Table 1.
MRS and PET glutamate studies in drug addiction.
| Reference | Sample | Mean Age (SD) |
Sex | Mean Abst Duration (SD) |
Medication and/or Tx |
Other Drug Use |
Psychiatric or Medical |
Regions of Interest |
Imaging Method |
Primary Glutamate Imaging Outcome (vs Controls) |
Clinical or Neuropsych Correlates |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Alcohol | |||||||||||
| (Bagga et al., 2014) | 35 AUD 35 HC |
36.5 (5) 35.2 (3.7) |
35M/0F 35M/0F |
17.5 (4.3) d | NR | NR | NR | R Occip | MRS | ↓ Glu-Gln/Cr | AUD: ↓ Glu-Gln/Cr corr ↓ visual-motor functioning |
| (Bauer et al., 2013) | 29 AUD 31 HC |
29M/0F 31M/0F |
40.2 (7.5) 36.6 (10.1) |
≤ 10 d | Inpatient Detox; Benzos |
Nic | NR | pACC, VS | MRS | ↑ VS Glu | AUD: ↑ VS & ACC Glx corr ↑ craving |
| (Ende et al., 2013) | 21 AUD 9 HC |
13M/8F 8M/1F |
48.5 (10.7) 40.9 (4.5) |
Unspec | NR | Nic | NR | dACC into adjacent WM) |
MRS | NS Glu (modulation by loss of control) |
AUD: ↑ Glu corr ↓Alc severity |
| (Hermann et al., 2012b) | 47 AUD 57 HC |
46.3 (1.5) 45.1 (1.5) |
38M/9F 44M/13F |
1 d, 14 d (within) |
Inpatient Detox; clonidine, Benzos |
Nic | NR | ACC | MRS | 1 d: ↑Glu | AUD, 1 d: ↑ Glu corr ↑ breath Alc & 3-mo severity |
| (Jalan et al., 2000) | 6 AUD 11 HC |
61 55 |
4M/2F 8M/3F |
≥ 6 mo | NR | NR | Cirrhosis | Cereb, Cerebel, BG |
MRS | ↑ Glx/Cr | NA |
| Lee et al., 2007) | 13 AUD 18 HC |
33.8 (5.8) 32.9 (0.9) |
13M/0F 18M/0F |
15.5 d (min 14 d) |
Thiamine | Nic | NR | ACC, Ins | MRS | ↑ ACC Glu/Cr | ↑ ACC Glu/Cr corr ↑ memory & recent Alc use |
| (Miese et al., 2006) | 26 AUD 18 HC |
61.1 (12.4) 54.3 (12.7) |
18M/8M 14M/5M |
During study (Unspec) |
NR | NR | Cirrhosis | BG, Occip |
MRS | ↑ Glx/Cr | NA |
| (Mon et al., 2012) | 44 AUD 16 HC |
53.9 (8.8) 49.0 (10.1) |
39M/5F 14M/2F |
TP1: 9 (4) TP2: 34 (7) |
VA Medical Center, Other Tx; Benzos |
Nic | Hep C, type 2 diabetes, ↑ BP, depress |
pACC, DLPFC, Occip |
MRS | ↓ ACC Glu | ↑ ACC Glu corr ↑ Abst |
| (Nery et al., 2010) | 22 AUD 54 HC |
39.1 (11.4) 38.7 (12.4) |
6M/16F 14M/40F |
6.8 (6.5) y | Lithium, AntiDepress, antiPsy, Benzos |
Mari, Coc, Stim, opioids |
Bipolar, anxiety | DLPFC | MRS | NS Glu, Glx | NS |
| (Pennington et al., 2014) | 10 AUD 28 PTSD 20 HC |
51.9 (13.9) 35.4 (10.5) 36.3 (12.4) |
10M/0F 28M/0F 20M/0F |
NS | VA Medical Center |
NR | AUD also had PTSD |
ACC Occip Temp |
MRS | ↓Glu | AUD: ↑ Glu corr ↑ divided attention |
| (Seitz et al., 1999) | 11 AUD 10 HC |
44 (10) 38 (12) |
8M/3F 9M/3F |
3–6 d | Inpatient Detox |
NR | Frontal & cerebellar atrophy |
Vermis | MRS | NS Glx/Cr | NA |
| (Thoma et al., 2011) | 7 AUD 6 AUD Abst 17 HC |
35.5 (8.2) 35.4 (5.7) 32.3 (7.9) |
5M/2F 5M/1F 9M/8F |
≥48 h | University Tx | Nic, sedatives, Marij, opioids, Coc, Halluc |
Abnormal liver function, bipolar, Depress, Psy, anxiety, OCD, PTSD, phobias |
dACC | MRS | ↓Glu (AD Abst only), ↑ Gln (AD only) |
AUD: ↓Glu corr ↑drinking consequences |
| (Yeo et al., 2013) | 213 AUD 66 HC |
31.0 (9.0) 29.5 (8.3) |
153M/60F 37M/29F |
≥24 h | Unspec Tx (n=97/213) |
Nic, Marij | Depres | dACC | MRS | NS Glu-Gln | ↑ Glu-Gln corr ↑ years drinking & ↑ smoking severity |
| Nicotine/Smoking | |||||||||||
| (Akkus et al., 2013) | 14 SM 14 SM Abst 14 HC |
36.1 (10.2) 37.7 (10.1) 36.8 (9.6) |
6M/8F 8M/6F 6M/8F |
None 25.0 (19.4) |
NR | NR | Depress, anorexia |
6 Cereb, 3 Limbic, STR, Thal, 1 brainste m |
PET [11C]ABP6 88 |
↓ DVR Amyg, Striat (caudate), PFC, Temp, PCC |
Sh Abst: ↓ BPND brainstem corr ↑ cigs per day |
| (Akkus et al., 2015) | 14 SM 14 Sh Abst 14 Lg Abst 14 HC |
36.1 (10.2) 37.7 (10.1) 37.8 (10.1) 36.8 (9.6) |
6M/8F 8M/6F 8M/6F 6M/8F |
None 25.0 (19.4) 473.6 (336.1) |
NR | NR | Depress, anorexia |
6 Cereb, 3 Limbic, STR, Thal |
PET [11C]ABP6 88 |
↓ BPND ACC, Temp, MedOFC (SM, Sh Abst only) |
NS |
| (Durazzo et al., 2015) | 35 SM 30 HC |
48.6 (10.1) 49.1 (12.0) |
26M/4F 31M/4F |
Unspec | NR | Alc | NR | pACC, DLPFC |
MRS | ↓ Glu (acceleration with ↑ age) |
All: ↑ DLPFC Glu corr ↑ NP function |
| (Gallinat and Schubert, 2007) | 13 SM 9 SM Abst 16 HC |
35.4 (10.0) 41.5 (9.7) 32.8 (9.6) |
5M/8F 5M/4F 8M/8F |
None 16.5 (2.9) y |
NR | Alc | NR | ACC, Hipp |
MRS | NS Glu | NS |
| (Gutzeit et al., 2013) | 14 SM 10 HC |
50.4 (12.6) 36.6 (9.2) |
14M/0F 10M/0F |
None, 24 h (within) |
NR | NR | NR | Ins | MRS | ↑ Gln (withdrawal) |
NA |
| (Mennecke et al., 2014) | 12 SM 12 HC |
25.7 (3.1) 26.2 (2.7) |
6M/6W 6M/6W |
None, 3 d (within) |
NR | NR | NR | dACC, Hipp |
MRS | ↑ left dACC Glx/Cr |
NA |
| (O’Neill et al., 2014) | 18 SM 16 HC |
35.4 (2.1) 33.2 (2.6) |
11M/7F 8M/8F |
Unspec | NR | Marij, Alc, anorexia |
NR | Thal | MRS | NS Glu | SM: ↓ Glu & Glx corr ↑ Cigarettes/day and pack-years |
| Opiates | |||||||||||
| (Greenwald et al., 2015) | 7 HD 5 HC |
42.4 (7.5) 45.2 (7.2) |
6M/1F 3M/2F |
Unspec | Methadone (high vs. low, within) |
Nic | NR | pACC, Thal |
MRS | NS Glu (versus either methadone dose) |
NS |
| (Hermann et al., 2012a) | 17 HD 20 HC |
36.9 (9.7) 36.4 (10.3) |
11M/6F 13M/9F |
Unspec | Opiate maintenance |
Marij, Alc, Benzos, Amph, MDMA |
NR | dACC | MRS | NS Glu or Glx (moderation by age) |
HD: ↑ Glu & Glx corr ↑ #withdrawals |
| (Verdejo-Garcia et al., 2013) | 24 HD 24 HC |
29.8 (6.9) 29.6 (6.5) |
13M/11F 13M/11F |
≥24 h | Methadone (n=10), Bup (n=14) |
Marij, benzos, heroin |
NR | dACC | MRS | ↓ Glx (hemisphere x medication effects) |
HD: ↑ Glx corr ↑ methadone dose |
| (Yücel et al., 2007) | 24 HD 24 HC |
29.8 (6.9) 29.6 (6.5) |
13M/11F 13M/11F |
≥24 h | Methadone (n=10), Bup (n=14) |
Marij, Benzos, heroin |
NR | dACC | MRS | ↓ Glx (across medication) |
NS |
| Cocaine | |||||||||||
| (Chang et al., 1997) | 11 CD 16 HC |
32.0 (7.9) 32.6 (9.1) |
26M/0F 26M/0F |
66.4 (26.2) mo | NR | Alc, Marij, Amph, PCP |
NR | Mid Occip |
MRS | NS Glx/Cr | CD: ↓ Glx corr ↓ Coc use yrs |
| (Hulka et al., 2014a) | 18 CD 18 HC |
36.2 (7.6) 35.8 (8.3) |
18M/0F 18M/0F |
7.6 (6.8) d | NR | Nic, Alc, Marij, MDMA |
Depress | pACC, R DLPFC |
MRS | NS Glu/Cr or Gln/Cr |
CD: ↓ pACC Gln/Cr corr ↑ Coc frequency |
| (Martinez et al., 2014) | 15 CD 14 HC |
43 (3) 41 (4) |
14M/1F 13M/1F |
10–14 d | University Inpatient |
Nic | NR | STR | MRS; PET [11C]ABP6 88 |
↓ BPND VS, putamen; NS Glx/H2O |
NS |
| (Milella et al., 2014) | 9 CD 9 HC |
37.7 (8.7) 37.2 (8.8) |
7M/2F 6M/3F |
5.7 (4.1) d | NR | Nic, Alc, Marij |
NR | 3 STR, 4 PFC, 4 Limbic |
PET [11C]ABP6 88 |
↓ BPND striatum, Amyg, Ins |
↓ BPND striatum, Amyg, Ins |
| (Yang et al., 2009) | 14 CD 14 HC |
37 (4.9) 34 (9.0) |
10M/4F 7M/7F |
44 (21) h | NR | Nic | NR | pACC | MRS | ↓Glu/Cr | ↓ Glu/Cr corr ↓ Coc use yrs |
| Methamphetamine | |||||||||||
| (Crocker et al., 2014) | 29 MA 29 Psy 45 HC |
25.6 (2.6) 21.9 (3.4) 22.4 (3.3) |
18M/11F 23M/6F 36M/9F |
370 d (median) |
Unspec Tx; Psy: Antipsychotic |
NR | NR | ACC / MedPFC |
MRS | ↓ Glu | NS |
| (Ernst and Chang, 2008) | 25 MA 28 HC |
31.8 (7.4) 32.6 (8.8) |
11M/14W 14M/14W |
2.1 (3.0) mo | Unspec Tx | Nic | NR | PFC, BG | MRS | ↓ PFC Glx (≤ 1 mo Abst) |
MA: ↓ PFC Glx corr ↓ Abst & ↑ craving |
| (Howells et al., 2014) | 16 MA 10 MA- Psy 19 HC |
24.0 (3.7) 24.0 (1.3) 25.0 (5.7) |
13M/3F 10M/1F 16M/3F |
56 (60) d 60 (53) d |
Unspec Rehab, Hospital; MA- Psy: Haloperidol |
Nic, Alc, Marij, Quaalude |
NR | Bilat ACC, DLPFC |
MRS | NS: Glu or Glx | NA |
| (O’Neill et al., 2015) | 44 MA 24 HC |
33.0 (9.4) 33.0 (7.4) |
25M/19F 13M/11F |
7–10 d | University Inpatient |
Nic, Marij, Alc |
NR | PCC, Precun, Bilat PFC |
MRS | ↓ Glx PCC, Precun, R PFC |
MA: ↓ Glx PCC corr ↑ use yrs |
| (Sailasuta et al., 2010) | 18 MA 22 HC |
35.0 (9.3) 31.9 (9/7) |
11M/7F 12M/10F |
3–8 wk (7), >20 wk (11) |
Rehab or “halfway house” |
Coc, Marij, Alc |
NR | Med Occip |
MRS | NS Glu | NA |
| Cannabis | |||||||||||
| (Muetzel et al., 2013) | 27 MJ 26 HC |
19.5 (0.6) 19.3 (3.1) |
16M/11F 10M/16F |
≥12 h | NR | Alc | NR | Dorsal STR |
MRS | ↓ Glx (F only) | NA |
| (Chang et al., 2006) | 24 MJ 30 HC |
36.3 (2.3) 42.2 (2.2) |
20M/4F 24M/6F |
51.8 (16.7) mo | NR | Nic, Alc, Coc | NR | BG, Thal | MRS | ↓ Glu BG | NS |
| (Prescot et al., 2011) | 17 MJ 17 HC |
17.8 (1.1) 16.2 (2.1) |
15M/2F 8M/9F |
Unspec | AntiD | Alc | Depress | ACC | MRS | ↓ Glu | NS |
| Multiple Substances | |||||||||||
| (Hulka et al., 2014b) | 18 CD 18 HC |
36.2 (7.6) 36.2 (8.4) |
18M/0W 18M/0W |
Unspec | Unspec Tx centers & hospitals |
Nic, Alc, Marij, Amph, MDMA |
Depress | 5 PFC, 2 STR, 5 limbic |
PET [11C]ABP6 88 |
↓Vnorm (all regions) in smokers (no CD effect) |
↓ Vnorm corr more recent smoking |
| (Mason et al., 2006) | 12 AD 8 HC |
39 (8.2) 39 (9.0) |
12M/0F 8M/0F |
5.0 (4.0) d | Inpatient Tx | Marij, Nic, Coc |
NR | Occip | MRS | NS Glx; AD: ↑ Glx SM versus non-SM |
NA |
Abbreviations: (p or d)ACC = (pregenual or dorsal) anterior cingulate cortex, Abst = abstinence, Alc = alcohol, AntiD = antidepressant medication, Approx = approximated values, AUD = alcohol use disorder, Amyg = amygdala, Amph = amphetamine, BG = basal ganglia, Benzos = benzodiazepines, BP = blood pressure, Bup = buprenorphine, Cereb = cerebral cortex, Coc = cocaine, corr = was correlated with, Cr = creatine, Depress = depression, Detox = detoxification program, F= females, GM = gray matter, Glu = glutamate, Hall = hallucinogen use disorder, Hipp = hippocampus, Ins = insula, Lg = long, M = males, MA = methamphetamine use disorder, MJ = marijuana, MDMA = ecstasy, Med = medial, Mid = middle, MJ = marijuana use disorder, mo = month, MRS = magnetic resonance spectroscopy, NA = not applicable, Nic = nicotine, NR = none reported, NS = not significant, Occip = occipital lobe, OCD = obsessive compulsive disorder, OFC = orbitofrontal cortex, ParHipp = parahippocampal gyrus, Pariet = parietal cortex, PET = positron emission tomography, PFC = prefrontal cortex, Pos = posterior, PS = polysubstance users, Psy = psychosis, PTSD, posttraumatic stress disorder, R =right, Sh = short, SM = smoker, Stim = stimulants, STR = striatum, Subco = subcortical regions, Temp = temporal cortex, Thal = thalamus, TP = time point, Tx = treatment, Unspec = unspecified, VS = ventral striatum, wk = week