Important research by Cox and colleagues (2017) demonstrated that even among non-dependent cocaine users, cues associated with consumption of the drug produces dopamine release in an area of the brain thought to promote compulsive drug using.

Cocaine Cues Produce Pavlovian Response

The “Pavlovian” response to cocaine and other stimulants was first demonstrated over 20 years ago, when Volkow, Wang and colleagues utilized advanced brain imaging technology and “pulled back the curtain” to observe this phenomenon in real-time. By using positron emission tomography (PET) in cocaine-addicted subjects, their work demonstrated that exposure to neutral drug-related cues, such as a crack pipe, or a particular song, or image could elicit release of dopamine in the ventral striatum, in volumes similar to those that occur when a cocaine addict actually uses cocaine. As a result, Volkow coined the phrase “hijacking the brain” because of how cocaine (and all addictive drugs) fool the brain by producing reward for self-destructive behavior. In clinical settings, cocaine addicts can accurately describe the particular stimulus that “hijacks” their brain, which they experience as intense wanting, anticipatory pleasure, desire and motivation to use. When this occurs, relapse is usually just a matter of time.

“I’m not addicted to cocaine, I only used it on pay days.” –Darien, 37, Former CPA

We have established what happens when addicted persons are triggered by external drug cues. But what about non-addicted people who have tried cocaine a few times, but have not crossed the line to addiction? The findings from Cox et al, have demonstrated that after initial doses of cocaine, non-addicted persons produce the same drug cue responses in the ventral striatum that occurs among addicted persons. This evidence demonstrates that initial, occasional cocaine use results in a Pavlovian response, in which preoccupation with cocaine-induced euphoria, a narrowing of interests, and increased susceptibility to addiction occur.

Why does this happen?

Exposure to drug-related cues associated with cocaine and other stimulants hasten dopamine release in the ventral striatum of healthy volunteers after only three doses. Moreover, similar response in the dorsal striatum occurs in persons with cocaine use disorders. What was previously unknown is whether dopamine responses can be seen in the dorsal striatum prior to the onset of an addiction. To answer this question, the authors used PET scan with [C]raclopride to measure dopamine responses to cocaine-paired cues in non-addicted cocaine users. The results showed that a single cocaine exposure had profound effects on the brain that may require intervention to contain or halt the neuroadaptation from progressing to addiction.

Why Does This Matter?

The initial dose of cocaine produces a robust euphoria and neuroadaptation to the degree that preoccupation with cocaine and cocaine seeking make continued use likely. We used to say that the brain is unprepared by evolution for crack or cocaine. Thus, the brain is alerted and told to pay attention to everything that preceded the cocaine use, probably to find it and use it again.

Moreover, exposure to highly personalized cues associated with cocaine initiation, increases extracellular dopamine levels in the dorsal striatum in individuals who have merely dabbled with cocaine. This is the first study to demonstrate the cue driven anticipatory effects of cocaine occur prior to the onset of substance use disorder. Progression to addiction is likely a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by cocaine. This finding gives credence to an old street saying regarding cocaine: “One hit is too many, and a thousand is never enough.”