Cannabis is increasingly used medicinally to treat a variety of conditions, including epilepsy, multiple sclerosis, and chronic pain. In addition, drugs based on the main psychoactive ingredient in marijuana, THC, have been approved by the US FDA to treat nausea and vomiting in patients with cancer who are undergoing chemotherapy.
However, the THC comes with several troubling side effects, such as short-term memory impairment and cognitive deficits, and there are currently no FDA-approved medications to mitigate these "adverse" events (quotations used since this is subjective...most recreational users of marijuana would consider this a "therapeutic" effect).
For the study, researchers examined a group of mice repeatedly administered THC, to see what substance could help minimize these adverse effects. Repeated administration of THC produced a dose- and time-dependent induction of COX-2, an enzyme that converts arachidonic acid to prostanoids (inflammatory compounds) in the brain.The researcherS state that this observation was unexpected and is caused by activity of cannabinoid receptor type 1 (CB1R).
Based on this, what they found was that by inhibiting COX-2, through use of the NSAID celecoxib, or rimonabant (a CB1R selective antagonist), the THC-induced memory impairments disappeared. However, concerned that inhibiting COX-2 might eliminate marijuana's beneficial effects, the investigators then examined a mouse model of Alzheimer's disease (AD). Marijuana has been shown to reduce the beta-amyloid plaques, which is a hallmark of AD and one of the precursors to neurodegeneration.
Let me stop here and point out that if marijuana is shown to prevent beta-amyloid plaques and neurodegeneration...should I...?
Although once-daily treatment of THC for 4 weeks decreased beta-amyloid plaques and neurodegeneration in the mice with AD, concurrent use of celecoxib did not decrease the effects. In other words, the use of pain medications not only reduced COX-2 levels in the mice but also prevented THC-induced memory problems and neurodegeneration. This means that the study may have solved (or at least shed some light) on the longtime mystery of how marijuana causes neuronal and memory impairments.
"Our results suggest that the unwanted side effects of cannabis could be eliminated or reduced, while retaining its beneficial effects, by administering a COX-2 inhibitor along with THC for the treatment of intractable medical conditions," the researchers said. "There are no effective medications currently available for treating Alzheimer's. But THC, used with COX-2 inhibition, might bring hope for preventing or delaying development of this disease."
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Source: Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling
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