Monthly Archives: January 2023

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss

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“Objectives: Ten million new cases of dementia are recorded annually worldwide, with agitation and idiopathic weight loss being the most common symptoms. Several pharmacological therapies have emerged in recent years, but the clinical use of cannabis extracts in older patients with AD is constantly growing. This retrospective, analytical, observational, spontaneous trial aimed to enhance the clinical action of THC: CBD cannabis extract administration in AD patients with severe symptoms such as agitation, weight loss, cognitive impairment, and sleep disturbance.

Methods: Thirty patients (9 men and 21 women) diagnosed with mild, moderate, or severe AD, aged 65-90 years, appealing to our Second Opinion Medical Consultation (Modena, Italy), were enrolled and required to use oil-diluted cannabis extract, Bedrocan® (22% THC, 0.5% CBD, Olive Oil 50 ml), twice a day for 12 weeks. The efficacy of cannabinoid therapy was evaluated at baseline and 12 weeks after therapy, employing three self-administered questionnaires completed by the parents of the enrolled patients: NPI-Q, CMAI, and MMSE.

Key findings: The NPI-Q demonstrated a reduction (p<0.0001) in agitation, apathy, irritability, sleep disturbances, and eating disturbances, consequently improving caregiver distress. Levels of physically and verbally aggressive behaviours, measured using the CMAI questionnaire, were lower (p<0.0001) in all patients. The MMSSE questionnaire confirmed a significant decrease (p<0.0001) in cognitive impairment in 45% of the patients.

Conclusion: Our anecdotical, spontaneous, and observational study demonstrated the efficacy and safety of oil-diluted cannabis extract in patients with AD. The limitations of our study are: 1) small patient cohort, 2) absence of control group, 3) self-administered questionnaires that are the most practical but not objective instruments to assess the neurologic functions of AD patients.”

https://pubmed.ncbi.nlm.nih.gov/36655645/

Efficacy and Safety of Medical Marijuana in Migraine Headache: A Systematic Review

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“Medical marijuana treatment for migraine is becoming more common, although the legality and societal acceptance of marijuana for medical purposes in the United States have been challenged by the stigma attached to it as a recreational drug.

These substances function to reduce nociception and decrease the frequency of migraine by having an impact on the endocannabinoid system.

Our study reviewed the clinical response, dosing, and side effects of marijuana in migraine management. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a literature search in PubMed, Google Scholar, and Science Direct, and nine studies were included in the systematic review.

The studies demonstrated that medical marijuana has a significant clinical response by reducing the length and frequency of migraines. No severe adverse effects were noted. Due to its effectiveness and convenience, medical marijuana therapy may be helpful for patients suffering from migraines. However, additional clinical trials and observational studies with longer follow-ups are required to study the efficacy and safety of the drug.”

https://pubmed.ncbi.nlm.nih.gov/36660507/

“The main objective of this article is to assess the efficacy and safety of medical marijuana for the treatment of migraine headaches. All the studies showed encouraging findings on the therapeutic effects of medicinal marijuana in migraine treatment. Additionally, medical marijuana is well-tolerated with fewer side effects and is safe to use in migraine patients.”

https://www.cureus.com/articles/118190-efficacy-and-safety-of-medical-marijuana-in-migraine-headache-a-systematic-review

Cannabinoids in neuroinflammatory disorders: Focusing on multiple sclerosis, Parkinsons, and Alzheimers diseases

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“The medicinal properties of cannabis and cannabinoid-derivative are entirely investigated and known. In addition, the identification of psychotropic plant cannabinoids has led to more studies regarding the cannabinoid system and its therapeutic features in the treatment and management of clinical symptoms of neuroinflammatory disorders, such as multiple sclerosis (MS), Parkinsons disease (PD), and Alzheimers disease (AD). In fact, cannabinoid agonists are able to control and regulate inflammatory responses. In contrast to the cannabinoid receptor type 1 (CB1) and its unwanted adverse effects, the cannabinoid receptor type 2 (CB2) and its ligands hold promise for new and effective therapeutic approaches. So far, some successes have been achieved in this field. This review will discuss an outline of the endocannabinoid system’s involvement in neuroinflammatory disorders. Moreover, the pharmacological efficacy of different natural and synthetic preparations of phytocannabinoids acting on cannabinoid receptors, particularly in MS, PD, and AD, will be updated. Also, the reasons for targeting CB2 for neurodegeneration will be explained.”

https://pubmed.ncbi.nlm.nih.gov/36637897/

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.1936

Chemical constituents of industrial hemp roots and their anti-inflammatory activities

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BMC-Springer-Nature-MIDM - Greehey Children's Cancer Research Institute

“Objective: Although the chemical constituents of the aerial parts of Cannabis have been extensively studied, phytochemicals of Cannabis roots are not well characterized. Herein, we investigated the chemical constituents of industrial hemp (Cannabis sativa L.) roots and evaluated the anti-inflammatory activities of phytochemicals isolated from the hemp roots extract.

Methods: An ethyl acetate extract of hemp roots was subjected to a combination of chromatographic columns to isolate phytochemicals. The chemical structures of the isolates were elucidated based on spectroscopic analyses (by nuclear magnetic resonance and mass spectrometry). The anti-inflammatory effects of phytochemicals from hemp roots were evaluated in an anti-inflammasome assay using human monocyte THP-1 cells.

Results: Phytochemical investigation of hemp roots extract led to the identification of 32 structurally diverse compounds including six cannabinoids (1-6), three phytosterols (26-28), four triterpenoids (22-25), five lignans (17-21), and 10 hydroxyl contained compounds (7-16), three fatty acids (29-31), and an unsaturated chain hydrocarbon (32). Compounds 14-21, 23, 27, and 32 were identified from the Cannabis species for the first time. Cannabinoids (1-5) reduced the level of cytokine tumor necrosis-alpha (by 38.2, 58.4, 47.7, 52.2, and 56.1%, respectively) and 2 and 5 also decreased the interleukin-1β production (by 42.2 and 92.4%, respectively) in a cell-based inflammasome model. In addition, non-cannabinoids including 11, 13, 20, 25, 29, and 32 also showed selective inhibition of interleukin-1β production (by 23.7, 22.5, 25.6, 78.0, 24.1, 46.6, and 25.4%, respectively) in THP-1 cells.

Conclusion: The phytochemical constituent of a hemp roots extract was characterized and compounds from hemp roots exerted promising anti-inflammatory effects.”

https://pubmed.ncbi.nlm.nih.gov/36642726/

“The medicinal uses of Cannabis roots for a variety of maladies are supported by empirical practice and emerging scientific evidence.

Several pre-clinical studies reported that cannabis root extracts exert various pharmacological effects including anti-inflammatory, estrogenic, liver protective, and anti-cancer activities.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00168-3

Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration

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SpringerLink

“The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.”

https://pubmed.ncbi.nlm.nih.gov/36635488/

https://link.springer.com/article/10.1007/s11095-023-03469-1

Cannabidiol inhibits lung proliferation in monocrotaline-induced pulmonary hypertension in rats

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Biomedicine & Pharmacotherapy

“Cannabidiol (CBD) is a safe and well-tolerated plant-derived drug with anti-proliferative properties. Pulmonary hypertension (PH) is a rapidly progressive and still incurable disease. CBD diminishes monocrotaline (MCT)-induced PH, including reduced right ventricular systolic pressure, pulmonary vascular hypertrophy, and right ventricular remodeling. The aim of our study was to investigate the effect of chronic administration of CBD (10 mg/kg once daily for 21 days) on selected remodeling parameters in the lung of MCT-induced PH rats. In MCT-induced PH, we found an increase in profibrotic parameters, e.g., transforming growth factor β1 (TGF-β1), galectin-3 (Gal-3), procollagen I, collagen I, C-propeptide, matrix metalloproteinase 9 (MMP-9) and an increased number of mast cells. In our study, we observed that the TGF-β1, Gal-3, procollagen I, collagen I, C-propeptide, and mast cell levels in lung tissue were decreased after CBD administration to MCT-treated rats. In summary, CBD treatment has an anti-proliferative effect on MCT-induced PH. Given the beneficial multidirectional effects of CBD on PH, we believe that CBD can be used as an adjuvant PH therapy, but this argument needs to be confirmed by clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/36634588/

https://www.sciencedirect.com/science/article/pii/S0753332223000227?via%3Dihub

Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment

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Browse Articles | Research Square

“Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X syndrome (FXS). This review describes the ECS, its role in the central nervous system, how it is dysregulated in FXS, and the potential role of cannabidiol as a treatment for FXS. FXS is caused by deficiency or absence of the fragile X messenger ribonucleoprotein 1 (FMR1) protein, FMRP, typically due to the presence of >200 cytosine, guanine, guanine sequence repeats leading to methylation of the FMR1 gene promoter. The absence of FMRP, following FMR1 gene-silencing, disrupts ECS signaling, which has been implicated in FXS pathogenesis. The ECS facilitates synaptic homeostasis and plasticity through the cannabinoid receptor 1, CB1, on presynaptic terminals, resulting in feedback inhibition of neuronal signaling. ECS-mediated feedback inhibition and synaptic plasticity are thought to be disrupted in FXS, leading to overstimulation, desensitization, and internalization of presynaptic CB1 receptors. Cannabidiol may help restore synaptic homeostasis by acting as a negative allosteric modulator of CB1, thereby attenuating the receptor overstimulation, desensitization, and internalization. Moreover, cannabidiol affects DNA methylation, serotonin 5HT1A signal transduction, gamma-aminobutyric acid receptor signaling, and dopamine D2 and D3 receptor signaling, which may contribute to beneficial effects in patients with FXS. Consistent with these proposed mechanisms of action of cannabidiol in FXS, in the CONNECT-FX trial the transdermal cannabidiol gel, ZYN002, was associated with improvements in measures of social avoidance, irritability, and social interaction, particularly in patients who are most affected, showing ≥90% methylation of the FMR1 gene.”

https://pubmed.ncbi.nlm.nih.gov/36624400/

“FXS is caused by deficiency or absence of FMRP, typically due to the presence of >200 CGG repeats and methylation in the promoter region of the FMR1 gene. The absence of FMRP downregulates the ECS signaling, which has been implicated in FXS pathogenesis. Synaptic homeostasis and plasticity may be regulated by the ECS through the postsynaptic “on demand” production of endocannabinoids, which then bind to CB1 receptors on presynaptic terminals, resulting in regulation of glutamate signaling and GABAergic signaling. The ECS-mediated feedback inhibition and synaptic plasticity are thought to be disrupted in FXS due to dysregulation of enzymes that are integral to the ECS (e.g., DAGL), leading to overstimulation, desensitization, and internalization of presynaptic CB1 receptors.

Cannabidiol may help restore synaptic homeostasis by acting as a negative allosteric modulator of CB1, thereby attenuating CB1 receptor overstimulation, internalization, and desensitization. Moreover, cannabidiol has effects on DNA methylation, 5HT1A signal transduction, GABAA receptor signaling, and dopamine D2 and D3 receptor signaling, which may contribute to beneficial effects in patients with FXS. Consistent with these proposed mechanisms of action of cannabidiol in FXS, the transdermal cannabidiol gel, ZYN002, was associated with improvements in measures of social avoidance, irritability, and social interaction in the CONNECT-FX trial, particularly among patients with ≥90% methylation of the FMR1 gene.”

https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-023-09475-z

How do phytocannabinoids affect cardiovascular health? An update on the most common cardiovascular diseases

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SAGE Journals Home

“Cardiovascular disease (CVD) causes millions of deaths worldwide each year. Despite the great progress in therapies available for patients with CVD, some limitations, including drug complications, still exist. Hence, the endocannabinoid system (ECS) was proposed as a new avenue for CVDs treatment. The ECS components are widely distributed through the body, including the heart and blood vessels, thus the action of its endogenous and exogenous ligands, in particular, phytocannabinoids play a key role in various pathological states. The cardiovascular action of cannabinoids is complex as they affect vasculature and myocardium directly via specific receptors and exert indirect effects through the central and peripheral nervous system. The growing interest in phytocannabinoid studies, however, has extended the knowledge about their molecular targets as well as therapeutical properties; nonetheless, some areas of their actions are not yet fully recognized. Researchers have reported various cannabinoids, especially cannabidiol, as a promising approach to CVDs; hence, the purpose of this review is to summarize and update the cardiovascular actions of the most potent phytocannabinoids and the potential therapeutic role of ECS in CVDs, including ischemic reperfusion injury, arrhythmia, heart failure as well as hypertension.”

https://pubmed.ncbi.nlm.nih.gov/36636553/

“Accumulating evidence supports the crucial role of ECS in a wide range of physiological and pathophysiological conditions. In the cardiovascular system, ECS is involved in the inflammatory process, hemodynamic homeostasis, or cardiac rhythm control. Thus, it is not surprising that in many CVDs, ECS is highly active. Hence, pharmacological manipulation of the ECS, both by endocannabinoids and pCBs, may offer a novel therapeutic approach to cardiac disorders. Among many components of the Cannabis plant, studies on CBD demonstrate the greatest potential in experimental models of described herein CVDs. Although animal models and in vitro experiments have shown promising outcomes, data from human studies are still extremely limited and only these clinical trials may shed light on the actual therapeutic effect of CBD. Even though some effects of Cannabis compounds on the cardiovascular system are widely known, a thorough examination of their mechanism of action would greatly advance the understanding of pCBs. Molecular targets of Δ9-THC, CBG, CBC, CBN as well as THCV indicate their protective impact on the heart and blood vessels; nonetheless, the lack of in vitro, animal, or human studies creates a huge knowledge gap in this field.”

https://journals.sagepub.com/doi/10.1177/20406223221143239

Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder

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Pharmacological Research

“Fetal alcohol spectrum disorder (FASD) includes neuropsychiatric disturbances related to gestational and lactational ethanol exposure. Available treatments are minimal and do not modulate ethanol-induced damage. Developing animal models simulating FASD is essential for understanding the underlying brain alterations and searching for efficient therapeutic approaches. The main goal of this study was to evaluate the effects of early and chronic cannabidiol (CBD) administration on offspring exposed to an animal model of FASD. Ethanol gavage (3g/kg/12h, p.o.) was administered to C57BL/6J female mice, with a previous history of alcohol consumption, between gestational day 7 and postnatal day 21. On the weaning day, pups were separated by sex, and CBD administration began (30mg/kg/day, i.p.). After 4-6 weeks of treatment, behavioral and neurobiological changes were analyzed. Mice exposed to the animal model of FASD showed higher anxiogenic and depressive-like behaviors and cognitive impairment that were evaluated through several experimental tests. These behaviors were accompanied by alterations in the gene, cellular and metabolomic targets. CBD administration normalized FASD model-induced emotional and cognitive disturbances, gene expression, and cellular changes with sex-dependent differences. CBD modulates the metabolomic changes detected in the hippocampus and prefrontal cortex. Interestingly, no changes were found in mitochondria or the oxidative status of the cells. These results suggest that the early and repeated administration of CBD modulated the long-lasting behavioral, gene and protein alterations induced by the FASD model, encouraging the possibility of performing clinical trials to evaluate the effects of CBD in children affected with FASD.”

https://pubmed.ncbi.nlm.nih.gov/36642113/

“The results of the present study reveal that the early and chronic administration of CBD repairs the emotional and cognitive alterations observed in male and female mice exposed to the animal model of FASD. Likewise, CBD modulates sex-dependently the gene expression changes and metabolomic targets affected by the model exposure. Interestingly, the data suggest the absence of mitochondrial and oxidative targets in CBD-induced modulation, pointing out that lipid and protein metabolism could be another pathway involved in the cellular reparation observed after CBD chronic administration. The modulation of Pparβ/δ gene expression could be one of the multiple targets involved in CBD’s induced cellular reparation and behavioral modulation. However, further studies are required to explore the real implication of this target in CBD’s mechanism of action in this model of FASD. Taken together, these results strongly stimulate the possibility of performing clinical trials to evaluate the effects of CBD in children affected with FASD.”

https://www.sciencedirect.com/science/article/pii/S1043661823000117?via%3Dihub

The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model

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Epilepsy Research

“In the present study, cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), and combinations of CBD and THC, were evaluated in the mouse maximal electroshock (MES) seizure test – an animal model of generalized-onset seizures. Male CF-1 mice were injected intraperitoneally (i.p.) with either CBD, THC or a combination of CBD and THC. The MES test was conducted 2 h after the injection of CBD and 1 h after the injection of THC. A wide range of doses was tested to allow the construction of dose-response curves. Toxicity was assessed using a behavioral rating scale.

It was found that: 1) the ED50 for THC alone was 52 mg/kg and its therapeutic index (TI) was 1.7; 2) the ED50 for CBD alone was 190 mg/kg and its TI was 2.4; and 3) the ED50 for a 15:1 combination of CBD+THC was 130 mg/kg + 8.6 mg/kg (CBD + THC). Thus, CBD and THC were both effective in the MES model, and CBD was somewhat more effective in the presence of low (non-therapeutic) doses of THC.

The improvement in CBD’s effect, however, was less dramatic than that seen in past experiments with the amygdala-kindling model (Fallah et al., 2021). Both CBD alone and CBD+THC in combination might be useful in the treatment of generalized-onset seizures. The advantage of adding THC to CBD, however, might be less than in the treatment of focal-onset seizures.”

https://pubmed.ncbi.nlm.nih.gov/36646020/

https://www.sciencedirect.com/science/article/abs/pii/S0920121123000128?via%3Dihub