Cited by 243Substance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on BehaviorOpioid Use Disorder Treatment

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Pharmacological approaches to methamphetamine dependence: a focused review

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Karila, Laurent, Weinstein, Aviv, Aubin, Henri‐Jean, Benyamina, Amine, Reynaud, Michel, Batki, Steven L.·2010·British Journal of Clinical Pharmacology

DOI 10.1111/j.1365-2125.2010.03639.xPMC PMC2883750

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Abstract

Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double‐blind placebo‐controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d‐amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.

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Wong, C., Lee, Y., Chiang, Y., Fan, L., Ho, I.-K., & Tien, L. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.10.027 · Cited by 28
Methanolic extract of Morinda citrifolia Linn. unripe fruit attenuates methamphetamine-induced conditioned place preferences in mice
Pandy, V., Wai, Y. C., Roslan, N. F. A., Sajat, A., Jallb, A. H. A., & Vijeepallam, K. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.08.008 · Cited by 28
Outcomes of compulsory detention compared to community-based voluntary methadone maintenance treatment in Vietnam
Vuong, T. T. A., Ritter, A. J., Shanahan, M., Ali, R., Nguyen, N. T., Pham, K., Vuong, T. T. A., & Giang, L. M. (2018) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2018.01.011 · Cited by 27
“There is currently no proven effective medication/pharmacotherapy treatment for methamphetamine dependence (Karila et al., 2010; Anderson et al., 2015) and this lack of treatment option is causingmuch concern in the region.”
Background
Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression
Jiang, M., Chen, Y., Li, C., Peng, Q., Fang, M., Liu, W., Qun-zhao, K., Lin, Y., Yung, K. K. L., & Mo, Z. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.03.004 · Cited by 27
Goofballing of Opioid and Methamphetamine: The Science Behind the Deadly Cocktail
Hazani, H. M., Mohamed, I. N., Mustapha, M., Mohamed, W. M. Y., Yahaya, M. F., Teoh, S. L., Mohamed, R. M. P., Isa, M. F. M., Abdulrahman, S. M., Ramadah, R., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.859563 · Cited by 25
Bioenergetics Failure and Oxidative Stress in Brain Stem Mediates Cardiovascular Collapse Associated with Fatal Methamphetamine Intoxication
Li, F. C. H., Yen, J., Chan, S. H. H., & Chang, A. Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030589 · Cited by 26
Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats
Reichel, C. M., & See, R. E. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000988 · Cited by 26
“To date, no approved medications exist for Meth dependence, although multiple compounds have been suggested (Karila et al. 2010; Ling et al. 2006; Rose & Grant, 2008 ; Vocci & Appel, 2007).”
Background
The Effects of Methylphenidate on Cognitive Control in Active Methamphetamine Dependence Using Functional Magnetic Resonance Imaging
Jan, R. K., Lin, J. C., McLaren, D. G., Kirk, I. J., Kydd, R. R., & Russell, B. R. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00020 · Cited by 26
Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines
Tungkum, W., Jumnongprakhon, P., Tocharus, C., Govitrapong, P., & Tocharus, J. (2017) · The Journal of Toxicological Sciences · doi:10.2131/jts.42.63 · Cited by 26
“Methamphetamine (METH) is one of most prevalent addictive central nervous system (CNS) stimulant drugs (Cruickshank and Dyer, 2009; Krasnova and Cadet 2009; Karila et al., 2010; Marshall and O’Dell, 2012).”
Protective Effect of Melatonin on Methamphetamine-Induced Apoptosis in Glioma Cell Line
Jumnongprakhon, P., Govitrapong, P., Tocharus, C., Tungkum, W., & Tocharus, J. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9419-y · Cited by 25
The effect of N-acetylcysteine or bupropion on methamphetamine self-administration and methamphetamine–triggered reinstatement of female rats
Charntikov, S., Pittenger, S. T., Pudiak, C., & Bevins, R. A. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.03.021 · Cited by 24
Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users
Marks, K. R., Lile, J. A., Stoops, W. W., & Rush, C. R. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3449-x · Cited by 24
“Despite extensive efforts by the scientific and treatment communities, an effective medication has not yet been identified for amphetamine abuse (e.g., Elkashef et al. 2008; Karila et al. 2010; Rush et al. 2009).”
Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap?
Hersey, M., Bacon, A. K., Bailey, L. G., Coggiano, M. A., Newman, A. H., Leggio, L., & Tanda, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.656475 · Cited by 25
Synthesis and Pharmacological Characterization of a Novel Sigma Receptor Ligand with Improved Metabolic Stability and Antagonistic Effects Against Methamphetamine
Seminerio, M. J., Robson, M. J., Abdelazeem, A. H., Mésangeau, C., Jamalapuram, S., Avery, B. A., McCurdy, C. R., & Matsumoto, R. R. (2011) · The AAPS Journal · doi:10.1208/s12248-011-9311-8 · Cited by 24
“One-way ANOVA confirmed that there was a significant difference between all treatment groups (F(5,41)=19.”
Influential
Role of Serine Racemase in Behavioral Sensitization in Mice after Repeated Administration of Methamphetamine
Horio, M., Kohno, M., Fujita, Y., Ishima, T., Inoue, R., Mori, H., & Hashimoto, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035494 · Cited by 23
“There is currently no standard pharmacological treatment for the wide range of symptoms associated with METH abuse [1,6,7].”
Background
Atomoxetine for amphetamine-type stimulant dependence during buprenorphine treatment: A randomized controlled trial
Schottenfeld, R. S., Chawarski, M. C., Sofuoglu, M., Chooi, W.-T., Zaharim, N. M., Yasin, M. A. M., Ahmad, I., Jaapar, S. Z. S., & Vicknasingam, B. K. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.01.017 · Cited by 23
“Through these effects, atomoxetine targets many of the core features of ADHD that are also associated with ATS use disorder and relapse risk following discontinuation of ATS use, including impairments of executive function (attention, concentration, working memory, planning, and decision-making) and emotional dysregul…”
Background
ELISA Detection of 30 New Amphetamine Designer Drugs in Whole Blood, Urine and Oral Fluid using Neogen®“Amphetamine” and “Methamphetamine/MDMA” Kits
Nieddu, M., Burrai, L., Baralla, E., Pasciu, V., Varoni, M. V., Briguglio, I., Demontis, M. P., & Boatto, G. (2016) · Journal of Analytical Toxicology · doi:10.1093/jat/bkw060 · Cited by 22
Effects of berberine hydrochloride on methamphetamine-induced anxiety behaviors and relapse in rats.
Rezaeian, L., Moghaddam, H. K., Mohseni, F., Khaksari, M., & Rafaiee, R. (2020) · PubMed Central · doi:10.22038/ijbms.2020.47285.10884 · Cited by 24
“No Food and Drug Administration (FDA)-approved drug is available to treat METH addiction and to prevent relapse (32).”
Background
Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: Low doses induce hypolocomotion
Singh, R. A. K., Kosten, T. A., Kinsey, B. M., Shen, X., Lopez, A. Y., Kosten, T. R., & Orson, F. M. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.08.013 · Cited by 22
“The effects of meth use include euphoria and many of the same stimulant effects seen with cocaine, but these effects may last much longer [reviewed in [10]].”
Background
The Mglur5 Positive Allosteric Modulator CDPPB Does not Alter Extinction or Contextual Reinstatement of Methamphetamine-Seeking Behavior in Rats
Widholm, J. J., Gass, J. T., & Cleva, R. M. (2012) · Journal of Addiction Research & Therapy · doi:10.4172/2155-6105.s1-004 · Cited by 22
“Based on these observations, it could be speculated that mGluR5 PAMs may be of limited therapeutic benefit in cue exposure-based therapies for the treatment of addiction to methamphetamine, which is characterized by high rates of relapse and a lack of approved medications for the treatment of this disorder [38-40].”
Background
Office-Based Addiction Treatment in Primary Care
Edelman, E. J., Oldfield, B. J., & Tetrault, J. M. (2018) · Medical Clinics of North America · doi:10.1016/j.mcna.2018.02.007 · Cited by 21
Dépendance à la méthamphétamine : de nombreuses conséquences et complications
Karila, L., Petit, A., Cottencin, O., & Reynaud, M. (2010) · La Presse Médicale · doi:10.1016/j.lpm.2010.09.003 · Cited by 20
“Il n’existe pas à l’heure actuelle de traitement pharmacologique validé par les autorités compétentes pour ce trouble addictif mais des pistes thérapeutiques très prometteuses régulièrement documentées dans la littérature (pour revue, voir [6]).”
Self-citation
Subjective and physiological effects of acute intranasal methamphetamine during d-amphetamine maintenance
Rush, C. R., Stoops, W. W., Lile, J. A., Glaser, P. E. A., & Hays, L. R. (2010) · Psychopharmacology · doi:10.1007/s00213-010-2067-5 · Cited by 20
“Despite intense research efforts, a widely effective pharmacotherapy has not yet been identified for methamphetamine dependence (for reviews, see Elkashef et al. 2008; Karila et al. 2010; Rush et al. 2010a; Vocci and Appel 2007).”
Comparison of demographic characteristics and psychiatric comorbidity among methamphetamine-, heroin- and methamphetamine-heroin co- dependent males in Hunan, China
Dong, H., Yang, M., Liu, L., Zhang, C., Liu, M., Shen, Y., Liu, H., & Hao, W. (2017) · BMC Psychiatry · doi:10.1186/s12888-017-1346-7 · Cited by 20
“MA and heroin differ greatly in many respects, including pharmacological features, patterns of use, clinical effects, and withdrawal symptoms [23, 26] and drug users with comorbidities have greater psychosocial and medical problems, poorer prognoses, and higher rates of relapse than those with only substance use disor…”
Background
Brain Histamine N-Methyltransferase As a Possible Target of Treatment for Methamphetamine Overdose
Kitanaka, J., Kitanaka, N., Hall, F., Uhl, G., & Takemura, M. (2016) · Drug Target Insights · doi:10.4137/dti.s38342 · Cited by 13
A Scoping Review on Cue Reactivity in Methamphetamine Use Disorder
Seow, E., Ong, W. J., Hombali, A. S., Asharani, P. V., & Subramaniam, M. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17186504 · Cited by 20
“(GABA)-ergic, and/or glutamatergic brain pathways have already been underway [19,59] and despite the increasing efforts made to review medications for the treatment of methamphetamine dependence, many of these trials failed to consider their course of action on cue-induced reactivity.”
Background
Efficacy of Repetitive Transcranial Magnetic Stimulation in Patients With Methamphetamine Use Disorder: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
Chang, C.-H., Liou, M.-F., Liu, C., Lu, W.-H., & Chen, S.-J. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.904252 · Cited by 19
Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine
Marks, K. R., Lile, J. A., Stoops, W. W., Glaser, P. E. A., Hays, L. R., & Rush, C. R. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000488 · Cited by 19
Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake
Eastwood, E., & Phillips, T. J. (2013) · Genes Brain & Behavior · doi:10.1111/gbb.12100 · Cited by 19
“Although several pharmacological treatments to reduce MA use and dependence have been studied, effectiveness has been low (Karila et al. 2010).”
The role of thioredoxin-1 in resisting methamphetamine-induced rewarding effect
Huang, M., Kong, L., Yang, L., Li, X., Zhou, X., Li, Y., & Bai, J. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.047 · Cited by 18
“DA is thought to mediate the rewarding effects of psychostimulants, which lead to drug dependence [8], thus blocking the pronounced release of DA by METH may therefore be an effective therapeutic option for the treatment of METH dependence [9].”
Neural mechanisms linked to treatment outcomes and recovery in substance-related and addictive disorders
Mestre‐Bach, G., & Potenza, M. N. (2023) · Dialogues in Clinical Neuroscience · doi:10.1080/19585969.2023.2242359 · Cited by 21
“cations like d-amphetamine and methylphenidate, although none have formal indications (Karila et al. 2010).”
Background
Addiction à la cocaïne et aux psychostimulants
Lacoste, J., Delavenne, H., Charles‐Nicolas, A., Garcia, F. D., & Jehel, L. (2012) · La Presse Médicale · doi:10.1016/j.lpm.2012.07.013 · Cited by 18
Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug
Vilca, S. J., Margetts, A. V., Höglund, L., Fleites, I., Bystrom, L. L., Pollock, T. A., Bourgain‐Guglielmetti, F., Wahlestedt, C., & Tuesta, L. M. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.05.038 · Cited by 19
“Sex is an important consideration when studying MUD (McHugh et al., 2018).”
Influential
Differential behavioral responses of the spontaneously hypertensive rat to methylphenidate and methamphetamine: lack of a rewarding effect of repeated methylphenidate treatment
Peña, I. D., Lee, J. C., Lee, H. L., Woo, T. S., Lee, H. C., Sohn, A. R., & Cheong, J. H. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.02.090 · Cited by 17
c-Fos immunoreactivity of neural cells in intoxication due to high-dose methamphetamine
Tomita, M., Katsuyama, H., WATANABE, Y., Shibaike, Y., Yoshinari, H., Tee, J. W., Iwachidou, N., & Miyamoto, O. (2013) · The Journal of Toxicological Sciences · doi:10.2131/jts.38.671 · Cited by 16
“Methamphetamine (METH) possesses high potential for abuse and addiction, and METH use has become a serious social problem worldwide (Maxwell and Rutkowski, 2008; Karila et al., 2010).”
Background
Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance
Lile, J. A., Stoops, W. W., Glaser, P. E. A., Hays, L. R., & Rush, C. R. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.06.006 · Cited by 16
“Efforts are ongoing to develop a medication for methamphetamine-use disorders that would reduce this publichealth burden, but a widely accepted, effective pharmacotherapy has not been identified (Elkashef et al., 2008; Karila et al. 2010; Rush et al., 2010a; Vocci and Appel, 2007).”
Background
The effect of VMAT2 inhibitor GZ-793A on the reinstatement of methamphetamine-seeking in rats
Alvers, K. M., Beckmann, J. S., Zheng, G., Crooks, P. A., Dwoskin, L. P., & Bardo, M. T. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2748-3 · Cited by 16
“Some dopaminergic agents have shown moderate success in reducing METH use (bupropion, modafinil, risperidone, and D-amphetamine), but overall, evidence for efficacious treatment is weak (Karila et al. 2010).”
Immunopharmacotherapeutic advancements in addressing methamphetamine abuse
Lee, J. C., & Janda, K. D. (2020) · RSC Chemical Biology · doi:10.1039/d0cb00165a · Cited by 16
Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals
Bolin, B. L., Stoops, W. W., Sites, J. P., & Rush, C. R. (2016) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000000206 · Cited by 15
“INTRODUCTION T he identification of putative pharmacotherapies to manage cocaine-use disorders is a high priority (Kampman, 2008; Montoya and Vocci, 2008), but few promising medications have been identified, and even the most promising candidates demonstrate limited efficacy (Elkashef et al., 2008; Herin et al., 2010;…”
Background
Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice
Kitanaka, N., Kitanaka, J., Hall, F. S., Uhl, G. R., Watabe, K., Kubo, H., Takahashi, H., Tanaka, K.-I., Nishiyama, N., & Takemura, M. (2014) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000030 · Cited by 15
“To date, there remain no effective pharmacotherapies for treating METH-induced psychotic symptoms, which include paranoia, hallucinations, delusions, and bizarre behaviors (Kantak, 2003; Karila et al., 2010).”
Background
Investigating Methamphetamine Craving Using the Extinction-Reinstatement Model in the Rat
Kufahl, P. R., & Olive, M. F. (2012) · Journal of Addiction Research & Therapy · doi:10.4172/2155-6105.s1-003 · Cited by 15
“Finally, it is worth noting that the compounds evaluated so far represent a partial overlap of the total number of drugs actively being researched in clinical studies for the same ultimate purpose [179].”
Background
Methamphetamine Dependency
Lashkaripour, K., & Torbati, E. (2012) · international journal high risk behaviors & addiction · doi:10.5812/ijhrba.5336 · Cited by 15

Authors: Karila, L., Weinstein, A., Aubin, H., Benyamina, A., Reynaud, M., & Batki, S. L.
Affiliations: Inserm (FR)
Hadassah Medical Center (IL)
San Francisco VA Medical Center (US)
Corresponding author: Karila, Laurent
ORCID: Karila, Laurent
Weinstein, Aviv
Aubin, Henri‐Jean
Benyamina, Amine
Reynaud, Michel
Batki, Steven L.
Venue: British Journal of Clinical Pharmacology
Publisher: Wiley
Published: 2010-05-10
Volume: 69
Issue: 6
Pages: 578-592
ISSN: 0306-5251 (ISSN-L)
1365-2125
DOI: 10.1111/j.1365-2125.2010.03639.x
PMC: PMC2883750
OpenAlex: W1747110054
Cited by: 242
References: 135
Citations by year: 2026: 8 · 2025: 11 · 2024: 9 · 2023: 12 · 2022: 16 · 2021: 15 · 2020: 8 · 2019: 13 · 2018: 20 · 2017: 15 · 2016: 18 · 2015: 12 · 2014: 16 · 2013: 18 · 2012: 29
FWCI: 2.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: British Journal of Clinical Pharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (U10DA015815, R01DA016764, UG1DA015815)
Topics: Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords: methamphetamine dependence, pharmacotherapy, partial dopamine agonist, aripiprazole, GABAergic agents, gabapentin, serotonergic agents, modafinil, bupropion, naltrexone, d-amphetamine, methylphenidate, drug addiction
MeSH terms: Animals, Calcium Channel Blockers, Humans, Immunotherapy, Methamphetamine, Narcotic Antagonists, Antipsychotic Agents, Neurotransmitter Agents, Amphetamine-Related Disorders, Rats

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Pharmacological approaches to methamphetamine dependence: a focused review

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