Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?

Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?

This study aimed at helping researchers understand how a medication called haloperidol can affect insulin action in the brain. Insulin is a hormone in the body that controls sugar levels in part by lowering the amount of glucose produced by the liver. After eating a meal, insulin levels go up in both the blood and the brain. Insulin in the brain has also been shown to affect the way the brain works and processes information (also known as "cognition"). Haloperidol, is an antipsychotic medication used to treat a variety of disorders such as schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder, but long-term use can have metabolic side effects, like weight gain, type 2 diabetes, and cardiovascular disease. The purpose of this study is to investigate how antipsychotic medications, such as haloperidol, which carries the risk of metabolic changes, might interrupt the effect of insulin action in the brain. This will help researchers learn how to potentially reduce metabolic risk for people who take these kinds of medications in the future.

Inclusion Criteria:

1. Must be deemed to have the capacity to provide informed consent
2. Must sign and date the informed consent form
3. Stated willingness to comply with all study procedures;
4. Age: 18-35
5. Body Mass Index (BMI) 18.5-24.9 kg/m2
6. Both sexes

Exclusion Criteria:

1. History of psychiatric illness, including any substance use (screened using the Mini International Neuropsychiatric Interview (MINI))
2. Pre-diabetes or diabetes (fasting glucose ≥6.0 mmol/L, HbA1c>6% or use of anti-diabetic drug),
3. Evidence of impaired insulin sensitivity, assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥2.5
4. Family history of diabetes in a first degree relative (parent or sibling)
5. Use of weight reducing agents
6. History of kidney or liver disease
7. History of cell blood disorders
8. Irregular menstrual cycles (e.g., menstruation occurs less than 21 days or more than 35 days apart, or not having menstruated for three months (or 90 days), or conditions such as endometriosis or polycystic ovary syndrome (PCOS) or prior surgical interventions such as a hysterectomy or oophorectomy)
9. Current use of hormonal birth control (e.g., pill, patch, hormonal intrauterine device [IUD], ring). Participants must have had at least 2 regular menstrual cycles following the discontinuation of hormonal birth control [50]
10. Current use of progesterone, estrogen, testosterone, or fertility treatment.
11. Pregnant, gave birth in the last year, or breastfeeding. Participants must have at least 3 regular menstrual cycles post-breastfeeding before beginning the study.
12. Major medical or surgical event within the last 6 months
13. Contraindications for MRI, including metal implants, pacemakers, cochlear implants, claustrophobia, weight >250 lbs
14. Any contraindications to the investigational products as listed in the product monographs including known hypersensitivity to the drug or the excipients of the product (note: enzymatic lactose intolerance is NOT exclusionary),
15. Any medications that increases risk of hypoglycemia or could contribute to hyperglycemia
16. Any medical conditions that constitute as a warning/precaution for haloperidol, lorazepam, benztropine, or insulin.
17. Use of any of the prohibited medications listed in the product monograph of haloperidol, lorazepam, benztropine, or insulin (Pheochromocytoma, barbiturates, and narcotics are exclusionary, any use of painkillers and antihistamines must be reviewed by PI but are not exclusionary