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Time-dependent neuronal changes associated with craving in opioid dependence

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Time-dependent neuronal changes associated with craving in opioid dependence

17 September 2018

'Time-dependent neuronal changes associated with craving in opioid dependence: an fMRI study' was recently published in Addiction Biology, a journal published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA), covering research on substance abuse. Change Grow Live's Medical Director, Dr Prun Bijral, contributed to the article, as well as Dr Anna Murphy, who has kindly written this piece summarising the study and its findings.

How observations of a salivating dog influenced our understanding of the triggers of drug craving

In the late 1800s the Russian physiologist, Ivan Pavlov made a groundbreaking discovery that would influence the way we understand drug craving. Like most key scientific discoveries, it occurred purely by chance. Pavlov was studying the salivary reflex in dogs in response to food.  In his experiment, a laboratory assistant entered the room and then put some food down in front of the dogs. The dogs salivated, no surprise there. However, Pavlov soon noticed that after a while, the dogs began to salivate as soon as the laboratory assistant entered the room before they put the food down, and also when they came in without food at all.

This chance observation led to Pavlov’s seminal theory of  ‘Classical Conditioning’.  It may not be immediately obvious what a salivating dog has anything to do with addiction.  However, the brain processes or ‘conditioning mechanisms’ that resulted in the dog salivating to the lab assistant alone are the same that result in craving responses to stimuli such as money, friends and certain environments (referred to as ‘drug cues’) in addiction. According to Classical Conditioning, a previously ‘neutral’ stimulus (i.e. the laboratory assistant before they ever brought food in the above example, or money before it was ever used to buy drugs) acquires the ability to produce a strong emotional/physiological response (salivating in the above example, or craving for drug), just by being repeatedly closely associated with an innately rewarding stimulus (the food in the above example, or drugs).

The brain ‘expects’ drug reward after drug cue exposure

The brain learns that these stimuli are often followed by the reward (drugs or food) and so the brain expects the reward whenever it encounters these stimuli.  This expectation is largely unconscious, so the person encountering the drug cues may not consciously think that a drug reward is coming. However, exposure to drug cues triggers a range of responses readying the body for drug reward, craving is one of these.   

The aim of our study

As craving is known to contribute to relapse, clinicians and scientists like me are interested in understanding exactly what brain processes contribute to the craving response. Identifying brain areas that contribute to craving will help us develop targeted drug therapy or psychological treatment to block or lessen craving and help maintain abstinence. Understanding these processes was the aim of our study, published in Addiction Biology.

How we investigated craving

We used a video of drug cues produced with the help and guidance of staff and service users of the Chapman-Barker Unit (CBU), to trigger drug craving in newly  detoxified opioid-dependent participants (with their consent) using non-invasive brain imaging technology to ‘look’ inside their brains. We used a novel approach to examine the minute-by-minute changes in brain activity that tracked the waxing and waning of craving over time.

What we found

We found activity in the amygdala, a key emotional processing region of the brain, increased and decreased in line with craving.   This led us to conclude the amygdala was a key region involved in generating craving. Interestingly, we found that activity in a brain region, the anterior cingulate cortex (ACC) (which has been previously associated with craving), did not fluctuate in line with craving rather ACC activity increased as craving decreased.  This led us to conclude that the ACC is involved in the inhibition, and not the generation, of craving.

Next steps

We wish to use our craving paradigm as a screen to test for new treatments that might reduce activity in the amygdala or increase anterior cingulate activity in the hope of finding a treatment that abolishes craving to help maintain abstinence.