Tag Archives: cannabis

Cannabidiol protects livers against nonalcoholic steatohepatitis induced by high-fat high cholesterol diet via regulating NF-κB and NLRP3 inflammasome pathway.

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“Cannabidiol (CBD), an abundant nonpsychoactive constituent of marijuana, has been reported previously to protect against hepatic steatosis.

In this study, we studied further the functions and mechanisms of CBD on liver inflammation induced by HFC diet.

Mice feeding an HFC diet for 8 weeks were applied to test the protective effect of CBD on livers. RAW264.7 cells were incubated with LPS + ATP ± CBD to study the mechanisms of the effect of CBD against inflammasome activation.

We found that CBD alleviated liver inflammation induced by HFC diet.

CBD significantly inhibited the nuclear factor-κappa B (NF-κB) p65 nuclear translocation and the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome both in vivo and in vitro studies, which lead to the reduction of the expression of inflammation-related factors in our studies.

In addition, Inhibitor of activation of NF-κB partly suppressed the NLRP3 inflammasome activation, while adding CBD further inhibited NF-κB activation and correspondingly suppressed the NLRP3 inflammasome activation in macrophages.

In conclusion, the suppression of the activation of NLRP3 inflammasome through deactivation of NF-κB in macrophages by CBD might be one mechanism of its anti-inflammatory function in the liver.”

https://www.ncbi.nlm.nih.gov/pubmed/31032942

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.28728

Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage.

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Behavioural Brain Research

“Preconditioning, a phenomenon where a minor noxious stimulus protects from a subsequent more severe insult, and post-conditioning, where the protective intervention is applied following the insult, offer new insight into the neuronal mechanism(s) of neuroprotection and may provide new strategies for the prevention and treatment of brain damage. We have previously reported that a single administration of an extremely low dose of Δ(9)-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to mice induced minor long-lasting cognitive deficits.

In the present study we examined the possibility that such a low dose of THC will protect the mice from more severe cognitive deficits induced by the epileptogenic drug pentylenetetrazole (PTZ). THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses that induce the conventional effects of THC) was administered 1-7 days before, or 1-3 days after the injection of PTZ (60 mg/kg). The consequences of this treatment were studied 3-7 weeks later by various behavioral tests that evaluated different aspects of memory and learning.

We found that a single administration of THC either before or after PTZ abolished the PTZ-induced long-lasting cognitive deficits.

Biochemical studies indicated a concomitant reduction in phosphorylated-ERK (extracellular signal-regulated kinase) in the cerebella of mice 7 weeks following the injection of THC.

Our results suggest that a pre- or post-conditioning treatment with extremely low doses of THC, several days before or after brain injury, may provide safe and effective long-term neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/21315768

https://www.sciencedirect.com/science/article/pii/S0166432811001094?via%3Dihub

Cannabidiol-loaded microspheres incorporated into osteoconductive scaffold enhance mesenchymal stem cell recruitment and regeneration of critical-sized bone defects.

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Materials Science and Engineering: C

“Recruitment of mesenchymal stem cells (MSCs) to an injury site and their differentiation into the desired cell lineage are implicated in deficient bone regeneration. To date, there is no ideal structure that provides these conditions for bone regeneration. In the current study, we aim to develop a novel scaffold that induces MSC migration towards the defect site, followed by their differentiation into an osteogenic lineage. We have fabricated a gelatin/nano-hydroxyapatite (G/nHAp) scaffold that delivered cannabidiol (CBD)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres to critical size radial bone defects in a rat model. The fabricated scaffolds were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), and then analyzed for porosity and degradation rate. The release profile of CBD from the PLGA microsphere and CBD-PLGA-G/nHAp scaffold was analyzed by fluorescence spectroscopy. We performed an in vitro assessment of the effects of CBD on cellular behaviors of viability and osteogenic differentiation. Radiological evaluation, histomorphometry, and immunohistochemistry (IHC) analysis of all defects in the scaffold and control groups were conducted following transplantation into the radial bone defects. An in vitro migration assay showed that CBD considerably increased MSCs migration. qRT-PCR results showed upregulated expression of osteogenic markers in the presence of CBD. Histological and immunohistochemical findings confirmed new bone formation and reconstruction of the defect at 4 and 12 week post-surgery (WPS) in the CBD-PLGA-G/nHAp group. Immunofluorescent analysis revealed enhanced migration of MSCs into the defect areas in the CBD-PLGA-G/nHAp group in vivo. Based on the results of the current study, we concluded that CBD improved bone healing and showed a critical role for MSC migration in the bone regeneration process.”

https://www.ncbi.nlm.nih.gov/pubmed/31029357

https://www.sciencedirect.com/science/article/pii/S0928493118303606?via%3Dihub

Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity.

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“Two major constituents of cannabis are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component; CBD may buffer the user against the harmful effects of THC.

AIMS:

We examined the effects of two strains of cannabis and placebo on the human brain’s resting-state networks using fMRI.

CONCLUSIONS:

THC disrupts the DMN, and the PCC is a key brain region involved in the subjective experience of THC intoxication. CBD restores disruption of the salience network by THC, which may explain its potential to treat disorders of salience such as psychosis and addiction.”

https://www.ncbi.nlm.nih.gov/pubmed/31013455

https://journals.sagepub.com/doi/abs/10.1177/0269881119841568?journalCode=jopa

“CBD in cannabis could reduce psychosis risk from high strength skunk, study shows. Buffer effect could point to a protective mechanism that may help ‘treat disorders like psychosis and addiction’. Cannabidiol (CBD), a chemical derived from the cannabis plant, can counteract the effects of high strength “skunk” strains and may help to reduce the risk of serious mental health conditions like psychosis, according to a new study.” https://www.independent.co.uk/news/health/cannabis-skunk-cbd-thc-psychosis-addiction-ucl-a8882991.html

Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results.

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Epilepsy Research

“Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice.

We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.

CONCLUSIONS:

Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.”

https://www.ncbi.nlm.nih.gov/pubmed/31022635

https://www.sciencedirect.com/science/article/pii/S0920121118305837?via%3Dihub

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions.

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“Cannabis and cannabinoids offer significant therapeutic benefits for a wide scope of pathological conditions. Among them, the clinical issues rooted in inflammation stand out, nonetheless, the underlying mechanisms are not yet plainly understood. Circumstantial evidence points to polymorphonuclear leukocytes (PMN) as targets for the anti-inflammatory effects of cannabis. Therefore, we conducted this study to assess the effects of CM5, a novel Cannabis sativa L. extract standardized in 5% cannabidiol (CBD), on human PMN functions, including cell migration, oxidative metabolism and production of tumour necrosis factor (TNF)-α. We then sought to investigate whether such effects could be ascribed to its content in CBD. Cell migration was assessed by the Boyden chamber assay, oxidative metabolism by means of spectrofluorimetric measurement of reactive oxygen species (ROS) production, and TNF-α was measured by real time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results show that both CM5 and CBD inhibit PMN migration, ROS and TNF-α production, indicating that CBD may be the main item responsible for the effects of CM5. CM5 is however more potent than CBD on cell migration and TNF-α production, and less effective on ROS production, suggesting that beyond CBD, other components of the cannabis plant may contribute to the biological effects of the extract. As a whole, such results support the use of cannabis standardized extract and CBD to stem inflammation; however, they also warrant in-depth investigation of the underlying cellular and molecular mechanisms to better exploit their therapeutic potential.”

https://www.ncbi.nlm.nih.gov/pubmed/31013912

https://www.mdpi.com/1422-0067/20/8/1833

Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.

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“Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/31013866

https://www.mdpi.com/1420-3049/24/8/1459

Quality of life in adults enrolled in an open-label study of cannabidiol (CBD) for treatment-resistant epilepsy.

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“Treatment-resistant epilepsy (TRE) is associated with low quality of life (QOL). Cannabidiol (CBD) may improve QOL, but it is unclear if such improvements are independent of improvements in seizure control. Our aim was to compare QOL at baseline and after 1 year of treatment with CBD. We hypothesized that QOL would improve independent of changes in seizure frequency (SF) or severity, mood, or adverse events. We assessed QOL using Quality of Life in Epilepsy-89 (QOLIE-89) in an open-label study of purified CBD (Epidiolex®) for the treatment of TRE. All participants received CBD, starting at 5 mg/kg/day and titrated to 50 mg/kg/day in increments of 5 mg/kg/day. We collected QOLIE-89 in adult participants at enrollment and after 1 year of treatment, or at study exit if earlier. We analyzed if the change in QOLIE-89 total score could be explained by the change in SF, seizure severity (Chalfont Seizure Severity Scale, CSSS), mood (Profile of Moods States, POMS), or adverse events (Adverse Event Profile, AEP). Associations among the variables were assessed using bivariate tests and multiple regression. Fifty-three participants completed enrollment and follow-up testing, seven at study termination. Mean QOLIE-89 total score improved from enrollment (49.4 ± 19) to follow-up (57 ± 21.3; p = .004). We also saw improvements in SF, POMS, AEP, and CSSS (all p ≤ .01). Multivariable regression results showed QOLIE-89 at follow-up associated with improvements in POMS at follow-up (p = .020), but not with AEP, CSSS, or SF (p ≥ .135). Improvement in QOL after treatment with CBD is associated with better mood but not with changes in SF, seizure severity, or AEP. Cannabidiol may have beneficial effects on QOL and mood that are independent of treatment response.”

https://www.ncbi.nlm.nih.gov/pubmed/31003195

https://www.epilepsybehavior.com/article/S1525-5050(19)30116-7/fulltext

Attenuation of Novelty-Induced Hyperactivity of Gria1-/- Mice by Cannabidiol and Hippocampal Inhibitory Chemogenetics.

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“Gene-targeted mice with deficient AMPA receptor GluA1 subunits (Gria1-/- mice) show robust hyperlocomotion in a novel environment, suggesting them to constitute a model for hyperactivity disorders such as mania, schizophrenia and attention deficit hyperactivity disorder. This behavioral alteration has been associated with increased neuronal activation in the hippocampus, and it can be attenuated by chronic treatment with antimanic drugs, such as lithium, valproic acid, and lamotrigine. Now we found that systemic cannabidiol strongly blunted the hyperactivity and the hippocampal c-Fos expression of the Gria1-/- mice, while not affecting the wild-type littermate controls. Acute bilateral intra-dorsal hippocampal infusion of cannabidiol partially blocked the hyperactivity of the Gria1-/- mice, but had no effect on wild-types. The activation of the inhibitory DREADD receptor hM4Gi in the dorsal hippocampus by clozapine-N-oxide robustly inhibited the hyperactivity of the Gria1-/- mice, but had no effect on the locomotion of wild-type mice. Our results show that enhanced neuronal excitability in the hippocampus is associated with pronounced novelty-induced hyperactivity of GluA1 subunit-deficient mice. When this enhanced response of hippocampal neurons to novel stimuli is specifically reduced in the hippocampus by pharmacological treatment or by chemogenetic inhibition, Gria1-/- mice recover from behavioral hyperactivity, suggesting a hippocampal dysfunction in hyperactive behaviors that can be treated with cannabidiol.”

https://www.ncbi.nlm.nih.gov/pubmed/30984001

https://www.frontiersin.org/articles/10.3389/fphar.2019.00309/full

The New Runner’s High? Examining Relationships Between Cannabis Use and Exercise Behavior in States with Legalized Cannabis

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“Results indicated that the majority (81.7%) of participants endorsed using cannabis concurrently with exercise. In addition, the majority of participants who endorsed using cannabis shortly before/after exercise reported that doing so enhances their enjoyment of and recovery from exercise, and approximately half reported that it increases their motivation to exercise.” https://www.frontiersin.org/articles/10.3389/fpubh.2019.00099/abstract
“Cannabis doesn’t make you a lazy pothead, in fact, it might actually motivate you to workout: study. A new study published in the medical journal Frontiers in Public Health has found that consuming cannabis may help motivate users to exercise and improve their workouts.” https://leaderpost.com/cannabis-health/cannabis-doesnt-make-you-a-lazy-pothead-in-fact-it-might-actually-motivate-you-to-workout-study/wcm/bb0beff4-eea0-417a-8812-c5ba10841b34
“Study finds marijuana motivates people to exercise, smashing lazy stoner stereotype. Most people who use marijuana report that consuming before or after exercising improves the experience and aids in recovery, according to a new study. And those who do use cannabis to elevate their workout tend to get a healthier amount of exercise.” https://www.bostonglobe.com/news/marijuana/2019/04/16/study-finds-marijuana-motivates-people-exercise-smashing-lazy-stoner-stereotype/FHHsXxyTrTHrSisso0GC3H/story.html
“A published scientific study claims using weed before workout either “increases motivation” to exercise or “enhances recovery from exercise.”

“Exercise activates the endocannabinoid system.”   https://www.ncbi.nlm.nih.gov/pubmed/14625449