Jermaine Jones, PhD
Assistant Professor of Clinical Neurobiology (in Psychiatry)
I was born in Henderson, Texas and attended college at the University of Virginia majoring in Psychology and Biology. Throughout my post-secondary education I was involved in several summer undergraduate research internships at: Carnegie Mellon, the Univ. of Illinois and Johns Hopkins. While obtaining my doctoral degree at American University, I found a balance between behavioral and biological investigations that best fit my interests. My research in Dr. Anthony L. Riley’s Psychopharmacology Laboratory focused on understanding alcohol’s effects on cocaine-induced affective responses, along with neuropharmacological mediation of cocaine’s aversive effects and their impact on its abuse liability. Working under Dr. George Uhl and Scott Hall at the Molecular Neurobiology Division at NIDA, I researched the genetic contribution to cocaine’s aversive effects. My graduate training provided me the opportunity to learn from two well respected substance abuse investigators. Under the tutelage of Dr. Riley I learned the importance of information gained by integrating behavioral assays into pharmacological research. Through my time with Dr. Uhl, I developed an appreciation for the influence that genetic factors have on behavioral responses to drugs.
In order to gain a comprehensive view of drug abuse and addiction I sought to obtain experience performing clinical research, in my postdoctoral training. Working with Dr. Sandra Comer at the Substance Abuse Division at Columbia University College of Physicians and Surgeons, I was involved in a number of human behavioral pharmacological investigations. I also had the opportunity to perform clinical rotations with the Substance Use Treatment and Research Service (STARS), and the DAYTOP therapeutic community. In 2011 I became an assistant professor and received a K01 award in order to continue my career development at Columbia/New York State Psychiatric Institute. My current research integrates human laboratory models of drug abuse with my own interest in complex disorder genetics.
My career goal is to become a leading academic researcher integrating genetic techniques into the behavioral pharmacology of drug abuse. As an independent investigator I would like for my research to focus on understanding how genetic and epigenetic factors affect initiation and course of drug use disorders. My experience as a pre-clinical researcher heightened my awareness of how genetics contributes considerably to our understanding of substance abuse, and the lack of hypothesis-driven research being performed at the clinical level. In my career as a researcher, I would like to take clinical genetics beyond that of correlational analyses. My goal is to identify the proximal consequences of genetic variation and epigenetic modifications, as they pertain to the individual users (e.g., more robust positive subjective effects, more severe withdrawal).
Project 1: Contribution of Various Genetic Polymorphisms to Oxycodone’s Abuse Liability.
Project Summary: Although many opioid drugs have significant abuse liability (Comer et al, 2008, 2009), no methods currently exist for identifying individuals who are at increased risk of developing opioid abuse. Researchers have begun to investigate the role of genetic factors contributing to drug dependence, focusing on genes that alter the clinical pharmacology of each specific drug class. The genetic contribution to the vulnerability to opioid addiction has been estimated at over 50%, which is greater than for any other drug class (van den Bree et al., 1998). Part 1 of the proposed study will examine the prevalence of various genetic polymorphisms thought to be involved in opioid abuse in three populations: prescription opioid abusers (N=150), heroin abusers (N=150), and non-drug abusers (N=150). Participants will complete a number of questionnaires that will allow us to learn more about their drug use history and current patterns of abuse. Eligible participants will be asked to provide a small blood sample (30 oz) for analyses of variations in genes that encode for the mu opioid receptor, the proinflammatory cytokine interleukin 1β, and cytochrome P450 2D6,. Part 2 of the proposed study (Laboratory Testing) will involve a single laboratory session to evaluate the subjective, cognitive, and analgesic effects of oxycodone in a subset of individuals who participated in Part 1 of the study. More specifically, 10 non-opioid-dependent individuals possessing one of three target genotypes [118G, 511C (or 31T), or CYP2D6 (*3,*4,*5,*6,*7, or *8), along with wild type controls], from two of the populations [prescription opioid abusers (N=60) and non-drug abusers (N=60)] will complete the laboratory session (heroin abusers will not be tested in the laboratory session due to concerns about the potentially confounding effects of physical dependence upon study measures). Data from a variety of sources suggest that functional consequences of each of these particular SNPs may mediate response to opioid drugs and therefore contribute to their abuse liability (Drakenburg et al., 2006; Liu et al., 2010; Ross et al., 2005). Accordingly, we will evaluate the effects of ascending doses of oxycodone (cumulative doses of 0, 10, and 30 mg) in a single laboratory session. By combining behavioral assays and genetic assessments, this study should yield important information about the relationship between genetic variation and the abuse potential of opioids.
Project 2: A Randomized, Double-Blind, Placebo-Controlled, Crossover Design Study of CERC 501 in a Human Laboratory Model of Smoking Behavior.
Project Summary: There is a significant unmet medical need for treatments that reduce the abuse and dependence of addicting drugs, including tobacco, alcohol, cocaine and opiates. In recent years, opiate antagonists such as naltrexone and nalmefene have been shown to be effective treatments for alcohol and opioid abuse. The effects on tobacco users is equivocal, with well-established effects in short-term laboratory studies of subjective effects, but lack of clear sustained effect on abstinence, perhaps due to the chronic negative effects of mu opioid receptor blockade. Accumulating evidence indicates that selective antagonism of kappa-opioid receptors (KORs) may provide therapeutic benefit in the treatment of depression. A therapeutic role for KORs in major depressive disorder (MDD) is based upon an emerging scientific literature showing that KORs and the endogenous ligand dynorphin are highly expressed within the prefrontal cortico-striatal loop, which mediates reward and affective states.1 KOR antagonists have been shown to block stress-induced potentiation of cocaine and conditioned place preference, an animal model of drug relapse. CERC-501 (previously known as LY2456302) is a high-affinity, selective KOR antagonist being developed for the treatment of substance abuse and MDD, by blocking aversive signaling cascades in the brain triggered by chronic psychological or physical stress. In a mouse model of precipitated nicotine withdrawal, CERC-501 decreased anxiety-like behavior, somatic signs of withdrawal and hyperalgesia. However, the effects on anxiety and pain behavior had a U-shaped dose response curve, suggesting that doses that selectively block KOR will have the greatest overall effect on symptoms clinically. In three previous human trials, CERC-501 has been shown to be safe and well tolerated at single oral doses up to 60 mg. At multiple daily doses of 10 mg or less, CERC-501 provides substantial blockade of KOR as assessed in positron emission tomography (PET) imaging studies with minimal effect on mu opiate receptors as assessed by fentanyl induced miosis. The current study will evaluate the effect of CERC-501 on the latency to start smoking and the number of cigarettes smoked during the smoking self-administration period after an 18 hour period of abstinence. Subjective measures of cravings, positive and negative mood, and withdrawal symptoms will also be assessed.
Project 3: Risk and Benefits of Overdose Education and Naloxone Prescribing to Heroin Users.
Project Summary: A significant cause of mortality among opioid users is overdose (Gilson et al., 2004; SAMSHA, 2010), which commonly occurs following voluntary (opioid detoxification) or involuntary (incarceration) opioid abstinence. Nearly 85% of overdoses occur in the presence of a witness. Common methods of intervention by individuals without medical training are ineffective techniques such as shaking the victim or injecting salt water (Pollini et al., 2006). Naloxone is an opioid antagonist that has long been used successfully by trained medical personnel during emergency resuscitation following opioid overdose. In an effort to reduce fatal and non-fatal opioid overdose, a number of states are implementing programs in which non-medical personnel are provided brief instruction in recognizing the signs of opioid overdose and administering naloxone. However, most of the existing programs are not designed to collect empirical data on the safety and effectiveness of this intervention. Reporting of naloxone use is voluntary and without incentive, and the experience of those who have been trained and prescribed naloxone is not followed. The proposed investigation will be one of the first large-scale, prospective attempts to obtain data on the effectiveness of naloxone distribution among opioid-abusing populations at high risk of unintentional opioid poisoning. Specifically, opioid abusers will be recruited from drug detoxification sites as well as those accessing services at needle exchange programs. All participants (N=700) will receive the standard opioid overdose education and naloxone. One third of the participants will be randomized to receive additional in-depth psychosocial education focusing on recognition and prevention of opioid overdose, and appropriate use of naloxone. Another third of the participants will receive the extensive training and be required to engage a spouse, partner, relative, or friend in this supplementary intervention. We plan to randomize individuals to each group [Treatment as Usual (TAU) vs. Extensively Trained (ET) vs. Extensively Trained with a Significant Other (ETwSO)] and, through continued follow up over one year, we will compare self-reported overdose reversal attempts (with and without naloxone use), naloxone-related adverse events, and changes in patterns of heroin and other drug use. In addition to comparing outcome variables in the TAU, ET and ETwSO groups prospectively, we will analyze data collected before study initiation to compare fatal and non-fatal opioid overdose rates in neighborhoods with facilities that offer overdose prevention training and naloxone to those that do not, using data provided by our collaborators at the NYC DOHMH.
Project 4: Lorcaserin: Evaluation of its Ability to Alter the Abuse Liability of Oxycodone.
Project Summary: Healthy, adult men and women, aged 21 to 59 years, who abuse opioids and are physically dependent on them will be recruited to participate in a study to examine the ability of lorcaserin (0, 20 mg/day (10 mg BID)) to alter the subjective and reinforcing effects of oxycodone (up to 35 participants will be enrolled in the study in order to obtain 12 completers). After participants complete the screening process, they will be scheduled for admission onto the General Clinical Research Unit on 5-South where they will reside during a 7-week study. During Week 1, participants will be detoxified from opioids. During detox, participants will be treated for emergent withdrawal symptoms with supplemental medications (e.g., clonidine, clonazepam, compazine, ketorolac tromethamine, ondansetron, ibuprofen or acetaminophen, trazodone, and/or zolpidem) until withdrawal symptoms have dissipated, based on physician judgment and using SOWS scores as a guide. During Week 2 after the detoxification period, participants will be randomized to receive either active (20 mg) or placebo (0 mg) lorcaserin (orally) as their first maintenance dose. During Weeks 3-4, either active (Week 3) or placebo oxycodone (Week 4) will be available. During Weeks 3-4 on Mon morning, participants will receive $10 and a sample dose of intransasal (IN) oxycodone (0 or 10 mg). The sampled dose/$ will be available during subsequent choice sessions on Mon-Thu. On Fri, participants will receive $10 and 10 mg IN oxycodone during a sample session (the oxycodone dose on Fri morning is always active). Following the sample session on Fri, participants will complete a cue exposure session during which they will be presented with neutral cues followed by drug cues. This procedure will allow the investigators to determine whether the study medication affects reactivity to drug-related cues. After the cue exposure session on Fri, participants will be given the opportunity to self-administer drug and/or money using a progressive ratio procedure. During Week 5, participants will be stabilized on the other maintenance dose (lorcaserin 0 mg or 20 mg). Weeks 6-7 will be identical to Weeks 3-4. At the conclusion of the study, participants will be given an exit interview during which the study will be described (see the table below). Those who are interested in treatment for their drug use at the end of the study will be offered referrals to studies at our Substance Treatment and Research Service or other treatment providers. Participants will return weekly for their study payments for several weeks after study completion. At each of these weekly visits, we will assess participants’ interest in treatment and drug use patterns (via self-report and urine drug toxicology). Within 1 week after discharge, we will assess adverse events using the SAFTEE, pregnancy (using a urine pregnancy test), general health (complete blood count, blood chemistry, urinalysis, blood pressure, heart rate, body weight, EKG), and suicide (Columbia Suicide Severity Rating Scale).
Adjunct Faculty: City College of New York (Psyc 3500: Drug and Alcohol Abuse)
Adjunct Faculty: St. John's University (Psyc 838: Addictive Behaviors)
Jones J.D., Busse G,D., & Riley A. L. (2006) Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions. Pharmacology, Biochemistry and Behavior 83; 554-560.
Jones J.D., Hall F.S., Uhl G.R., Rice K., & Riley A. L. (2009) Differential Involvement of the Norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacology, Biochemistry & Behavior 93; 75-81.
Jones J.D., Hall F.S., Uhl G.R., & Riley A. L. (2010) Dopamine, norepinephrine and serotonin transporter gene deletions differentially alter cocaine-induced taste aversion. Pharmacology, Biochemistry & Behavior Pharmacology, Biochemistry & Behavior 94; 580-587.
Jones J.D., Manubay, J.M., Vosburg, S.K., & Comer S.D. (2010) Oxycodone abuse in New York City: Characteristics of intravenous and intranasal users. American Journal on Addictions 20; 190–195.
Jones J.D., Sullivan, M.A., Manubay, J.M., Vosburg, S.K., & Comer S.D. (2011) The Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Patients with Chronic, Non-Malignant Pain who are Maintained on Sublingual Buprenorphine/Naloxone. Neuropsychopharmacology 36, 411–422.
Jones J.D., Mogali S. & Comer S.D. (2012) Polydrug abuse: A review of opioid and benzodiazepine combination use. Drug and Alcohol Dependence 125(1-2):8-18.
Jones J.D., Speer T., Nunes E., Comer S.D., Ross S., Rotrosen J.& Reid M.S. (2013) Opioid-like effects of the Neurokinin 1 antagonist aprepitant in patients maintained on and briefly withdrawn from methadone. American Journal of Drug and Alcohol Abuse 39(2):86-91.
Jones J.D., Roux P., Stancliff S., Matthews W., & Comer S.D. (2013) Brief overdose education can significantly increase accurate recognition of opioid overdose among heroin users. International Journal of Drug Policy 166-170.
Jones J.D., & Comer S.D. (2013) A review of human drug self-administration procedures. Behavioural Pharmacology 24(5-6): 384-395.
Jones J.D., Madera G., & Comer S.D. (2014) The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users. Pharmacology, Biochemistry & Behavior 122: 299–306.
Jones J.D., Sullivan M.A., Vosburg S.K., Manubay J.M., Mogali S., Metz V., Comer S.D. (2014) Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users. Addiction Biology 20(4): 784-798.
Jones J.D., Comer S.D., & Kranzler H.K. (2015) The Pharmacogenetics of Alcohol Use Disorder. Alcoholism: Clinical and Experimental and Research 39(3): 391-402.
Jones J.D., Comer S.D., & Kranzler H.K. (2015) A Review of Pharmacogenetic Studies of Drug Use Disorders. Drug and Alcohol Dependence 152:1-14.
Jones J.D., Atchison J.J., Madera G, Metz V.E, Comer S.D. (2015) Need and utility of a polyethylene glycol marker to ensure against urine falsification among heroin users. Drug Alcohol Depend. 153: 201-206.
Jones J.D., Luba R.L., Vogelman J., & Comer S.D. (2016) Evidence of Genetic Modulation of Opioid Withdrawal Severity. American Journal on Addictions DOI: 10.1111/ajad.12316. [Epub ahead of print]. Jones J.D., Sullivan, M.A., Manubay, J., Metz V., Mogali S., & Comer, S.D. (2016) The Effects of Pioglitazone, a PPARγ Receptor Agonist, on the Abuse Liability of Oxycodone. Physiology and Behavior (In Press).
Jones J.D., Vadhan N.P., Luba R.R., & Comer, S.D. (2016) The Effects of Heroin Administration and Drug Cues on Impulsivity. Journal of Clinical and Experimental Neuropsychology. (In Press).