A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats.

“Thrombin mediates the life-threatening cerebral edema and blood-brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH).

We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH).

We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved.

The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia…

We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage.”

http://www.ncbi.nlm.nih.gov/pubmed/26376816

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Neural correlates of cannabidiol and Δ9-tetrahydrocannabinol interactions in mice: implications for medical cannabis.

“It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ9-tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC.

The aim of this study is to investigate whether CBD modulates THC-induced functional effects and c-Fos expression in a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.

These data re-affirm that CBD modulates the pharmacological actions of THC and provide information regarding brain regions involved in the interaction between CBD and THC.”

http://www.ncbi.nlm.nih.gov/pubmed/26377899

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[Cannabis – therapy for the future?]

“Despite all the progress achieved in the treatment of chronic gastrointestinal diseases, in some patients the treatment does not reach long-term optimum effectiveness. Therefore a number of patients have turned to complementary and alternative medicine (CAM).

Of the different types of CAM patients with GIT diseases tend to prefer in particular homeopathy, acupuncture and not least phytotherapy, where therapeutic use of cannabis may also be included.

The pathophysiological basis of therapeutic effect of curative cannabis has not been fully clarified so far.

Many scientists in many fields of medicine and pharmacology have been engaged in the study of effects of cannabinoids on the body since the beginning of the 20th century with the interest significantly increasing in the 1980s.

The discovery of CB receptors (1988) and endogenous molecules which activate these receptors (1992) led to the discovery of the endocannabinoid system.

Pharmacological modulation of the endogenous cannabinoid system offers new therapeutic possibilities of treatment of many illnesses and symptoms including the GIT disorders, including of nausea, vomiting, cachexia, IBS, Crohns disease and some other disorders.

Cannabinoids are attractive due to their therapeutic potential – they affect a lot of symptoms with minimum side effects.

Experience of patients with GIT disorders show that the use of cannabis is effective and helps in cases where the standard therapy fails.”

http://www.ncbi.nlm.nih.gov/pubmed/26375695

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The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats.

“The role of the cannabinoid (CB) system in the tolerance to analgesic effect of opioid remains obscure. The aim of the present study was to evaluate the effects of the endocannabinoid nonselective receptor agonist anandamide (AEA) and CB1 receptor antagonist rimonabant (SR141716) on morphine analgesia and tolerance in rats.

The findings suggested that AEA in combination with morphine produced a significant increase in expression of analgesic tolerance to morphine.

Conversely, cannabinoid receptor antagonist SR141716 attenuated morphine analgesic tolerance.

In addition, administration of AEA with morphine increased morphine analgesia.

In conclusion, we observed that the cannabinoid receptor agonist anandamide and CB1 receptor antagonist SR141716 plays a significant role in the opioid analgesia and tolerance.”

http://www.ncbi.nlm.nih.gov/pubmed/26374993

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New insights on the role of the endocannabinoid system in the regulation of energy balance.

“Within the last 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, since it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories.

An overactive endocannabinoid-cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders.

However, due to psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as anti-obesity treatment was removed from the European market in late 2008.

Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26374449

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Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids.

“The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia.

Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis.

However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry.

Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis.

However, research regarding the links between stress and the endocannabinoid system is in its infancy.

Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic-pituitary-adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis.

Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis.

Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.”

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Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by Hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.

“The effect of nutrition and dietary supplements as environmental factors has been suggested as possible factors affecting both disease risk and progression in on the course of multiple sclerosis with complex genetic-risk profiles.

This study was aimed to assess regulation of surface-membrane enzymes such as Delta-6-desaturase (FADS2), secretory Phospholipase A2(sPLA2) by hemp seed and evening primrose oils as well as Hot-natured dietary intervention in relapsing remitting multiple sclerosis (RRMS) patients…

The co-supplemented hemp seed and evening primrose oils with Hot nature diet can have beneficial effects in improving clinical symptoms and signs in RRMS patients which were confirmed by regulation of surface-membrane enzymes.”

http://www.ncbi.nlm.nih.gov/pubmed/26365444

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Cannabis as a substitute for alcohol and other drugs.

Logo of harmred

“This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients.

The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction.

Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/19958538

“The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.

This brings up two important points. First, self determination, the right of an individual to decide which treatment or substance is most effective and least harmful for them. If an individual finds less harm in cannabis than in the drug prescribed by their doctor, do they have a right to choose? Secondly, the recognition that substitution might be a viable alternative to abstinence for those who are not able, or do not wish to stop using psychoactive substances completely.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795734/

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Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: The impact of contextual factors.

“The present study examines the use of cannabis as a substitute for alcohol, illicit substances and prescription drugs among 473 adults who use cannabis for therapeutic purposes.

Substituting cannabis for one or more of alcohol, illicit drugs or prescription drugs was reported by 87% of respondents, with 80.3% reporting substitution for prescription drugs, 51.7% for alcohol, and 32.6% for illicit substances.

Respondents who reported substituting cannabis for prescription drugs were more likely to report difficulty affording sufficient quantities of cannabis, and patients under 40 years of age were more likely to substitute cannabis for all three classes of substance than older patients.

The finding that cannabis was substituted for all three classes of substances suggests that the medical use of cannabis may play a harm reduction role in the context of use of these substances,”

http://www.ncbi.nlm.nih.gov/pubmed/26364922

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Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.

“Multiple sclerosis is associated with muscle stiffness, spasms, pain, and tremor. Much anecdotal evidence suggests that cannabinoids could help these symptoms.

Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis.

There was evidence of a treatment effect on patient-reported spasticity and pain, with improvement in spasticity…

INTERPRETATION:

Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale. However… objective improvement in mobility and patients’ opinion of an improvement in pain suggest cannabinoids might be clinically useful.”

http://www.ncbi.nlm.nih.gov/pubmed/14615106

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