A new study published in Nature Communications has uncovered specific brain regions and networks that are activated when drugs are administered intravenously versus orally, providing insight into the mechanisms underlying drug reward and addiction.
The findings could pave the way for new treatments targeting brain areas involved in drug-induced euphoria and addiction.
The research was conducted by scientists at the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), parts of the US National Institutes of Health (NIH).
Intravenous Drugs Act Faster But Increase Addiction Risk
It has long been known that drugs which are injected or smoked enter the brain more rapidly than oral drugs, making them more addictive. However, the brain mechanisms underlying this phenomenon have been unclear.
As senior author Nora Volkow, Director of NIDA, explained: “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. Now, using one of the newest and most sophisticated imaging technologies, we have some insight.”
Understanding how different routes of administration affect the brain is key for developing new treatments for substance abuse disorders and addressing the escalating drug overdose epidemic.
Scientists Compare Oral And IV Methylphenidate
To investigate this question, the researchers conducted a double-blind placebo-controlled study with 20 healthy volunteers.
Participants received a single low dose of methylphenidate (Ritalin), a stimulant drug used to treat ADHD, either orally or intravenously on separate visits. Methylphenidate was used as it produces euphoria and serves as a safe model drug for studying brain responses to stimulants.
After drug administration, the researchers used PET and fMRI neuroimaging to compare dopamine changes and brain activation patterns produced by the two routes of administration.
IV Drug Causes Rapid Dopamine Surge
The PET scans revealed that intravenous methylphenidate caused dopamine levels to surge within 5-10 minutes, whereas oral administration led to a delayed dopamine peak after 60+ minutes.
This confirms that intravenous drugs result in faster dopamine increases in brain reward regions, which is believed to strengthen addictive behaviors.
Distinct Brain Responses To Different Routes
Analysis of the fMRI data uncovered surprising differences in brain responses to oral versus intravenous methylphenidate.
Both routes deactivated the ventromedial prefrontal cortex, involved in emotion and decision-making. However, only intravenous administration activated the dorsal anterior cingulate cortex (dACC) and insula, core regions of the brain’s salience network.
The salience network regulates attention by tagging important external stimuli and internal states. Hyperactivity in this network is linked to drug craving and addiction.
Notably, insula damage can eliminate drug addiction, highlighting its key role. The new finding that insula activation occurs exclusively following intravenous drug delivery helps explain why addiction risk increases with faster drug uptake.
Brain Activity Aligns With Euphoria
Additionally, the research team asked participants to rate their subjective feelings of drug-induced euphoria in real-time.
Strikingly, the activity observed in the salience network closely matched the self-reported intensity and time-course of the drug high after intravenous administration. The greater the brain activation, the higher the reported euphoria.
As lead author Dr. Peter Manza commented: “I’ve been doing imaging research for over a decade now, and I have never seen such consistent and clear fMRI results across all participants in one of our studies.”
This tight link between regional brain activation and conscious drug reward supports the idea that the identified network participates directly in mediating subjective drug effects.
Targeting Brain Areas To Treat Addiction
The findings provide some of the strongest evidence to date implicating the salience network in drug-induced euphoria and addiction liability based on how quickly a drug reaches the brain.
The next phase will be investigating whether blocking activity in these regions can reduce drug-induced highs. If successful, it would validate the salience network as a promising target for new medication-assisted therapies for substance abuse.
“These results add to the evidence that the brain’s salience network is a target worthy of investigation for potential new therapies for addiction,” summarized Dr. Manza.
In summary, this pioneering NIH study used neuroimaging to demonstrate that intravenous and oral drug administration produce distinct activation patterns in brain regions governing reward, craving, and addictive behaviors.
Intravenous delivery more robustly activated the salience network, providing insight into why faster-acting drugs have higher addiction potential.
Targeting overactivity in this network may lead to innovative treatments to suppress drug euphoria and modify addictive behaviors. Overall, the research significantly advances our understanding of how route of administration impacts brain function and addiction liability.
These findings open exciting new frontiers in addiction neuroscience and could catalyze development of life-changing new therapies for substance abuse disorders. With over 100,000 Americans dying annually from drug overdoses, scientific advances like this study bring hope that we can stem the tragic tide of the opioid epidemic and save lives.