Investigating the long-term effects of cocaine on brain and behaviour, including the imbalance in steroidal hormones and its implications for decision-making
Recipient organisationNIHR Wellcome Trust Cambridge Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Ongoing
In plain English
AI plain-English summary
Cocaine users who struggle to quit show long-term changes in brain dopamine and hormone levels that make it harder to adjust their behaviour to changing circumstances. Unlike heroin or alcohol addiction, cocaine addiction has no approved drug treatments, and psychological therapies alone often fail to keep patients abstinent after treatment ends. The problem is that regular cocaine use initially boosts dopamine but eventually depletes it, disrupting steroid hormones and impairing decision-making. This study compares three groups: regular cocaine users, people with naturally low dopamine due to gene variants, and healthy controls. Participants provide urine, blood, and saliva samples, play computerised games, complete questionnaires, and undergo brain scans. The key insight is that people with genetic low dopamine do not struggle with behavioural regulation, suggesting they have compensatory mechanisms. If researchers can identify how these individuals maintain normal decision-making despite low dopamine, it could reveal new targets for pharmacological treatments for cocaine addiction. This is fundamental science into brain chemistry and behaviour, with no immediate clinical application, but similar discoveries about dopamine pathways have previously led to treatments for Parkinson’s disease and ADHD.
View original technical description
The UK has one of the highest levels of powdered cocaine use and the highest of crack-cocaine use in Europe. Unlike for heroin or alcohol, there are no approved pharmacological treatments for cocaine, and psychological interventions have been less successful in helping patients achieving abstinence or remaining abstinent after treatment discharge. One of the reasons for the lack of treatment are the powerful effects of cocaine on the availability of the brain chemical dopamine. Although cocaine increases dopamine levels shortly after use, regular cocaine-induced boosts lead to a decrease in dopamine availability over time and disrupt hormone levels. These changes are thought to make it difficult for patients with cocaine addiction to adjust their behaviour to changing circumstances. As well as people who regularly use cocaine, people with certain gene variants can also have low concentrations of dopamine in the brain, but unlike patients with cocaine addiction, they have no problems in regulating their behaviour. Understanding how they compensate for their low levels of dopamine and how this affects their hormone levels may help us develop new treatments for people with cocaine addiction. In our study, we compare people with different levels of brain dopamine and people who use cocaine regularly. The study has two sessions. In both sessions, we ask participants to provide a urine sample on arrival, play some computerised games and puzzles, and complete some questionnaires. In the second session, we ask participants to undergo a brain scan and to provide two blood and saliva samples: one on arrival before participants have breakfast and another one before lunch. The blood/saliva samples will be analysed for genetic and hormone levels. For both sessions, participants receive a total of £150 and a picture of their brain to take home. Travel expenses will be reimbursed separately.
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