Tag Archives: cannabinoid

Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB1 receptor-mediated anti-inflammatory effects

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“Cannabinoids have been proposed as promising therapeutic agents in MS given their capability to alleviate specific MS symptoms (e.g., spasticity, pain).

Although MS has been considered mainly an inflammatory disorder, recent evidence, however, revealed the importance of neurodegenerative events, opening the possibility that cannabinoid agonists, given their cytoprotective properties, may also serve to reduce oligodendrocyte death and axonal damage in MS.

Thus, the treatment with WIN55,512-2, a potent CB1 and CB2 agonist, was reported to be effective to ameliorate tremor and spasticity in mice with chronic relapsing experimental autoimmune encephalomyelitis, a murine model of MS, but also to delay disease progression in this and other murine models of MS….”

http://www.sciencedirect.com/science/article/pii/S0028390812000500

Control of Spasticity in a Multiple Sclerosis Model is mediated by CB1, not CB2, Cannabinoid Receptors

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Figure 1

“There is increasing evidence to suggest that cannabis can ameliorate muscle-spasticity in multiple sclerosis, as was objectively shown in experimental autoimmune encephalomyelitis models. The purpose of this study was to investigate further the involvement of CB1 and CB2 cannabinoid receptors in the control of experimental spasticity…

Conclusions and Implications:

The CB1 receptor controls spasticity and cross-reactivity to this receptor appears to account for the therapeutic action of some CB2 agonists.

 As cannabinoid-induced psychoactivity is also mediated by the CB1 receptor, it will be difficult to truly dissociate the therapeutic effects from the well-known, adverse effects of cannabinoids when using cannabis as a medicine.

The lack of knowledge on the true diversity of the cannabinoid system coupled with the lack of total specificity of current cannabinoid reagents makes interpretation of in vivo results difficult, if using a purely pharmacological approach.

Gene knockout technology provides an important tool in target validation and indicates that the CB1 receptor is the main cannabinoid target for an anti-spastic effect.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189718/

Cannabidiol (CBD) Shown To Kill Breast Cancer Cells

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 “Cannabidiol (CBD) has been on the receiving end of a lot of attention from the scientific community for several decades now. However, it is only now that we are really starting to begin to get a grasp on how wonderful this cannabinoid truly is.

 

A study from 2011 states that cannabidiol is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD works in this capacity is yet to be understood. The study, titled “Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy,” focuses on how CBD can kill breast cancer cells. Breast cancer is the second leading cause of cancer-related death in women in the United States.

What the scientists found was that CBD influences apoptosis by interacting with a key protein, called beclin-1, found within the cancerous cell. Beclin-1 is also known to play a key role in autophagy, or cellular self-degradation of non-vital components, which may lead to programmed cell death. This causes a distortion of the electrical signals between the outer mitochondrial membrane and the rest of the cell, disrupting the transfer to the cell interior of certain molecules that are necessary for metabolism. What this means is that the cell cannot transfer energy, and the cell starves to death, and in doing so activates the self-destruction process of apoptosis.

The study concludes by stating, “In summary, we showed that CBD, a plant-derived cannabinoid, preferentially kills breast cancer cells by inducing ER stress, inhibiting mTOR signaling, enhancing ROS generation, and mediating a complex balance between autophagy and mitochondria-mediated apoptosis in MDA-MB-231 breast cancer cells. These findings support the continued exploration of CBD as an alternative agent for breast cancer treatment.””

http://cbdgum.networkofhemp.com/cannabidiol-cbd-shown-to-kill-breast-cancer-cells/

“Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy… In summary, we showed that CBD, a plant-derived cannabinoid, preferentially kills breast cancer cells…” http://mct.aacrjournals.org/content/10/7/1161.full

Dronabinol, a cannabinoid agonist, reduces hair pulling in trichotillomania: a pilot study.

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“Trichotillomania is characterized by repetitive pulling causing noticeable hair loss. Pharmacological treatment data for trichotillomania are limited.

Dronabinol appears to reduce the exocitotoxic damage caused by glutamate release in the striatum and offers promise in reducing compulsive behavior.

 

RESULTS:

The medication was well-tolerated, with no significant deleterious effects on cognition.

CONCLUSIONS:

This study, the first to examine a cannabinoid agonist in the treatment of trichotillomania, found that dronabinol demonstrated statistically significant reductions in trichotillomania symptoms, in the absence of negative cognitive effects.

Pharmacological modulation of the cannabinoid system may prove useful in controlling a range of compulsive behaviors…”

http://www.ncbi.nlm.nih.gov/pubmed/21590520

Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans.

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“Pre-extinction administration of Δ9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction…

 This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD.

 Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24055595

Cannabinoid facilitation of fear extinction memory recall in humans.

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“Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear…

 We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 h prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 h after extinction learning.

Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 h after extinction learning, suggesting that THC prevented the recovery of fear.

These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. This article is part of a Special Issue entitled ‘Cognitive Enhancers’.”

http://www.ncbi.nlm.nih.gov/pubmed/22796109

Cannabinoid Receptor 2 Activation: A Means to Prevent Monocyte-Endothelium Engagement.

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“This Commenatry highlights the article by Rom et al which shows that selective cannabinoid receptor 2 activation in leukocytes decreases key steps in monocyte-blood brain barrier engagement suppressing inflammatory leukocyte responses and preventing neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/24055258

Selective Activation of Cannabinoid Receptor 2 in Leukocytes Suppresses Their Engagement of the Brain Endothelium and Protects the Blood-Brain Barrier.

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“Cannabinoid receptor 2 (CB2) is highly expressed in immune cells and stimulation decreases inflammatory responses. We tested the idea that selective CB2 activation in human monocytes suppresses their ability to engage the brain endothelium and migrate across the blood-brain barrier (BBB), preventing consequent injury…

These results indicate that selective CB2 activation in leukocytes decreases key steps in monocyte-BBB engagement, thus suppressing inflammatory leukocyte responses and preventing neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/24055259

The role of androgen receptor in transcriptional modulation of cannabinoid receptor type 1 gene in rat trigeminal ganglia.

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“We have previously shown that anti-hyperalgesic effects of cannabinoid agonists under inflammatory condition are much greater in male than female, and that inflammatory cytokines upregulate cannabinoid receptor type 1 (CB1) expression in male, but not female, trigeminal ganglia (TG) in a testosterone-dependent manner. In this study, we investigated the mechanisms underlying the testosterone-mediated regulation of peripheral CB1 expression…

These experiments provided compelling evidence that testosterone regulates CB1 gene transcription in TG through AR following cytokine stimulation.

These results should provide mechanistic bases for understanding cytokine-hormone-neuron interactions in peripheral cannabinoid systems, and have important clinical implications for pain patients in whom testosterone level is naturally low, gradually declining or pharmacologically compromised.”

http://www.ncbi.nlm.nih.gov/pubmed/24055403

Therapeutic Potential of a Novel Cannabinoid Agent CB52 in the Mouse Model ofExperimental Autoimmune Encephalomyelitis.

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“The endocannabinoid system has recently emerged as a promising therapeutic target for MS. The protective mechanisms of cannabinoids are thought to be mediated by activation of cannabinoid receptor 1 (CB1) and 2 (CB2)…

activation of CB1 receptors contributes significantly to the anti-inflammatory and neuroprotective effects of cannabinoids on MS.”

http://www.ncbi.nlm.nih.gov/pubmed/24036373