Yesterday, the Los Angeles Times ran a story regarding Alzheimer’s patients – and how they might benefit from combining marijuana’s cannabinoids with a “side of ibuprofen” as a “buzz killing RX for Alzheimer’s.” The article explained how new research has identified ibuprofen as being beneficial when used in conjunction with tetrahydrocannabinol – more commonly referred to as THC – to eliminate medical marijuana’s collateral damage…universally known as “The high.”
The times article pointed to a new study that was recently published in the Journal Cell, which explained a couple of things. First, why common anti-inflammatory drugs like ibuprofen and other prescription analgesics have the ability to blunt out marijuana’s high – suppressing the negative cognitive effects. Second, that getting high on pot to chill out, stunts the growth of the tendrils that lash brain cells together, while weakening memory and cognitive processing functions. And that the bundled buzz of effect-and-side-effect seemed to be inseparable.
Yet, as it turns out, it can be separated, and the unwanted high can be killed, by simply suppressing the induction of cyclooxygenase-2 (COX-2), a multifaceted neurochemical process typically set off by inflammation: “Add a COX-2 inhibitor to the mix — or even a non-selective COX inhibitor such as ibuprofen — and the anti-inflammatory effects of THC remain. The “buzz,” the lethargy and negative cognitive effects of long-term use, however, are extinguished.”
Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.