Mol. Pharm.

ASAP Web Release Date: 09-Aug-2006.



. . . Here, we demonstrate that the active component of marijuana, delta-9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid beta-peptide (A-beta) 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-beta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

Marijuana may block Alzheimer's

Tuesday, 22 February, 2005



Scientists showed a synthetic version of the compound may reduce inflammation associated with Alzheimer's and thus help to prevent mental decline.

Tuesday, 22 February, 2005Scientists showed a synthetic version of the compound may reduce inflammation associated with Alzheimer's and thus help to prevent mental decline.

. . .



Using cell cultures, the researchers confirmed that cannabinoids counteracted the activation of microglia and thus reduced inflammation.



[original research article by Ramirez et al., 2005

. . .Using cell cultures, the researchers confirmed that cannabinoids counteracted the activation of microglia and thus reduced inflammation.

what a surprise! but seriously, see but seriously, see Ranganathan & D'Souza, 2006 for a comprehensive review]

Robbe D, Montgomery SM, Thome A, Rueda-Orozco PE, McNaughton BL, Buzsaki G. (2006). Cannabinoids reveal importance of spike timing coordination in hippocampal function Nat Neurosci . 9: 1526-1533.



Cannabinoids impair hippocampus-dependent memory in both humans and animals, but the network mechanisms responsible for this effect are unknown. Here we show that the cannabinoids Delta(9)-tetrahydrocannabinol and CP55940 decreased the power of theta, gamma and ripple oscillations in the hippocampus of head-restrained and freely moving rats. These effects were blocked by a CB1 antagonist. The decrease in theta power correlated with memory impairment in a hippocampus-dependent task. By simultaneously recording from large populations of single units, we found that CP55940 severely disrupted the temporal coordination of cell assemblies in short time windows (less than 100 ms) yet only marginally affected population firing rates of pyramidal cells and interneurons. The decreased power of local field potential oscillations correlated with reduced temporal synchrony but not with firing rate changes. We hypothesize that reduced spike timing coordination and the associated impairment of physiological oscillations are responsible for cannabinoid-induced memory deficits.



cannabinoids impair all stages of memory including encoding, consolidation, and retrieval



References

J Neurosci

Psychopharmacology