Combining low-dose tetrahydrocannabinol (THC) with nonsteroidal anti-inflammatory drug (NSAID) celecoxib improved cognition and reduced Alzheimer’s-related brain pathology in mice. The corresponding study was published in Aging and Disease.
THC has been considered a potential therapeutic agent for Alzheimer’s disease for some time. How well it prevents cognitive decline, however, remains unknown.
Previous research shows that THC increases levels of the enzyme cyclooxygenase-2 (COX-2) in the brain, which has been linked to learning and memory impairment. This mechanism has made it difficult to use THC for treating neurological conditions.
Simply blocking COX-2, however, is not a solution. Trials involving high doses of COX-2 inhibitors alongside THC for Alzheimer's disease did not improve cognition and instead produced serious cardiovascular side effects.
In the current study, researchers investigated whether pairing THC with a low dose of COX-2 inhibitor, celecoxib, could block the compound’s pro-inflammatory effects while preserving its beneficial properties.
To do so, they tested low-dose THC alone and together with low-dose celecoxib in mouse models of Alzheimer’s disease. Oral doses were given once daily for 30 days. Treatment began before the onset of memory symptoms to assess the combination’s ability to prevent or delay the onset of Alzheimer’s symptoms.
Although low-dose THC alone improved cognitive performance and reduced some pathological markers, it also increased inflammatory signalling. By comparison, THC combined with celecoxib improved learning and memory performance, reduced beta-amyloid and tau pathology, and decreased markers of neuroinflammation. Single-cell RNA sequencing found that genes involved in synaptic function, inflammation, and Alzheimer’s disease risk reverted to a healthier profile after treatment.
“What really mattered was behavior. If cognition is not improved, then the treatment doesn’t matter. And that’s where the combination clearly worked better than THC alone,” said Chu Chen, PhD, professor at the Department of Cellular and Integrative Physiology at The University of Texas at San Antonio, said in a press release.
“If you develop a new compound, it can take 10 to 20 years to reach patients. In this case, both drugs are already approved. That gives us a real advantage. We’re at a point where basic neuroscience discoveries are pointing toward something that could realistically move into the clinic,” he concluded.
Sources: EurekAlert, Aging and Disease