Tag Archives: cannabinoid receptors

Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint.

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“Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.

Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration…

These findings suggest that targeting CB2 receptors may have therapeutic potential for treating OA pain.”

http://www.ncbi.nlm.nih.gov/pubmed/24282543

In vivo type 1 cannabinoid receptor availability in Alzheimer’s disease.

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“The endocannabinoid system (ECS) is an important modulatory and potentially neuroprotective homeostatic system in the brain.

  We have investigated CB1R availability in vivo in patients with AD…

 In conclusion, we found no in vivo evidence for a difference in CB1R availability in AD compared to age-matched controls.

 Taken together with recently reported in vivo CB1R changes in Parkinson’s and Huntington’s disease, these data suggest that the CB1R is differentially involved in neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24189376

 

The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.

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“These results indicate that exercise could activate the endocannabinoid system, producing antinociception.

Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE.

Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels.”

http://www.ncbi.nlm.nih.gov/pubmed/24148812

Endocannabinoid system and pain: an introduction.

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“The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS.

 The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated.

 To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia.

Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states.

 The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states.”

http://www.ncbi.nlm.nih.gov/pubmed/24148358

The endocannabinoid system and multiple sclerosis.

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“Multiple sclerosis (MS) is a neurodegenerative disease that is characterised by repeated inflammatory/demyelinating events within the central nervous system (CNS). In addition to relapsing-remitting neurological insults, leading to loss of function, patients are often left with residual, troublesome symptoms such as spasticity and pain. These greatly diminish “quality of life” and have prompted some patients to self-medicate with and perceive benefit from cannabis.

Recent advances in cannabinoid biology are beginning to support these anecdotal observations, notably the demonstration that spasticity is tonically regulated by the endogenous cannabinoid system.

Recent clinical trials may indeed suggest that cannabis has some potential to relieve, pain, spasms and spasticity in MS. However, because the CB(1) cannabinoid receptor mediates both the positive and adverse effects of cannabis, therapy will invariably be associated with some unwanted, psychoactive effects.

In an experimental model of MS, and in MS tissue, there are local perturbations of the endocannabinoid system in lesional areas. Stimulation of endocannabinoid activity in these areas either through increase of synthesis or inhibition of endocannabinoid degradation offers the positive therapeutic potential of the cannabinoid system whilst limiting adverse events by locally targeting the lesion.

 In addition, CB(1) and CB(2) cannabinoid receptor stimulation may also have anti-inflammatory and neuroprotective potential as the endocannabinoid system controls the level of neurodegeneration that occurs as a result of the inflammatory insults.

Therefore cannabinoids may not only offer symptom control but may also slow the neurodegenerative disease progression that ultimately leads to the accumulation of disability.”

http://www.ncbi.nlm.nih.gov/pubmed/18781983

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/

Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists.

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“The purpose of this study was the generation of central nervous system (CNS)-excluded cannabinoid receptor agonists to test the hypothesis that inhibition of spasticity, due to CNS autoimmunity, could be controlled by affecting neurotransmission within the periphery…

In summary, CNS-excluded CB1 receptor agonists are a novel class of therapeutic agent for spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/24121462

Parkinson’s Symptoms Reduced by Smoking Cannabis – Parkinson Research Foundation

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Cannabis_Clones_in_Box

 “Ruth Djaldetti, M.D., of Tel Aviv University in Israel, presented the findings of her research at a recent International Congress on Parkinson’s Disease and Movement Disorders.  She reported improvement in tremor, pain, rigidity and bradykinesia (slowness of movement).  Twenty subjects, all in their mid-sixties, and were rated using the Unified Parkinson’s Disease Rating Scale (UPDRS) both before and after smoking.  Their overall “before” scores were over 30 and within 30 minutes of smoking, their scores dropped to 24..  Their tremor scores averaged 7.5 on the UPDRS before and dropped to a score of 3.5 after smoking cannabis.  Bradykinesia scores dropped from 13.2 to 8.6 and rigidity went from 7.4 to 6.4.  Dr. Djaldetti also saw a marked relief in the pain her subjects were experiencing and this relief of pain led to better sleep and feeling more rested.

This bears out the results of other studies.  A study done in Great Britain that was published in 2011 found the principal ingredient in cannabis provided neuroprotection for people with Parkinson’s disease.  Its neuroprotective properties included reduction of inflammation and control of spasms, making it an ideal drug for treating Parkinson’s.  However, its confusing legal status make it very difficult for people to obtain or consider using and for doctors to even recommend to patients.

Another interesting study done in 2010 found that cannabinoid receptors are located in many parts of the brain and that cannabinoids are produced naturally in the brain.  People with Parkinson’s have even higher levels of endocannabinoids (cannabinoids produced within the brain).  The main ingredient in cannabis, Tetrahydrcannibol (THC) actually increases dopamine production temporarily.  Cannabidiol (CBD) another component of cannabis, also provides neuroprotective properties and has been shown to reduce dystonias .  CDB could be a very vital improvement for treating Parkinson’s, and a recent study has shown it useful in treating certain cancers as well.

While there have been many, many people reporting the anecdotal benefits of smoking cannabis, clinical trials are lagging behind.  Laboratory and animal studies have shown many benefits, but perplexing issues around the legality of cannabis are slowing the efforts and impeding progress.”

http://parkinsonresearchfoundation.org/blog/2013/07/11/parkinsons-symptoms-reduced-by-smoking-cannabis/

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