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Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the field. The substantial progress made over the last decade has revealed genes, signalling pathways, molecules, and neuronal networks in pain control thus opening new clinical perspectives in pain management. In this respect, data on the epigenetic modulation of opioid and cannabinoid receptors, key actors in the modulation of pain, offered new perspectives to preserve the activity of opioid and endocannabinoid systems to increase the analgesic efficacy of opioid- and cannabinoid-based drugs. Similarly, upcoming data on cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant Cannabis sativa, suggests analgesic, anti-inflammatory, antioxidant, anticonvulsivant and ansiolitic effects and supports its potential application in clinical contexts such as cancer, neurodegeneration, and autoimmune diseases but also in health and fitness with potential use in athletes. Hence, in this review article, we summarize the emerging epigenetic modifications of opioid and cannabinoid receptors and focus on CBD as an emerging non-psychoactive cannabinoid in pain management in clinical practice, health, and fitness.

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Athlete performance and post-load recovery can be considered one of the most important and actively discussed topics in professional sport. One substance aimed at improving performance is cannabidiol (CBD), which has been actively gaining popularity with several studies published in recent years. The PubMed, Scopus, and Cochrane Library databases were searched from inception to April 2024 according to PRISMA recommendations to identify studies on the effects of CBD on exercise capacity and post-load recovery. An initial search identified 901 publications, of which seven fully met the inclusion criteria. Current evidence supports a limited beneficial effect of CBD on a number of physiological parameters, such as VO2, mean power, and relative mean power. At the same time, there were limited data on the beneficial effects of CBD on strength parameters (including vertical jump, counter movement jump, one repetition max bench press, and barbell back squat) and post-load recovery. Notably, most of the studies included in the analysis were conducted between 2021 and 2024, indicating a growing interest among researchers in the use of CBD in healthy, physically active individuals. Further studies are needed to assess the safety of different CBD administration protocols in professional athletes.

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Oleosomes are natural lipid droplets that can be extracted intact from oil seeds, forming oil/water emulsions. Their lipid cores, surrounded by a monolayer of phospholipids and proteins, make oleosomes suitable as carriers of hydrophobic bioactive compounds like cannabidiol (CBD). As CBD is crystalline at room temperature, it first has to be liquified to allow better encapsulation. This was done by heating (80 °C for 4 h) or by pre-solubilizing CBD in ethanol and then the liquified CBD was mixed with oleosome dispersions for the encapsulation. Both methods exhibit good encapsulation efficiency, but the results were significantly influenced by the ratio of CBD to lipid contents, regardless of the encapsulation method applied. At higher concentrations of CBD relative to that of the lipid in the oleosomes, the encapsulation efficiency decreased as saturation was attained. Moreover, the in vitro digestion analysis was conducted to investigate the potential of oleosomes as carriers to transport CBD. The relatively slow and steady release of CBD from oleosomes indicates that oleosomes are a slow-release carrier for hydrophobic functional ingredients. An important finding is that the encapsulation and in vitro digestive properties of the oleosomes remain unaffected by the presence of CBD, heating treatment or ethanol, which could bring more opportunities for the applications of oleosomes as carriers in various fields.

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The aim of this study was to determine the antiviral activity of cannabidiol (CBD) against SARS-CoV-2 infection. CBD is the second most studied cannabinoid obtained from Cannabis plants. We investigated the potential use of CBD, which has so far proven to have a positive effect on different diseases, in the SARS-CoV-2 infection. To test this, in vivo studies were carried out using K18-hACE2 transgenic mice. To reveal the potential therapeutic effect of the CBD at the histopathological and molecular level challenge experiments were performed. The study was designed with two groups (n = 10) and in the treatment group animals were infected with SARS-CoV-2 virus strain B.1.1.7 alpha before the administration of CBD. While the disease progressed and resulted in death in the control group that was infected by the virus alone, it was observed that the infection slowed down and the survival rate increased in the mice treated with CBD along with the virus. In this study, K18-hACE2 transgenic mice infected with the wild SARS-CoV-2 virus were used to investigate and prove the antiviral activity of CBD.

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There is increasing evidence that cannabidiol (CBD) use is associated with clinically significant liver enzyme (LE) elevations and drug-induced liver injury (DILI). The proportion of LE elevations and DILI events reported in the literature meet the Council for International Organizations of Medical Sciences' (CIOMS) classification of a common adverse drug reaction. However, these potential adverse events are unknown to many clinicians and may be overlooked. The increasing use of CBD for both medical and non-medical use necessitates clear direction in the diagnosis and management of CBD-associated hepatotoxicity. To our knowledge, no such clinical guidance currently exists. For people presenting with elevated LEs, CBD use should be screened for and be considered in the differential diagnosis. This narrative review will provide clinicians with guidance in the prevention, detection, and management of CBD-related hepatotoxicity.

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Due diligence is a fundamental component of ensuring a sustainable and legal wildlife trade that is also supportive of the livelihoods and businesses that depend on the trade. This is particularly true with species listed on the Convention on International Trade in Endangered Species (CITES) that are considered threatened or may become threatened by trade. Undertaking due diligence exercises requires access to information on which to base such decisions; however, the extent to which information is available is unclear. We used the trade in tropical pitcher plants (Nepenthes) for horticultural purposes as a case study to determine the extent to which information is available. A systematic survey of online trade was conducted for species described from 1996 to 2016. For the species found in trade, these were cross-referenced with the CITES trade database, and inquiries were made to the relevant CITES Management Authorities and National Focal Points Access and Benefit Sharing (ABS). Of 83 newly described species, 61% were offered for sale online in 2018. Despite all Nepenthes species being listed on CITES, only 23% (n = 19) of the species being sold online were reported in trade on the CITES Trade Database, and only 3 were from the countries of origin. Thirty-two of these species had no international trade recorded according to the database. Management authorities of CITES for the countries of origin confirmed trade had been permitted for 5 of 32 species. Lack of CITES records may be explained by trade under "Nepenthes spp." or as exempt parts and derivatives. However, permits to collect and commercialize are likely to be required as part of the Nagoya Protocol on ABS from the Convention on Biological Diversity. The ABS National Focal Points were contacted to determine whether collection or commercialization permits had been issued for the remaining species. Only 2 of 7 focal points replied, and both stated no permits had been issued. Lack of traceability information or response related to the issuance of collection and commercialization permits is concerning and hinders the due diligence of businesses and consumers wanting to ensure their trade is legal, sustainable, and ethical.

Definición de la legalidad de especies recién catalogadas en CITES en la horticultura comercial de plantas de jarra tropicales (Nepenthes) Resumen La diligencia debida es un componente fundamental para garantizar un comercio de vida silvestre legal y sostenible que también apoye los medios de subsistencia y las empresas que dependen del comercio. Esto es especialmente cierto en el caso de las especies incluidas en la Convención sobre el Comercio Internacional de Especies Amenazadas de Fauna y Flora Silvestres (CITES) que se consideran amenazadas o pueden verse amenazadas por el comercio. La realización de ejercicios de diligencia debida requiere acceso a información con la cual fundamentar tales decisiones; sin embargo, no está claro hasta qué punto se dispone de información. Usamos como estudio de caso el comercio de plantas de jarra tropicales (Nepenthes) con fines hortícolas para determinar cuánta información hay disponible. Realizamos un estudio sistemático del comercio en línea de las especies descritas entre 1996 y 2016. Para las especies encontradas en el comercio, hicimos referencias cruzadas con la base de datos de comercio CITES y consultamos a las Autoridades Administrativas CITES pertinentes y a los Puntos Focales Nacionales de Acceso y Distribución de Beneficios. De las 83 especies con descripción reciente, el 61% se pusieron a la venta en línea en 2018. A pesar de que todas las especies de Nepenthes están catalogadas en CITES, sólo el 23% (n = 19) de las especies que se vendían en línea figuraban en la base de datos sobre comercio CITES, y sólo tres procedían de los países de origen. Treinta y dos de estas especies no tenían comercio internacional registrado según la base de datos. Las autoridades de gestión de CITES de los países de origen confirmaron que se permitió el comercio de 5 de las 32 especies. La falta de registros CITES puede explicarse por el comercio de «Nepenthes spp¼ o como partes y derivados exentos. Sin embargo, es probable que se exijan permisos de recolección y comercialización en el marco del Protocolo de Nagoya sobre Acceso y Participación en los Beneficios (APB) del Convenio sobre la Diversidad Biológica. Contactamos a los Puntos Focales Nacionales de APB para determinar si se habían expedido permisos de recolección o comercialización para las especies restantes. Sólo dos de los siete puntos focales respondieron y ambos afirmaron que no se había expedido ningún permiso. La falta de información de rastreo o de respuesta en relación con la expedición de permisos de recolección y comercialización es preocupante y obstaculiza la diligencia debida de las empresas y los consumidores que desean asegurarse de que su comercio es legal, sostenible y ético.

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The 2 most known cannabinoids are Δ9-tetrahydrocannabidiol (THC) and cannabidiol (CBD). Both chemicals are extracted from the cannabis plant but can also be synthetically produced. Δ9-Tetrahydrocannabidiol is extracted from the subspecies of the cannabis plant known as the marijuana plant, which contains a high concentration of THC (0.3% to 30%). Δ9-Tetrahydrocannabidiol is a major psychoactive and intoxicating component of the cannabis plant and is not recommended for use in dogs due to its toxic effect. Cannabidiol is extracted from the subspecies of the cannabis plant known as the hemp plant and must contain less than 0.3% THC. Cannabidiol is a major nonpsychoactive component of the cannabis plant, and its effect has been investigated for epilepsy, neoplasia, and osteoarthritis in dogs. Public interest in the medical use of cannabinoids for various diseases and disorders has grown in the last couple of years. The attention has extended to veterinary medicine, where veterinarians and pet owners are curious about what diseases the nontoxic CBD can be used for to treat companion animals. The use of CBD for ophthalmic diseases has also been investigated due to its anti-inflammatory and neuroprotective effects. Intraocular pressure regulation for glaucoma, corneal diseases (eg, keratitis and corneal pain), uveal diseases (eg, endotoxin-induced uveitis), and retinal/optic nerve head diseases (eg, diabetic retinopathy) are areas where CBD's effect has been investigated in humans and animals. The aim of this review is to give an update on what is known regarding the use of cannabinoids, especially CBD, for ophthalmic diseases in dogs.

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Since the passage of the 2018 Agriculture Improvement Act (2018 Farm Bill), the number of products containing cannabis-derived compounds available to consumers have rapidly increased. Potential effects on liver function as a result from consumption of products containing cannabidiol (CBD), including hemp extracts, have been observed but the mechanisms for the effects are not fully understood. In this study, hepatocytes derived from human induced pluripotent stem cells (iPSCs) were used to evaluate potential hepatic effects of CBD and hemp extract at exposure concentrations ranging from 0.1 to 30 µM. Despite that a significant reduction in cell viability occurred only in the 30 µM group for both CBD and hemp extract, significant changes to cytochrome P450 activity, mitochondrial membrane potential, and lipid accumulation occurred within the concentration range of 0.1-3 µM for both CBD and hemp extract. Albumin and urea production, caspase 3/7 activity, and intracellular glutathione were significantly affected within the concentration range of 3-30 µM by CBD or hemp extract. These findings indicate that CBD and hemp extract can alter hepatic function and metabolism. The current study contributes data to help inform the evaluation of potential hepatotoxic effects of products containing cannabis-derived compounds.

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The non-psychoactive cannabinoids cannabidiol (CBD) and cannabidiolic acid (CBDA) are available on the market in different forms, mostly for their anti-inflammatory and potential analgesic properties. These substances are prohibited during equine competitions. CBD and CBDA are naturally present in hemp straw, commonly used as a bedding substitute for wheat straw. Unfortunately, horses can eat it, which therefore could lead to a possible risk of positive findings for CBD/CBDA in biological samples after doping control tests. The goals of this study were, first, to provide recommendations on the use of hemp straw before competition and, second, to assess if discrimination between hemp bedding exposure and CBD oil administration is possible. Several CBD equine in vivo studies have been conducted, including one on hemp straw used as bedding and one after administration of CBD oil by topical and sublingual routes. In hemp straw, CBDA was detected in higher quantities than CBD, and other cannabinoids have been observed. After hemp straw exposure, CBDA was also detected in higher quantities than CBD in all urine samples. It appeared that hemp straw should not be used as bedding for equine competition except if a delay of at least 48 h is respected. Regarding the CBD oil product analysis, CBD was the main compound detected. After administration, 7-hydroxy CBD was identified in the urine. In conclusion, based on these data, we highlighted that it could be possible to discriminate the exposure of a horse to hemp straw from an administration of a CBD oil product thanks to the main presence of CBDA.

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PURPOSE OF REVIEW: This document critically examines the role of cannabinoids in cancer care during an era marked by rapid advancements in oncology and changing perceptions on cannabis. It traces the historical context of cannabis in medicinal use, navigating its journey from widespread acceptance, subsequent criminalization, to its resurgence in modern therapeutic applications, particularly within the framework of Evidence-Based Medicine (EBM). RECENT FINDINGS: Anchored in EBM principles, this study synthesizes current research from clinical trials, systematic reviews, and meta-analyses to evaluate the efficacy and safety of cannabinoids in oncology. The focus is on their palliative effects, considering the nuances of effectiveness, risk assessment, and challenges inherent in translating these findings into clinical guidelines. The study seeks to bridge the gap between scientific research and clinical practice, offering insights to inform future oncological therapies and symptom management strategies involving cannabinoids. The potential benefits and risks of cannabinoid use in cancer treatment are assessed to guide clinicians and researchers in developing comprehensive, evidence-based approaches to patient care.

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BACKGROUND: Cannabis is the most widely used psychoactive drug in the United States. While multiple studies have associated acute cannabis consumption with alterations in cognitive function (e.g., visual and spatial attention), far less is known regarding the effects of chronic consumption on the neural dynamics supporting these cognitive functions. METHODS: We used magnetoencephalography (MEG) and an established visuospatial processing task to elicit multi-spectral neuronal responses in 44 regular cannabis users and 53 demographically matched non-user controls. To examine the effects of chronic cannabis use on the oscillatory dynamics underlying visuospatial processing, neural responses were imaged using a time-frequency resolved beamformer and compared across groups. RESULTS: Neuronal oscillations serving visuospatial processing were identified in the theta (4-8 Hz), alpha (8-14 Hz), and gamma range (56-76 Hz), and these were imaged and examined for group differences. Our key results indicated that users exhibited weaker theta oscillations in occipital and cerebellar regions and weaker gamma responses in the left temporal cortices compared to non-users. Lastly, alpha oscillations did not differ, but alpha connectivity among higher-order attention areas was weaker in cannabis users relative to non-users and correlated with performance. CONCLUSIONS: Overall, these results suggest that chronic cannabis users have alterations in the oscillatory dynamics and neural connectivity serving visuospatial attention. Such alterations were observed across multiple cortical areas critical for higher-order processing and may reflect compensatory activity and/or the initial emergence of aberrant dynamics. Future work is needed to fully understand the implications of altered multispectral oscillations and neural connectivity in cannabis users.

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STUDY OBJECTIVES: Cannabidiol (CBD) is increasingly used as a health supplement, though few clinical studies have demonstrated benefits. The primary objective of this study was to evaluate the effects of an oral CBD-terpene formulation on sleep physiology in individuals with insomnia. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, 125 individuals with insomnia received an oral administration of CBD (300 mg) and terpenes (1 mg each of linalool, myrcene, phytol, limonene, α-terpinene, α-terpineol, α-pinene, and ß-caryophyllene) for ≥ 4 days/week over 4 weeks using a crossover design. The study medication was devoid of Δ9-tetrahydrocannabinol (Δ9-THC). The primary outcome measure was the percentage of time participants spent in the combination of slow wave sleep (SWS) and rapid eye movement (REM) sleep stages, as measured by a wrist-worn sleep-tracking device. RESULTS: This CBD-terpene regimen marginally increased the mean nightly percentage of time participants spent in SWS + REM sleep compared to the placebo [mean (SEM), 1.3% (0.60%), 95% C.I. 0.1 to 2.5%, P = 0.03]. More robust increases were observed in participants with low baseline SWS + REM sleep, as well as in day sleepers. For select participants, the increase in SWS + REM sleep averaged as much as 48 minutes/night over a four-week treatment period. This treatment had no effect on total sleep time (TST), resting heart rate or heart rate variability, and no adverse events were reported. CONCLUSIONS: Select CBD-terpene ratios may increase SWS + REM sleep in some individuals with insomnia, and may have the potential to provide a safe and efficacious alternative to over-the-counter (OTC) sleep aids and commonly prescribed sleep medications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT05233761.

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Hemp (Cannabis sativa L.) is an important source of fibre and seed oil and protein. By-products of industrial hemp fibre production, like hemp seeds and cakes, can be used as feed for all animal species as fat and protein source and the whole hemp plant (including stalk and leaves) might be a suitable fibre source for ruminants. However, a previous feeding experiment with leaf-flower-seed hemp silage, made from an industrial hemp variety, demonstrated detrimental effects on cow health parameters and a significant transfer of several cannabinoids, including the psychoactive tetrahydrocannabinol (∆9-THC), into cow's milk, posing a potential risk to the safety of consumers. Based on those observations, the present study tested the hypothesis that anaerobic fermentation, as during ensiling, increases the content of ∆9-THC in hemp. Therefore, silages of whole plants from the industrial hemp Cannabis sativa L. var. Ivory were prepared in a multifactorial design, with the four treatments 1) untreated control (CON), 2) addition of 10 mL per kg fresh weight homofermentative lactobacilli at 105 cfu/mL (LBAC), 3) addition of 10 mL per kg fresh weight homofermentative lactobacilli at 105 cfu/mL plus 30 g molasses (LBACmol) and 4) addition of propionic acid (10 mL/kg fresh weight) (PRO). Ultra high performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionisation (UHPLC-MS/MS) was performed for analysis of cannabinoids in fresh hemp material and after 10 and 90 days of ensiling. The study revealed that ensiling decreased all acid forms of analysed cannabinoids in hemp at about 40-65% of the initial values after 90 days of storage, with the exception of cannabinolic acid (CBNA), and CBGA, the acidic form of cannabigerol (CBG). This decrease in most acidic forms was accompanied by an increase of the corresponding non-acidic forms of all cannabinoids, including the psychoactive ∆9-THC. Thus, although ensiling decreases the total cannabinoid content, psychoactive compounds like ∆9-THC can increase, enhancing the risk for animal health and a transfer of these substances into animal derived products.

Industrial hemp can be ensiled with different additives, despite its high buffering capacityUltra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was used for analysis of cannabinoidsEnsiling decreased total cannabinoid content in industrial hemp, but increased individual compounds like ∆9-THC, likely through decarboxylation of the precursor ∆9-THCA.

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In this paper, we present analytical methodologies for the determination of the thiazolidine fungicide flutianil (trade name GATTEN) and its primary metabolite OC56635 in hemp cannabis matrices. A total of nine crop matrices were tested: whole seed, fiber, flower buds, hemp hearts, hemp seed oil, hemp meal, hemp flour, ethanol extracted CBD resin (CBD-E), and supercritical CO2 extracted CBD resin (CBD-C). Processing of the CBD-E and CBD-C crop fractions was carried out in-house using methods detailed herein. Field sample analysis utilized sequential extractions, stacked solid phase extraction (SPE) column cleanups, and evaporation to prepare the samples for LC-MS/MS quantitation. Method validations for each fraction were carried out using untreated hemp matrices over a minimum of three levels, with lowest levels of method validation (LLMV) of 0.010 µg/g for all fractions except the CBD resins, for which LLMV was 0.020 µg/g. Flutianil-treated samples from nine field sites were collected from several crop production regions and analyzed to determine the distribution of incurred flutianil and OC56635 residues within the different hemp matrices. This data was generated in support of nationwide registration with the United States Environmental Protection Agency (USEPA).

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BACKGROUND: Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI. METHODS: Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests. RESULTS: GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus. CONCLUSIONS: The use of an FDA-approved CBD (Epidiolex®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.

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RATIONALE AND OBJECTIVE: Rodents acquire food information from their conspecifics and display a preference for the conspecifics' consumed food. This social learning of food information from others promotes the survival of a species, and it is introduced as the socially transmitted food preference (STFP) task. The cholinergic system in the basal forebrain plays a role in the acquisition of STFP. Cannabidiol (CBD), one of the most abundant phytocannabinoids, exerts its therapeutic potential for cognitive deficits through versatile mechanisms of action, including its interaction with the cholinergic system. We hypothesize a positive relationship between CBD and STFP because acetylcholine (ACh) is involved in STFP, and CBD increases the ACh levels in the basal forebrain. MATERIALS AND METHODS: Male C57BL/6J mice were trained to acquire the STFP task. We examined whether CBD affects STFP memory by administering CBD (20 mg/kg, i.p.) before the STFP social training. The involvement of cholinergic system in CBD's effect on STFP was examined by knockdown of brain acetylcholinesterase (AChE), applying a nonselective muscarinic antagonist SCO (3 mg/kg, i.p.) before CBD treatment, and measuring the basal forebrain ACh levels in the CBD-treated mice. RESULTS: We first showed that CBD enhanced STFP memory. Knockdown of brain AChE also enhanced STFP memory, which mimicked CBD's effect on STFP. SCO blocked CBD's memory-enhancing effect on STFP. Our most significant finding is that the basal forebrain ACh levels in the CBD-treated mice, but not their control counterparts, were positively correlated with mice's STFP memory performance. CONCLUSION: This study indicates that CBD enhances STFP memory in mice. Specifically, those which respond to CBD by increasing the muscarinic-mediated ACh signaling perform better in their STFP memory.

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BACKGROUND: Limited research considers the quantity and potency of cannabis products along with social context on the subjective effects of real-world cannabis use. AIMS: This study examined the subjective effects of acute use as a function of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) doses and social context during cannabis use episodes. METHOD: Ninety-six participants (43.75% male, Mage = 35.73) reporting weekly cannabis use completed a baseline self-report battery assessing cannabis use. Then, THC and CBD potency and quantity of the cannabis product, social context, and subjective experience were assessed through self-initiated surveys after cannabis use episodes during a 14-day ecological momentary assessment (EMA). RESULTS: Greater feeling high and liking were significantly associated with a higher THC dose than one's average (b = 0.03, p < 0.001; b = 0.02, p < 0.001) and social use (b = 0.38, p < 0.001; b = 0.20, p = 0.01). A higher CBD dose than one's average (b = 0.01, p = 0.04) was significantly associated with greater liking. A significant interaction effect of THC dose and social context (b = 0.01, p = 0.02) was observed such that solitary use had a negative association between THC dose and disliking (b = -0.01, p = 0.04), and social use had a null association (b = 0.003, p = 0.25). Individuals with greater cannabis problems reported lower liking (b = -0.18, p = 0.03) and higher disliking (b = 0.08, p = 0.02), but not feeling high, on average, across the EMA protocol. CONCLUSION: Social context plays an important role in the subjective experience of cannabis use. Interventions targeting cannabis problems could highlight the evidence that individuals with greater cannabis problems might experience less liking but more disliking in general across use episodes to effectively challenge expectancies/motives of use.

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RATIONALE: Cannabidiol (CBD) is increasingly used as a sleep aid for insomnia; yet neurocognitive and subjective state effects following daily therapeutic use are unclear. OBJECTIVES: To measure the effect of daily CBD use on neurocognitive performance and daily subjective mood in a population with primary insomnia. METHODS: This study used a randomized, placebo-controlled, parallel design incorporating a single-blind placebo run-in week followed by a two-week double-blind dosing period, during which participants consumed 150 mg CBD (N = 15) or placebo (N = 15) sublingually 60-minutes daily before bed. Attention, executive function, reasoning, information processing, working and episodic memory were assessed using the CogPro system at the beginning of the placebo run-in, after 1-week and 2-weeks of dosing. Subjective states using visual analogue scales and side effects were recorded daily. RESULTS: Cognitive performance was unaffected by nightly CBD supplementation (all p > 0.05). From baseline to trial conclusion, those receiving CBD reported greater experience of calmness, clear-headedness, coordination and were more likely to report side-effects of dry mouth relative to placebo (all p < 0.05). CONCLUSIONS: Relative to placebo, daytime cognitive functioning following nightly supplementation as a therapeutic aid for primary insomnia was preserved under trial conditions. Results suggested an overall favourable safety profile, with larger controlled trials and thorough analyses of varying insomnia phenotypes necessary to corroborate these findings.

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Obstructive jaundice occurs when an obstruction in the bile duct system prevents bile from flowing from the liver into the intestine, accumulating bilirubin in the blood. This condition can result from various causes, including gallstones, tumors, or inflammation of the bile ducts. The management of obstructive jaundice depends on the underlying cause (malignant obstructions such as cholangiocarcinoma or pancreatic cancer), indicating the need for surgical intervention. The Whipple procedure (pancreaticoduodenectomy) is the standard curative approach for resectable distal common bile duct (CBD) adenocarcinoma. Doctors usually recommend adjuvant chemotherapy to reduce the risk of recurrence. We report the case of a 70-year-old male with a history of untreated hypertension, type 2 diabetes, and long-term smoking, who presented with classic signs of obstructive jaundice, including yellowing of the eyes, itching, right upper quadrant pain, and intermittent fevers. Laboratory findings revealed elevated inflammatory markers, bilirubin, liver enzymes, and leukocyte count, indicative of an inflammatory and obstructive biliary condition. Imaging studies confirmed a distal CBD stricture, including abdominal ultrasound, computed tomography scans, and endoscopic retrograde cholangiopancreatography (ERCP). Brush cytology obtained during ERCP revealed a well-differentiated adenocarcinoma of the distal CBD. The patient's treatment plan included preoperative optimization, surgical resection via the Whipple procedure, and postoperative adjuvant therapy. This case emphasizes the importance of a thorough diagnostic workup and a multidisciplinary treatment strategy in managing complex cases of obstructive jaundice in the elderly, highlighting the need for personalized care to achieve optimal outcomes.

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OBJECTIVE: KCNT1-related epilepsies encompass three main phenotypes: (i) epilepsy of infancy with migrating focal seizures (EIMFS), (ii) autosomal dominant or sporadic sleep-related hypermotor epilepsy [(AD)SHE], and (iii) different types of developmental and epileptic encephalopathies (DEE). Many patients present with drug-resistant seizures and global developmental delays. In addition to conventional anti-seizure medications (ASM), multiple alternative therapies have been tested including the ketogenic diet (KD), cannabidiol (CBD-including Epidyolex © and other CBD derivatives) and quinidine (QUIN). We aimed to clarify the current state of the art concerning the benefits of those therapies administered to the three groups of patients. METHODS: We performed a literature review on PubMed and EMBase with the keyword "KCNT1" and selected articles reporting qualitative and/or quantitative information on responses to these treatments. A treatment was considered beneficial if it improved seizure frequency and/or intensity and/or quality of life. Patients were grouped by phenotype. RESULTS: A total of 43 studies including 197 patients were reviewed. For EIMFS patients (32 studies, 135 patients), KD resulted in benefit in 62.5% (25/40), all types of CBD resulted in benefit in 50% (6/12), and QUIN resulted in benefit in 44.6% (25/56). For (AD)SHE patients (10 studies, 32 patients), we found only one report of treatment with KD, with no benefit noted. QUIN was trialed in 8 patients with no reported benefit. For DEE patients (10 studies, 30 patients), KD resulted in benefit for 4/7, CBD for 1/2, and QUIN for 6/9. In all groups, conventional ASM are rarely reported as beneficial (in 5%-25% of patients). SIGNIFICANCE: Ketogenic diet, CBD, and QUIN treatments appear to be beneficial in a subset of patient with drug-resistant epilepsy. The KD and CBD are reasonable to trial in patients with KCNT1-related epilepsy. Further studies are needed to identify optimal treatment strategies and to establish predictive response factors. PLAIN LANGUAGE SUMMARY: We performed an extensive review of scientific articles providing information about the therapeutic management of epilepsy in patients with epilepsy linked to a mutation in the KCNT1 gene. Conventional anti-seizure treatments were rarely reported to be beneficial. The ketogenic diet (a medical diet with very high fat, adequate protein and very low carbohydrate intake) and cannabidiol appeared to be useful, but larger studies are needed to reach a conclusion.

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