Identification of cannabichromevarin as a potent stabilizer of the measles virus prefusion F protein: structural insights from long-timescale molecular dynamics

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“Measles virus (MeV) remains a serious public health concern, necessitating the development of effective antivirals targeting the viral fusion (F) glycoprotein.

This study employed a robust computational pipeline, including molecular docking, 1000 ns all-atom molecular dynamics (MD) simulations, and free energy landscape (FEL) analysis, to evaluate minor cannabinoids as novel inhibitors of the MeV F protein.

Initial virtual screening identified Cannabichromenic acid (CBCA), Cannabichromevarin (CBCV), and Cannabiripsol (CBR) as high-affinity leads, with docking scores of – 8.5, – 8.2, and – 8.1 kcal/mol, respectively, outperforming the reference inhibitor AS-48 (- 7.6 kcal/mol). Post-MD binding free energy calculations (MM-GBSA) further confirmed the thermodynamic superiority of CBCV (ΔGbind = – 44.7 kcal/mol) and CBCA (ΔGbind = – 30.1 kcal/mol) over the reference.

Dynamic analyses revealed that CBCV and CBCA effectively stabilize the F protein in its inactive prefusion conformation through a conformational locking mechanism. CBCV induced the most significant structural compaction (Rg = 2.4 nm) and displayed the sharpest global energy minimum (0.3 kcal/mol) in the FEL. Furthermore, ADMET profiling and ProTox-3.0 toxicity modeling identified CBCV as the most promising lead, possessing excellent drug-likeness, an inactive toxicity profile, and predicted blood-brain barrier permeability.

This work establishes minor cannabinoids as novel scaffolds for anti-MeV drug development, positioning CBCV as a strong candidate for treating systemic and neurological complications of measles, such as Subacute Sclerosing Panencephalitis.”

https://pubmed.ncbi.nlm.nih.gov/42286054

https://www.nature.com/articles/s41598-026-50199-6

“Cannabichromevarin (CBCV), also known as cannabivarichromene) is one of over 100 variants of cannabinoid chemical compounds that act on cannabinoid receptors. CBCV is a phytocannabinoid found naturally in cannabis, and is a propyl cannabinoid and an effective anticonvulsant and used to treat brain cancer and epilepsy“

Comparing cannabinoid extracts for treating cancer-related symptoms: a randomized placebo-controlled, triple-blind aggregate n-of-1 clinical trial

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“Context Despite widespread use of medical cannabinoids for cancer-related symptom management, systematic reviews consistently call for more clinical trial evidence.

Objectives This study aimed to determine and explore responses to medical cannabis extracts for cancer-related symptoms using patient-centred methodology.

Methods An aggregate N-of-1 study of clinically stable but symptomatic outpatients from 8 Canadian cancer centres, comparing three blinded sublingual extracts (THC; CBD; 1:1) with placebo, self-titrated within a prescribed schedule for four consecutive days each in randomized sequence for up to three cycles (total 16-48 days). The primary outcome was the frequency of at least a 1.4-point (20%) improvement in a 7-point Patient Global Impression of Change (PGIC) for at least one extract over placebo.

Results The primary outcome was achieved in 50/89 (56%) participants (p<0.001), with no significant preference of one extract over another on average, but a clear preference between extracts for most individuals. Changes in a modified Edmonton Symptom Assessment score and participant preference (n=91) confirmed these findings. Improved sleep, tiredness and anxiety contributed most to the overall improvement regardless of primary symptom. There were no demographic predictors of response. Mild adverse effects were common with all extracts including placebo but resolved rapidly on dose reduction/cessation. Moderate/severe adverse effects were rare but associated with THC.

Conclusions Medical cannabis extracts can be meaningfully beneficial for cancer-related symptoms in approximately 50% of patients, particularly for sleep and related symptoms. A starting dose of 2.5mg of THC/CBD three times a day was well-tolerated. Personalization of treatment is required to optimize response.

Key Messages Three cannabinoid extracts (THC; CBD; and 1:1) were significantly more effective than placebo based on a Patient Global Impression of Change, a modified Edmonton Symptom Assessment System and participant preference. The most helpful extract differed between individuals. Benefits were mostly in sleep, anxiety, and daytime tiredness irrespective of primary symptom.”

https://www.medrxiv.org/content/10.64898/2026.05.31.26354558v1

Acute Effects of Cannabinoid Combination Therapies in a Western Diet-Induced Murine Model of Metabolic Liver Disease

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“Pharmacological treatment of metabolic-dysfunction-associated steatohepatitis remains challenging due to its complex pathophysiology. The endocannabinoidome (eCB) has emerged as a promising therapeutic target given its central role in energy homeostasis and its pharmacological tractability. Western-style diets high in fat and sugar exacerbate metabolic liver disease, highlighting the need for effective interventions.

Here, we investigated the therapeutic potential of cannabinoid combinations targeting the eCB-liver axis in a Western diet-induced model of metabolic dysfunction.

Two weeks of treatment reduced body weight, improved glycaemic control, and ameliorated liver pathology. These effects were accompanied by decreased liver weight, improved liver enzyme profiles, and reduced histological features of steatosis and injury.

Overall, these findings suggest that modulation of the eCB system can induce acute improvements in metabolic and hepatic parameters under conditions of diet-induced metabolic stress. These results support further investigation into the eCB system as a therapeutic target, particularly to elucidate underlying mechanisms and longer-term effects.”

https://pubmed.ncbi.nlm.nih.gov/42278403

“To our knowledge, this is the first study to investigate the therapeutic effects of combination cannabinoid treatment in a mouse model of metabolic liver disease.

Targeting the endocannabinoid system, even acute treatment markedly improved metabolic parameters, including significant weight loss, reduced fasting blood glucose, and improved liver condition.

The triple cannabinoid combination produced the most pronounced effects, improving markers of hepatic injury and inflammation.

Mechanistically, modulation of the LPI/GPR55 and GPR119/incretin axes highlights the therapeutic potential of targeting the gut–liver axis using small-molecule agonists and endogenous bioactive lipids.”

https://www.mdpi.com/1422-0067/27/11/4872

Chemical Characterization and Biological Potential of the Essential Oils from the Flowers of Two Cannabis sativa L. Cultivars from Komga, South Africa

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“Cannabis sativa L. is a medicinal plant cultivated globally due to its remarkable historical and scientific relevance. Through the consumption of its flowers, also referred to as inflorescences, which contain a high content of cannabinoids, terpenes and polyphenols, the therapeutic properties of C. sativa can be harnessed.

This study therefore aimed to determine the chemical profile, antioxidant and anti-inflammatory activities of the essential oils (EOs) obtained from the fresh and dried flowers of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, to assess which cultivar has greater biological potential.

The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while the in vitro antioxidant and anti-inflammatory activity of the EOs was analyzed using the DPPH and EAD methods, respectively. The identified constituents from the EOs were molecularly docked against NOX2 and NIK (NF-κB-inducing kinase) protein, which are implicated in oxidative stress. The afforded EOs were yellow (pale and bright yellow) in color with a sweet to mildly sweet aroma description.

A total of 51 constituents were identified in both fresh and dry oils from the Lifter cultivar, while the Cherrywine cultivar contained a total of 44 constituents. Eighteen compounds, were found to be the main chemical constituents consistent in the flower EOs of both cultivars, notably, caryophyllene (10.71-19.96%), levo-β-pinene (1.37-13.21%), humulene (5.88-9.77%), caryophyllene oxide (4.32-7.49%), D-limonene (1.40-5.48%), α-pinene (2.22-5.22%), nerolidol (0.63-4.97%), cis-β-ocimene (0.22-4.37%), linalool (1.12-4.28%), selina-3,7(11)-diene (0.15-4.23%), humulene-1,2-epoxide (1.23-3.32%), guaiol (0.17-2.60%), (+)-β-selinene (1.20-2.51%), trans-α-bergamotene (0.68-2.37%), β-ocimene (0.90-2.27%), fenchol exo- (0.15-1.27), terpineol (0.14-1.38%) and α-terpineol (0.19-0.75%). The fresh Lifter flower oil (LFO) showed 50% inhibition at 100 μg/mL, with an IC50 of 69.50 ± 4.05 µg/mL against DPPH, suggesting moderate to low radical scavenging activity. The maximum percentage inhibition response of DLFO, CFO and DCFO remained below 50% at all concentrations.

The antioxidant activity of fresh LFO may be attributed to its overall chemical composition. The flower oils showed in vitro inhibition of protein denaturation; however, the high standard deviation relative to the mean IC50 values limited the ability to rank the samples’ potencies. Further in silico studies on the putative constituents in the Lifter and Cherrywine cultivars revealed β-bisabolene and α-curcumene as potential molecular targets, with binding energy scores of -7.7 and -7.9 kcal/mol, respectively.

Thus, the study findings highlight the promising biological importance of C. sativa inflorescences in the management of oxidative stress-related conditions. Further studies may investigate the influence of environmental growing conditions on their chemical composition, total ROS analysis, pharmacokinetic properties, and in vivo efficacy against oxidative damage to DNA, proteins and lipids. Evaluating the toxicity of the flower EOs is also recommended.”

https://pubmed.ncbi.nlm.nih.gov/42280118

https://www.mdpi.com/1420-3049/31/11/1814


Cannabidiol corrects sleep deficits and reduces spontaneous seizures in Angelman syndrome model mice

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“The off-label use of cannabidiol (CBD) has outpaced investigation. We assessed the effects of CBD in Angelman syndrome model mice lacking the Ube3a gene and found that chronic injection of CBD increased rapid-eye movement sleep during the dark cycle, restored “Siesta”, improved sleep homeostasis, and reduced spontaneous seizures following flurothyl kindling.”

https://pubmed.ncbi.nlm.nih.gov/42265437

“Cannabidiol (CBD), a major non-psychoactive and non-psychotomimetic phytocannabinoid constituent of cannabis, is gaining attention for its medical benefits. The multitarget and complex pharmacological nature of CBD in the central nervous system makes it a unique candidate for treating a wide range of complex neurological and psychiatric conditions, including seizures and sleep deficits.”

“This study primarily suggests that CBD restores REM sleep deficits in AS model mice. One hypothesis is that this effect may be related to CBD’s ability to enhance acetylcholine signaling, a central regulator of REM sleep. CBD’s ability to reduce the frequency of SRS, beyond its effects on induced-seizure suppression, further strengthens the preclinical evidence supporting its potential for clinical translation.” 

https://www.nature.com/articles/s41386-026-02462-7

Cannabidiol reduces atypical absence seizures and epileptic spasms in a Gabrb3+/D120N mouse model of Lennox-Gastaut syndrome

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“Objective: Lennox-Gastaut syndrome (LGS) is a drug-resistant developmental and epileptic encephalopathy (DEE). Preclinical drug development for LGS is constrained by a lack of syndrome-relevant animal models. We aimed to evaluate a Gabrb3+/D120N knock-in (KI) mouse model of LGS by quantifying atypical absence seizures and epileptic spasms and assessing their sensitivity to antiseizure agents.

Methods: Video-EEG recordings of adult (10-week-old) KI and wild-type (WT) littermates were scored for atypical absence seizures, and the acute effects of ethosuximide (200 mg/kg), ulixacaltamide (60 mg/kg), and cannabidiol (CBD, 100 mg/kg) on seizure incidence and duration were evaluated using a within-subjects, crossover design. Video recordings of postnatal day 16 (P16) KI and WT littermates were scored for epileptic spasms, and the effects of once-daily dosing with vigabatrin (100 mg/kg) and CBD (100 mg/kg) from P13 to P15 were evaluated against vehicle.

Results: Adult KI but not WT mice exhibited spontaneous atypical absence seizures. CBD, ethosuximide, and ulixacaltamide reduced seizure incidence and duration. Epileptic spasms were more frequent in KI than in WT mice at P16. CBD and vigabatrin significantly reduced spasm frequency compared to the vehicle.

Significance: Gabrb3+/D120N mice display robust atypical absence seizures and neonatal spasms that respond to antiseizure agents, supporting the predictive validity of this model as a preclinical platform for LGS drug discovery. CBD produced reductions in both atypical absence seizures and infantile spasms, suggesting that this model may be utilized as a translational tool for evaluating novel cannabinoid therapeutics for DEEs.

Plain language summary: Lennox-Gastaut syndrome (LGS) is a rare type of epilepsy that’s hard to treat and poses a challenge for developing new drugs. Finding suitable animal models that accurately represent LGS is crucial. This article describes the development of a mouse model of LGS with a genetic mutation that increases seizures and epileptic spasms. We tested how different antiseizure drugs affect the mice. CBD, ethosuximide, and ulixacaltamide reduced seizure incidence and duration. CBD and vigabatrin also reduced spasm frequency in young mice. These promising results suggest the mouse model could be a valuable tool for drug discovery in LGS.”

https://pubmed.ncbi.nlm.nih.gov/42274296

“We report for the first time that the clinically approved cannabinoid ASM CBD can reduce both atypical absence seizures and infantile spasms in the Gabrb3+/D120N mouse, providing a benchmark for future evaluation of cannabinoid therapies.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70289

Therapeutic Drug Monitoring of Cannabinoids: Therapeutic Reference Ranges for Delta-9-tetrahydrocannabinol in Medical Cannabis, Nabiximols, Dronabinol and Nabilone

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“Medical cannabis, nabiximols, dronabinol and nabilone are used for various medical conditions.

Despite their pronounced pharmacokinetic variability and complex concentration-effect relationships, therapeutic drug monitoring recommendations are lacking. We aimed to identify therapeutic reference ranges based on blood concentration-clinical effect relationships. Studies reporting blood concentrations and clinical effects/adverse effects or assessing cannabinoid receptors 1 and 2 occupancy were selected through a systematic literature search in the MEDLINE database via PubMed. Twenty-three articles were selected for vaporized/smoked medical cannabis, three for nabiximols, nine for dronabinol and one for nabilone. No article was identified for delta-9-tetrahydrocannabinol-dominant cannabis extracts.

For vaporized/smoked medical cannabis, an orienting therapeutic reference range of 15-30 ng/mL delta-9-tetrahydrocannabinol was identified for pain reduction in diabetic peripheral neuropathy, while concentrations of <20 ng/mL delta-9-tetrahydrocannabinol were significantly correlated with intraocular pressure reduction and 7.5-10 ng/mL with improvement of tic symptoms. Half-maximum effective concentrations of 7-29 ng/mL delta-9-tetrahydrocannabinol were reported for “high” effects.

For nabiximols, a preliminary therapeutic reference range of 1-10 ng/mL delta-9-tetrahydrocannabinol was determined for treating neuropathic pain and spasticity in adults with multiple sclerosis. For chemotherapy-induced nausea and vomiting, a preliminary therapeutic reference range of 1-5 ng/mL for nabilone and 5-15 ng/mL delta-9-tetrahydrocannabinol for dronabinol was assessed.

In conclusion, relatively low concentrations may be sufficient to achieve therapeutic effects across all substances studied, with medical cannabis demonstrating these effects at lower concentrations than typically observed in recreational use. Nevertheless, adverse effects at therapeutic reference ranges cannot be excluded.”

https://pubmed.ncbi.nlm.nih.gov/42269696

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2853-4984

Endocannabinoid system and skeletal muscle health: insights from cannabidiol

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“The endocannabinoid (EC) system is a complex network comprising endogenous ligands, enzymes responsible for their synthesis and degradation, and various receptors (including CB1 and CB2).

Present in many peripheral tissues, including skeletal muscle, EC system is now recognized to influence key physiological processes such as insulin sensitivity, mitochondrial metabolism, protein homeostasis and muscle development. Alterations in this system are associated with a variety of pathologies, including obesity, type 2 diabetes, sarcopenia, cachexia and muscle dystrophies.

In this context, cannabidiol (CBD), a phytocannabinoid devoid of psychoactive properties, is attracting growing interest as a potential therapeutic agent.

This article provides an analysis of the mechanisms by which the EC system, and more specifically the CB1 receptor, influences skeletal muscle development and function, while exploring emerging data on the potential benefits of CBD in various pathological conditions affecting skeletal muscle.”

https://pubmed.ncbi.nlm.nih.gov/42264146

“The endocannabinoid system (ECS) is composed of endogenous ligands (AEA, 2-AG), enzymes for their synthesis or degradation, and receptors (e.g., CB1, CB2). It also includes exogenous molecules like cannabidiol (CBD) produced from Cannabis sativa. Widely expressed in peripheral tissues such, the ECS plays a central role in the regulation of key skeletal muscle physiological processes, including insulin sensitivity, mitochondrial metabolism, protein homeostasis and skeletal muscle development.

Dysregulation of this system is associated with the development of metabolic and muscular disorders, such as obesity, type 2 diabetes, sarcopenia, cachexia and muscular dystrophies.

In this context, CBD, a non-psychoactive phytocannabinoid, has emerged as a potential therapeutic agent capable of modulating ECS activity, thereby contributing to the restoration of skeletal muscle function and homeostasis.”

https://www.sciencedirect.com/science/article/pii/S2212877826000803?via%3Dihub

Targeting Phantom Limb Pain with Cannabinoids in a Rat Model

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“Introduction: Phantom limb pain (PLP) is a debilitating neuropathic condition arising after limb loss or nerve injury, with limited effective treatments. Cannabinoids, including cannabidiol (CBD), β-caryophyllene (BCP), and Δ9-tetrahydrocannabinol (THC), possess analgesic and anti-inflammatory properties. This study evaluated their combined efficacy as preventive or delayed interventions in a rodent model of PLP.

Methods: To model PLP, a chronic constriction injury was used to mimic pre-amputation pain, followed by formalin-induced localized inflammation and complete sciatic nerve transection to simulate extremity amputation. Cannabinoid treatments (CBD/BCP/THC, CBD/BCP, or THC) or vehicle control were administered either preemptively on the day of axotomy (prevention paradigm) or after the emergence of pain behaviors (reversal paradigm). Progression of pain behaviors were assessed over a 72-day period, and modulation of spinal cytokine levels, glial reactivity, and GABAergic signaling was evaluated.

Results: Preemptive THC or CBD/BCP reduced PLP onset and severity, while the full combination was less effective. In contrast, with delayed treatment, CBD/BCP and the CBD/BCP/THC combination were most effective in mitigating PLP. Pain reduction was correlated with restoration of spinal GABAergic inhibition. All cannabinoid treatments decreased microglial and astrocyte reactivity and shifted cytokines toward an anti-inflammatory state.

Conclusion: Cannabinoid-based interventions demonstrate significant therapeutic promise for PLP, showing efficacy as both early and delayed treatments. Findings suggest that THC may exert greater therapeutic effects when administered pre-emptively, while CBD and BCP may offer greater therapeutic advantages in established pain states. These findings highlight the therapeutic potential of tailored cannabinoid interventions for neuropathic pain and underscore the importance of optimizing dosing strategies for maximal analgesic effect.”

https://pubmed.ncbi.nlm.nih.gov/42267080

“Cannabis contains a complex mixture of cannabinoids, terpenes, and flavonoids that have demonstrated therapeutic potential in a variety of pathologies and conditions. Their anti-inflammatory, analgesic, and antioxidant activities are believed to play a central role in mediating pain relief.”

“Our findings support the therapeutic potential of cannabinoid-based treatments in both preventing and reversing PLP, with efficacy varying by cannabinoid pairing and timing of treatment.

Together, these results underscore the therapeutic promise of cannabinoid-based treatments while highlighting the need to carefully consider how specific compounds and dosing strategies interact in different stages of pain.”

https://karger.com/mca/article/9/1/92/946968/Targeting-Phantom-Limb-Pain-with-Cannabinoids-in-a

Cannabidiol Protects Against 1-Methyl-4-Phenylpyridinium and Manganese-Induced Neurotoxicity via Nod-Like Receptor Protein 3 Inflammasome Suppression

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“Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurodegeneration, alpha-synuclein (α-Syn) accumulation, and neuroinflammation. The NOD-Like Receptor (NLR) family pyrin domain containing 3 NLRP3 inflammasome has recently been identified as a central mediator of PD-associated inflammatory responses.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid, exhibits anti-inflammatory and neuroprotective properties; however, its effects on NLRP3 inflammasome in PD remain insufficiently understood.

This study investigated the neuroprotective effects of CBD-rich oil against 1-methyl-4-phenylpyridinium (MPP+) and manganese-induced neurotoxicity in SH-SY5Y cells.

Cells were exposed to these substances with or without CBD co-treatment, and cell viability, α-Syn, dopamine, inflammatory markers [C reactive protein (CRP) and interleukin 18 (IL-18)], and NLRP3 expressions were evaluated.

MPP+ and manganese exposures significantly decreased cell viability and dopamine levels while increasing α-Syn accumulation and inflammatory markers. Manganese induced an approximately twofold upregulation in NLRP3 mRNA and 1.5-fold increase in protein expression.

CBD co-treatment preserved dopamine levels, attenuated α-Syn accumulation, reduced IL-18 and CRP concentrations, and attenuated NLRP3 expression.

These findings demonstrate that CBD-rich oil exerts neuroprotective effects in a PD cellular model by attenuating α-Syn accumulation, preserving dopamine homeostasis, which is associated with reduced NLRP3 expression and potential modulation of inflammasome-related signaling, supporting further investigation of CBD as a potential therapeutic strategy for PD.”

https://pubmed.ncbi.nlm.nih.gov/42262723

“There is growing interest in phytocannabinoids as potential interventions for neurodegenerative disorders. Cannabidiol (CBD), a non-intoxicating constituent of Cannabis sativa, exhibits neuromodulatory and neuroprotective properties, including anti-inflammatory and antioxidant effects mediated through multiple molecular targets relevant to basal ganglia function and PD symptomatology.”

“Accordingly, the present study investigated the neuroprotective potential of CBD-rich oil in an in vitro PD model using SH-SY5Y cells exposed to MPP+ and/or manganese.”

“In conclusion, CBD-rich oil mitigated multiple PD-relevant pathological features in a neurotoxicant-based cellular model. CBD reduced α-synuclein accumulation, preserved dopamine content, attenuated inflammatory markers, and was associated with reduced NLRP3 expression at both mRNA and protein levels. These findings support CBD as a potential neuroprotective agent and suggest that NLRP3 modulation may be a contributing mechanism.”

https://onlinelibrary.wiley.com/doi/10.1002/jbt.70957