The endocannabinoid system and multiple sclerosis.

“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

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

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/

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

“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.

“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.

“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

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

“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

Cannabinoids may be a target for new strategies in cancer treatment

“Cannabis-like substances that are produced by the body have both therapeutic and harmful properties, besides their well-known intoxicating effects, and the body’s cannabinoid system may be a target for new strategies in cancer treatment…

Cannabinoids have moreover been shown to affect the fate of cells. Cannabinoids protect some brain cells, whereas cells in certain types of brain tumors, such as glioma, are stimulated to commit controlled cell suicide (apoptosis)…

In summary, the findings of Sofia Gustafsson’s studies show that cannabinoids can be toxic for cancer cells… These findings are important for our knowledge both of the potential of the cannabinoid system as a target system for new strategies in cancer treatment…”

More: http://www.news-medical.net/news/20120229/Cannabinoids-may-be-a-target-for-new-strategies-in-cancer-treatment.aspx

Activation of spinal cannabinoid cb2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

“The role of spinal cannabinoid systems in neuropathic pain of streptozotocin-induced diabetic mice was studied…

 … A low dose of WIN-55,212-2  significantly recovered the tail-flick latency in streptozotocin-induced diabetic mice… The selective cannabinoid CB2 receptor agonist L-759,656 also dose-dependently recovered the tail-flick latency in streptozotocin-induced diabetic mice…

 These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23892011

Role of the cannabinoid system in the transit of beta-amyloid across the blood–brain barrier

“Emerging evidence suggests beta-amyloid (Aβ) deposition in the Alzheimer’s disease (AD) brain is the result of impaired clearance, due in part to diminished Aβ transport across the blood–brain barrier (BBB). Recently, modulation of the cannabinoid system was shown to reduce Aβ brain levels and improve cognitive behavior in AD animal models…

 The purpose of the current studies was to investigate the role of the cannabinoid system in the clearance of Aβ across the BBB.

  The current studies demonstrate, for the first time, a role for the cannabinoid system in the transit of Aβ across the BBB.

These findings provide insight into the mechanism by which cannabinoid treatment reduces Aβ burden in the AD brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

http://www.sciencedirect.com/science/article/pii/S104474311300064X

Marijuana May Be Legitimate Treatment for Alzheimer’s Disease, Report Says

“Researchers at the Roskamp Institute in Florida recently published a study in the journal Molecular and Cellular Neuroscience revealing that cannabinoids could delay the effects of Alzheimer’s disease, and could quite plausibly terminate the disease entirely.”

medical marijuana alzheimers Marijuana May Be Legitimate Treatment for Alzheimers Disease, Report Says

“Corbin Bachmeier, Ph.D, lead researcher of the study, declared that Alzheimer’s disease is “the result of impaired Aβ [Amyloid-β protein] clearance from the brain”. According to this particular study, cannabinoids can resolve this problem, which makes it a prospective treatment.

Bachmeier’s examination determined that “modulation of the cannabinoid system was shown to reduce Aβ [Amyloid-β protein] brain levels and improve cognitive behavior in Alzheimer’s disease animal models.”

The study’s abstract states that the objective of the study was to “investigate the role of the cannabinoid system in the clearance of Aβ across the blood–brain barrier (BBB).”

For the first time in recorded history, the study in question establishes that the cannabinoid system does indeed play a role in the transit of Amyloid-β protein across the blood-brain barrier.

Bachmeier concluded that his discoveries “provide insight into the mechanism by which cannabinoid treatment reduces Aβ [Amyloid-β protein] burden in the AD [Alzheimer’s disease] brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

This is good news for individuals suffering with this specific ailment and for their loved ones. Cannabinoids seem to be boundless in respect to the medicinal benefits they have to offer.”

http://ivn.us/2013/07/24/marijuana-may-be-legitimate-treatment-for-alzheimers-disease-report-says/