Countermeasures for Preventing and Treating Opioid Overdose

France, Charles P.; Ahern, Gerard P.; Averick, Saadyah; Disney, Alex; Enright, Heather A.; Esmaeli‐Azad, Babak; Federico, Arianna; Gerak, Lisa R.; Husbands, Stephen M.; Kolber, Benedict; Lau, Edmond Y.; Lao, Victoria; Maguire, David R.; Malfatti, Michael A.; Martinez, Girardo; Mayer, Brian P.; Pravetoni, Marco; Sahibzada, Niaz; Skolnick, Phil; Snyder, Evan Y.; Tomycz, Nestor; Valdez, Carlos A.; Zapf, Jim

doi:10.1002/cpt.2098

Countermeasures for Preventing and Treating Opioid Overdose

Journal Article · Wed Oct 28 00:00:00 EDT 2020 · Clinical Pharmacology and Therapeutics

DOI:https://doi.org/10.1002/cpt.2098· OSTI ID:2281798

France, Charles P. ^[1]; Ahern, Gerard P. ^[2]; Averick, Saadyah ^[3]; Disney, Alex ^[4]; Enright, Heather A. ^[5]; Esmaeli‐Azad, Babak ^[6]; Federico, Arianna ^[6]; Gerak, Lisa R. ^[1]; Husbands, Stephen M. ^[4]; Kolber, Benedict ^[7]; Lau, Edmond Y. ^[5]; Lao, Victoria ^[5]; Maguire, David R. ^[1]; Malfatti, Michael A. ^[5]; Martinez, Girardo ^[6]; Mayer, Brian P. ^[5]; Pravetoni, Marco ^[8]; Sahibzada, Niaz ^[2]; Skolnick, Phil ^[9]; Snyder, Evan Y. ^[10] more »

Univ. of Texas at San Antonio, TX (United States)
Georgetown Univ., Washington, DC (United States)
Allegheny Health Network, Pittsburgh, PA (United States). Neuroscience Institute
Univ. of Bath (United Kingdom)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
CiBots, Inc., San Diego, CA (United States)
Univ. of Texas at Dallas, Richardson, TX (United States)
Univ. of Minnesota, Minneapolis, MN (United States). Medical School
Opiant Pharmaceuticals, Inc., Santa Monica, CA (United States)
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (United States)

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Due to its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic “nanosponge” decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: Defense Threat Reduction Agency (DTRA); National Institutes of Health (NIH); USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 2281798

Report Number(s):: LLNL-JRNL--858806; 1087909

Journal Information:: Clinical Pharmacology and Therapeutics, Journal Name: Clinical Pharmacology and Therapeutics Journal Issue: 3 Vol. 109; ISSN 0009-9236

Publisher:: American Society for Clinical Pharmacology & Therapeutics - WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (71)

Nanoparticles in the clinic: An update Anselmo, Aaron C.; Mitragotri, Samir Bioengineering & Translational Medicine, Vol. 4, Issue 3 https://doi.org/10.1002/btm2.10143	journal	July 2019
Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose Krieter, Philip; Gyaw, Shwe; Chiang, C. Nora The Journal of Clinical Pharmacology, Vol. 59, Issue 7 https://doi.org/10.1002/jcph.1384	journal	January 2019
NMR spectroscopic investigation of inclusion complexes between cyclodextrins and the neurotoxin tetramethylenedisulfotetramine: Cyclodextrin-TETS inclusion complexes Mayer, Brian P.; Albo, Rebecca L. F.; Hok, Saphon Magnetic Resonance in Chemistry, Vol. 50, Issue 3 https://doi.org/10.1002/mrc.3803	journal	March 2012
The Pharmacokinetics and Pharmacodynamics of Carfentanil After Recreational Exposure: A Case Report Uddayasankar, Uvaraj; Lee, Colin; Oleschuk, Curtis Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Vol. 38, Issue 6 https://doi.org/10.1002/phar.2117	journal	May 2018
Acute opioid dependence: characterizing the early adaptations underlying drug withdrawal Harris, Andrew C.; Gewirtz, Jonathan C. Psychopharmacology, Vol. 178, Issue 4 https://doi.org/10.1007/s00213-005-2155-0	journal	February 2005
Methocinnamox (MCAM) antagonizes the behavioral suppressant effects of morphine without impairing delayed matching-to-sample accuracy in rhesus monkeys Minervini, Vanessa; Disney, Alex; Husbands, Stephen M. Psychopharmacology, Vol. 237, Issue 10 https://doi.org/10.1007/s00213-020-05592-y	journal	August 2020
Carfentanil: a weapon of mass destruction Shafer, Steven L. Canadian Journal of Anesthesia/Journal canadien d'anesthésie, Vol. 66, Issue 4 https://doi.org/10.1007/s12630-019-01295-x	journal	January 2019
National Institutes of Health (NIH) Executive Meeting Summary: Developing Medical Countermeasures to Rescue Opioid-Induced Respiratory Depression (a Trans-Agency Scientific Meeting)—August 6/7, 2019 Yeung, David T.; Bough, Kristopher J.; Harper, Jill R. Journal of Medical Toxicology, Vol. 16, Issue 1 https://doi.org/10.1007/s13181-019-00750-x	journal	December 2019
Nasal administration of naloxone for detection of opiate dependence Loimer, Norbert; Hofmann, Peter; Chaudhry, Haroon Rashid Journal of Psychiatric Research, Vol. 26, Issue 1 https://doi.org/10.1016/0022-3956(92)90014-F	journal	January 1992
Serotonin 1A-receptor activation suppresses respiratory apneusis in the cat Lalley, Peter M.; Bischoff, Anna-Maria; Richter, Diethelm W. Neuroscience Letters, Vol. 172, Issue 1-2 https://doi.org/10.1016/0304-3940(94)90662-9	journal	May 1994
Cell cholesterol efflux: integration of old and new observations provides new insights Rothblat, George H.; de la Llera-Moya, Margarita; Atger, Veronique Journal of Lipid Research, Vol. 40, Issue 5 https://doi.org/10.1016/S0022-2275(20)32113-1	journal	May 1999
Treatment of apneustic respiratory disturbance with a serotonin-receptor agonist Wilken, B.; Lalley, P.; Bischoff, A. M. The Journal of Pediatrics, Vol. 130, Issue 1 https://doi.org/10.1016/S0022-3476(97)70315-9	journal	January 1997
Evaluation of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) gels as a release vehicle for percutaneous fentanyl Liaw, Jiahorng; Lin, Yen-Chao Journal of Controlled Release, Vol. 68, Issue 2 https://doi.org/10.1016/S0168-3659(00)00268-6	journal	August 2000
Residual polyvinyl alcohol associated with poly (d,l-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake Sahoo, Sanjeeb K.; Panyam, Jayanth; Prabha, Swayam Journal of Controlled Release, Vol. 82, Issue 1 https://doi.org/10.1016/S0168-3659(02)00127-X	journal	July 2002
Transdermal delivery of fentanyl: rapid onset of analgesia using skin electroporation Vanbever, R. Journal of Controlled Release, Vol. 50, Issue 1-3 https://doi.org/10.1016/S0168-3659(97)00147-8	journal	January 1998
Lidocaine-loaded biodegradable nanospheres. I. Optimization of the drug incorporation into the polymer matrix GÃ¶rner, T. Journal of Controlled Release, Vol. 57, Issue 3 https://doi.org/10.1016/S0168-3659(98)00121-7	journal	February 1999
Recent discoveries in pharmacokinetics of drugs of abuse Cone, Edward J. Toxicology Letters, Vol. 102-103 https://doi.org/10.1016/S0378-4274(98)00292-6	journal	December 1998
Polylactic acid (PLA) controlled delivery carriers for biomedical applications Tyler, Betty; Gullotti, David; Mangraviti, Antonella Advanced Drug Delivery Reviews, Vol. 107 https://doi.org/10.1016/j.addr.2016.06.018	journal	December 2016
Severe opioid withdrawal precipitated by Vivitrol® Wightman, R. S.; Nelson, L. S.; Lee, J. D. The American Journal of Emergency Medicine, Vol. 36, Issue 6 https://doi.org/10.1016/j.ajem.2018.03.052	journal	June 2018
One-Year Mortality of Patients After Emergency Department Treatment for Nonfatal Opioid Overdose Weiner, Scott G.; Baker, Olesya; Bernson, Dana Annals of Emergency Medicine, Vol. 75, Issue 1 https://doi.org/10.1016/j.annemergmed.2019.04.020	journal	January 2020
Comparison of the antinociceptive effect of acute morphine in female and male Sprague–Dawley rats using the long-lasting mu-antagonist methocinnamox Peckham, Elizabeth M.; Barkley, Laura M.; Divin, Mary F. Brain Research, Vol. 1058, Issue 1-2 https://doi.org/10.1016/j.brainres.2005.07.060	journal	October 2005
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Hoffmann, Markus; Kleine-Weber, Hannah; Schroeder, Simon Cell, Vol. 181, Issue 2 https://doi.org/10.1016/j.cell.2020.02.052	journal	April 2020
Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort Morgan, Jake R.; Schackman, Bruce R.; Weinstein, Zoe M. Drug and Alcohol Dependence, Vol. 200 https://doi.org/10.1016/j.drugalcdep.2019.02.031	journal	July 2019
Involvement of PI3K-Akt-Bad pathway in apoptosis induced by 2,6-di-O-methyl-β-cyclodextrin, not 2,6-di-O-methyl-α-cyclodextrin, through cholesterol depletion from lipid rafts on plasma membranes in cells Motoyama, Keiichi; Kameyama, Kazuhisa; Onodera, Risako European Journal of Pharmaceutical Sciences, Vol. 38, Issue 3 https://doi.org/10.1016/j.ejps.2009.07.010	journal	October 2009
Ex vivo evaluation of bioadhesive films for buccal delivery of fentanyl Diaz del Consuelo, Isabel; Falson, Françoise; Guy, Richard H. Journal of Controlled Release, Vol. 122, Issue 2 https://doi.org/10.1016/j.jconrel.2007.05.017	journal	September 2007
An overview of clinical and commercial impact of drug delivery systems Anselmo, Aaron C.; Mitragotri, Samir Journal of Controlled Release, Vol. 190 https://doi.org/10.1016/j.jconrel.2014.03.053	journal	September 2014
Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment Comer, Sandra D.; Cahill, Catherine M. Neuroscience & Biobehavioral Reviews, Vol. 106 https://doi.org/10.1016/j.neubiorev.2018.12.005	journal	November 2019
Neural Control of Breathing and CO2 Homeostasis Guyenet, Patrice G.; Bayliss, Douglas A. Neuron, Vol. 87, Issue 5 https://doi.org/10.1016/j.neuron.2015.08.001	journal	September 2015
Development of vaccines to treat opioid use disorders and reduce incidence of overdose Pravetoni, Marco; Comer, Sandra D. Neuropharmacology, Vol. 158 https://doi.org/10.1016/j.neuropharm.2019.06.001	journal	November 2019
Blockade of dorsolateral pontine 5HT1A receptors destabilizes the respiratory rhythm in C57BL6/J wild-type mice Dhingra, R. R.; Dutschmann, M.; Dick, T. E. Respiratory Physiology & Neurobiology, Vol. 226 https://doi.org/10.1016/j.resp.2016.01.007	journal	June 2016
Solution-State Structure and Affinities of Cyclodextrin:Fentanyl Complexes by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation Mayer, Brian P.; Kennedy, Daniel J.; Lau, Edmond Y. The Journal of Physical Chemistry B, Vol. 120, Issue 9 https://doi.org/10.1021/acs.jpcb.5b12333	journal	February 2016
Predicting a Drug’s Membrane Permeability: A Computational Model Validated With in Vitro Permeability Assay Data Bennion, Brian J.; Be, Nicholas A.; McNerney, M. Windy The Journal of Physical Chemistry B, Vol. 121, Issue 20 https://doi.org/10.1021/acs.jpcb.7b02914	journal	May 2017
Covalent Poly(lactic acid) Nanoparticles for the Sustained Delivery of Naloxone Kassick, Andrew J.; Allen, Heather N.; Yerneni, Saigopalakrishna S. ACS Applied Bio Materials, Vol. 2, Issue 8 https://doi.org/10.1021/acsabm.9b00380	journal	July 2019
Introduction and General Overview of Cyclodextrin Chemistry Szejtli, József Chemical Reviews, Vol. 98, Issue 5 https://doi.org/10.1021/cr970022c	journal	July 1998
Monoclonal Antibodies for Combating Synthetic Opioid Intoxication Smith, Lauren C.; Bremer, Paul T.; Hwang, Candy S. Journal of the American Chemical Society, Vol. 141, Issue 26 https://doi.org/10.1021/jacs.9b04872	journal	June 2019
Nalmefene: Intravenous safety and kinetics of a new opioid antagonist Dixon, Ross; Howes, John; Gentile, Joseph Clinical Pharmacology and Therapeutics, Vol. 39, Issue 1 https://doi.org/10.1038/clpt.1986.9	journal	January 1986
Effects of acute and repeated treatment with methocinnamox, a mu opioid receptor antagonist, on fentanyl self-administration in rhesus monkeys Maguire, David R.; Gerak, Lisa R.; Sanchez, Jesus J. Neuropsychopharmacology, Vol. 45, Issue 12 https://doi.org/10.1038/s41386-020-0698-8	journal	May 2020
The Partial 5-Hydroxytryptamine1A Receptor Agonist Buspirone does not Antagonize Morphine-induced Respiratory Depression in Humans Oertel, B. G.; Schneider, A.; Rohrbacher, M. Clinical Pharmacology & Therapeutics, Vol. 81, Issue 1 https://doi.org/10.1038/sj.clpt.6100018	journal	January 2007
Mechanisms of fatal opioid overdose White, Jason M.; Irvine, Rodney J. Addiction, Vol. 94, Issue 7 https://doi.org/10.1046/j.1360-0443.1999.9479612.x	journal	July 1999
Management of Opioid Analgesic Overdose Boyer, Edward W. New England Journal of Medicine, Vol. 367, Issue 2 https://doi.org/10.1056/NEJMra1202561	journal	July 2012
The Role of Science in Addressing the Opioid Crisis Volkow, Nora D.; Collins, Francis S. New England Journal of Medicine, Vol. 377, Issue 4 https://doi.org/10.1056/NEJMsr1706626	journal	July 2017
Massive OxyContin ingestion refractory to naloxone therapy Schneir, Aaron B.; Vadeboncoeur, Tyler F.; Offerman, Steven R. Annals of Emergency Medicine, Vol. 40, Issue 4 https://doi.org/10.1067/mem.2002.128143	journal	October 2002
Unexpected “gas” casualties in Moscow: A medical toxicology perspective Wax, Paul M.; Becker, Charles E.; Curry, Steven C. Annals of Emergency Medicine, Vol. 41, Issue 5 https://doi.org/10.1067/mem.2003.148	journal	May 2003
Biologics to treat substance use disorders: Current status and new directions Pravetoni, Marco Human Vaccines & Immunotherapeutics, Vol. 12, Issue 12 https://doi.org/10.1080/21645515.2016.1212785	journal	July 2016
Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery† Ahonen, J.; Olkkola, K. T.; Hynynen, M. British Journal of Anaesthesia, Vol. 85, Issue 4 https://doi.org/10.1093/bja/85.4.533	journal	October 2000
Plasma Concentrations of Heroin and Morphine-Related Metabolites after Intranasal and Intramuscular Administration Skoppl, Gisela; Ganssmann, Beate; Cone, Edward J. Journal of Analytical Toxicology, Vol. 21, Issue 2 https://doi.org/10.1093/jat/21.2.105	journal	March 1997
5-HT1A Receptor Agonist Befiradol Reduces Fentanyl-induced Respiratory Depression, Analgesia, and Sedation in Rats Ren, Jun; Ding, Xiuqing; Greer, John J. Anesthesiology, Vol. 122, Issue 2 https://doi.org/10.1097/ALN.0000000000000490	journal	February 2015
Opioid Half-lives and Hemlines Kharasch, Evan D. Anesthesiology, Vol. 122, Issue 5 https://doi.org/10.1097/ALN.0000000000000634	journal	May 2015
Fatal Fentanyl: One Pill Can Kill Sutter, Mark E.; Gerona, Roy R.; Davis, M. Thais Academic Emergency Medicine, Vol. 24, Issue 1 https://doi.org/10.1111/acem.13034	journal	October 2016
Blockade of synaptic inhibition within the pre‐Bötzinger complex in the cat suppresses respiratory rhythm generation in vivo Pierrefiche, O.; Schwarzacher, S. W.; Bischoff, A. M. The Journal of Physiology, Vol. 509, Issue 1 https://doi.org/10.1111/j.1469-7793.1998.245bo.x	journal	May 1998
Long-Lasting Effects of Methocinnamox on Opioid Self-Administration in Rhesus Monkeys Maguire, David R.; Gerak, Lisa R.; Woods, James H. Journal of Pharmacology and Experimental Therapeutics, Vol. 368, Issue 1 https://doi.org/10.1124/jpet.118.252353	journal	November 2018
Reversal and Prevention of the Respiratory-Depressant Effects of Heroin by the Novel μ-Opioid Receptor Antagonist Methocinnamox in Rhesus Monkeys Gerak, Lisa R.; Maguire, David R.; Woods, James H. Journal of Pharmacology and Experimental Therapeutics, Vol. 368, Issue 2 https://doi.org/10.1124/jpet.118.253286	journal	November 2018
Fighting Fire with Fire: Development of Intranasal Nalmefene to Treat Synthetic Opioid Overdose Krieter, Philip; Gyaw, Shwe; Crystal, Roger Journal of Pharmacology and Experimental Therapeutics, Vol. 371, Issue 2 https://doi.org/10.1124/jpet.118.256115	journal	April 2019
Methocinnamox Produces Long-Lasting Antagonism of the Behavioral Effects of µ-Opioid Receptor Agonists but Not Prolonged Precipitated Withdrawal in Rats Gerak, Lisa R.; Minervini, Vanessa; Latham, Elizabeth Journal of Pharmacology and Experimental Therapeutics, Vol. 371, Issue 2 https://doi.org/10.1124/jpet.119.260331	journal	August 2019
Mu Opioids and Their Receptors: Evolution of a Concept Pasternak, Gavril W.; Pan, Ying-Xian Pharmacological Reviews, Vol. 65, Issue 4 https://doi.org/10.1124/pr.112.007138	journal	September 2013
'I saved a life': a heroin addict's reflections on managing an overdose using 'take home naloxone' George, S.; Boulay, S.; Begley, D. Case Reports, Vol. 2010, Issue sep06 1 https://doi.org/10.1136/bcr.05.2010.2986	journal	September 2010
Degree and Duration of Reversal by Naloxone of Effects of Morphine in Conscious Subjects Evans, J. M.; Hogg, M. I. J.; Lunn, J. N. BMJ, Vol. 2, Issue 5919 https://doi.org/10.1136/bmj.2.5919.589	journal	June 1974
Naloxone in opioid poisoning: walking the tightrope Clarke, S. F. J. Emergency Medicine Journal, Vol. 22, Issue 9 https://doi.org/10.1136/emj.2003.009613	journal	September 2005
The role of medullary serotonin (5-HT) neurons in respiratory control: contributions to eupneic ventilation, CO₂ chemoreception, and thermoregulation Hodges, Matthew R.; Richerson, George B. Journal of Applied Physiology, Vol. 108, Issue 5 https://doi.org/10.1152/japplphysiol.01270.2009	journal	May 2010
Buspirone, an Anxiolytic Drug That Stimulates Respiration Garner, Stuart J.; Eldridge, Frederic L.; Wagner, Paul G. American Review of Respiratory Disease, Vol. 139, Issue 4 https://doi.org/10.1164/ajrccm/139.4.946	journal	April 1989
Effects of Buspirone on Sleep and Respiration Mendelson, Wallace B.; Martin, Joseph V.; Rapoport, David M. American Review of Respiratory Disease, Vol. 141, Issue 6 https://doi.org/10.1164/ajrccm/141.6.1527	journal	June 1990
Naloxone dosage for opioid reversal: current evidence and clinical implications Rzasa Lynn, Rachael; Galinkin, Jl Therapeutic Advances in Drug Safety, Vol. 9, Issue 1 https://doi.org/10.1177/2042098617744161	journal	December 2017
Higher doses of naloxone are needed in the synthetic opioid era Moss, Ronald B.; Carlo, Dennis J. Substance Abuse Treatment, Prevention, and Policy, Vol. 14, Issue 1 https://doi.org/10.1186/s13011-019-0195-4	journal	February 2019
Brain targeting studies on buspirone hydrochloride after intranasal administration of mucoadhesive formulation in rats Khan, Ms Shagufta; Patil, Kundan; Yeole, Pramod Journal of Pharmacy and Pharmacology, Vol. 61, Issue 5 https://doi.org/10.1211/jpp.61.05.0017	journal	January 2010
Repinotan, a Selective 5-HT1A-R-Agonist, Antagonizes Morphine-Induced Ventilatory Depression in Anesthetized Rats Guenther, U.; Wrigge, H.; Theuerkauf, N. Anesthesia & Analgesia, Vol. 111, Issue 4 https://doi.org/10.1213/ANE.0b013e3181eac011	journal	October 2010
An Efficient, Optimized Synthesis of Fentanyl and Related Analogs Valdez, Carlos A.; Leif, Roald N.; Mayer, Brian P. PLoS ONE, Vol. 9, Issue 9 https://doi.org/10.1371/journal.pone.0108250	journal	September 2014
Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse Raleigh, M. D.; Peterson, S. J.; Laudenbach, M. PLOS ONE, Vol. 12, Issue 12 https://doi.org/10.1371/journal.pone.0184876	journal	December 2017
Comprehensive molecular pharmacology screening reveals potential new receptor interactions for clinically relevant opioids Olson, Keith M.; Duron, David I.; Womer, Daniel PLOS ONE, Vol. 14, Issue 6 https://doi.org/10.1371/journal.pone.0217371	journal	June 2019
From Receptor Selectivity to Functional Selectivity: The Rise of Biased Agonism in 5-HT1A Receptor Drug Discovery Sniecikowska, Joanna; Newman-Tancredi, Adrian; Kolaczkowski, Marcin Current Topics in Medicinal Chemistry, Vol. 19, Issue 26 https://doi.org/10.2174/1568026619666190911122040	journal	December 2019
The Frequency of Naive and Early-Activated Hapten-Specific B Cell Subsets Dictates the Efficacy of a Therapeutic Vaccine against Prescription Opioid Abuse Laudenbach, Megan; Baruffaldi, Federico; Vervacke, Jeffrey S. The Journal of Immunology, Vol. 194, Issue 12 https://doi.org/10.4049/jimmunol.1500385	journal	June 2015
When Epidemics Collide: Coronavirus Disease 2019 (COVID-19) and the Opioid Crisis Becker, William C.; Fiellin, David A. Annals of Internal Medicine, Vol. 173, Issue 1 https://doi.org/10.7326/M20-1210	journal	July 2020

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