Decreased dopamine activity predicts relapse in methamphetamine abusers
Open accessAbstract
Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.
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Decreased dopamine activity and receptor supersensitivity during psychostimulant withdrawal are biological factors that correspond with likelihood of return to use during treatment.
“Furthermore, decreased dopamine activity and receptor supersensitivity during psychostimulant withdrawal are biological factors that correspond with likelihood of return to use during treatment (20).”
From Clinical management of psychostimulant withdrawal: review of the evidence (2023) · cites this paper as [20]
The Conclusion reports that methamphetamine users with poorer dopamine function during early withdrawal were more likely to relapse at follow-up. The Results also report lower D2 receptor availability among those who relapsed. Neither passage establishes receptor supersensitivity as a factor associated with return to use. (LLM, conf=0.89)
Experimental — accuracy not yet measuredMethamphetamine-dependent individuals with striatal D2 receptor availability in the normal range had better treatment outcomes, potentially reflecting greater ability to acquire new reward-related behaviours and pursue healthy goals.
“Methamphetamine-dependent individuals with striatal D2 receptor availability within the normal range had better treatment outcomes, potentially reflecting a greater ability to acquire new reward-related behaviours and the pursuit of healthy goals.126”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [126]
Factors associated with returning to use include injecting drugs, having a parent with alcohol or substance use disorder, low striatal dopamine (DA D2) receptor availability, and experience of stress.
“Factors associated with returning to use include injecting drugs (91), having a parent with alcohol or substance use disorder (92), low striatal dopamine (DA D2) receptor availability (20), and experience of stress (93).”
From Clinical management of psychostimulant withdrawal: review of the evidence (2023) · cites this paper as [20]
Blunted stimulant-induced dopamine release has been shown in cocaine abuse, alcohol dependence, opiate dependence, methamphetamine abuse, and cigarette smoking.
“This finding has been shown in cocaine abuse (Malison et al., 1999; Martinez et al., 2011; Martinez et al., 2007; Volkow et al., 1997), alcohol dependence (Martinez et al., 2005; Volkow et al., 2007b), opiate dependence (Martinez et al., 2012), methamphetamine abuse (Wang et al., 2012), and cigarette smoking (Busto et al., 2009)”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Wang et al., 2012
In both studies, treatment responders did not differ from controls in measures of D2 receptor levels or dopamine release.
“Importantly, in both studies the subjects who responded to treatment did not differ from the control group in measures of D2 receptors levels or dopamine release.”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Wang et al., 2012
Methamphetamine-abusing subjects who successfully maintained abstinence had higher D2 receptor binding and dopamine release than those who did not respond to treatment.
“The results showed that the methamphetamine-abusing subjects who successfully maintained abstinence had higher values for both D2 receptor binding and dopamine release, compared to methamphetamine abusers who did not respond to treatment (Wang et al., 2012).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Wang et al., 2012
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References 39 · Cited by 214
- Authors
- Wang, G. J., Smith, L., Volkow, N. D., Telang, F., Logan, J., Tomasi, D., Wong, C. T., Hoffman, W., Jayne, M., Alia-Klein, N., Thanos, P., & Fowler, J. S.
- Affiliations
- Brookhaven National Laboratory (US)
- University of California, Los Angeles (US)
- National Institute on Drug Abuse (US)
- National Institute on Alcohol Abuse and Alcoholism (US)
- Portland VA Medical Center (US)
- Corresponding author
- Wang, G J
- Venue
- Molecular Psychiatry
- Published
- 2011-07-12
- Volume
- 17
- Issue
- 9
- Pages
- 918-925
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3261322
- OpenAlex
- W1995122212
- Cited by
- 214
- References
- 39
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 15 · 2021: 13 · 2020: 12 · 2019: 16 · 2018: 10 · 2017: 15 · 2016: 20 · 2015: 22 · 2014: 29 · 2013: 28 · 2012: 10
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000124)
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000550, ZIAAA000550)
- National Institute on Drug Abuse (R01DA006891)
- National Center for Research Resources (M01RR010710, MO1 RR10710)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- methamphetamine abuse, dopamine, striatum, recurrence prediction, caudate nucleus, putamen, abstinence, detoxification
- MeSH terms
- Adult, Carbon Radioisotopes, Corpus Striatum, Dopamine, Female, Humans, Male, Methamphetamine, Methylphenidate, Recurrence, Time Factors, Case-Control Studies, Receptors, Dopamine D2, Amphetamine-Related Disorders, Raclopride, Positron-Emission Tomography
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