Grant-Funded Lab Projects
Combining Varenicline and Naltrexone for Smoking Cessation and Drinking Reduction (Smoking Cessation Study)
There is a strong positive association between cigarette smoking and alcohol use. It is estimated that approximately 20-25% of current smokers are also heavy drinkers. Greater alcohol use is associated with decreased odds of smoking cessation and it is estimated that smokers are 4 times more likely to experience a smoking lapse during drinking episodes. Despite these data, there are no available treatments tailored to heavy drinking smokers, a sizeable and treatment-resistant sub-group. This proposal seeks to address this gap in the literature by conducting a double-blind, randomized clinical trial using three group medication design consisting of VAR alone (1 mg twice daily), NTX alone ( 50 mg once daily), and the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) for smoking cessation and alcohol use reduction in a sample of heavy drinking daily smokers (i.e., individuals who smoke ≥ 10 cigarettes/day and who meet NIAAA guidelines for heavy drinking).The PI has recently completed a laboratory trial with non-treatment seeking heavy drinking which found that the combination of VAR + NTX was superior to monotherapy and to placebo in attenuating nicotine- and alcohol-induced reward during alcohol and cigarette administration in the lab. Further, the combination group significantly reduced cigarette and alcohol consumption during the active medication period, as compared to placebo. Based on the preliminary evidence from our human laboratory trial, this proposal extends these findings to treatment seeking populations by testing the combination of VAR and NTX for smoking cessation among heavy drinking smokers. A total of 274 treatment-seeking heavy drinking smokers will be randomized to (1) VAR only, (2) NTX only, or (3) VAR + NTX. Medication will be titrated over a 14-day period and all participants will receive individual counseling for smoking and drinking and will complete the laboratory testing session prior to the quit day. Smoking abstinence, verified by carbon monoxide (CO) levels and alcohol consumption will be measured at 2, 8, 12, 16, and 26 weeks after quit date. This study will test whether VAR + NTX result in higher rates of point prevalence smoking abstinence at 2, 8, 12, 16, and 26 weeks compared to monotherapy. It will also examine the effects of medication on alcohol use. The secondary aims are to test mechanisms of pharmacotherapy response by examining laboratory markers of nicotine and alcohol response as predictors of treatment outcome. Building upon our previous work, these aims will elucidate the combination of VAR + NTX is superior to monotherapy for alcohol use and smoking cessation in heavy drinking smokers. Click here to participate.
A Randomized Controlled Clinical Trial of the Neuroimmune Modulator Ibudilast for the Treatment of Alcohol Use Disorder (Ibudilast Alcohol Study)
Alcohol use disorder (AUD) is a chronic and relapsing condition for which current pharmacological treatments are only modestly effective. The development of efficacious medications for AUD remains a high research priority with recent emphasis on identifying novel molecular targets for AUD treatment and to efficiently screen new compounds aimed at those targets. To that end, modulation of neuroimmune function represents a promising novel target for AUD. Chronic alcohol consumption produces a sustained inflammatory state, such that individuals with AUD have increased neuroinflammation throughout the brain, and alcohol-induced neuroinflammation is thought to contribute to chronic alcohol seeking behavior and to the behavioral and neurotoxic effects of alcohol. Ibudilast (IBUD) has been advanced as a novel addiction pharmacotherapy that targets neurotrophin signaling and neuroimmune function. IBUD inhibits phosphodiesterases -4 (PDE4) and -10 (PDE10) and macrophage migration inhibitory factor (MMIF). Additionally, IBUD enhances neurotrophin expression, reduces pro-inflammatory cytokine release, and attentuates neuronal death. Our laboratory has recently completed a randomized, double-blind, placebo-controlled crossover laboratory study of IBUD in non-treatment seeking individuals with AUD, and concluded that IBUD is well tolerated and associated with mood improvements during stress- and alcohol-cue exposures in conjunction with a reduction in tonic levels of alcohol craving. This current study seeks to advance medication development for AUD by conducting a 12-week, double-blind, placebo-controlled randomized clinical trial of IBUD. A total of 132 treatment-seeking drinkers that meet criteria for moderate or severe AUD will be randomized to either IBUD or placebo.The primary aims of this study are to (1) to test whether IBUD will decrease percent heavy drinking days, and (2) test the efficacy of IBUD on secondary alcohol consumption endpoints, alcohol craving, and negative mood, compared to placebo, and over the course of the 12-week trial.
A Randomized Controlled Clinical Trial of the Neuroimmune Modulator Ibudilast for the Treatment of Alcohol Use Disorder: A Pilot Study Examining Withdrawal-Related Dysphoria (DDA Study)
Alcohol use disorder (AUD) is a prevalent and disabling psychiatric disorder with few, and only moderately efficacious, treatment options. Consequently, the identification of novel treatment targets and the development of rigorous laboratory paradigms to screen and optimize novel therapeutics represents a research priority. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. Recently in an AUD sample, IBUD was shown to decrease reactivity to a psychological stressor. Furthermore, IBUD was effective in blunting alcohol reward among participants with greater depressive symptoms, a hallmark symptom of protracted withdrawal. It is still unknown how neuroimmune modulation impacts brain processes that underlie alcohol reward processing. Recently, preclinical research in opiates has demonstrated that drug withdrawal is necessary for microglia activation and neuroinflammation in reward networks, suggesting that IBUD may be most effective among patients who experience withdrawal-related dysphoria. Therefore, this study aims to examine withdrawal-related dysphoria as a moderator of IBUD efficacy in the natural environment measured using Daily Diary Assessment (DDA) approaches.
UCLA Psychology Cognitive Behavioral Therapy (CBT) Treatment for Alcohol Use Disorder (AUD) Clinic
Alcohol problems are highly prevalent among adults in the U.S. Specifically, twenty-five percent of adults in the U.S. report either currently having alcohol-related problems or drinking patterns that put them at risk for developing problems. Further, only 1 in 5 individuals with alcohol problems seek treatment and the available treatments are often not informed by science. In order to address the service needs of our community and to provide a training opportunity for advanced doctoral students in clinical psychology at UCLA, we propose to develop an outpatient alcoholism clinic providing evidence-based cognitive behavioral therapy for individuals with alcohol problems. In keeping with our service, training, and research missions, this clinical protocol will combine a research component with evidence-based practices. Specifically, participants will be asked to complete an alcohol cue-reactivity testing session at the end of their intake session and will discuss their reactions to alcohol cues with the therapist. Participants will be asked to repeat the alcohol cue-reactivity testing session after completing the 12-week CBT protocol. The CBT protocol will be derived from the Project MATCH Treatment Manual, which is an effective and well-disseminated evidence-based intervention for alcohol use disorder. Participants will complete a battery of assessments at the intake visit (30 minutes of assessments at intake) as well as weekly assessments immediately prior to their clinic visits (10-15 minutes of assessments each week), including a breathalyzer test, and random urine toxicology tests (one at intake and three random tests over the course of the 12-week treatment).