Marijuana Compound a Novel Treatment for Alzheimer's?

Pam Harrison

September 05, 2014

Extremely low levels of delta-9-tetrahydrocannabinol (THC), the active compound in marijuana, may offer a novel and viable treatment for Alzheimer's disease (AD), preliminary research suggests.

Investigators at the University of South Florida in Tampa found that THC both decreases the production of amyloid beta (Aβ) and inhibits its aggregation in cell cultures. In addition, it does so at extremely safe doses.

These observations have implications for a potentially new therapeutic approach to the treatment of Alzheimer's disease (AD), as researchers suggest.

"Our group believes that amyloid aggregation is the initiator of AD, so we wanted to see if THC can inhibit amyloid beta aggregation in vitro," study investigator Chuanhai Cao, PhD, a neuroscientist at the Byrd Alzheimer's Institute, College of Pharmacy, University of South Florida, told Medscape Medical News.

"And in our in vitro cell cultures, we discovered that THC inhibits amyloid beta production as well as aggregation at extremely low doses and that it enhances mitochondrial function as well. These observations suggest that THC has anti-Alzheimer's activity."

The study was published online August 27 in the Journal of Alzheimer’ Disease.

Amyloid Lowering

For the study, investigators incubated THC together with a variant of Aβ protein precursor cells and assayed the culture for the presence of Aβ levels at the 6-, 24-, and 48-hour time points.

TCH was also tested for synergy with caffeine to see whether the combination of the 2 led to greater reductions in the Aβ levels of these Aβ protein precursor cells in vitro.

"From the results, we have discovered THC to be effective at lowering Aβ levels in [Aβ protein precursor cells] at extremely low concentrations in a dose-dependent manner," the investigators report.

However, the combination of TCH and caffeine did not prove to be synergistic, inasmuch as there was no additive effect on Aβ levels when the 2 compounds were combined in vitro.

Investigators also observed that the same active compound in marijuana directly interacts with Aβ peptide, thereby inhibiting its aggregation. Low doses of THC can enhance mitochondria function as well.

Mitochondria function helps supply energy, transmit signals, and maintain a healthy brain, all of which decrease with age, said Dr. Cao. Previous research by this team has shown that Aβ migrates into the mitochondria with age, impairing its function.

"Thus, if THC can inhibit amyloid beta aggregation and reduce its production, it is going to enhance mitochondria function." Dr. Cao said.

Neuroprotective Effect

Concerns about memory impairment are frequently raised in the context of any research associated with potential therapeutic benefits of THC.

However, Dr. Chao emphasized, memory impairment is only observed at "abuse" concentrations of THC, which are more than a thousand times higher than the doses used in their own in vitro experiments.

Newer research also suggests that such ultra-low doses of TCH have a neuroprotective effect and are not harmful, as has been previously suggested.

"This research is no excuse to smoke marijuana to prevent AD," Dr. Cao said.

"But we have provided some evidence of how TCH works in terms of its anti-Alzheimer's potential, and we feel that patients particularly in the earlier stages of Alzheimer's could benefit from this natural compound, provided we use the compound properly."

Both early-onset familial AD as well as late-onset sporadic AD are characterized by extracellular Aβ peptide and by amyloid plaques along with tau-containing neurofibrillary tangles.

The continuous aggregation of Aβ peptides along with hyperphosphorylation of the tau protein inside the cell causing neurofibrillary tangle formation are generally accepted as the major etiologic factors behind the neuronal cell death associated with AD progression.

"Large Leap"

Commenting on the findings for Medscape Medical News, Barbara Koppel, MD, chief of neurology and professor of clinical neurology, New York Medical College, in Valhalla, said it was a "large leap" to say that the use of THC clinically might slow progression of AD.

"Nevertheless," she noted, "the series of in vitro experiments conducted by Dr. Cao and colleagues that measured a lowering of levels of production and aggregation of amyloid beta suggests there is a connection between the function of the endocannabinoid system found in the normal brain and the destruction of neurons by toxic amyloid deposition."

Dr. Koppel added that the exact mechanism behind this connection is complicated, and even with the other experiments described by the investigators, the interrelationship between neurodegeneration and the role of cannabinoids is intricate and complex.

"Of course, translation to patients with minor cognitive impairment or AD will require studies of the best route for efficacy and minimization of toxicity in patients who may already suffer from cognitive impairment from their underlying condition," she said.

"But given the fact that the THC 'dose' used in these experiments is much less than what is used recreationally, there is a possible place for cannabinoid therapy in this otherwise progressive neurodegenerative disease."

Dr. Cao and Dr. Koppel report no relevant financial relationships.

J Alzheimers Dis. Published online August 27, 2014. Abstract

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