Δ9-Tetrahydrocannabinol Treatment During Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection

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“The major psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation.

THC treatment of primary human monocytes during differentiation reduced HIV-1 infection…

THC treatment of monocytes during differentiation into MDMs suppresses HIV-1 infection. 
Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019698/

The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain.

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“The therapeutic effects of the cannabinoid anandamide and the putative CB2 agonist palmitoylethanolamide were tested in a model of persistent visceral pain (turpentine inflammation of the urinary bladder)…

The results confirm the analgesic potential of endogenous ligands at cannabinoid receptor sites.

The anti-nociceptive effect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally mediated effect.

This observation might be exploited to separate central psychotropic effects from peripheral analgesic actions of the cannabinoids, under inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/9696473

Cannabinoid receptor 2 is increased in acutely and chronically inflamed bladder of rats.

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“Cannabinoid receptors are expressed in the urinary bladder and may affect bladder function… CB2 receptors may be a viable target for pharmacological treatment of bladder inflammation and associated pain…

In this study, we have shown that CB1 and CB2 are present in the bladder and its innervation, and that expression of CB2 is increased in the bladders of rats with acute and chronic cystitis. Bladder inflammation and pain is the summation of a number of biological events, including participation of the endocannabinoid system.

The endocannabinoid system could play an important role in modulation of severity of bladder inflammation and pain, and it may be possible to take advantage of the cannabinoid system in the bladder to decrease inflammation and resultant pain.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592089/

Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis.

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Figure 4.

“The role of anandamide in the development of inflammatory hyperalgesia and visceral hyperreflexia was studied in the rat urinary bladder…

These results suggest that anandamide, through activating TRPV1, contributes to the development of hyperreflexia and hyperalgesia during cystitis.”

http://www.jneurosci.org/content/24/50/11253.long

Increased cannabinoid receptor 1-immunoreactive nerve fibers in overactive and painful bladder disorders and their correlation with symptoms.

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“To study the expression of cannabinoid receptor 1 (CB1) in human urinary bladder hypersensitivity and overactivity disorders, and correlate changes with symptoms. Cannabinoid receptor agonists have been shown to modulate urinary bladder contractility and reduce pain after bladder inflammation; their clinical efficacy on lower urinary tract symptoms was demonstrated in the Cannabinoids in Multiple Sclerosis study…

CONCLUSIONS:

The results of this study suggest that increased nerve fibers, which express CB1, may be related to bladder pain in PBS (painful bladder syndrome) and urgency in IDO (idiopathic detrusor overactivity).

Our findings support clinical trials of CB1 agonists in bladder disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/20346490

Differential expression of functional cannabinoid receptors in human bladder detrusor and urothelium.

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“Although cannabinoid receptor expression has been demonstrated in human brain and other peripheral neuronal tissues, definitive expression of these receptors in the human bladder has not been reported. Consequently we investigated the expression of functional cannabinoid 1 and 2 receptors in human bladder detrusor and urothelium…

CONCLUSIONS:

Together these findings suggest a physiological role of cannabinoid 1 and 2 receptors in the human bladder.

Moreover, these results confirm the presence of functional cannabinoid 1 and 2 receptors in the human bladder, which can serve as a target for drugs acting on symptoms of interstitial cystitis/painful bladder syndrome.”

http://www.ncbi.nlm.nih.gov/pubmed/19237176

Functional and immunohistochemical characterization of CB1 and CB2 receptors in rat bladder.

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“To determined the localization of CB(1) and CB(2) receptors in rat bladder and investigate the effect of a mixed CB(1)/CB(2) receptor agonist, ajulemic acid (AJA), on chemically evoked release of the sensory neuropeptide calcitonin gene-related peptide (CGRP)…

CONCLUSIONS:

CB(1) and CB(2) receptors are localized in the urothelium of rat bladder, and application of AJA inhibits the evoked release of CGRP by acting on CB(1) and CB(2) receptors.

These findings identify a potential new pathway for study in the evaluation and treatment of painful bladder syndrome/interstitial cystitis.”

http://www.ncbi.nlm.nih.gov/pubmed/18468662

Treatment with a Cannabinoid Receptor 2 Agonist Decreases Severity of Established Cystitis.

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“We investigated whether treatment with the selective cannabinoid receptor 2 agonist… would ameliorate the severity of experimental cystitis…

Treatment with a selective cannabinoid receptor 2 agonist decreased severity of established acrolein induced cystitis and inhibited bladder inflammation associated increased referred mechanical sensitivity and increased bladder urinary frequency.

Our data indicate that cannabinoid receptor 2 is a potential therapeutic target for treatment of painful inflammatory bladder diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24184363

Activation of cannabinoid receptor 2 inhibits experimental cystitis.

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“Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells…

The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23515618