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Brain Network Uniquely Activated by Injection Could be Target for SUD Treatment
A clinical trial conducted by researchers at the National Institute on Drug Abuse (NIDA) has found that a group of brain regions, known collectively as the “salience network,” is activated after a drug is taken intravenously, but not when the same drug is taken orally.
Findings from the study, published online in the journal Nature Communications, could help explain why drugs entering the brain quickly, such as through injection or smoking, are more addictive than when taken orally.
“We’ve known for a long time that the faster a drug enters the brain, the more addictive it is—but we haven’t known exactly why,” NIDA Director Nora Volkow, MD, said in a news release. Now, using one of the newest and most sophisticated imaging technologies, we have some insight.
“Understanding the brain mechanisms that underlie addiction is crucial for informing prevention interventions, developing new therapies for substance use disorders, and addressing the overdose crisis.”
To better understand how the route of drug administration impacts a brain’s response to the substance, NIDA researchers conducted a double-blind, randomized, counterbalanced clinical trial.
Over 3 separate sessions, 20 healthy adult trial participants received either a small dose of placebo or methylphenidate, a stimulant commonly known by the brand name Ritalin that is prescribed to treat attention-deficit/hyperactivity disorder (ADHD). The placebo and methylphenidate were administered to patients either orally or intravenously. Researchers simultaneously looked at differences in dopamine levels through PET imaging and brain activity through fMRI imaging while patients reported their subjective euphoric experience in response to the drug.
Consistent with prior research, when participants received methylphenidate orally, dopamine increases peaked more than an hour after administration, while among those who received the drug through intravenous injection, dopamine increases peaked within 5 to 10 minutes of administration. Through fMRI, researchers observed that the ventromedial prefrontal cortex was less active after both oral and intravenous administration, but 2 regions that are part of the salience network—the dorsal anterior cingulate and the insula—were activated only after injections. The finding was consistent among all 20 study participants.
Patients’ self-reported, real-time conscious experience of drug reward closely matched patterns observed by both forms of imaging.
The study authors said a next step for research will be to study whether inhibiting the salience network when a drug is taken can effectively block the feeling of being high—a finding that could support the salience network as an appropriate target for substance use disorder treatment.
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