About 40% of HIV infections lead to some sort of brain impairment, such as HIV-1 associated cognitive impairment (HAND) and dementia, according to a team at the school’s Division of Experimental Medicine.
“HIV goes to the brain in an early stage during the HIV infection and causes mostly mild HAND disease,” explains Hava Avraham, Ph.D, who co-authored the new study.
“Although there are quite effective HIV drugs, standard antiretroviral therapy, to treat this stage, many of these drugs cannot cross the blood-brain barrier and therefore cannot really prevent the damage that HIV causes in the brain.”
But cannabinoids can cross the blood-brain barrier and have been shown to protect the brain in a variety of conditions.
In the latest study, published in the British Journal of Pharmacology, Dr. Avraham and her colleagues found that cannabinoids may also offer protection from a toxic protein created by the HIV virus, known as Gp120 protein.
“This molecule (Gp120) crosses the blood-brain barrier and causes a very toxic effect on the brain, especially on neuronal cells, which are very important for the functionality of the brain.”
She adds that a process called neurogenesis plays a key role in the development of the brain’s neurons, which are generated from neural stem cells and progenitor cells.
Using a cannabinoid called AM2421, which acts only on the CB2 receptors of the brain (not CB1), the researchers were able to protect the progenitor and neural stem cells from doses of Gp120, which Dr. Avraham says had “very positive effects on stem cells surviving.”
Experiments in animal models revealed similar results.
“Based on these in vitro studies, we went and analyzed neurogenesis in vivo in the mice brain. The mice were either untreated or treated with AM2421. Then we checked different parameters of neurogenesis and we found very positive results (with AM2421).”
While the researchers focused mainly on the CB2-specific cannabinoid AM2421, Dr. Avraham says cannabinoids that act on CB1 receptors – which are responsible for the marijuana high – were also effective. But like many others, she believes the side effects of CB1 activity could pose a problem in clinical settings.
“We also saw in our in vitro data that CB1 agonists, that we used, also have protective effects. The problem is really whether you can treat patients with CB1 agonists (without) addiction and having some other very significant side effects.”
Dr. Avraham says a number of CB2-specific drugs have already been developed for treating other conditions, and believes that it could be quicker to have them approved for HIV-related impairments.
Interestingly, previous studies suggest that various cannabinoids in marijuana may have positive effects on neurogenesis as well.
Dr. Avraham also believes that her latest findings might have wider implications than HIV, but hopes that further research will be done in order to bring investigators closer to human trials.
The study was funded by the Department of Experimental Medicine at Beth Israel Deaconess Medical Center