HIV has had perhaps the greatest impact of any single disease on the U.S. in recent times, both culturally and medically. Unlike most other viruses, HIV is a retrovirus, meaning rather than producing RNA in cells to then produce the protein needed to build more copies, it sneaks itself directly into cell’s original DNA. This type of virus is hard to detect until the person is already infected, at which point, the infection will continue indefinitely. HIV targets the immune system by duplicating inside of cells that attack disease. Left untreated, the immune system then begins to fail, with enough time becoming unable to defend the body from even minor disease. This condition is known as AIDS and caught medicine by surprise in the 80s, proving to be one of the most dangerous and difficult to treat diseases. Fortunately, we now have medications that prevent the HIV infection from spreading, which greatly decreases the likelihood of developing AIDS and means that people with HIV in countries with developed medicine continue to lead long, full lives with mostly minor symptoms.

Despite retroviral therapy, one serious symptom, HIV-associated neurocognitive disorder (HAND), occurs in 30-50% of patients. In this disorder, patients begin to display a decrease in brain functionality, with decreases in operational memory, emotional response, and executive function. In most cases, the effect is mild, although in some cases, this can progress to HIV-induced dementia, rendering the patient unable to take care of his/herself and requiring daily living assistance. The cause of this heart-breaking effect is not fully understood, although it is commonly believed that the immune response plays a function, essentially being tricked into destroying brain cells and connections. Additionally, immune cells that are actively infected with HIV secrete neurotoxins that further damage. Recent studies have indicated that the expression of the HIV-1 transactivator of transcription (Tat) induces neuron injury and disrupts connections between neurons as well. It is believed this is a result of Tat eliciting an increase in frequency and amplitude of inhibitory post-synaptic currents that then deregulates brain function. Ideally, these inhibitory post-synaptic currents caused by Tat could be blocked or reduced by a neuroprotective treatment.

As we’ve reported previously, cannabinoids, the family of natural and artificial chemicals that includes THC and CBD from cannabis as well as 2-AG and anandamide from the human body, are known to have neuroprotective effects. From multiple sclerosis, to Parkinson’s disease and Alzheimer’s disease, cannabinoids have been shown to prevent the immune system from needlessly destroying brain cells, thus reducing the impact of these conditions. As a result, one team of researchers lead by the University of North Carolina investigated the impact of cannabinoids on animal models of neurodegeneration caused by the HIV virus.

To do this, scientists euthanized male and female mice and prepared thin slices of their brains, specifically from the pre-frontal cortex (PFC) areas. First, researchers stained several samples to identify the location and existence of CB1 cannabinoid receptors. This reconfirmed (as is already well known), that a dense network of CB1 receptors exists throughout the PFC area of the brain. Next, researchers preserved these samples in a solution that allowed them to continue living, albeit outside of their natural context. Finally, researchers added HIV-1 Tat to the solution bath and measured pre and post synaptic current. This confirmed, again, that Tat decreases post-synaptic current and has a destructive effect on brain functioning. However, the most interesting part of the experiment occurred when researchers began to add WIN55,212-2, a synthetic cannabinoid that bonds selectively to the CB1 receptor. Addition of WIN55,212-2 seemed to reduce the frequency of inhibitory post-synaptic currents generated by Tat. Curious at how far this could go, researchers then added anandamide instead of WIN55,212-2 to baths. Anandamide is the body’s natural equivalent of THC, again bonding primarily to the CB1 receptor. In this case, results were once again similar to adding WIN55,212-2, with reduction of the frequency but not amplitude of inhibitory post-synaptic currents cased by HIV’s Tat.

To establish if this effect was occurring through the CB1 receptor itself or via another unknown interaction with WIN55,212-2, researchers then made a trial adding Rimonabant to the chemical bath, which effectively shuts off all CB1 receptors. In this case, the addition of WIN55,212-2 did nothing and the original effects of Tat alone were observed, indicating that indeed, CB1 cannabinoid receptor activation is responsible for the blockage of Tat damage in the brain. Additionally, as would be expected of an effect mediated through the CB1 receptor alone, when researchers applied a CB2 cannabinoid receptor blocker, nothing changed in any scenario.

Stripping away all the technical talk and getting down to how this could potentially affect those suffering from HIV, what does this mean? According to this study, cannabinoids, specifically those that activate the CB1 cannabinoid receptor, seem to be able to reduce brain damage caused by HIV’s Transactivator of Transcription (Tat). It seems likely that consumption of cannabinoids such as those found in cannabis could prevent some of the brain damage that accompanies HIV. However, as always, there is a large difference in an effect observed in a cell culture and one observed in human patients. More studies must be performed to establish the effectiveness of externally consumed cannabinoids in treating neurodegeneration caused by HIV. However, if these studies prove conclusive, researchers might be able to develop a cannabinoid-based treatment designed specifically for HIV patients. In the meantime, we have little reason to believe that consuming cannabis can adversely affect brain growth, and this research indicates that THC might be an effective treatment already, so HIV patients may be interested in consuming small amounts of high-THC cannabis as a preventative measure.



Works Cited

Changqing Xu, Douglas Hermes, Ken Mackie, et al. Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices. Journal of NeuroImmune Pharmacology (2016), pre-published online March 2016. DOI: 10.1007/s11481-016-9664-y.