Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption.

“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology.

It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level.

We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation.

Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples.

Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation.

Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25799920

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells.

“Cannabidiol (CBD), the main non-psychoactive cannabinoid, has been previously shown by us to ameliorate clinical symptoms and to decrease inflammation in myelin oligodendrocyte glycoprotein (MOG)35-55-induced mouse experimental autoimmune encephalomyelitis model of multiple sclerosis as well as to decrease MOG35-55-induced T cell proliferation and IL-17 secretion. However, the mechanisms of CBD anti-inflammatory activities are unclear…

Our data suggests that CBD exerts its immunoregulatory effects via induction of CD4(+)CD25(-)CD69(+)LAG3(+) cells in MOG35-55-activated APC/TMOG co-cultures. This is accompanied by EGR2-dependent anergy of stimulated TMOG cells as well as a switch in their intracellular STAT3/STAT5 activation balance leading to the previously observed decrease in Th17 activity.”

http://www.ncbi.nlm.nih.gov/pubmed/25779454

Cost-effectiveness of Sativex in multiple sclerosis spasticity: new data and application to Italy.

“This study aims to evaluate the cost-effectiveness of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol oromucosal spray) when used as add-on therapy for management of resistant MS-related spasticity in the context of the Italian healthcare system…

Sativex can be regarded as a cost-effective treatment option for patients with MS-related spasticity in Italy.”

http://www.ncbi.nlm.nih.gov/pubmed/25771713

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Safety and Pharmacokinetics of Oral Cannabidiol When Administered Concomitantly With Intravenous Fentanyl in Humans.

“Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects.

Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.”

http://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Safety_and_Pharmacokinetics_of_Oral_Cannabidiol.99700.aspx

P414 Cannabidiol for symptomatic treatment of ulcerative colitis: Results from a randomised, double-blind, placebo-controlled, parallel group, multi-centred pilot study

“There is accumulating evidence that cannabidiol (CBD) has anti-inflammatory properties that could be exploited for the symptomatic relief of IBD.

This proof-of-concept double blind, randomised, placebo controlled trial assessed the efficacy, safety and tolerability of CBD botanical drug substance (BDS) in patients with mild to moderate UC…

…several signals suggest that GWP42003 may be beneficial for the symptomatic treatment of UC…”

https://www.ecco-ibd.eu/index.php/publications/congress-abstract-s/abstracts-2015/item/p414-cannabidiol-for-symptomatic-treatment-of-ulcerative-colitis-results-from-a-randomised-double-blind-placebo-controlled-parallel-group-multi-centred-pilot-study.html

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

Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.

The effect of THC was in part mediated by the cannabinoid receptor CB1.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…

In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models. 

This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

http://www.thctotalhealthcare.com/category/glaucoma-2/

Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT1A receptors and stressful experiences.

“The infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex are involved in behavioral responses observed during defensive reactions.

Intra-PL or IL injections of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, result in opposite behavioral effects in the contextual fear conditioning (CFC) paradigm…

Together these results indicate that CBD effects in the IL depend on the nature of the animal model, being influenced by previous stressful experiences and mediated by facilitation of 5HT1A receptors-mediated neurotransmission.”

http://www.ncbi.nlm.nih.gov/pubmed/25701682

Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol.

“Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects.

The present study evaluated if repeated treatment with CBD would attenuate the behavioral and glial changes observed in an animal model of schizophrenia…

These data reinforces the proposal that CBD may induce antipsychotic-like effects.

Although the possible mechanism of action of these effects is still unknown, it may involve CBD anti-inflammatory and neuroprotective properties.

Furthermore, our data support the view that inhibition of microglial activation may improve schizophrenia symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25680767

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

Fatty Acid Binding Proteins (FABPs) are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).

Image result for fatty acid binding proteins

“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex.

Recent reports suggest that CBD and THC elevates the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance.

Fatty acid binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH).

By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and we demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs.

Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption.

Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD.

Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids.

These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy towards epilepsy and other neurological disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25666611

A systematic review of the antipsychotic properties of cannabidiol in humans.

“Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side effects. Therefore, there is an urgent need for novel therapeutic targets for the treatment of schizophrenia.

A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system…

the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia.

Here we review studies that investigated the antipsychotic properties of CBD in human subjects.

Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration.

In addition, CBD may lower the risk for developing psychosis that is related to cannabis use.

These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex.

The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomised clinical trials will be needed before this novel therapy can be introduced into clinical practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25667194

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