“Current treatments for rapid eye movement (REM) sleep behavior disorder (RBD) are not always effective and can lead to dose-limited adverse events, and new treatments are needed for this condition.
We present a case of a patient with treatment-refractory isolated RBD who had a dramatic and sustained improvement in dream enactment behaviors using oral tinctures containing cannabidiol and tetrahydrocannabinol without adverse events over 5 years of follow-up.”
“Background: Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes.
Methods: Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ.
Results: CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP.
Conclusion: CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.”
“Objective: This real-world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between specific genetic subgroups and treatment response.
Methods: This study was conducted across 27 epilepsy centers and included patients with monogenic epileptic disorders (pathogenic or likely pathogenic variants) who were treated with highly purified CBD for at least 3 months.
Results: A total of 266 patients (135 females, 50.8%) with monogenic epilepsies were included with a median age at CBD initiation of 12 years (interquartile range [IQR] = 7-19) and a median follow-up duration of 17 months (IQR = 12-24). Overall, 77 different monogenic epilepsies have been included, with the most common genes being SCN1A (32.3%), TSC2 (13.5%), CDKL5, and MECP2 (4.5% each). The mean seizure reduction at the last follow-up was 38.6%, with 47.5% of patients achieving ≥50% seizure reduction and 7.4% achieving seizure freedom. The Clinical Global Impression scale indicated improvement in 65.8% of patients. The general linear mixed model revealed that a shorter maximum duration of seizure freedom before CBD initiation and a higher degree of intellectual disability were independently associated with lower CBD effectiveness. Conversely, no significant differences in seizure outcome were observed across different epilepsy syndromes (Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex epilepsy, and other developmental and epileptic encephalopathy), between approved indications and off-label use, or between concomitant clobazam use or not.
Significance: This study supports CBD as a potential treatment for monogenic epilepsies beyond its licensed indications, demonstrating comparable effectiveness between approved and off-label use and suggesting genetic subgroups with promising treatment responses.”
“Introduction: A growing number of publications are devoted to topical cannabinoid therapies in present-day cosmetology, as they appear to be safe and effective treatment modalities aimed at improving the comfort and quality of life of patients with atopic dermatitis (AD). A thorough patient interview, physical examination, clinical picture, and aetiopathogenesis of AD allow for a correct diagnosis and enable the choice of the least invasive pharmacological treatment.
Purpose: In our medical experiment, we found a correlation between the findings of studies by other authors and the validation of our hypothesis that topical cannabinoid therapy is effective in the prevention and management of AD flares. A thorough analysis of the obtained results provided insights into the extent to which the applied ointment influenced the improvement of the skin’s biophysical parameters (hydration, lipid content, transepidermal water loss, and erythema).
Patients and methods: This medical experimental study was conducted from May to July 2022 and included a group of nine patients (five men and four women) aged 20- to 67-years-old were diagnosed with AD. The study involved transdermal delivery of an ointment compounded with cholesterol ointment, 30% cannabidiol (CBD), 5% cannabigerol (CBG), and hemp seed oil, and assessment of biophysical skin parameters, including corneometry (skin hydration), TEWL, sebumetry, and pH (acidity).
Results: A preliminary analysis of our pilot study points to the potential of employing ointments and creams containing 30% CBD and 5% CBG as alternatives to conventional auxiliary therapies during both flare-ups and remission. The results we achieved included improved skin hydration, sebum level, and TEWL as well as reduced erythema in the studied areas (forearms).
Conclusion: Our results demonstrate that topical cannabinoid therapy is effective in reducing itching and improving the quality of life of patients with AD, leading to symptom remission in some cases.”
“The preliminary analysis of the findings of the pilot study based on a review of recent EBM-compliant studies and the results of our experimental study conducted over a period of three months showed that the topical delivery of the ointment compounded with Cannabis Sativa L. var. sativa oil, cholesterol ointment, 30% CBD, and 5% CBG led to the remission of skin lesions on the forearms of the included patients. Furthermore, in the course of the therapy, patients adhering to the topical cannabinoid regimen achieved satisfactory skin parameters, including normal hydration and sebum levels, as well as improved TEWL and erythema, as opposed to patients who reported failure to comply with the regimen owing to the fatty texture of the formulation, despite the instructions they received.”
“An increase in the use of medicinal Cannabis for pain management has spurred research into the understudied bioactive compounds in Cannabis, such as terpenes.
In our previous work, we showed that isolated and purified terpenes were cannabimimetic and also relieved chemotherapy-induced peripheral neuropathy (CIPN) pain via activation of Adenosine A2a Receptors (A2aR) in the spinal cord. However, terpenes are most often consumed by the public as complex extracts and mixtures, not purified individual terpenes, and whether this cannabimimetic and antinociceptive activity holds true in terpene extracts and blends is not clear.
In this study, we thus extracted terpene blends from three distinct Cannabis chemovars and assessed these blends in male and female CD-1 mice for their cannabimimetic activity in the tetrad assay and pain-relieving properties in a CIPN model.
Each terpene blend was unique in the relative amounts of different terpenes extracted. Though each blend was unique, each similarly elicited cannabimimetic behaviors of catalepsy, hyperlocomotion, and hypothermia, without tail flick analgesia.
All three terpene blends effectively relieved CIPN, though the antinociception was more robust in male than in female mice. This antinociception was recapitulated by purified Myrcene but not D-Limonene. The A2aR antagonist istradefylline blocked the pain-relieving effects of all three terpene blends, suggesting that the terpene blends act on A2aR to relieve CIPN pain.
Together, these findings suggest that terpene blends have similar pharmacological effects as purified single terpenes, and that observations made with single terpenes may be applicable to the complex terpene mixtures commonly consumed by the public.”
“The purpose of this study was to evaluate the participation of spinal peroxisome proliferator-activated receptor gamma (PPARγ) in the antiallodynic effect of cannabidiol, the expression of PPARγ in sites relevant to the spinal nociceptive processing, and the effect of this cannabinoid on cognitive deficits induced by neuropathic pain in female mice.
Either acute or repeated treatment with cannabidiol reduced tactile allodynia and spontaneous pain (flinching) in female neuropathic mice. Pioglitazone partially reduced tactile allodynia, and this effect was fully blocked by the PPARγ antagonist GW9662. Likewise, intrathecal injection of cannabidiol reduced tactile allodynia, while PPARγ antagonist GW9662 or 5-HT1A receptor antagonist WAY-100635, but not the PPARα antagonist GW6479, partially prevented this effect. GW9662 and WAY-100635 administrated per se did not modify tactile allodynia in neuropathic female mice. Co-administration of GW9662 and WAY-100635 fully prevented the antiallodynic effect of cannabidiol in mice. Nerve injury up-regulated PPARγ expression at the spinal cord and dorsal root ganglia, while cannabidiol further enhanced nerve injury-induced up-regulation of PPARγ expression in both tissues.
Repeated intrathecal injection of cannabidiol reduced tactile allodynia and several pain makers (ERK, p-ERK, p38MAPK and p-p38MAPK). In addition, this treatment restored nerve injury-induced interleukin-10 down-regulation and increased PPARγ expression at the spinal cord. Repeated treatment with cannabidiol also improved nerve injury-induced cognitive impairment in mice.
These results provide compelling evidence for the involvement of PPARγ in the antiallodynic effect of cannabidiol in mice and highlight its multifaceted therapeutic potential in neuropathic pain management and its comorbidities.
PERSPECTIVE: The present study reveals cannabidiol’s dual effects in female mice by reducing neuropathic pain through spinal PPARγ and 5-HT1A receptor activation and ameliorating nerve injury-induced cognitive impairment. These findings may assist clinicians seeking new therapeutic approaches for managing neuropathic pain and its associated cognitive deficits.”
“Hypercaloric diet (HCD) intake can lead to metabolic alterations, such as metabolic syndrome and type-2 diabetes mellitus.
Phytocannabinoid cannabidiol (CBD) is a GPR55 receptor antagonist involved in insulin secretion and other functions in pancreatic islet. The therapeutic use of CBD has been suggested for diabetes, but little is known regarding its effects on pancreatic islet physiology.
Our aim was to evaluate the effects of CBD oil on pancreatic islets, from Wistar rats under HCD.
Male rats were divided in 4 groups: Normal diet vehicle-treated (control) and CBD-treated group. Rats under HCD were subdivided in treated with vehicle (HCD) and with CBD oil administered 21 mg/Kg orally, 0.5 ml in 3 days per week; controls received coconut oil as vehicle. Body weight, food intake, and water consumption were recorded. After 20 weeks, glucose tolerance curve was performed; serum insulin was determined by ELISA, and pancreas was removed for histological and gene expression analysis for insulin, glucagon, PDX-1, MafA and GPR55 receptor.
CBD treatment reduced body weight and food intake but increased fluid consumption, independently of diets. In control group, CBD did not alter blood glucose and serum insulin, but modified expression for GPR55 receptor, glucagon, insulin and MafA. Rats under HCD and treated with CBD decreased glycaemia, insulinaemia, islets relative area, GPR55-positive cells, PDX-1 and MafA gene expression, meanwhile insulin and glucagon expression was increased.
In conclusion, CBD ameliorated HCD effects through changes in insulin, glucagon and GPR55 receptor expressions. We assume CBD interacts with other receptors beside GPR55.”
“The endocannabinoid system is a critical brain signaling pathway that is dysregulated in various brain disorders, including Alzheimer’s disease (AD). Cannabinoid-targeted therapies and imaging approaches have gained increasing interest; however, the biological impact of the endocannabinoid system in disease needs further validation. We aimed to study changes in cannabinoid receptor 1 (CB1) and monoacylglycerol lipase (MAGL), components of endocannabinoid signaling and degradation, in a mouse model of AD by PET imaging.
Methods: [18F]FMPEP-d2 and [18F]MAGL-2102 were produced on a commercial radiosynthesis module. PET-CT images with both tracers were acquired in a knock-in mouse model of AD bearing mutated human amyloid precursor protein (AppNL-G-F ) at 3 ages, and compared to wild-type mice. Excised brains were used for in vitro autoradiography with [18F]FMPEP-d2 and [18F]MAGL-2102, immunofluorescence, and western blotting. Male wild-type and 5xFAD mice were chronically treated with MAGL inhibitor JZL184 and imaged with [18F]MAGL-2102 two days after ending treatment.
Results: PET imaging showed sex-, age- and genotype-dependent changes in CB1 and MAGL availability. At 4-months (early-stage β-amyloid pathology), female AppNL-G-F mice had lower CB1 availability, and MAGL availability was increased in male AppNL-G-F, compared to wild-types. At 8-months, no genotype differences in CB1 were observed, yet MAGL availability was reduced in AppNL-G-F frontal cortex, and male AppNL-G-F mice exhibited higher MAGL than transgenic females brain-wide. At 12-months (late-stage β-amyloid pathology), significantly lower uptake of [18F]FMPEP-d2 was observed in AppNL-G-F compared to wild-type, with no changes in [18F]MAGL-2102 binding. AppNL-G-F plaque staging was confirmed by Thioflavin-S staining. Imaging findings were supplemented by autoradiography, immunofluorescence, and western blots. [18F]MAGL-2102 availability was responsive to target engagement of the MAGL inhibitor JZL184 in wild-type and 5xFAD mice.
Conclusions: The present study showed dynamic age-, sex- and pathology-related changes in CB1 and MAGL availability from early-stage β-amyloid pathology, suggesting that the endocannabinoid system is a useful target for diagnostics and treatment of AD. Finally, these results highlight that endocannabinoid sex differences should be considered in diagnostics and drug development.”
“Reactive astrocytes play a critical role in the initiation and progression of epilepsy, but their molecular subtypes and functional characterization are not fully understood.
In this study, we report the existence of neurotoxic reactive astrocytes, a recently identified subtype, that contribute to neuronal death in the epileptic brain.
In a kainic acid (KA)-induced mouse model of epilepsy, we show that neurotoxic reactive astrocytes are induced by microglia-secreted cytokines, including IL-1α, TNFα, and C1q, and are detectable as early as 7 days post-KA stimulation. These cells exhibit a distinct molecular signature marked by elevated expression of complement 3 and adenosine 2A receptor. Transcriptomics and metabolomics analyses of human brain tissues from temporal lobe epilepsy (TLE) patients and an epileptic mouse model reveal that neurotoxic reactive astrocytes induce neuronal damage through lipid-related mechanisms.
Moreover, our results demonstrate that the anti-seizure medication cannabidiol (CBD) and an adenosine 2A receptor antagonist can both suppress the formation of neurotoxic reactive astrocytes, mitigate gliosis, and reduce neuronal loss in a mouse model of epilepsy. Electrophysiological and behavioral studies indicate that cannabidiol attenuates seizure symptoms and enhances memory capabilities in epileptic mice.
Our findings suggest that neurotoxic reactive astrocytes are formed at an early stage in both the KA-induced mouse model of epilepsy and TLE patients and can contribute to neuronal loss through releasing toxic lipids.
Importantly, cannabidiol emerges as a promising therapeutic drug for targeted intervention against neurotoxic reactive astrocytes in adult epilepsy.”
“Processing hemp seeds into foods generates several by-products that are rich in nutrients and bioactive phytochemicals. This paper presents a thorough plant metabolite analysis and a comprehensive assessment of the nutrient content of 14 hemp seed-based foods and by-products and evaluates their feasibility to deliver dietary needs and daily recommendations.
The protein-85-product was the hemp food and hemp fudge the hemp by-product with the highest content of protein, 93.01 ± 0.18% and 37.66 ± 0.37%, respectively. Hemp seed-hull flour had the richest insoluble non-starch polysaccharide content (39.80 ± 0.07%). Linoleic acid was the most abundant fatty acid across all the hemp seed-based samples (ranging from 53.80 ± 2.02% in the protein-85-product to 69.53 ± 0.45% in the hemp cream). The omega-6 to omega-3 fatty acid ratio varied from 3:1 to 4:1 across all hemp seed-based samples.
The majority of hemp seed-based samples were rich sources of potassium, magnesium, and phosphorus. Gentisic acid, p-coumaric acid, and syringaresinol were the most abundant plant metabolites measured and found mainly in bound form.
Hemp seed by-products are valuable sources of nutrients capable of meeting dietary needs and, therefore, should be re-valorized into developing healthy food formulations to deliver a truly zero-waste hemp food production.”
“In conclusion, this study shows that hemp seed-based foods and by-products are rich sources of protein and fiber and are particularly rich in micronutrients, including potassium, magnesium, and phosphorus, and bioactive phytochemicals, particularly p-coumaric acid, gentisic acid, syringaresinol, p-hydroxybenzaldehyde, benzoic acid, and ferulic acid. Almost all the hemp seed-based samples have the potential to deliver the recommended daily reference nutrient intake for several micronutrients, including magnesium, phosphorus, manganese, and iron. One hundred grams of all the hemp seed-based samples delivered the recommended daily intake for fatty acids, including linoleic acid and alpha-linolenic acid. Furthermore, the omega-6:omega-3 ratio found in all the hemp seed-based foods and in all the by-products was between 3:1 and 4:1 across all the samples analyzed and was not altered during the food processing of hemp seed. Therefore, the findings of this study support the consumption of hemp seed foods as part of the diet to diversify and help meet dietary recommendations.”