Category Archives: Endocannabinoid System

A Link Between Autism and Cannabinoids

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“Two autism-related mutations in a synapse-adhesion protein lead to deficits in prolonged endocannabinoid signaling in mice. It’s a surprising connection that suggests such signaling problems could be implicated in autism spectrum disorders, according to a paper published today (April 11) in Neuron.

Tonic endocannabinoid signaling is long-lasting and contrasts with the brief pulses characteristic of phasic signaling. Endocannabinoid signaling in general affects memory formation, learning, pain, and other important processes, but the distinctions between tonic and phasic signaling have been poorly understood.

“It’s a very stimulating finding which could be a real turning point in understanding tonic endocannabinoids and how this otherwise mysterious lipid signaling really works,” said Bradley Alger, a neuroscientist at the University of Maryland School of Medicine…

Alger added that, if the endocannabinoid system does turn out to be connected to autism in humans, medical marijuana could turn out to hold possibility for treating autism.”

More: http://www.the-scientist.com/?articles.view/articleNo/35088/title/A-Link-Between-Autism-and-Cannabinoids/

Role of the cannabinoid system in the transit of beta-amyloid across the blood–brain barrier

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“Emerging evidence suggests beta-amyloid (Aβ) deposition in the Alzheimer’s disease (AD) brain is the result of impaired clearance, due in part to diminished Aβ transport across the blood–brain barrier (BBB). Recently, modulation of the cannabinoid system was shown to reduce Aβ brain levels and improve cognitive behavior in AD animal models…

 The purpose of the current studies was to investigate the role of the cannabinoid system in the clearance of Aβ across the BBB.

  The current studies demonstrate, for the first time, a role for the cannabinoid system in the transit of Aβ across the BBB.

These findings provide insight into the mechanism by which cannabinoid treatment reduces Aβ burden in the AD brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

http://www.sciencedirect.com/science/article/pii/S104474311300064X

Marijuana May Be Legitimate Treatment for Alzheimer’s Disease, Report Says

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“Researchers at the Roskamp Institute in Florida recently published a study in the journal Molecular and Cellular Neuroscience revealing that cannabinoids could delay the effects of Alzheimer’s disease, and could quite plausibly terminate the disease entirely.”

medical marijuana alzheimers Marijuana May Be Legitimate Treatment for Alzheimers Disease, Report Says

“Corbin Bachmeier, Ph.D, lead researcher of the study, declared that Alzheimer’s disease is “the result of impaired Aβ [Amyloid-β protein] clearance from the brain”. According to this particular study, cannabinoids can resolve this problem, which makes it a prospective treatment.

Bachmeier’s examination determined that “modulation of the cannabinoid system was shown to reduce Aβ [Amyloid-β protein] brain levels and improve cognitive behavior in Alzheimer’s disease animal models.”

The study’s abstract states that the objective of the study was to “investigate the role of the cannabinoid system in the clearance of Aβ across the blood–brain barrier (BBB).”

For the first time in recorded history, the study in question establishes that the cannabinoid system does indeed play a role in the transit of Amyloid-β protein across the blood-brain barrier.

Bachmeier concluded that his discoveries “provide insight into the mechanism by which cannabinoid treatment reduces Aβ [Amyloid-β protein] burden in the AD [Alzheimer’s disease] brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

This is good news for individuals suffering with this specific ailment and for their loved ones. Cannabinoids seem to be boundless in respect to the medicinal benefits they have to offer.”

http://ivn.us/2013/07/24/marijuana-may-be-legitimate-treatment-for-alzheimers-disease-report-says/

Cannabis Use, Effect And Potential Therapy For Alzheimer’s, MS and Parkinson’s

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“The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems — the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.

One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy.

Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered…

The endocannabinoid system acts as a guardian against various attacks on the mammalian body.

Conclusion

The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:

  • The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
  • The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles — in particular in neuroprotection.
  • These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
  • The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer’s and Parkinson’s disease which raises hope for novel therapeutic opportunities for these diseases.”

More: http://www.sciencedaily.com/releases/2007/10/071014163644.htm

CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations.

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“Drugs that modulate the endocannabinoid system and endocannabinoids typically play an anticonvulsant role although some proconvulsant effects have been reported both in humans and animal models.

 This study aims to characterize the role of cannabinoids in specific areas of the cortico-thalamic network involved in oscillations that underlie seizures in a genetic animal model of absence epilepsy, the WAG/Rij rat.

These results, together with previous reports, support therapeutic potential for endocannabinoid system modulators in absence epilepsy and highlight that attenuated endocannabinergic function may contribute to the generation and maintenance of seizures. Furthermore, the entire cortico-thalamic network responds to cannabinoid treatment, indicating that in all areas considered, CB receptor activation inhibits the pathological synchronization that subserves absence seizures.

 In conclusion, our result might be useful for the identification of future drug therapies in absence epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/23860329

Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.

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“A role for endocannabinoid signaling has been reported in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we have investigated the possible epigenetic regulation of these genes by selected phytocannabinoids, plant-derived cannabinoids holding potential as novel therapeutics for various human diseases.

CONCLUSIONS AND IMPLICATIONS:

These findings identify the phytocannabinoids cannabidiol and cannabigerol as transcriptional repressors that can control cell proliferation and differentiation, suggesting (especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23869687

The Cannabinoid Receptor Agonist THC Attenuates Weight Loss in a Rodent Model of Activity-Based Anorexia

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“Anorexia nervosa (AN) is characterized by anhedonia whereby patients experience little pleasure or reward in many aspects of their lives. Reward pathways and the endocannabionid system have been implicated in the mediation of food intake. The potential to exploit these systems to reverse weight loss is investigated in a rodent model of activity-based anorexia (ABA).

Given the powerful role of the endocannabionid system in stimulating reward processes and the apparent poor development of these processes in AN, it is important to test the hypothesis that exogenous administration of cannabinoid type 1 (CB1) receptor agonists can reverse the anorexia displayed in a rodent ABA model…

Importantly, the data presented here show for the first time the efficacy of THC  in retarding the progression of ABA…

In conclusion, these data establish for the first time the effectiveness of THC in rescuing animals from profound body weight loss associated with the development of ABA, independent of physical activity, which is enhanced if allowed access to highly palatable foods.

These results from the animal-based model of AN highlight the potential of cannabinoids and of the endocannabinoid system in the treatment of human anorexia.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096804/

Cannabis and Δ9-tetrahydrocannabinol (THC) for weight loss?

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“Obesity is one of the highest preventable causes of morbidity and mortality in the developed world. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the ‘munchies’). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome.

This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market.

We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age.

Here, we propose that this effect is directly related to exposure to the Δ(9)-tetrahydrocannabinol (THC) present in cannabis smoke.

We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.”

http://www.ncbi.nlm.nih.gov/pubmed/23410498

Cannabinoid receptor subtypes 1 and 2 mediate long-lasting neuroprotection and improve motor behavior deficits after transient focal cerebral ischemia.

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“The endocannabinoid system is crucially involved in the regulation of brain activity and inflammation… we show that the endocannabinoid system assembles a comprehensive machinery to defend the brain against the devastating consequences of cerebral ischemia.

 In summary, this study underlines the therapeutic potential of CB1 and/or CB2 receptor agonists against neurodegenerative diseases or injuries involving acute or chronic imbalances of cerebral blood flow and energy consumption.”

http://www.ncbi.nlm.nih.gov/pubmed/23069763

Alcohol and cannabis use and mortality in people with schizophrenia and related psychotic disorders.

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“The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use.

…In a Cox model, predicted mortality risk was higher in age group 35-55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p = 0.005) in a survival model.

 We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments.

 Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/22595870