The abuse of, and addiction to, d-methamphetamine (METH) interferes with many aspects of personal health, vocational performance, interpersonal relationships and financial well being. Behavioral consequences of METH abuse and the METH trade also strain legal and emergency medical resources throughout the US. METH is therefore a significant and continuing public health concern. Current therapeutic approaches for METH addiction are less than completely effective and no approved pharmacotherapies for METH addiction exist. Recent successes in early clinical trials using immunotherapeutic approaches for cocaine and nicotine addiction have motivated interest in creating similar approaches for methamphetamine addiction. Work under the initial funding interval of this project has created the MH6 vaccine which was shown to generate antibodies which sequester METH in the blood. The vaccine also attenuated METH effects on locomotor activity, thermoregulation and intravenous self-administration of METH. New studies seek to optimize the vaccine for higher antibody titer by determining effects of different carrier proteins and adjuvants. Studies in rats will use converging models of drug-related reward, including intracranial self-stimulation reward and the dopamine response in the nucleus accumbens shell, to determine how the vaccine alters the acquisition of self- administration. Additional work will determine if an optimized vaccine can prevent the escalation to unregulated METH intake using a long-access procedure and if the vaccine can reverse an established self-administration pattern. Together these studies will make significant progress on optimizing both the design and likely translational application of an anti-METH vaccine.

Public Health Relevance

Methamphetamine (METH) abuse and dependence continues to be a significant problem for personal health and well-being as well as a challenge for public health and law enforcement. Current treatment options for substance abuse have limited effect but recent vaccination strategies have shown promise. Thus the proposed studies to generate vaccines against METH have the potential to improve the treatment of METH addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA024705-06A1
Application #
8636303
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Chiang, Nora
Project Start
2008-08-15
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
6
Fiscal Year
2014
Total Cost
$473,750
Indirect Cost
$223,750
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Javadi-Paydar, Mehrak; Nguyen, Jacques D; Vandewater, Sophia A et al. (2018) Locomotor and reinforcing effects of pentedrone, pentylone and methylone in rats. Neuropharmacology 134:57-64
Aarde, Shawn M; Taffe, Michael A (2017) Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration. Curr Top Behav Neurosci 32:145-164
Gooyit, Major; Miranda, Pedro O; Wenthur, Cody J et al. (2017) Influencing Antibody-Mediated Attenuation of Methamphetamine CNS Distribution through Vaccine Linker Design. ACS Chem Neurosci 8:468-472
Nguyen, Jacques D; Bremer, Paul T; Ducime, Alex et al. (2017) Active vaccination attenuates the psychostimulant effects of ?-PVP and MDPV in rats. Neuropharmacology 116:1-8
Nguyen, J D; Bremer, P T; Hwang, C S et al. (2017) Effective active vaccination against methamphetamine in female rats. Drug Alcohol Depend 175:179-186
Wenthur, Cody J; Zhou, Bin; Janda, Kim D (2017) Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity. Nature 548:476-479
Collins, Karen C; Schlosburg, Joel E; Bremer, Paul T et al. (2016) Methamphetamine Vaccines: Improvement through Hapten Design. J Med Chem 59:3878-85
Nguyen, Jacques D; Aarde, Shawn M; Cole, Maury et al. (2016) Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology. Neuropsychopharmacology 41:2759-71
Aarde, S M; Huang, P K; Dickerson, T J et al. (2015) Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats. Psychopharmacology (Berl) 232:1867-77
Aarde, Shawn M; Miller, Michelle L; Creehan, Kevin M et al. (2015) One day access to a running wheel reduces self-administration of D-methamphetamine, MDMA and methylone. Drug Alcohol Depend 151:151-8

Showing the most recent 10 out of 23 publications