Acetyl-L-carnitine and Mental Health A meta-analysis demonstrated that the administration of acetyl-L-carnitine (ALCAR) (vs. placebo) is associated with a significant decrease in depressive symptoms. The effectiveness of ALCAR as an adjunctive agent to standard ADs has not been tested so far in clinical studies but results of another meta-analysis of three RCTs (two of them included people with dysthymia, while one of them included people with fibromyalgia) indicated that ALCAR confers a comparable effect to standard ADs in alleviating depressive symptoms ALCAR is compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating dementia, depression, chronic fatigue syndrome, peripheral neuropathies and cognitive impairment associated with various conditions. ALCAR has been proposed as a valid treatment strategy for anhedonia in abstinent substance-use disorder - highly tolerated and generally without any adverse effects - neuroprotective, neurotrophic, antidepressive and analgesic effects - promising antidepressant-like effects preclinically and clinically, exerts rapid-acting antidepressant-like effects (epigenetic). - increase neurogenesis in prefrontal–limbic areas - positive effects on mitochondrial metabolism - Enhancement of dopamine release (including in the nucleus accumbens where it persistently increases dopamine outflow in the NAc) and positive effect on age-related changes in the dopaminergic system - efficacy and safety of ALCAR (particularly IV) in the treatment of anhedonia, melancholia, and negative symptoms in abstinent anhedonic alcoholics - increases NGF production and NGF binding in vivo - exerts a cholinergic effect 1 -modulates the release of monoaminergic neurotransmitters and the biosynthesis and release of glutamate with effects on serotonergic, noradrenergic and GABA neurotransmission - administration of ALCAR increases β-endorphin and cortisol plasma levels in healthy subjects, and normalises them in patients with dementia - good tolerability and efficacy in dysthymic disorder and on depressive symptoms - Potential role in reversing stress-induced deficits in social avoidance and alterations to the nucleus accumbens (increased dopamine and serotonin output in the nucleus accumbens shell) In cognitive impairment: - positive cognitive and behavioral effects, slows the progression in cognitive deterioration and behavioral disturbances 2