Mood & Anxiety Nootropics
34Mood-supporting nootropics modulate GABA, serotonin, and dopamine systems to reduce anxiety, improve emotional resilience, and support a positive mental state. These are particularly relevant for people whose cognitive performance is limited by stress or anxiety rather than raw cognitive capacity.
5-HTP
5-Hydroxytryptophan is the immediate precursor to serotonin, derived from the seeds of Griffonia simplicifolia. By providing the rate-limiting intermediate in serotonin synthesis, 5-HTP effectively raises brain serotonin levels. Used for mood support, anxiety, sleep, and appetite control. More effective than L-Tryptophan because it bypasses the rate-limiting enzyme step.
Agmatine Sulfate
A metabolite of L-arginine produced by decarboxylation. Agmatine is an endogenous neuromodulator that acts on multiple receptor systems — it blocks NMDA receptors, activates imidazoline receptors, inhibits nitric oxide synthase, and modulates opioid signaling. This makes it useful for neuropathic pain, mood, stress resilience, and as a complement to other nootropics. Also enhances insulin sensitivity and nitric oxide production.
ALCAR
Acetyl-L-Carnitine is an acetylated form of L-Carnitine that crosses the blood-brain barrier more effectively than regular L-Carnitine. In the brain, it donates its acetyl group for acetylcholine synthesis and supports mitochondrial fatty acid oxidation for energy. Used clinically for age-related cognitive decline, depression, and diabetic neuropathy.
Aniracetam
A fat-soluble racetam roughly 5-10x more potent than Piracetam by weight. Known for its anxiolytic (anti-anxiety) properties alongside cognitive enhancement — a combination that makes it popular for social situations and creative work. It modulates both glutamate and dopamine/serotonin systems, giving it a unique mood-lifting quality that other racetams lack.
Ashwagandha
An Ayurvedic adaptogen used for over 3,000 years that has become one of the most popular and well-studied supplements for stress, anxiety, and cognitive function. Ashwagandha (Withania somnifera) significantly reduces cortisol levels, improves stress resilience, and enhances memory and reaction time. KSM-66 and Sensoril are the two most studied standardized extracts.
B-Complex
The B vitamins (B1, B2, B3, B5, B6, B9, B12) are essential coenzymes in brain energy metabolism, neurotransmitter synthesis, and methylation reactions. Deficiency in any B vitamin impairs cognitive function. B12 and folate deficiency specifically cause irreversible neurological damage if untreated. A high-quality B-complex is foundational for any nootropic regimen, particularly for vegetarians, older adults, and those under chronic stress.
Black Seed Oil
Extracted from Nigella sativa seeds, black seed oil contains thymoquinone — a compound with potent anti-inflammatory, antioxidant, and neuroprotective properties. Used in traditional Middle Eastern medicine for over 2,000 years, modern research supports cognitive benefits through anti-neuroinflammation, acetylcholinesterase inhibition, and GABA modulation. Also supports metabolic health and immune function.
Emoxypine (Mexidol)
A vitamin B6 derivative with powerful antioxidant and anxiolytic properties, widely prescribed in Russia and Eastern Europe for anxiety, cognitive impairment, and cerebrovascular disease. Emoxypine inhibits lipid peroxidation, modulates GABA-A and benzodiazepine binding sites, and improves cerebral blood flow. It provides anxiolytic effects similar to benzodiazepines without sedation, tolerance, or addiction.
Fasoracetam
A newer racetam that uniquely upregulates GABA-B receptors, making it potentially useful for people who have developed tolerance to GABAergic substances like Phenibut or benzodiazepines. It also enhances glutamate and acetylcholine signaling. Being studied in clinical trials for ADHD in adolescents with specific glutamate receptor gene mutations.
GABA
Gamma-aminobutyric acid is the brain's primary inhibitory neurotransmitter. As a supplement, GABA's effectiveness is debated because it does not cross the blood-brain barrier efficiently. However, some users report calming effects, possibly through the enteric nervous system (gut-brain axis) or limited BBB penetration. Pharma-GABA (natural fermented form) may have better efficacy than synthetic GABA.
Gotu Kola
Centella asiatica is an Ayurvedic and Chinese medicine herb known as the 'herb of longevity.' It has been used for centuries to enhance memory, promote wound healing, and reduce anxiety. Modern research confirms it increases BDNF, enhances collagen synthesis, improves microcirculation, and has anxiolytic effects. Unlike most adaptogens, gotu kola has clinical evidence for improving memory and attention in healthy adults.
Holy Basil (Tulsi)
An Ayurvedic adaptogen (Ocimum tenuiflorum) revered as 'The Incomparable One' in traditional Indian medicine. Holy basil reduces cortisol, supports clear thinking under stress, and has mild anxiolytic effects. It is gentler than ashwagandha and rhodiola, making it suitable for people who find stronger adaptogens overstimulating or sedating. Often consumed as a pleasant-tasting tea.
L-Theanine
An amino acid found naturally in green tea that promotes calm focus without drowsiness. L-Theanine is one of the most popular and well-studied nootropics, famous for its synergy with caffeine — the combination provides clean, jitter-free focus that neither compound achieves alone. It crosses the blood-brain barrier and modulates alpha brain waves associated with relaxed attention.
Lemon Balm
Melissa officinalis is a member of the mint family with a long history of use for anxiety, sleep, and cognitive function. Lemon balm inhibits GABA-transaminase (the enzyme that breaks down GABA), effectively raising GABA levels in the brain. Clinical studies show it improves calmness, alertness, and memory — a rare combination of relaxation without sedation at moderate doses.
Maca Root
A cruciferous root vegetable (Lepidium meyenii) grown at high altitude in the Peruvian Andes, used for over 2,000 years for energy, stamina, and libido. Maca does not directly modulate hormones — instead it acts on the hypothalamus and pituitary to normalize endocrine function. It improves energy and mood without stimulation, making it a true adaptogen. Different colors (red, black, yellow) have different properties.
Magnesium Glycinate
A highly bioavailable form of magnesium chelated with glycine. The glycine component adds its own calming effects (inhibitory neurotransmitter), making this form particularly effective for anxiety, sleep, and stress. Better tolerated than magnesium citrate or oxide with fewer GI side effects. Magnesium deficiency affects an estimated 50-80% of adults and directly impairs cognitive function.
NAC
N-Acetyl Cysteine is a precursor to glutathione — the body's master antioxidant. In the brain, NAC provides potent neuroprotection against oxidative stress and also modulates glutamate signaling through the cystine-glutamate antiporter. It is used clinically for acetaminophen overdose and is studied for OCD, addiction, and neurodegenerative diseases.
NAC (N-Acetyl Cysteine)
The acetylated form of the amino acid L-cysteine and the most effective oral supplement for raising glutathione — the body's master antioxidant. NAC has an unusually broad range of evidence-based applications: it is used as a prescription drug for acetaminophen overdose, as a mucolytic, and as an adjunct treatment for OCD, addiction, and bipolar disorder. In nootropics, it protects neurons from oxidative stress and modulates glutamate.
Omega-3 (DHA)
DHA (docosahexaenoic acid) makes up approximately 40% of the polyunsaturated fatty acids in the brain and is essential for neuronal membrane structure, fluidity, and signaling. DHA deficiency is associated with cognitive decline, depression, and neuroinflammation. It is one of the few supplements with strong evidence for maintaining brain health across the lifespan.
PEA (Palmitoylethanolamide)
An endogenous fatty acid amide produced naturally in the body in response to pain and inflammation. PEA activates PPAR-alpha receptors and indirectly enhances endocannabinoid signaling without binding to cannabinoid receptors. It has strong evidence for neuropathic pain, neuroinflammation, and neuroprotection. Unlike anti-inflammatory drugs, it resolves inflammation rather than merely suppressing it.
Phenibut
A GABA-B agonist and alpha-2-delta voltage-gated calcium channel blocker developed in Russia for anxiety, insomnia, and PTSD. It crosses the blood-brain barrier (unlike GABA supplements) and produces potent anxiolytic and social confidence effects. However, it carries significant addiction and withdrawal risks — tolerance develops within days of daily use, and withdrawal can be severe.
Phosphatidylserine
A phospholipid that constitutes 15% of the brain's total phospholipid pool and is concentrated in neuronal cell membranes. Phosphatidylserine (PS) supports memory, cognitive function, and cortisol regulation. It is the only nootropic with an FDA-qualified health claim: 'consumption may reduce the risk of cognitive dysfunction in the elderly.' Particularly effective for age-related cognitive decline.
Polygala Tenuifolia
Known as Yuan Zhi in Traditional Chinese Medicine, Polygala tenuifolia has been used for thousands of years as a 'will-strengthening' and memory-enhancing herb. Modern research shows it enhances BDNF expression, inhibits acetylcholinesterase, and promotes neurogenesis. Users commonly report improved verbal fluency, dream vividness, and motivation. One of the more noticeable adaptogens with acute effects.
Reishi
Known as the 'mushroom of immortality' in Chinese medicine, Reishi (Ganoderma lucidum) is an adaptogenic mushroom primarily used for stress reduction, immune support, and sleep improvement. Unlike the stimulating effects of Cordyceps or Lion's Mane, Reishi is calming and is best taken in the evening. Its triterpene compounds modulate the HPA axis and support GABAergic relaxation.
Rhodiola Rosea
An arctic adaptogen used traditionally in Scandinavia and Russia for physical endurance and mental resilience. Rhodiola's key compounds, salidroside and rosavin, reduce mental fatigue and improve performance under stress. It is one of the few adaptogens with robust evidence for acute cognitive effects — improvements can be noticed within hours of a single dose.
SAMe
S-Adenosyl-L-Methionine is a naturally occurring compound involved in over 100 methylation reactions in the body. In the brain, SAMe is essential for neurotransmitter synthesis (dopamine, serotonin, norepinephrine) and myelin maintenance. Used as a prescription antidepressant in Europe and as a supplement in the US. Also supports liver function and joint health.
Sulbutiamine
A synthetic derivative of thiamine (vitamin B1) that crosses the blood-brain barrier far more effectively than regular thiamine. Developed in Japan to address thiamine deficiency-related fatigue, sulbutiamine raises thiamine levels in the brain much more than standard B1 supplementation. It has noticeable acute effects on motivation, energy, and mental endurance — but tolerance develops within 7-10 days of daily use.
Taurine
An abundant amino acid in the brain that acts as a major inhibitory neuromodulator, antioxidant, and osmolyte (cell volume regulator). Despite its association with energy drinks, taurine is actually calming — it modulates GABA receptors and reduces neural excitability. Recent research has shown taurine supplementation reverses aging markers in multiple organ systems including the brain.
Taurine
An amino sulfonic acid (not technically an amino acid) abundant in the brain, heart, and retina. Taurine is a key neuromodulator — it activates GABA-A and glycine receptors, providing calming effects without sedation. Recent landmark research (Science, 2023) showed taurine supplementation extended healthy lifespan in animal models by improving mitochondrial function and reducing cellular senescence. It also protects neurons from excitotoxicity.
Tianeptine
An atypical antidepressant with unique nootropic properties. Unlike SSRIs which increase serotonin, tianeptine is a mu-opioid receptor agonist and enhances serotonin reuptake. It reduces stress-induced neuronal damage in the hippocampus and amygdala, improving mood, cognition, and stress resilience simultaneously. Prescription medication in many countries but carries abuse potential at high doses.
Uridine
A nucleotide base that plays a critical role in brain cell membrane synthesis, synapse formation, and dopamine receptor expression. Part of the well-known 'Mr. Happy Stack' (Uridine + Fish Oil + Choline) that synergistically supports mood and cognitive function. Uridine monophosphate is the preferred supplemental form for brain bioavailability.
Uridine Monophosphate
A nucleotide base essential for RNA synthesis and a key component of the 'Mr. Happy Stack' — uridine + omega-3 + choline. This combination promotes synaptogenesis (new synapse formation) by providing the building blocks for phosphatidylcholine in neuronal membranes. Uridine alone enhances dopamine release and supports mood. It is one of the few supplements with evidence for promoting new synapse growth in adults.
Vitamin D3
Technically a hormone, not a vitamin. Vitamin D3 (cholecalciferol) receptors are found throughout the brain, particularly in the hippocampus and prefrontal cortex. Deficiency — affecting an estimated 40-75% of adults worldwide — is associated with cognitive impairment, depression, and increased Alzheimer's risk. Supplementation is one of the most impactful interventions for people with low levels.
Zinc
An essential trace mineral concentrated in the brain's hippocampus, where it plays a critical role in synaptic transmission and memory formation. Zinc modulates NMDA and GABA receptors, supports BDNF expression, and is required for proper neurotransmitter release. Deficiency is common (estimated 17-25% of the global population) and directly impairs memory, attention, and mood.