Web Release Date: August 9,
A Molecular Link between the Active Component of Marijuana and Alzheimer's Disease Pathology
and
Departments of Chemistry, Immunology, and Molecular Biology, Molecular and Integrated Neurosciences Department, The Skaggs Institute for Chemical Biology, and Worm Institute for Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
Received June 11, 2006
Abstract:
Alzheimer's disease is the leading cause of dementia among the elderly, and with
the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple
over the next 50 years. Consequently, the development of treatments that slow or halt the disease
progression have become imperative to both improve the quality of life for patients and reduce
the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active
component of marijuana, 
9-tetrahydrocannabinol (THC), competitively inhibits the enzyme
acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid 
-peptide (A)
aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of
the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the
critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed
for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of A
aggregation, and this study provides a previously unrecognized molecular mechanism through
which cannabinoid molecules may directly impact the progression of this debilitating disease.
Keywords: Cannabinoids; Alzheimer's disease; acetylcholinesterase
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