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Showing Original Post only (View all)Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology [View all]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology
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 as well as reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ 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 Aβ 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
Introduction
Since the characterization of the Cannabis sativa-produced cannabinoid, Δ9-tetrahydrocannabinol (THC) (Figure 1), in the 1960's,1 this natural product has been widely explored as an anti-emetic, anti-convulsive, anti-inflammatory, and analgesic.2 In these contexts, efficacy results from THC binding to the family of cannabinoid receptors found primarily on central and peripheral neurons (CB1) or immune cells (CB2).3 More recently, a link between the endocannabinoid system and Alzheimer's disease has been discovered4 which has provided a new therapeutic target for the treatment of patients suffering from Alzheimer's disease.5 New targets for this debilitating disease are critical as Alzheimer's disease afflicts over 20 million people worldwide, with the number of diagnosed cases continuing to rise at an exponential rate.6,7 These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ toxicity.8-10 Yet, it is important to note that in these reports, cannabinoids serve as signaling molecules which regulate downstream events implicated in Alzheimer's disease pathology and are not directly implicated as effecting Aβ at a molecular level.
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Conclusion
We have demonstrated that THC competitively inhibits AChE, and furthermore, binds to the AChE PAS and diminishes Aβ aggregation. In contrast to previous studies aimed at utilizing cannabinoids in Alzheimer's disease therapy,8-10 our results provide a mechanism whereby the THC molecule can directly impact Alzheimer's disease pathology. We note that while THC provides an interesting Alzheimer's disease drug lead, it is a psychoactive compound with strong affinity for endogenous cannabinoid receptors. It is noteworthy that THC is a considerably more effective inhibitor of AChE-induced Aβ deposition than the approved drugs for Alzheimer's disease treatment, donepezil and tacrine, which reduced Aβ aggregation by only 22% and 7%, respectively, at twice the concentration used in our studies.7 Therefore, AChE inhibitors such as THC and its analogues may provide an improved therapeutic for Alzheimer's disease, augmenting acetylcholine levels by preventing neurotransmitter degradation and reducing Aβ aggregation, thereby simultaneously treating both the symptoms and progression of Alzheimer's disease.
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Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology [View all]
G_j
Mar 2013
OP
K&R. There's a scientist (biochemist IIRC) in Colorado Springs that has been working on this
Egalitarian Thug
Mar 2013
#3
They already have a pill but they don't work, that's why you don't hear much about it.
Dustlawyer
Mar 2013
#41
And it doesn't work very well, but does cost a lot. Corporatocracy. n/t
Egalitarian Thug
Mar 2013
#63
As someone who smoked pot on a prodigious level many years ago it most certainly is not.
KittyWampus
Mar 2013
#37
I know several medical marijuana patients who would strongly disagree with you
liberal_at_heart
Mar 2013
#52
WTF does that have to do with the FACT MJ effects short term memory. Cause that's all I addressed.
KittyWampus
Mar 2013
#64
You're putting anecdotal evidence on the same footing with A LOT of statistical
tpsbmam
Mar 2013
#71
Here's the meta analysis that showed NO impairment after 25 days of abstinence.
RainDog
Mar 2013
#66
Absolutely - that's why my post stated "although smoking is definitely not a good thing overall"
aint_no_life_nowhere
Mar 2013
#58
After years of painstaking independent research I can report only one worrisome side effect...
Indepatriot
Mar 2013
#25
I my case study of 1 I found that it helps my small fiber sensory neuropathy which is,
Dustlawyer
Mar 2013
#43
Awesome! I smoked so much herb from the time that I was 18 until I was 33 that I should
Zorra
Mar 2013
#40
The US Government owns the patent on cannabinoids as treatment for Alzheimer's and other illnesses.
Fire Walk With Me
Mar 2013
#42