Tag Archives: therapeutic

The Potential Therapeutic Effects of THC on Alzheimer’s Disease.

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“The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer’s disease.

N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways.

From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together.

We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin’s enhancement of mitochondria function.

These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.”

https://pubmed.ncbi.nlm.nih.gov/25024327

https://journals.sagepub.com/doi/abs/10.3233/JAD-140093


Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice

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Fig. 1.

“…endogenous cannabinoid signaling mechanisms may represent a key component of cell-survival programs mobilized in the injured brain.

In addition to their neuroprotective effects, cannabinergic systems may also have an important role in brain development…

…expression of endocannabinoids and cannabinoid receptors in brain…

Neurogenesis, or the birth of new neurons, continues to occur beyond development and into adulthood, and several lines of evidence suggest that cannabinoid signaling may be involved in this process as well…

In addition to the well known effects of growth factors, a variety of drugs has been shown to influence adult neurogenesis. These include excitatory amino acid receptor antagonists, antidepressants, lithium, nitric oxide donors, phosphodiesterase inhibitors, and statins.

Together with the finding that neurogenesis can be regulated by cannabinoids, these observations imply that a broad range of pharmacological approaches may exist through which to modify neurogenesis for therapeutic purposes.”

http://molpharm.aspetjournals.org/content/66/2/204.full

Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington’s disease brain.

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“Huntington’s disease (HD) is an inherited neurological disease with motor, cognitive and psychiatric symptoms. Characterised by neuronal degeneration, HD pathology is initially apparent in the striatum and cortex.

Considerable research has recently suggested that the neurological immune response apparent in brain injury and disease may provide a valuable therapeutic target.

Cannabinoid CB2 receptors are localised and up-regulated on a number of peripheral immune cell types following inflammation and injury.

…our observation that CB2 is present on blood vessel cells, with increased CD31 co-localisation in HD may represent a new context for CB2 therapeutic approaches to neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24978314

http://www.thctotalhealthcare.com/category/huntingtons/

Ligand Activation of Cannabinoid Receptors Attenuates Hypertrophy of Neonatal Rat Cardiomyocytes.

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“Endocannabinoids are bioactive amides, esters and ethers of long chain polyunsaturated fatty acids. Evidence suggests that activation of the endocannabinoid pathway offers cardioprotection against myocardial ischemia, arrhythmias, and endothelial dysfunction of coronary arteries.

…may represent a novel therapeutic approach to cardioprotection.”

http://www.ncbi.nlm.nih.gov/pubmed/24979612

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury.

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“Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae.

Because of the fact that there is still no specific treatment for perinatal brain lesions due to the complexity of neonatal hypoxic-ischemic pathophysiology, the search of new neuroprotective therapies is of great interest.

In this regard, therapeutic possibilities of the endocannabinoid system have grown lately.

The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant.

Concerning perinatal asphyxia, the neuroprotective role of this endogenous system is emerging these years.

The present review mainly focused on the current knowledge of the cannabinoids as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

http://www.ncbi.nlm.nih.gov/pubmed/21788999

Compounds in cannabis could limit stroke damage

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A cannabis plant

“Chemical compounds found in cannabis may help to reduce brain damage following a stroke, new research has revealed.

 Researchers at the University of Nottingham conducted a meta-analysis of experimental studies into cannabinoids; chemicals related to those found in cannabis, some of which also occur naturally in the body. The findings showed that the compounds could reduce the size of stroke and improve neurological function.
Cannabinoids can be classified into those found naturally in the body (endocannabinoids), those made artificially (synthetic cannabinoids) or those derived from extracts from the plant cannabis sativa (phytocannabinoids).”

Marijuana Use Linked To Lower Stroke Risk

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(Photo: comedy_nose/Flickr)

“Those who use marijuana may benefit from a reduced chance of stroke, according to a new study.

As part of The Stroke Prevention in Young Adults Study, researchers from the University of Maryland analyzed past marijuana use among 751 stroke cases and 813 controls.

The results, which spanned 16 years, showed that those who used marijuana were less likely to suffer a stroke. 28.8% of stroke patients reported marijuana use verses 32.7% of those with no history of stroke.

“The question is still out there, the research still needs to be done. Patients are interested, and I think this lays a foundation for that,” said Dr. Billinghurst.

However, cochair Jennifer Majersik, MD, of the University of Utah, said the study “should be reassuring” to people who smoked marijuana in the 1960s or 1970s, adding that Baby Boomers have yet to show any negative marijuana-associated effects.

Factors that seemed to increase the risk of stroke included tobacco and alcohol use and a history of diabetes and hypertension. Stroke sufferers also tended to be male.

‘Extremely Promising’

Other studies have suggested a link between marijuana use and an increased risk of stroke, but opinions remain divided. On the other hand, there is a growing body of evidence that supports a beneficial role of medical marijuana following a stroke.

In 2013, researchers at the University of Nottingham analyzed pre-existing evidence and concluded that marijuana compounds, called cannabinoids, show promise in reducing the severity of stroke and improving patient outcomes.

“The data are guiding the next steps in experimental stroke in order to be able to progress onto initial safety assessments in a clinical trial,” said lead author and stroke specialist Dr. Tim England.

An earlier analysis of cannabinoids in post-stroke treatment, published in 2012, concluded that “both synthetic cannabinoids and endocannabinoids represent extremely promising therapeutic compounds.”

According to the 2012 findings, compounds that bind to the body’s marijuana pathways may offer protection against post-stroke injury due to their “potent anti-inflammatory” effects.”

http://www.leafscience.com/2014/05/13/marijuana-use-linked-lower-stroke-risk/

The Cannabinoid WIN55212-2 Promotes Neural Repair After Neonatal Hypoxia–Ischemia

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Figure 1.

“In the last years, cannabinoids have emerged as promising neuroprotective agents in several animal paradigms of acute and degenerative brain damage. Most neuroprotective effects of cannabinoids result from the activation of cannabinoid Type 1 (CB1R) and Type 2 (CB2R) receptors in neural and immune cells.

Besides, the stimulating effect of cannabinoids on proliferation, survival, and differentiation of neural progenitor cells provides interesting prospects for long-term neural repair after acute brain damage.

The endocannabinoid system has been involved in the modulation of neural stem cells proliferation, survival and differentiation as well as in the generation of new oligodendrocyte progenitors in the postnatal brain. The present work aims to test the effect of the synthetic Type 1 and Type 2 cannabinoid receptor agonist WIN55212-2 on these processes in the context of neonatal rat brain hypoxia–ischemia (HI)…

Our results suggest that the activation of the endocannabinoid system promotes white and gray matter recovery after neonatal HI injury…

In conclusion, we have demonstrated that the synthetic cannabinoid WIN55212-2 enhances SVZ cell proliferation, oligodendrogenesis, white matter remyelination, and neuroblast generation after neonatal HI.

These findings, summed to the previously described neuroprotective properties of cannabinoids after acute brain damage, may possess therapeutic repercussions in the long-term management of neonatal HI encephalopathy, a prevalent and devastating condition for which no pharmacological treatments are yet available.”

http://stroke.ahajournals.org/content/41/12/2956.full

 

Cannabis Counter Brain Cell Damage After a Stroke

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“New research by University of Otago scientists suggests some mechanisms in the brain targeted by cannabis could become drugs targets to counter brain cell damage after a stroke.

Researchers from the Medical School’s Department of Pharmacology and Toxicology have been the first in the world to show the cannabinoid CB2 receptor appears in the rat brain following a stroke.

Their findings were published recently in the journal Neuroscience Letters.

Dr John Ashton says the CB2 receptor is a protein produced as part of the body’s immune response system.

“This response is triggered by stroke and causes the inflammation that leads to damage in the area of the brain around where the stroke has occurred.

“If the inflammation can be stopped or reduced then it offers the hope of reducing the extent of the damage caused by stroke – and CB2 offers a potential target for such a drug.”

Dr Ashton says cannabis targets both the CB2 and the related CB1 receptors.

“THC, the major active ingredient of cannabis, acts mainly on CB1 but it also affects CB2. While THC is known to have some positive effects in terms of pain management its use is severely limited because of the way it triggers the psychoactive CB1 receptors in the brain,” he says.

“The aim would be to develop a drug that targets the CB2 receptor without affecting CB1.”

Dr Ashton says the relationship between cannabis and cannabinoid drugs has similarities to the relationship between heroin and codeine.

“Heroin and codeine share common targets, but by designing codeine in such a way that it eliminated the psychoactive side-effects seen with heroin, a therapeutically useful drug was developed. There is the potential to do the same with cannabinoids.”

Drugs targeting CB2 could also have potential therapeutic use in other conditions involving inflammatory damage to the brain, such as Huntington’s Disease and Alzheimer’s Disease. There may also be scope to use them in pain management.

“CB2 cells are also found in the spinal cord. They regulate pain signals making them a potential target for new pain killing drugs.””

http://www.hightimes.com/read/cannabis-counter-brain-cell-damage-after-stroke

Effects of the novel cannabinoid CB1 receptor antagonist PF 514273 on the acquisition and expression of ethanol conditioned place preference.

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“The centrally expressed cannabinoid receptor (CB1) has been considered a potential therapeutic target in treating alcoholism.

Though CB1 receptors have been shown to modulate primary and conditioned ethanol reward, much of this research employed animal models that require ethanol ingestion or oral routes of administration. This is problematic considering CB1 antagonist drugs have high anorectic liability and have been used clinically in the treatment of obesity. Therefore, the present study examined CB1 antagonism in DBA/2J mice using an unbiased ethanol-induced conditioned place preference (CPP) procedure, a paradigm that does not require ethanol ingestion…

Results from the present study appear inconsistent with other studies that have demonstrated a role for CB1 antagonism in ethanol reward using oral administration paradigms.

Our findings suggest that CB1 antagonism may have greater involvement in consummatory behavior than ethanol reward.”

http://www.ncbi.nlm.nih.gov/pubmed/24954022

http://www.thctotalhealthcare.com/category/addiction/