THC and Memory
Recently it was announced that tetrahydrocannabinol (THC), the active ingredient in cannabis, may help prevent Alzheimer's disease:Eubanks LM, Rogers CJ, Beuscher IV AE, Koob GF, Olson AJ, Dickerson TJ, Kim D. Janda (2006). A molecular link between the active component of marijuana and Alzheimer's Disease pathology. 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.
see also:
Marijuana may block Alzheimer'sHowever, even more recently, we've seen the report that THC is bad for your memory [what a surprise! but seriously, see Ranganathan & D'Souza, 2006 for a comprehensive review] because it disrupts synchronous cell firing in the hippocampus:
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.
. . .
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]
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.So it seems that short-term episodic and working memory (Ranganathan & D'Souza, 2006)...
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...can be compromised with a long-term goal of preventing Alzheimer's disease!
More news stories!
Marijuana's Key Ingredient Might Fight Alzheimer's
Why Marijuana Impairs Memory
Marijuana's High Times Not Memorable with Neurons Out of Sync
References
Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. (2005). Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 25: 1904-1913.
Ranganathan M, D'Souza DC. (2006). The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology 188: 425-444.
posted by The Neurocritic @ 11:08 PM
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12 Comments:
I recently saw the Nature Neuroscience article about THC and spike timing coordination - it's interesting. The whole collection of marijuana research is riddled with contradictory findings, which makes some sense if you know that cannabinoids act presynaptically as well as postsynaptically - meaning they can have opposing effects on the same function.
Marijuana has been shown to be effective in pain treatment, and even preventing conditioned anticipatory nausea/vomitting in chemotherapy patients - so it clearly warrants more research, but the obstacles that stand in the way often make it difficult.
Personally as a memory researcher, I find the effects of THC confusing - how is it that something can be harmful in the short-term, but beneficial in the long term? Is there some sort of experience related tolerance to the short term effects that needs to be acheived before any long term benefits can express themselves? Maybe, maybe not!
Thanks for your comments.
I have to admit that I don't know much about cannabinoid receptors. I just learned that THC is a partial agonist at CB1 receptors, that there are CB1 receptors in in astrocytes, microglia, and oligodendrocytes (Ramirez et al. 2005), and that the neuroprotective effects of cannabinoid receptor agonists are presynaptic and involve inhibiting the release of glutamate (Shen & Thayer, 1998)
It's no surprise that acute intoxication impairs working memory but various studies show no residual effects in a)non-heavy current users and b)former users (including heavy ones) who have been abstinent on the order of months.
See:
Long-term effects of frequent cannabis use on working memory and attention: an fMRI study.
Neurocognitive consequences of marihuana--a comparison with pre-drug performance.
Neuropsychological consequences of regular marijuana use: a twin study.
Neuropsychological performance in long-term cannabis users.
Daksya, thanks for the links to articles that demonstrate the lack of long-term cognitive consequences in abstinent former users. It's good to draw attention to that point.
Also among non-heavy current users.
Yes, it's also true of "frequent but relatively moderate cannabis users" (Jager et al., 2006).
CONCLUSION: No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence. Nonetheless, frequent cannabis use may affect brain function, as indicated by altered neurophysiological dynamics in the left superior parietal cortex during working memory processing.
I'm certainly not a prohibitionist, just pointing out that some brain changes were observed (albeit without a concomitant decline in memory and attention).
The longitudinal study (2nd) which looked at light users also did not find any significant differences in moderate users, so the hedged statement you emphasized should be evaluated in that context. Also, I "love" it that when something physiological is found different in users, then the automatic implication is that the change is detrimental, sorta like the biological version of the anthropic principle. Half-seriously, for all we know, those changes may be beneficial but the combined clinical findings are clear.
It would be really interesting to gather epidemiological data from a large population of elderly people who've been long-term light-to-moderate users, and compare to nonusers, to determine whether there is a lower incidence of Alzheimer's in cannabis users.
The oldest of the 60's era hippies are getting up there in age...
We all know that ∆9-tetrahydrocannabinol is lipid soluble. We also know that smoking cannabis and absorbing it through the alveoli rout is dependent on serum lipid THC saturation. Do any of these studies accurately quantify the amount of THC which could actually be crossing the blood brain barrier.
We all know that ∆9-tetrahydrocannabinol is lipid soluble. We also know that smoking cannabis and absorbing it through the alveoli rout is dependent on serum lipid THC saturation. Do any of these studies accurately quantify the amount of THC which could actually be crossing the blood brain barrier.
You might want to look at this article:
Nahas GG. (2001). The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking. Hum Psychopharmacol 16:247-255.
155 articles came up from a PubMed search of THC absorption.
Oh, this one looks interesting:
Ashton CH, Moore PB, Gallagher P, Young AH. (2005). Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential. J Psychopharmacol. 19:293-300. Review.
ei neurocritic. nice topics there. especially abpbiut prosopagmnasia. nice faceless pic of Peanut Syndicate character.
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