The main objective of the FLAIR-i study is to study the causal role of inflammation in affecting effort-based decision making in brain and behaviour in overweight and obesity, by comparing the effect of the anti-inflammatory agent colchicine vs. placebo.

Obesity is a major health problem worldwide and is characterized by increases in low-grade, systemic inflammation. Outside the field of obesity, increases in inflammation have been related to loss of motivation and effortful behaviour, which can be objectively measured with effort-based decision making in brain and behaviour. Here, the investigators hypothesise that low-grade inflammation is causing altered striatal brain responses and effortless 'fast food' choices in overweight and obesity. The objective of this study is to study the causal role of inflammation in affecting effort-based decision making in brain and behaviour in overweight and obese participants, by comparing the effect of the anti-inflammatory agent colchicine vs. placebo. In addition, it will be investigated whether this primary objective translates to more ecologically valid measures/settings.

Inclusion Criteria:

• BMI ≥ 27 kg/m2
• Female sex
• Right-handed
• Age: 18-59 years
• Shoulder width of < 68 cm (to fit into the MRI scanner)
• Dutch speaking - Sufficient level to understand task instructions
• Low-grade inflammatory state, as measured by C-reactive protein (CRP) between 3.0 and 10.0 mg/L

Exclusion Criteria:

• Having been vaccinated by any type of vaccine in the 4 weeks preceding the first test session
• Having had an infection characterized by a fever, or diagnosed by a medical physician in the 4 weeks preceding the first test session
• Diagnosed with Diabetes Mellitus type I or II
• Gained or lost >2 points in BMI (kg/m2) over the last 6 months
• Followed an energy restricting diet during the last 2 months
• Having had bariatric surgery in the past 5 years
• Regular use of anti-inflammatory, anti-diabetic, weight-loss, and psychoactive medication
• Regular use of CYP3A4 inhibitors, P-glycoprotein inhibitors, statins, fibrates, ciclosporin, and digoxin, as a contraindication for colchicine
• Have renal impairment as evidenced by serum creatinine >150 μmol/l or eGFR <50mL/min/1.73m2, determined maximum 12 weeks before inclusion
• Have moderate to severe hepatic disease
• (History of) clinically significant psychiatric or neurological disorder
• (History of) clinically significant metabolic, cardiovascular, renal, liver, endocrinological, autoimmune or chronic inflammatory disease
• General medical conditions, such as sensorimotor handicaps, deafness, blindness or colour-blindness, as judged by the investigator
• Current or history of alcohol and/or drugs abuse (i.e. >14 units per week)
• Habitual smoking, i.e. one or more cigarettes per day
• Pregnant, lactating or wishing to become pregnant in the period between the screening and until 3 months after the last study visit
• Participation in another weight loss, lifestyle or anti-inflammatory intervention in the context of research at the time of inclusion or during the study
• Contraindications for MRI