OTC Meds May Prevent Marijuana-Induced Memory Problems

Deborah Brauser

December 03, 2013

Over-the-counter pain medications may help reduce memory problems associated with the use of medical marijuana, new research suggests.

A mouse study showed that repeated exposure to λ9-tetrahydrocannabinol (THC) increased levels of cycolooxygenase-2 (COX-2) in the hippocampus, a brain region associated with learning and memory.

However, the use of pain medications not only reduced COX-2 levels in the mice but also prevented THC-induced memory problems and neurodegeneration.

"Our study has solved the longtime mystery of how marijuana causes neuronal and memory impairments," said senior study author Chu Chen, PhD, from the Neuroscience Center of Excellence at Louisiana State University in New Orleans, in a release.

"This was a surprise, and the findings suggest that the use of medical marijuana can be broadened if patients concurrently take a nonsteroidal anti-inflammatory drug [NSAID] such as ibuprofen, depending on how much dosage you use," Dr. Chen added in a statement to Medscape Medical News.

In further analysis, the investigators found that THC reduced degenerated neurons in a mouse model of Alzheimer's disease (AD) ― an effect that remained even during the simultaneous use of a COX-2 inhibitor.

"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," said Dr. Chen.

The study was published in the November 21 print edition of Cell.

Unexpected Finding

Cannabis is used medicinally to treat a variety of conditions, including epilepsy, multiple sclerosis, and chronic pain.

In addition, drugs based on THC, the main active ingredient in marijuana, have been approved by the US Food and Drug Administration (FDA) to treat nausea and vomiting in patients with cancer who are undergoing chemotherapy.

However, the compound comes with several troubling side effects, such as memory impairment and cognitive deficits, and there are currently no FDA-approved medications to mitigate these adverse events.

Dr. Chu Chen

"Until now, little was known about the molecular pathways underlying these impairments," the researchers note.

For this study, they examined a group of mice repeatedly given THC.

Results showed that exposure to THC produced a dose- and time-dependent induction of COX-2, an "enzyme that converts arachidonic acid to prostanoids in the brain," the investigators write.

They add that this observation was unexpected and is caused by cannabinoid receptor type 1 (CB1R) coupling with G protein ßƳ subunits.

In addition, inhibiting COX-2 "blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated λ9-THC exposures," they write.

This inhibition came through use of the NSAID celecoxib (Celebrex, GD Searle LLC) or use of rimonabant, a CB1R selective antagonist, or through genetic deletion of CB1R.

Memory Impairment "Disappeared"

Decreasing COX-2 levels also eliminated THC-impaired long-term synaptic plasticity and working and fear memories in the hippocampus.

"When using the COX-2 inhibitors, the THC-induced memory impairments disappeared. And that's just amazing," said Dr. Chen.

Worried that inhibiting COX-2 might eliminate marijuana's beneficial effects, the investigators then examined a mouse model of AD. Although once-daily treatment of THC for 4 weeks decreased ß- amyloid plaques and neurodegeneration in the mice with AD, concurrent use of celecoxib did not decrease the effects.

"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," Dr. Chen summarized.

The investigators have now submitted a proposal to the National Institutes of Health (NIH) for funding to try to replicate these findings in a clinical setting.

The study was funded by grants from the NIH and the National Institute on Drug Abuse. The National Institute of Mental Health Drug Supply Program provided the THC, rimonabant, and celecoxib samples used in the study. The study authors have disclosed no relevant financial relationships.

Cell. 2013:155;1154-1165. Abstract

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