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IACM-Bulletin of 25 March 2012

Science/Cells: Cannabinoids inhibit spread of the HI-virus in late-stage AIDS

Researchers of Mount Sinai School of Medicine in New York, USA, have discovered that cannabinoids that bind to CB2- receptors activate other receptors on certain human immune cells that can directly inhibit the HI-virus in late-stage AIDS. "We knew that cannabinoid drugs like marijuana can have a therapeutic effect in AIDS patients, but did not understand how they influence the spread of the virus itself," said study author Dr. Cristina Costantino. "We wanted to explore cannabinoid receptors as a target for pharmaceutical interventions that treat the symptoms of late-stage AIDS and prevent further progression of the disease without the undesirable side effects of medical marijuana."

HIV infects certain immune cells, active T cells that carry the CD4-receptor, which makes these cells unable to fight off the infection. In order to spread, the virus requires that so-called resting T cells be activated. In advanced AIDS, HIV mutates so it can infect these resting T cells, gaining entry into the cell by using a signalling receptor called CXCR4. By treating the cells with a cannabinoid agonist that activates the CB2-receptor this signalling process was blocked and infection by the virus was suppressed. "Developing a drug that triggers only CB2 as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading," said Dr. Costantino. Because HIV does not use CXCR4 to enhance immune cell infection in the early stages of infection, CB2 agonists appear to be an effective antiviral drug only in late-stage disease.

As a result of this discovery in cell experiments, the research team led by Professor Benjamin Chen at Mount Sinai School of Medicine plans to develop a mouse model of late-stage AIDS in order to test the efficacy of a drug that activates the CB2 receptor. Last year a research team from the University of Louisana in New Orleans, USA, published research, according to which in rhesus monkeys infected with the SI-virus, which is an equivalent to the HI-virus, THC reduced the number of the viruses and inhibited progression of the AIDS-like disease.

More at:
- www.sciencedaily.com/releases/2012/03/120320195252.htm
- www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033961

(Sources: Science Daily of 20 March 2012; Costantino CM, Gupta A, Yewdall AW, Dale BM, Devi LA, Chen BK. Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells. PLoS One. 2012 March 20. [in press])

News in brief

Science/Cells: Endocannabinoids stimulate the production of melanin in the skin
Researchers of the University of Teramo, Italy, investigated the effects of endocannabinoids on the function of human melanocytes, skin cells, which produce melanin, the brown pigment in the skin. The endocannabinoids stimulated melanin production by activating CB1 receptors on these cells. (Source: Pucci M, et al. J Biol Chem. 2012 Mar 19. [in press])

Science/Animal: Endocannabinoids inhibit growth of skin cancer
Researchers of the Université Catholique de Louvain in Brussels, Belgium, found out that several endocannabinoids reduce the viability of melanoma cells. A combination of the endocannabinoid PEA (palmitoylethanolamine) and an inhibitor of PEA degradation (URB597) led to a decreased progression of melanoma, an aggressive skin cancer. (Source: Hamtiaux L, et al. BMC Cancer 2012;12(1):92.)

Science/Animal: Cannabinoids reduce inflammation in the brain caused by opioids
Scientists of the Universities of Ferrara and Parma, Italy, demonstrated that morphine enhances the release of pro-inflammatory substances in glia cells of the brain. In contrast, the activation of the CB2 receptor attenuated this inflammatory reaction. Authors wrote that "because glial activation opposes opioid analgesia and enhances opioid tolerance and dependence, we suggest that CB2 receptors, by inhibiting microglial activity, may be potential targets to increase clinical efficacy of opioids." (Source: Merighi S, et al. Br J Pharmacol. 2012 Mar 16. [in press])

Science/Cells: Anandamide inhibits a certain step in the progression of breast cancer
The Endocannabinoid Research Group of the University of Naples Federico II, Italy, investigated the mechanisms, by which the endocannabinoid anandamide inhibits breast cancer. Scientists used human breast cancer cells. They found a new anticancer effect of anandamide involving the inhibition of a certain step, which is important for the progression of cancer to invasion of the surrounding tissue. (Source: Laezza C, et al. EUR J Cancer. 2012 Mar 14. [in press])

Science/Animal: Inhibition of FAAH protects from damage to the stomach by indomethacin
Researchers at the Italian Institute of Technology in Genova, Italy, have discovered that inhibition of the enzyme FAAH (fatty-acid amide hydrolase) not only increases pain-reducing effects of indomethacin but also reduces the damage to the mucosa of the stomach caused by indomethacin. Inhibition of FAAH increases the levels of endocannabinoids. (Source: Sasso O, et al. Pharmacol Res. 2012 Mar 7. [in press])

Science/Animal: Cannabinoids impair working memory by activation of CB1 receptors on astrocytes
Researchers at Shaanxi Normal University in Xian, China, have discovered that the impairment of working memory by cannabinoids is due to the activation of CB1 receptors on astrocytes in the brain. Astrocytes are not nerve cells but provide nutritients to the nerve cells and perform immune and other functions. (Source: Han J, et al. Cell 2012;148(5):1039-50.)

Science/Human: Cannabis use may influence nerve cell organization in the brain
Scientists of Indiana University in Bloomington, USA, compared the network properties of nerve cells in the brain of 12 cannabis users and 13 non-using subjects by applying a certain magnetic resonance imaging (MRI). Cannabis users showed significantly decreased global network efficiency. These differences could be the results of cannabis use or the other way round these differences in brain organisation could increase the probability of cannabis use. (Source: Kim DJ, et al. Brain Connect. 2012 Feb 24. [in press])

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