Category Archives: Epilepsy

Cannabis and Cannabinoids: The Medical Potential of Cannabidiol in Mental and Neurological Disorders

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Cannabidiol (CBD) has become one of the most widely studied cannabis compounds for its potential effects on the brain and nervous system.

This review examines evidence across a range of mental and neurological disorders, including anxiety, depression, psychosis, epilepsy, neurodegenerative diseases and other conditions involving altered brain signaling or inflammation.

The research highlights CBD’s broad therapeutic potential while helping clarify the biological mechanisms that may underlie its effects.

“Background/Objectives: Mental and neurological disorders contribute substantially to the global burden of disease, affecting people of all ages and backgrounds. As their prevalence increases with age, their overall impact is expected to grow in the coming decades. Although psychological and pharmacological treatments are available, many patients fail to achieve satisfactory outcomes, underscoring the need for improved therapeutic strategies. Cannabis sativa L. has been used for medicinal purposes for centuries, and cannabidiol (CBD) has attracted increasing attention because of its broad therapeutic potential. Scientific studies indicate that CBD may be beneficial in several mental and neurological disorders. 

Methods: A comprehensive literature search was conducted to identify articles investigating the therapeutic potential of CBD and cannabis in selected disorders. 

Results: Evidence from preclinical and clinical studies, together with findings from the broader cannabis literature, indicates that CBD may offer therapeutic benefits in a range of conditions, including Alzheimer’s and Parkinson’s disease, anxiety disorders, and epilepsy. Emerging data also support its potential use as an adjunctive therapy for COVID-19. Current research has improved understanding of the neurobiological mechanisms underlying these disorders and the molecular pathways through which CBD may exert its effects. CBD has demonstrated good tolerability, with predominantly mild adverse effects and a favorable safety profile. 

Conclusions: Despite promising findings, many available studies are preclinical or involve small patient cohorts, and the mechanisms underlying the therapeutic effects of CBD remain incompletely understood. Further well-designed, randomized, controlled, multicenter trials are needed to establish the efficacy and safety of CBD and support its integration into clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/42653735

“The Cannabis plant has been used for medicinal purposes for thousands of years, with therapeutic indications mentioned in the medical texts of ancient civilizations.”

“These findings support the safety and clinical applicability of CBD and further suggest its potential as a therapeutic agent.”

“CBD is a promising therapeutic candidate for several mental and neurological disorders.”,

https://www.mdpi.com/1424-8247/19/8/1238


Anticonvulsant effects, safety, and sex-dependent molecular signatures of cannabidiol treatment in a preclinical model of audiogenic epilepsy

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Cannabidiol (CBD) is already well known for its anticonvulsant properties, but researchers are continuing to investigate how its effects may differ by sex and which molecular pathways are involved.

In this preclinical study, CBD reduced seizure activity in a model of audiogenic epilepsy while researchers also evaluated treatment safety and sex-dependent changes in gene expression and molecular signaling.

The findings add new detail to our understanding of how CBD may control seizures and suggest that biological sex could influence some of its underlying effects

“Roughly one-third of patients with epilepsy remain drug resistant, underscoring the need for novel therapeutic strategies. Although cannabidiol (CBD) has recently been approved for specific epileptic encephalopathies, its anticonvulsant mechanisms and the influence of biological sex on treatment response remain incompletely understood.

In this preclinical study, we evaluated the efficacy, tolerability, pharmacokinetics, and molecular effects of CBD in the GASH/Sal hamster, a genetic model of audiogenic generalized tonic-clonic seizures.

Animals received intraperitoneal CBD (200 mg/kg) either acutely or chronically for 14 days. CBD concentrations were measured in serum and brain, while seizure severity, latency, and neuroethological parameters were assessed following acoustic seizure induction. Safety was evaluated through body weight, hematological, and biochemical analyses, and gene expression profiling was performed in the inferior colliculus, the primary epileptogenic focus. CBD achieved measurable systemic and brain exposure after both acute and chronic administration, despite substantial inter-individual variability and no significant sex differences in drug concentrations.

CBD reduced audiogenic seizure severity in a time-dependent manner, with greater protection after chronic treatment.

CBD also prolonged latency to seizure onset in both sexes (earlier in females). Although complete seizure suppression was more frequent in females than males (37.5% vs. 12.5% after chronic treatment), direct sex comparisons did not reach statistical significance.

Notably, higher serum and brain CBD concentrations were associated with lower seizure severity. Chronic CBD administration was well tolerated in both sexes, affecting selected hematological parameters without altering body weight or liver function. Gene expression profiling revealed that transcriptional organization of the inferior colliculus was driven predominantly by biological sex rather than by seizure induction or CBD treatment. Marked sex-dependent differences were observed in serotonergic, endocannabinoid, purinergic, and Sigmar1-related neuroprotective pathways. Within this molecular context, seizure stimulation modulated Trpv1 and Slc29a1, whereas chronic CBD induced pathway-specific, sex-dependent changes involving 5-Htr1a, Adora1, and Cnr1, without eliciting widespread transcriptional remodeling.

Collectively, these findings identify CBD as a well-tolerated anticonvulsant in the GASH/Sal model and suggest that pharmacokinetic exposure and the sex-specific molecular organization of the epileptogenic focus contribute to variability in treatment response, highlighting the importance of considering biological sex in cannabinoid-based epilepsy research.”

https://pubmed.ncbi.nlm.nih.gov/42630256

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1745696/full


Cannabidiol Attenuates Seizure Progression and Recognition Memory Deficit Induced by Hippocampal HCN1 Knockdown in the Kindling Model of Epilepsy in Male Rats

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Epilepsy can involve both recurrent seizures and cognitive impairment, particularly when hippocampal signaling is disrupted. In male rats with reduced hippocampal HCN1 expression, cannabidiol (CBD) slowed seizure progression and improved recognition-memory deficits in the kindling model of epilepsy. The findings support CBD as a potential therapeutic approach for epilepsy involving HCN1 dysfunction and associated cognitive impairment.

“Epilepsy is a neurological disorder characterized by excessive neuronal firing, frequently originating in the hippocampus. Hyperpolarization-activated cyclic nucleotide-gated channel-1 (HCN1) regulates neuronal excitability and resting membrane potential, yet its role in seizure progression remains unclear.

Cannabidiol (CBD), an effective anticonvulsant, may exert part of its effects through HCN1.

This study investigated the contribution of HCN1 to seizure progression, synaptic plasticity, and CBD-mediated neuroprotection.

Rats were implanted with stimulation electrodes in the perforant path (PP) and recording electrodes with a guide cannula in the dentate gyrus (DG). One week later, lentiviral shRNA-HCN1 was injected into the DG, followed by PP electrical kindling. CBD (100 ng/2 μL) was administered every other day in shRNA-HCN1-treated or non-manipulated animals. Seizure severity was assessed using Racine’s scale. Synaptic transmission, paired-pulse plasticity, and long-term potentiation (LTP) were evaluated by extracellular field recordings, HCN1 function by whole-cell patch-clamp recordings of Ih (Hyperpolarization-activated current), HCN1 expression by RT-qPCR, and recognition memory using the novel object recognition (NOR) test.

Kindling reduced HCN1 mRNA expression, which was further decreased by shRNA-HCN1. HCN1 knockdown accelerated seizure progression, prolonged after-discharge duration, increased spike activity, reduced the sag ratio, and impaired synaptic transmission, paired-pulse plasticity, LTP, and object recognition memory in fully kindled rats.

CBD significantly attenuated these electrophysiological and recognition memory deficits, although its protective effects were partially reduced following HCN1 knockdown.

These findings indicate that HCN1 contributes to seizure progression and hippocampal dysfunction, while CBD exerts anticonvulsant and neuroprotective effects through both HCN1-dependent and HCN1-independent mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/42532179

“CBD attenuates seizure severity and rescues recognition memory deficits.”

“This study provides direct experimental evidence that hippocampal HCN1 channels play a vital protective role against seizure progression and recognition memory disturbance in the kindling model. Furthermore, we found that the functional involvement of these channels in the DG is an essential and novel mechanism underlying the anticonvulsant and neuroprotective effects of CBD.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390826002893?via%3Dihub

CBD-rich oil nanoemulsion mitigates long-term testicular and endocrine toxicity induced by prenatal valproic acid exposure in rats

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“Valproic acid is a widely used antiepileptic drug and a recognized model of developmental reproductive toxicity, as exposure during critical periods of testicular development can lead to persistent endocrine and reproductive dysfunction in adulthood.

Cannabidiol (CBD) has therapeutic potential in several pathological conditions but exhibits low oral bioavailability due to its lipophilic nature.

This study evaluated whether chronic treatment with a CBD-rich corn oil nanoemulsion could attenuate long-term testicular and endocrine alterations induced by prenatal valproic acid exposure in rats.

CBD-rich nanoemulsions were prepared and physicochemically characterized. On gestational day 12.5, pregnant rats received a single intraperitoneal dose of valproic acid (500mg/kg). In adulthood, male offspring from valproic acid-exposed dams were treated orally with CBD nanoemulsions at doses of 1 or 2mg/animal, administered twice daily. After euthanasia, testes were collected for morphometric, biochemical, and hormonal analyses.

Prenatal exposure to valproic acid induced persistent testicular alterations, including reduced Leydig cell number, decreased serum testosterone levels, reduced seminiferous epithelium height, and increased seminiferous tubule diameter. Increased activities of superoxide dismutase and glutathione S-transferase suggested an adaptive antioxidant response. These findings are consistent with long-term testicular and endocrine dysfunction following developmental exposure to an endocrine-disrupting drug.

Importantly, treatment with the CBD-rich nanoemulsion reversed the morphometric, hormonal, and oxidative alterations induced by valproic acid.

Overall, these results indicate that nanoformulated CBD may mitigate long-term reproductive toxicity induced by prenatal valproic acid exposure, highlighting the importance of drug formulation in determining the biological effects of cannabinoids on the male reproductive system.”

https://pubmed.ncbi.nlm.nih.gov/42342051

“In conclusion, our findings provide preclinical evidence that chronic treatment with a CBD-rich corn oil nanoemulsion attenuates several reproductive effects induced by prenatal exposure to valproic acid in male rats.”

https://www.sciencedirect.com/science/article/abs/pii/S0890623826001401?via%3Dihub

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

Whole Plant Cannabinoid Nonpharmaceutical Treatment Protocols for a Young Male With Dravet Syndrome

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“Objective: This case report describes the outcomes of a novel, conservative approach for a young male patient with Dravet syndrome, which is a genetic epileptic encephalopathy resulting in frequent and recalcitrant seizures and developmental delays.

Clinical features: A male infant began to experience seizures before 7 months of age, and genetic testing revealed an SCN1A mutation, confirming the diagnosis of Dravet syndrome. At age 7, despite standard polypharmacy consisting of antibiotics, steroids, and antiepileptic drugs, he continued to suffer from approximately 25 to 28 daily tonic-clonic refractory seizures.

Intervention and outcome: The clinical objective was to restore the function of the endocannabinoid system by integrating very low-dose, whole-plant extracted, naturally chiral, hemp-derived phytocannabinoid formulations, and broad environmental and dietary modifications. Within the first week of treatment, the patient had only 1 to 2 mild seizures per day. Four years later, all pharmaceuticals were discontinued, and by age 12, the patient’s daily hemp formulation was reduced to as-needed status. At the time of this writing, the patient was 16 years of age and had an average of 7 to 10 very mild petit mal seizures per month. The whole plant hemp formulations generated no observable side effects.

Conclusion: This case study demonstrates conservative comanagement of a patient with a catastrophic seizure disorder using novel nonpharmaceutical comanagement strategies.”

https://pubmed.ncbi.nlm.nih.gov/42152927

“The objective of this case report is to describe 10 years of treatment effects of whole plant hemp cannabidiol (CBD) extracts in a young male patient with Dravet syndrome, who was responding poorly to the standard polypharmacy approach.”

“Chronic seizure activity in a young male patient was reduced after the introduction of whole plant extracted hemp and diet modifications”

https://www.sciencedirect.com/science/article/abs/pii/S1556370725000379

Preliminary Prospective Study of Pharmaceutical-Grade Cannabidiol for Seizure Frequency, Anxiety, and Comorbid Symptoms in Pediatric Epilepsy: Associations With Circulating Endocannabinoids and Lipid Biomarkers

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“Anxiety commonly co-occurs with childhood epilepsy, yet treatments targeting both are limited.

Epidiolex (cannabidiol, CBD) is an FDA-approved treatment for seizures associated with rare pediatric epilepsies and may have anxiolytic effects. We evaluated its effects on seizures and anxiety in pediatric patients with refractory epilepsy, representing diverse seizure etiologies and circulating endocannabinoids and related biomarkers.

Twelve participants (12.17 ± 5.17 years; 6 female) initiated Epidiolex for 4-6 weeks. Caregivers completed pre- and post-treatment seizure diaries; validated anxiety and quality-of-life assessments; and plasma endocannabinoids, related lipids, and CBD metabolites-including 7-hydroxycannabidiol (7-OH-CBD)-were measured.

Post-treatment, 73% of caregivers reported improvements in anxiety and seizure frequency with minimal side effects and improved sleep. Plasma 2-arachidonoylglycerol increased from baseline to study end, with greater elevations in those with lower baseline concentrations. Plasma 7-OH-CBD increased from baseline to study end, confirming systemic CBD exposure.

Epidiolex may provide anxiolytic benefits across pediatric epilepsy, potentially involving endocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/42033397

https://journals.sagepub.com/doi/10.1177/08830738261439213

Real-world effectiveness of highly purified cannabidiol in epilepsy associated with 15q11.2-q13.1 duplication and deletion syndromes: A multicenter study

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“This multicenter retrospective study evaluated the effectiveness and safety of highly purified cannabidiol (CBD) in 22 patients with 15q11.2-q13.1 duplication or deletion syndromes (15q-DDS), including 12 with 15q duplication syndrome (dup15q) and 10 with Angelman syndrome (AS).

Median (interquartile range [IQR]) age at CBD initiation was 14.5 (10-22.5) years, with a median (IQR) follow-up of 21 (14-33) months. All dup15q and two AS patients presented with a Lennox-Gastaut phenotype.

At last observation, mean seizure reduction was 55.7% (95% confidence interval 38.7-72.7), with 63.6% patients achieving ≥50% reduction, 40.9% achieving ≥75% reduction, and 18.2% achieving seizure freedom. Tonic seizures in dup15q and myoclonic seizures in AS showed the most notable reductions. EEG improvement was observed in 7/16 patients, with marked improvement observed in two dup15q patients.

Clinical improvement on the Clinical Global Impression-Improvement scale was reported in 72.7%, alongside nonseizure benefits such as improved sleep, behavior, and attention in a subset of patients. CBD was well tolerated; no patient discontinued CBD due to side effects alone, and retention at last visit was 81.8%.

These findings suggest that CBD may provide clinically meaningful benefit in patients with 15q-DDS, including seizure reduction and improvements in sleep, behavior, and attention in selected cases.

PLAIN LANGUAGE SUMMARY: Epilepsy secondary to 15q11.2-q13.1 duplication or deletion syndromes (15q-DDS) is often severe, making daily life difficult for patients and their families. In this study, treatment with highly purified cannabidiol (CBD) reduced seizures in many patients with 15q-DDS. CBD was generally well tolerated, and caregivers also reported improvements in sleep, behavior, and attention in a number of cases.

Overall, these findings suggest that CBD may be a helpful treatment option for people with 15q-DDS.”

https://pubmed.ncbi.nlm.nih.gov/41992447

“Given the substantial disease burden and drug resistance typical of epilepsy in 15q-DDS, CBD may emerge as a promising therapeutic option in these patients.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70241

Real-world effectiveness and tolerability of highly purified cannabidiol in patients with monogenic developmental and epileptic encephalopathies with highly active epilepsy

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“Developmental and epileptic encephalopathies (DEEs) represent a group of disorders characterized by developmental slowing or regression together with seizures, that are often drug-resistant.”

“With this background, we investigated the effectiveness and tolerability of highly purified CBD in a cohort of monogenic DEEs, focusing on patients with highly active epilepsy.”

“Taken together, these findings suggest that CBD represents a valid therapeutic option for patients with DEEs and highly active epilepsy, providing meaningful seizure reduction even in the most treatment-refractory cases.”

“Our study shows that highly purified CBD may represent a feasible treatment option for patients with DEEs and highly active epilepsy.”

https://www.epilepsybehavior.com/article/S1525-5050(26)00157-5/fulltext

Elucidating the putative role of cannabigerol: a hypothesis-generating review of neuroinflammatory and neuroprotective mechanisms with implications for drug-resistant epilepsy

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“Drug-resistant epilepsy (DRE) affects approximately 30% of individuals with epilepsy and remains a major clinical challenge despite the availability of multiple antiseizure medications (ASMs). Beyond recurrent seizures, accumulating evidence implicates chronic neuroinflammation, blood-brain barrier (BBB) dysfunction, excitotoxic injury, and progressive neurodegeneration as processes associated with epileptogenesis and disease progression.

While cannabidiol (CBD) has demonstrated clinical efficacy in specific DRE syndromes, increasing recognition of these mechanisms has motivated interest in exploratory, mechanism-oriented approaches that extend beyond direct seizure suppression.

Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with a pleiotropic pharmacological profile, interacting with cannabinoid receptors, transient receptor potential (TRP) channels, nuclear receptors such as peroxisome proliferator-activated receptor gamma (PPARγ), and additional neuromodulatory targets.

Preclinical studies indicate that CBG can modulate inflammatory, oxidative, and cell-survival pathways across diverse experimental models of neuroinflammatory and neurodegenerative injury. Importantly, most available evidence derives from non-epilepsy paradigms or in vitro systems, and direct support for antiseizure efficacy or disease modification in epilepsy remains limited.

This review synthesizes current preclinical evidence on the molecular targets and mechanistic actions of CBG, with particular emphasis on neuroimmune modulation and neuronal vulnerability, while critically addressing the limitations and translational gaps of the existing literature. Rather than providing confirmatory evidence, this work is intended as a hypothesis-generating framework to inform future epilepsy-focused studies evaluating whether modulation of neuroinflammatory and neurodegenerative pathways by CBG may hold relevance within disease-modifying research strategies for DRE.”

https://pubmed.ncbi.nlm.nih.gov/41919226

“Recent preclinical research has highlighted CBG as a multi-target phytocannabinoid capable of modulating neuroinflammatory, oxidative, and cell-survival pathways across diverse experimental systems.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1755956/full