A clinical trial has identified that a group of brain regions, known as the “salience network”, is activated after a drug is taken intravenously, but not when that same drug is taken orally.
The speed at which a drug gets to your brain can predict addiction. When drugs enter the brain quickly, through smoking or injection, this is associated with developing a substance use disorder more quickly than when they enter the brain more slowly, such as when they are taken orally or by snorting.
However, the brain circuits underlying these differences are not well understood.
“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,” says Dr Nora Volkow, Director of the National Institute on Drug Abuse (NIDA) and chief of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging, in the US.
“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,” says Volkow, who is senior author on the study.
To better understand how the way a drug is administered impacts the brain’s response to it, 20 healthy adults received either a small dose of a placebo or of the stimulant drug methylphenidate orally or intravenously three times.
Methylphenidate, commonly known as Ritalin, is a safe and effective prescription medication used to treat attention deficit hyperactivity disorder (ADHD). It can also be used as a model drug to safely study the relationship between how drugs affect the brain and the subjective experience of drug reward in a research setting.
Participants were given the drug or placebo while researchers simultaneously looked at differences in dopamine levels (through PET imaging) and brain activity (through fMRI imaging) while they reported their subjective experience of euphoria.
The team found that when participants received Ritalin orally the rate of dopamine increase peaked more than an hour later, which is consistent with previous research. However, after intravenous injection this rate peaked much faster withing 5 to 10 minutes.
Additionally, across all 20 research participants, two specific brain regions were activated only after receiving the injection, but not oral administration, of methylphenidate.
These regions, the dorsal anterior cingulate cortex and the insula, are part of the brain’s salience network. The salience network attributes value to things in our environment and is important for recognising and translating internal sensations – including the subjective effects of drugs.
This research, which is published in Nature Communications, adds to the growing body of evidence that the salience network plays an important role in substance use and addiction.
Future research will involve studying whether actively inhibiting the salience network when someone takes a drug will effectively block the feeling of being high.
“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,” says Dr Peter Manza, research fellow at NIAAA and lead author on the study.
“These results add to the evidence that the brain’s salience network is a target worthy of investigation for potential new therapies for addiction.”
