Neuroscientists at the University of South Florida in Tampa have determined that extremely low levels of the psychoactive compound in marijuana called delta-9-tetrahydrocannabinol, or THC, may slow or halt Alzheimer’s disease progression.

Findings from a recent USF study using a cellular model of Alzheimer’s disease, were reported online in the Journal of Alzheimer’s Disease, and are consistent with findings of previous studies published in medical journals showing that THC itself appears to ease moderate pain (analgesic) and to be neuroprotective, reducing neuroinflammation and stimulating neurogenesis, making it potentially useful in treating Alzheimer’s Disease.

The USF study, entitled “Marijuana compound may offer treatment for Alzheimer’s disease” published in the Journal of Alzheimer’s Disease (J Alzheimers Dis. 2014 Jul 7. [Epub ahead of print] DOI: 10.3233/JAD-140093) is coauthored by Chuanhai Cao, Hui Liu, and Xiaoyang Lin of the University of South Florida College of Pharmacy and USF-Health Byrd Alzheimer’s Institute at Tampa; Yaqiong Li, Ge Bai, and Jianfeng Cai of the University of South Florida Department of Chemistry; Jonathan May of the USF-Health Byrd Alzheimer’s Institute; Kyle Sutherland of the University of South Florida College of Medicine; and Neel Nabar of Thomas Jefferson University, Philadelphia, PA.

The study investigated the potential therapeutic qualities of 9-tetrahydrocannabinol (THC) in slowing or stopping the primary characteristics associated with Alzheimer’s disease. The researchers at USF Health Byrd Alzheimers Institute explained in their study that N2a-variant amyloid- protein precursor (APP) cells were incubated in the lab along with THC, and then assayed for amyloid- (A) levels at the 6-, 24-, and 48-hour time marks. THC was additionally tested for caffeine synergy, in respect to the reduction of the A level in N2a/APPswe cells, and to determine if multiple treatments were beneficial.

Results revealed that THC administered in extremely low doses can reduce the creation of amyloid beta in the body, which is typically found in soluble form in most elderly brains, and also helps to prevent abnormal levels of this protein accumulating — a process that is considered to be a pathological hallmark that is evident in the early stages of memory loss associated with the disease. THC given in low concentrations was also found to selectively enhance mitochondrial function — a critical step needed to supply energy, transmit signals, and overall maintain healthy brain function.

From there, the MTT assay was then performed in order to test and determine the toxicity of THC in this experimental setting. Both Thioflavin T assays as well as western blots were conducted to test the direct anti-A aggregation significance of THC. Finally, THC was tested in order to determine its effects if any on glycogen synthase kinase-3 (GSK-3) and related signaling pathways.

From the study results, the scientists noted that they recognized THC to be measurably effective in lowering A levels in N2a/APPswe cells when used in extremely low concentrations in a dose-dependent manner. However, when caffeine and THC were combined together, no additive effect was noted. “We did discover that THC directly interacts with A peptide, thereby inhibiting aggregation,” they note, “Furthermore, THC was effective at lowering both total GSK-3 levels and phosphorylated GSK-3 in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin’s enhancement of mitochondria function.” The coauthors conclude that “These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.”

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Photo Caption: USF Health neuroscientist Chuanhai Cao, PhD, was the lead author of a study testing the effects of the marijuana compound THC on an Alzheimers disease cell model, Image Credit: University of South Florida

“THC is known to be a potent antioxidant with neuroprotective properties, but this is the first report that the compound directly affects Alzheimer’s pathology by decreasing amyloid beta levels, inhibiting its aggregation, and enhancing mitochondrial function, observes study lead author Chuanhai Cao, PhD and a neuroscientist at the Byrd Alzheimer’s Institute and the USF College of Pharmacy.

Decreased levels of amyloid beta means less aggregation, which may protect against the progression of Alzheimer’s disease. Since THC is a natural and relatively safe amyloid inhibitor, THC or its analogs may help us develop an effective treatment in the future.

The researchers point out that at the low doses studied, the therapeutic benefits of THC appear to prevail over the associated risks of THC toxicity and memory impairment.

nabarnNeel Nabar, a study co-author and MD/PhD candidate, recognized the rapidly changing political climate surrounding the debate over medical marijuana. “While we are still far from a consensus, this study indicates that THC and THC-related compounds may be of therapeutic value in Alzheimers disease,” Nabar says in a USF release. “Are we advocating that people use illicit drugs to prevent the disease? No. Its important to keep in mind that just because a drug may be effective doesn’t mean it can be safely used by anyone. However, these findings may lead to the development of related compounds that are safe, legal, and useful in the treatment of Alzheimer’s disease.”

It’s useful to note that the body’s own system of cannabinoid receptors interacts with naturally-occurring cannabinoid molecules, and these molecules function similarly to the THC isolated from the cannabis (marijuana) plant.

Dr. Cao’s laboratory at the Byrd Alzheimer’s Institute is currently investigating the effects of a drug cocktail that includes THC, caffeine as well as other natural compounds in a cellular model of Alzheimer’s disease, and will advance to a genetically-engineered mouse model of Alzheimer’s shortly.

“The dose and target population are critically important for any drug, so careful monitoring and control of drug levels in the blood and system are very important for therapeutic use, especially for a compound such as THC,” Dr. Cao says.

The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit:
http://www.health.usf.edu

Sources:
The University of South Florida
USF Health Byrd Alzheimers Institute
Journal of Alzheimers Disease

Image Credits:
The University of South Florida

USF Health Byrd Alzheimers Institute