Annabelle M. Belcher, PhD

• Loyola University New Orleans, BA, Psychology
• National Institute of Mental Health (NIMH-IRP/NIH), Laboratory of Neuropsychology (mentor: Mortimer Mishkin), Pre-Doctoral IRTA
• University of California, Irvine, PhD, Neurobiology & Behavior (mentor: John F. Marshall)
• University of California, Santa Barbara, MacArthur Foundation Law & Neuroscience Project Post-Doctoral Fellow (mentors: Michael Gazzaniga and Walter Sinnott-Armstrong)
• National Institute on Drug Abuse (NIDA-IRP/NIH), Neuroimaging Research Branch (mentors: Elliot A. Stein and Afonso C. Silva), Post-Doctoral IRTA

My research interests are in the identification of non-pharmacological approaches using placebo effects to increase positive outcomes from Medication-Based Treatment (MBT, primarily, methadone) for opioid use disorder (OUD; collaboration with the DTC [Eric Weintraub, Division Director, Aaron Greenblatt, Medical Director], Ted Kaptchuk at Harvard University and Luana Colloca at the UM School of Nursing). Additionally, I am interested in the psychosocial risk factors (anxiety, depression and catastrophizing) that determine retention and adherence to MBT.

Other areas of research interest include:

-Understanding barriers to naloxone access and use (collaboration with Eric Wish, PhD)

-Comprehensive urine drug screening in OUD-diagnosed individuals (collaboration with Eric Wish, PhD)

-Work-force re-entry for individuals with OUD (collaboration with Marianne Cloeren, MD)

-Characterization of impulsivity in treatment-seeking OUD-diagnosed individuals (collaboration with Kristen Hamilton, PhD)

-Non-reinforcing properties of methadone (collaboration with Sergi Ferre, MD, PhD)

-Clinical outcomes of telemedicine-based delivery of MBT (collaboration with Eric Weintraub, MD and Melanie Bennett, PhD)

Opioid Use Disorder, Learning and Memory, Substance Use Disorders, Methadone Maintenance Treatment, Individual Differences, Susceptibility and Resilience to SUD, Medication-Assisted Treatment, Telemedicine for OUD

(In ascending chronological order)

1. Methamphetamine-induced neural and cognitive changes in rodent models of psychostimulant abuse

Methamphetamine abuse in humans has long been associated with lasting neurocognitive deficits, including problems with executive function and various forms of learning and memory. Under the mentorship of Dr. John F. Marshall at the University of California, Irvine, my doctoral work sought to elucidate the basis for two of these impacted forms of cognition: recognition memory and cognitive flexibility. Using established models of passive methamphetamine exposure in rodents (“binge,” “escalating-dose” and low-dose “sensitizing” models of human methamphetamine use), I was able to show that high-dose, neurotoxic regimens of methamphetamine cause monoaminergic cell death in limbic and cortical brain regions implicated in these cognitive functions. Intriguingly, these methamphetamine-induced frank dopaminergic and serotonergic insults represent only the most visible form of damage to the brain; I further demonstrated long-lasting and enduring effects on dopamine-stimulated cortical function (Belcher et al., 2009). This work formed the basis of my PhD thesis, and I was responsible for all aspects of the project, from behavioral training of the rodents, drug administration, tissue preparation and staining, radioligand binding assays, and quantification and statistical analysis of the behavioral, binding, and cell quantification data. From this work, I produced four first-authored and two co-authored manuscripts which taken together, delineated a mechanistic understanding of how methamphetamine has direct impacts on discrete populations of neurotransmitter systems and their projections. These changes may underlie the neurocognitive dysfunction reported in humans who abuse psychostimulant drugs.

1. Belcher AM, O’Dell SJ and Marshall JF (2005). Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity. Neuropsychopharmacology 30:2026-2034.
2. Belcher AM, Feinstein EM, O’Dell SJ and Marshall JF (2008). Methamphetamine influences on recognition memory: comparison of escalating and single-day dosing regimens. Neuropsychopharmacology 33:1453-1463.
3. Belcher AM, O’Dell SJ, Marshall JF (2009). Long-term changes in dopamine-stimulated gene expression after single-day methamphetamine exposure. Synapse 63:403-412.
4. Izquierdo A, Belcher AM, Scott L, Cazares VA, Chen J, O'Dell SJ, Malvaez M, Wu T, Marshall JF (2010). Reversal-specific learning impairments after a binge regimen of methamphetamine in rats: possible involvement of striatal dopamine. Neuropsychopharmacology 35(2):505-14

2. Development of nonhuman primate neuroimaging models of brain function

Under the mentorship of Dr. Elliot Stein, my post-doctoral work at the National Institute on Drug Abuse (IRP) built on my post-baccalaureate experience working with nonhuman primates to use state-of-the-art neuroimaging-based (fMRI) tools for investigations of normal versus drug-exposed brain function. FMRI requires a motionless subject, usually achieved with the use of anesthesia. But anesthesia poses a challenge to fMRI investigations of normal brain function. Thus, my main focus was to extend an unanesthetized marmoset neuroimaging preparation created by Xiaoqin Wang (JHU) and Afonso Silva (NINDS-IRP) to study intrinsic brain network connectivity (resting-state fMRI). I was responsible for all aspects of the study, from behavioral training, fMRI data acquisition and analysis, and manuscript production, and I produced two first-authored publications from this work. This first-of-its-kind report in an awake New World nonhuman primate provided a platform for mechanistic neurobiological examination for existing disease models established in the marmoset. Additionally, I had a leading role in a separate study designed to investigate magnetic resonance spectroscopy-measured differences in neurometabolites in rhesus monkeys withdrawn from methamphetamine. For that study, I helped prepare and scan the monkeys in the MRI, helped with data analysis, and wrote the first draft of the manuscript.

1. Belcher AM, Yen CC, Stepp H, Lu H, Mackel J, Yang Y, Silva A, Stein EA (2013) Large-scale brain networks in awake, truly resting marmoset monkeys. Journal of Neuroscience 33: 16796-16804. *Presented at the NIDA Director’s Hot Science Meeting on January 29, 2014 and highlighted on the NIDA-IRP website as the “Paper of the Month” 3/2014.
2. Yang S*, Belcher AM*, Chefer S, Vaupel DB, Schindler CW, Stein EA, Yang Y (2015). Withdrawal from long-term methamphetamine self-administration 'normalizes' neurometabolites in rhesus monkeys: a (1) H MR spectroscopy study. Addiction Biology 20(1):69-79. *co-first author
3. Belcher AM, Yen C-C, Notardonato L, Ross TJ, Volkow ND, Yang Y, Stein EA, Silva A and Tomasi D (2016). Functional connectivity hubs and networks in the awake marmoset brain. Frontiers in Integrative Neuroscience 10:1-9.

3. Utilizing open-label placebo in methadone maintenance-treated Opioid Use Disorder individuals

In my newly-developed IRB-approved human research program at the University of Maryland School of Medicine, with the guidance of several mentors, I am principal investigator on a clinical trial designed to investigate whether conditioned placebo effects can be used to augment treatment outcomes in patients enrolled in medication-based (methadone) treatment for Opioid Use Disorder. In this context, I am exploring treatment-relevant outcomes (methadone dose, retention, adherence and objective and subjective measures of drug use while in treatment) as well as the individual differences (psychological and personality characteristics) that determine responses to treatment and the intervention.

1. Belcher AM*, Cole TO, Greenblatt AD, Hoag SW, Epstein DH, Wagner M, Billing AS, Massey E, Hamilton KR, Kozak Z, Welsh CJ, Weintraub E, Wickwire EM, Wish ED, Kaptchuk TJ, Colloca L. (in press, BMJ Open). Open-label dose-extending placebos for opioid use disorder: A protocol for a randomized controlled clinical trial with methadone treatment. *corresponding author
2. Belcher AM, Ferré S, Martinez PE, Colloca L (2018). Role of Placebo Effects in Pain and Neuropsychiatric Disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 87:298-306.
3. Cai NS, Quiroz C, Bonaventura J, Bonifazi A, Cole TO, Purks J, Billing AS, Massey E, Wagner M, Wish ED, Guitart X, Rea W, Lam S, Moreno E, Casadó-Anguera V, Greenblatt AD, Jacobson AE, Rice KC, Casadó V, Newman AH, Winkelman JW, Michaelides M, Weintraub E, Volkow ND, Belcher AM*, Ferré S* (2019). J Clin Investigation Complexes of mu-opioid and galanin receptors determine the dopaminergic effects of opioids. *co-corresponding author

4. Other published work on the role of personality traits in the development of Substance Use Disorders:

1. Belcher AM, Volkow ND, Moeller FG and Ferre S (2014). Personality traits and vulnerability or resilience to substance use disorders. Trends in Cognitive Sciences 18(4): 163-218.
2. Belcher AM, Volkow ND, Moeller F, Ferre S. The Cognitive Neurosciences V (fifth edition). Gazzaniga MS, Mangun GR, editors. Cambridge: MIT; 2014. Chapter 88, Society and addiction: Bringing understanding toward appreciation of a mental health disorder.; p.1035-1042.
3. Belcher AM, Lejuez CW, Moeller FG, Volkow ND and Ferre S (2018). Choice Impulsivity, a drug-modifiable personality trait. In: Pickard and Ahmed (eds.), The Routledge Handbook of Philosophy and Science of Addiction.