Det kan ikke udsættes længere, at dele dette interessante studie - som endda er offentlig tilgængelig i sin fulde form:
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors (Jeg synes selv, at min overskrift er lettest at sluge..
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Sådan en lidt lang historie kort, er der for mig to aspekter i denne artikel der er interessante. Det ene er den dybere forståelse for mekanismerne hvorved THC mediere [nogle af] sine effekter, hvilket i sig selv er spændende, men af mere vidtrækkende perspektiver, er udsigten til helt nye terapeutiske muligheder. Hvis resultaterne holder, vises det her, at den kombinerede effekt af d9-THC (og formodentlig også andre cannabinoider) ikke behøver at være en rodet blanding af mange positive som negative effekter, men at det teoretisk vil være muligt enten at designe stoffer der kan hæmme/mediere de negative effekter fra THC, eller THC-lignende stoffer der ikke vil have bestemte effekter.
På sigt kunne dette være et kæmpe plus for cannabinoider som integrerede dele af medicin, fremfor at være en rodet blanding af både effekter og aktive stoffer. Herunder fx muligheden for at bruge THC medicinsk, uden at skulle døje med dårlig hukommelse
Jeg placerer emnet det under cannabis generelt, fremfor videnskab, da det føles mere hjemme her.
Citat:
Abstract
Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.
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