Minocycline and Tobacco Craving in Smokers With Schizophrenia

Nicotine dependence is high in schizophrenia; nearly three times more prevalent than the general population. In smokers with schizophrenia, the risk of all-cause mortality is doubled and cardiovascular mortality risk is twelvefold higher than nonsmokers. Many factors influence smoking in persons with schizophrenia, but predictors of craving and smoking behavior are not well established. Craving is a major contributor to smoking behaviors, and, importantly, is a predictor of relapse risk. Since craving may precede relapse, it can be advantageous as a screening tool for those attempting cessation. In addition, focusing on treatments aimed to reduce craving may lead to better therapeutic targets. Minocycline may affect craving, perhaps due to inhibition of nitric oxide (NO) formation, as NO acts as a second messenger for glutamate and dopamine receptors. NO also facilitates the effects of nicotine in the reward circuit, and blockade of NO has been demonstrated to eliminate nicotine abstinence symptoms in rats. A small study has demonstrated that minocycline reduces cigarette craving in human subjects without severe mental illness. The investigators will conduct a two-week randomized, double-blind, placebo-controlled, parallel group pilot study to investigate the effects of minocycline vs. placebo on craving and indicators of smoking intensity in smokers with schizophrenia. Participants will take minocycline up to 200 mg daily or matching placebo for two weeks. Participants will complete cigarette cue-elicited craving platforms and related assessments at baseline, and after 1 and 2 weeks of minocycline or placebo treatment.

Inclusion criteria

• DSM-IV or DSM-5 diagnosis of schizophrenia or schizoaffective disorder
• Male or Female
• Age: 18 to 65 years
• Caucasian or Non-Caucasian
• Smoke at least 10 cigarettes daily
• Urine cotinine level ≥ 100 ng/ml (NicAlert® reading ≥ 3)
• Agrees to wear a head mounted display (HMD) for up to 45 minutes
• Able to complete the Evaluation to Sign Consent (ESC) with minimum score of 80%

Exclusion criteria

• History of organic brain disease
• DSM-IV diagnosis of Alcohol or Substance Dependence within the last six months (except nicotine) or DSM-5 diagnosis of Substance Use Disorder in the last six months (except nicotine)
• DSM-IV diagnosis of Alcohol or Substance Abuse within the last one month (except nicotine) or DSM-5 diagnosis of Substance Use Disorder in the last six months (except nicotine)
• Pregnancy or lactation
• Severe liver dysfunction (LFT 3X upper limit of normal)
• Previous known hypersensitivity to tetracyclines
• Current treatment with tetracycline or derivative
• Treatment with oral contraceptives (unless a second form of birth control is used and documented)
• Treatment with cholestyramine or colestipol
• Treatment with Urinary alkalinizers (e.g., sodium lactate, potassium citrate)
• Treatment with warfarin
• Treatment with bupropion, varenicline, or nicotine replacement products in the month prior to study inclusion
• Less than two months treatment of adjunctive medications AND less than one month on same dose: beta blockers, antidepressants, mood stabilizers, antianxiety medications.
• Medical condition whose pathology or treatment would significantly increase the risk associated with the proposed protocol.
• History of head injury, seizures, or stroke
• Positive urine toxicology screen for substances of non-therapeutic use prior to craving assessments