Page 91 - ITPS-8-1

INNOSC Theranostics and
Pharmacological Sciences Brain glutamate level after treatment with NAC

Placebo NAC glutamate. NAC can cross the blood–brain barrier and
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25.51±3.05 enhance extraneuronal cysteine levels. An antiporter
24.15±3.66 23.65±2.20
25 predominantly found on glial cells facilitates the reverse
25.07±2.21 transfer of glutamate and cysteine. This will increase the
20 21.96±3.53 presence of free glutamate in the extracellular extrasynaptic
YBOCS score 15 17.53±5.20 region. When inhibitory metabotropic glutamate receptors
(group 2) on nerve terminals are stimulated, extrasynaptic
glutamate can decrease the release of synaptic glutamate.
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10
Second, NAC acts in general antioxidant activities via
5 metabolic assistance to GSH formation by supplying
an extra concentration of cysteine. Increased GSH
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0
Baseline 4 weeks 10 weeks availability reduces oxidative and nitrosative stress, and
Time consequently cell damage, by scavenging toxic by-products
of glutamatergic and dopamine metabolism. NAC
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Figure 2. Changes in the Y-BOCS score over time in the placebo and
NAC arms improves the removal of synaptic glutamate in the central
Abbreviations: Y-BOCS: Yale–Brown obsessive–compulsive scale; nervous system by sparing glial cells from glutamate
NAC: N-acetylcysteine. toxicity. The anti-inflammatory effects of NAC are
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possibly the other mechanism underlying its benefits for
Table 4. Adverse effects in the placebo and NAC arms during OCD. In addition to a few studies that demonstrated the
treatment ability of NAC to reduce some inflammatory cytokines,
such as interleukin-6 and tumor necrosis factor-α, this
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Adverse Placebo+SSRI NAC+SSRI P x
effect (n=27) (%) (n=27) (%) idea was derived from the underlying role of inflammatory
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Constipation 2 (7.69) 1 (3.84) 0.89 cytokines in some psychiatric disorders, including OCD.
Dizziness 1 (3.84) 1 (3.84) Herein, after unblinding, no significant differences
Headache 2 (7.69) 1 (3.84) were observed in age or sex between the placebo and NAC
Insomnia 2 (7.69) 1 (3.84) arms. After 4 weeks, daily administration of NAC resulted
in a significant reduction of the Y-BOCS score in the NAC
Diarrhea 1 (3.84) 2 (7.69) arm; however, no reduction was noted in the placebo arm,
Nausea 1 (3.84) 2 (7.69) and a significant difference was noted between the placebo
Note: Chi-square (χ ) test was done. and NAC arms. Considerably, the improvement attributed
2
x
Abbreviations: NAC: N-acetylcysteine; SSRI: Selective serotonin to the addition of NAC is significant after 4 weeks. After
reuptake inhibitor. 10 weeks, this reduction was even greater, with an average
reduction of 8.4 points from baseline, and the difference
of patients in the NAC arm compared with those in the between the placebo and NAC arms was significant. Herein,
placebo arm during the trial. NAC was more effective than placebo in lowering the
Recently, the role of glutamate signaling pathways in severity of OCD symptoms. Furthermore, after 10 weeks
the pathophysiology of OCD has been recognized. 37,58 of follow-up, over half of the patients in the NAC arm
Consequently, the use of medicines that modulate demonstrated full clinical response, which was more than
glutamate levels has been proposed as a new approach that of the placebo arm. This finding was consistent with
to treating OCD. Despite the lack of studies in this area, the results of prior clinical trials and case reports on the
two studies explored the use of glutamate-modulating efficacy of NAC. 48,50,52,54 This may be due to the same NAC
medications as a monotherapy or augmentation strategy in doses and study duration. This finding was inconsistent
the OCDtreatment. Considering the neurotransmission- with those of other studies, 46,49,51 potentially due to the
10
regulating qualities of NAC and the involvement of longer OCD duration, comorbidities, and treatment-
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oxidative stress in psychological illnesses, NAC was resistant OCD. Previous studies involving patients with
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suggested as a psychoactive substance and was studied substance use disorders, addiction, and depression have
for various psychological disorders. NAC targets the produced conflicting results regarding the effectiveness of
44
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glutamatergic system and improves the general condition NAC as augmentation therapy. Herein, the findings did
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of patients with OCD. Despite the limited studies on its not align with those of another case series, which may be
effect on OCD symptoms, NAC is reasonably available and due to the presence of refractory OCD in the case series.
safe. 61,62 To our understanding, NAC affects the severity of Furthermore, this study analyzed the adverse effects
OCD symptoms in three mechanisms. First, it can modulate of NAC on OCD symptoms. NAC was well-tolerated. No
Volume 8 Issue 1 (2025) 85 doi: 10.36922/itps.4887