Tag Archives: Cannabinoids

Are Cannabinoids Effective for Orofacial Pain States?

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“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

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

Individual differences and vulnerability to drug addiction: a focus on the endocannabinoid system.

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“Vulnerability to drug addiction depends upon the interactions between the biological make-up of the individual, the environment, and age. These interactions are complex and difficult to tease apart.

Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure.

In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) have been considered a putative protective and risk factor, respectively, that can influence one’s susceptibility to continued drug abuse as well as the transition to addiction.

This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons.

Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle.

In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented.

Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/25714966

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

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

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“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

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“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/

Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-d-aspartate-induced AF5 cell death.

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“One of the most promising potential medical applications of cannabinoids involves their ability to protect cells from a variety of toxic events.

Cannabinoids have been reported to protect neurons from death…

Cannabinoids, such as the pharmacologically active component of marijuana (-)Δ9-tetrahydrocannabinol (THC)…

The neuroprotective effects of Δ9-tetrahydrocannabinol (THC) were examined…

Protective effects of Delta(9)-tetrahydrocannabinol… THC may function as an antioxidant to increase cell survival… 

THC can produce receptor-independent neuroprotective or cellular protective effects at micromolar concentrations as a result of its antioxidant properties…

In conclusion, THC produces a potent neuroprotective effect…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824211/

Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity.

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“Excitotoxic neuronal death underlies many neurodegenerative disorders…

Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity…

…desensitization of CB(1) receptors diminishes the neuroprotective effects of cannabinoids.

This study demonstrates the importance of agonist efficacy and the duration of treatment on the neuroprotective effects of cannabinoids.

It will be important to consider these effects on neuronal survival when evaluating pharmacologic treatments that modulate the endocannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/17140550

“Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity” http://molpharm.aspetjournals.org/content/69/3/691.long

Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity

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“Cannabinoids protect neurons from excitotoxic injury…

Endogenous or exogenous cannabinoids have shown neuroprotective effects…

The main finding reported here is that cannabinoids protect neurons from excitotoxic injury by a mechanism that involves the activation of CB1R and inhibition of NOS and PKA….

Cannabinoid receptor agonist drugs protect neurons…

By identifying the signaling pathways responsible for cannabinoid effects in animal models of disease and their human counterparts, it may be possible to design more specific and therefore more efficacious cannabinoid-based therapies.”

http://molpharm.aspetjournals.org/content/69/3/691.long

“Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity.”  http://www.ncbi.nlm.nih.gov/pubmed/17140550

Cannabinoids & Stress: Impact of HU-210 on behavioral tests of anxiety in acutely stressed mice.

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“Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles.

Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs.

This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioural testing.

Exogenouscannabinoid administration induced distinct behavioural phenotypes in stressed and unstressed mice…

These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner.

This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.”

http://www.ncbi.nlm.nih.gov/pubmed/25707713

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

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

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“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968

Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis.

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“The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation.

Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor.

Importantly, the lead of this series (26, hCB2: K i = 0.39 nM, hCB1: K i > 3000 nM) was found to protect mice against experimental colitis after oral administration.”

http://www.ncbi.nlm.nih.gov/pubmed/25699149

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