannabidiol is being studied as a possible opioid-sparing adjunct. In this preclinical study, CBD selectively enhanced aspects of opioid analgesia, allowing effective pain relief with less reliance on opioid signaling in certain conditions. The findings suggest that CBD may help improve the efficiency of opioid pain control rather than simply adding another analgesic effect. This supports further interest in cannabinoid-based strategies designed to reduce opioid requirements while maintaining meaningful pain relief.

“Cannabidiol, a major non-psychoactive constituent of cannabis, has generated interest as a novel therapeutic for managing several pathological conditions including chronic pain and opioid use disorder.

Here, we evaluated the effects of cannabidiol (3.2 or 10.0 mg/kg) on the antinociceptive and the reward-related effects of the opioid analgesic oxycodone (0.56 mg/kg) in rats (male and female Sprague-Dawley) using an operant facial pain assay, locomotor activity monitoring, and the conditioned place preference paradigm.

Cannabidiol enhanced the antinociceptive effect of oxycodone without affecting oxycodone-induced rearing behavior, or the acquisition and expression of oxycodone conditioned place preference under the conditions tested.

Together, these findings suggest that cannabidiol potentiates the analgesic effects of oxycodone without affecting its reward-related properties. These results support the potential of cannabidiol as an adjunctive, opioid-sparing agent in pain management.

PERSPECTIVE: Opioids remain important for treating moderate to severe pain, but adverse effects and misuse liability limit their use. These preclinical findings suggest cannabidiol may enhance oxycodone antinociception under acute painful conditions, without increasing abuse-relevant effects under the conditions tested, supporting further study as an opioid-sparing adjunct.”

https://pubmed.ncbi.nlm.nih.gov/42219047

https://www.jpain.org/article/S1526-5900(26)00156-2/abstract

Cannabinoids in Alzheimer’s disease: animal-human evidence and clinical pharmacology challenges

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Cannabinoids are being studied in Alzheimer’s disease for effects that extend beyond symptom control to inflammation, oxidative stress, amyloid and tau pathology, and neuroprotection. This review brings together animal and human evidence showing that cannabinoid-based treatments can influence several biological processes involved in Alzheimer’s disease while also showing clinical potential for symptoms such as agitation, sleep disturbance, and behavioral changes. The authors highlight THC, CBD, and other cannabinoid strategies as promising therapeutic approaches, with the growing body of evidence supporting continued development of cannabinoid-based treatments for both neurological and behavioral aspects of Alzheimer’s disease.

“Cannabinoids have emerged as potential modulators of pathological processes in Alzheimer’s disease (AD), including neuroinflammation, synaptic dysfunction, and protein aggregation. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main phytocannabinoids from Cannabis sativa, interact with the endocannabinoid system and may influence neuronal and glial signaling pathways relevant to AD pathology.

This mini review summarizes evidence from transgenic animal models and clinical studies evaluating CBD, THC, and their combination in AD.

Preclinical studies show that CBD and THC reduce β-amyloid accumulation, attenuate tau phosphorylation, and regulate neuroinflammatory responses, often associated with improvements in learning and memory. Cognitive outcomes appear to depend on cannabinoid composition, with CBD or THC administered individually showing more consistent effects, while combined CBD + THC effects appear dose- and ratio-dependent.

Clinical evidence in AD patients remains limited and primarily reports improvements in neuropsychiatric symptoms, such as reductions in agitation, nighttime activity, and behavioral disturbances, whereas cognitive improvements are modest. Cannabinoid-based treatments are generally well tolerated, with mild sedation, somnolence, or disorientation as the most reported adverse effects.

Overall, current data support the biological plausibility of cannabinoids as modulators of neuroinflammatory and synaptic processes in AD. However, heterogeneity in formulations, dosing, and study design limits firm conclusions. Future research should focus on dose optimization, biomarker-guided clinical trials, and long-term safety assessments to better define their therapeutic potential in AD.”

https://pubmed.ncbi.nlm.nih.gov/42211879

“The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.”

 “cannabinoids should be viewed as pleiotropic modulators of AD-relevant processes rather than as agents acting through a single unified mechanism.”

“cannabinoid-derived compounds with combined receptor-mediated and intrinsic antioxidant properties may represent promising therapeutic candidates.”

https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2026.1833021/full

Emerging preclinical evidence supports a potential role for cannabidiol in the management of sickle cell disease

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Sickle cell disease causes recurring pain, inflammation, vascular injury, and organ damage, creating a need for therapies that can address several disease mechanisms at once. Emerging preclinical research suggests that cannabidiol may have value through its analgesic, anti-inflammatory, antioxidant, and vascular effects. The evidence reviewed indicates that CBD can influence pathways involved in sickle cell pain and inflammatory injury while potentially helping protect tissues from downstream damage. Together, these findings support CBD as a promising therapeutic candidate for addressing both pain and underlying biological complications associated with sickle cell disease.

“Sickle cell disease (SCD) imposes a substantial global health burden, with acute and chronic pain representing a major component of morbidity. Standard pain management, largely opioid-based, carries significant risks and often provides inadequate long-term relief, highlighting an unmet need for alternative analgesics as well as disease modifiers.

Medicinal cannabinoids have analgesic and antiinflammatory properties; most clinical studies so far have used Δ9-tetrahydrocannabinol (THC)-containing products with conflicting outcomes. In contrast, purified cannabidiol (CBD) has a broader spectrum of action beyond the endocannabinoid system, lacks psychoactive effects and associated long-term risks, allows safe dose optimization and can be prescribed legally in many settings.

Here, we review evidence for CBD’s potential analgesic and disease-modifying properties for management of SCD.

Pain in SCD arises from local tissue inflammation and neuroinflammation, compounded by abnormal pain modulation and pro-nociceptive CNS alterations. CBD may attenuate the pathophysiological processes of SCD by modulating pro-inflammatory immune pathways, reducing oxidative stress and suppression of neurogenic inflammation. CBD also has a direct inhibitory effect on afferent nociceptive pathways. Furthermore, CBD has an important pain-modulating role by suppressing excitatory mechanisms in the dorsal root ganglia and CNS. Additionally, CBD may modulate pain-processing brain networks and attenuate opioidinduced reward-seeking behavior.

Although human data are very limited, emerging preclinical findings and early patient reports offer cautious optimism for CBD as a therapeutic option with potential disease-modifying properties in SCD. Clinically meaningful benefits may be expected in specific patient subgroups, identifiable through well-designed clinical and mechanistic studies focused on pain processing and neuroinflammation.”

https://pubmed.ncbi.nlm.nih.gov/42206420

https://haematologica.org/article/view/14205