Editors' ChoicePharmacology

Blunted Memories: Time for Decaf?

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Science Translational Medicine  10 Feb 2010:
Vol. 2, Issue 18, pp. ec22
DOI: 10.1126/scitranslmed.3000923

Cannabis is the number one illicit drug of abuse worldwide, with as many as 160 million users annually. Cannabis intoxication impairs cognition; alters attention, memory, and perception; and occasionally even produces psychosis. Although there are several valid clinical applications for this substance, long-term cannabis use is associated with drug dependence and an elevated risk of psychosis and cancer.

These various psychological effects may arise from altered cognition. Cannabis acts on the well-researched brain cannabinoid receptor (which normally binds endogenous modulators, the endocannabinoids), but the complex mechanisms by which these receptors modulate brain circuits are still being worked out. In a recent article, Hoffman and colleagues investigated hippocampal pyramidal neurons, which are critical to memory formation, for cannabinoid receptor–mediated effects. By recording extracellular electrical currents in slices from rat hippocampi, they found that increased concentrations of the neurotransmitter adenosine in synapses attenuated or abolished cannabinoid receptor–mediated inhibition of glutamate excitatory neurotransmission, which is these neurons’ primary mode of communication. This effect was reversed by caffeine, which antagonizes the receptor for adenosine, and it was absent in mice in which the adenosine receptor was knocked out.

These findings indicate that adenosine modulates cannabinoid effects on pyramidal cells and probably on cognition as well. Endogenous adenosine may serve as an important brake on the neural effects of cannabinoids, whether endogenous or ingested. Similarly, the sought-after effects of cannabis, as well as the potential risk of long-term use, may be enhanced by another commonly used addictive substance, caffeine.

A. F. Hoffman et al., Control of cannabinoid CB1 receptor function on glutamate axon terminals by endogenous adenosine acting at A1 receptors. J. Neurosci. 30, 545–555 (2010). [Abstract]

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