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Cells could be targeted to treat marijuana addiction

A newly published study by BYU researchers details how marijuana affects an adolescent brain’s reward center, at the cellular level.

The research, published Monday in the Journal of Neuroscience, finds the primary psychoactive compound in cannabis (THC) depresses cells in the brain whose job it is to inhibit dopamine release. The study provides evidence that marijuana doesn’t just stimulate dopamine release directly, it also could mediate reward indirectly by impacting the GABA cells that moderate dopamine cell activity.

“It turns out marijuana, like other drugs of abuse, can modify our synaptic plasticity, or the ability of synapses to strengthen or weaken over time,” said study lead author and BYU neuroscientist Jeff Edwards. “All psychoactive substances that alter synaptic plasticity long term — even once the drug is out of the system — are addictive. Non-addictive psychoactive substances normally do not alter plasticity.

“Knowing how drugs of abuse modify cellular activity and plasticity in the reward center of the brain give us an idea of how they can mediate reward and addiction, respectively,” he said.

When the synaptic plasticity of brain cells is modified, one effect is that normal pleasurable experiences aren’t rewarding any more, leading to withdrawal. Efforts to meet the higher reward threshold can lead to addiction.

Most of the psychoactive effects of THC in the brain are mediated by its actions on a cell receptor called CB1. Edwards and his team identified a novel form of synaptic plasticity in the reward area of the brain mediated by CB1, where direct application of THC to the brain (at similar levels to those attained by smoking marijuana) could mimic this plasticity and chronic THC injection for a week blocked this plasticity from occurring when THC was no longer in the system.

The finding suggests that this alteration of plasticity could mediate some of the reward or more negative addictive/withdrawal effects of THC. As there currently are no treatments available for marijuana addiction, or cannabis use disorder, this cellular mechanism provides at least a novel target for potential treatment. According to the National Institutes of Health, more than 6 percent of adults in the U.S. have experienced cannabis use disorder in their lives. For those entering substance abuse treatment programs marijuana surprisingly ranks third behind only alcohol and opiate-related substance abuse.

The study was carried out on the brain cells of adolescent mice, but the receptor in question, CB1, can be found in both mice and human brains and is in the same region of the brain in both species.

Edwards, a professor of physiology and developmental biology and associate director of the BYU Neuroscience Center, said the study has high importance for teenagers, as it suggests marijuana is altering brain pathways that are still developing in youth.

“While US states debate whether to legalize recreational or medicinal use of marijuana, the negative impact of THC on adolescents should be considered as part of the equation,” Edwards said. “If you’re a 12-16-year-old and taking addictive drugs, you’re hardwiring your brain to increase the chance of being addicted long-term.”

The new study is adding to the relatively sparse research on marijuana’s effects on the brain. Co-authors include BYU grad students Lindsey Friend, Jared Weed, Philip Sandoval, Teresa Nufer and Isaac Ostlund.