Mood has a great deal to do with cognition and memory and both memory and mood are both tied closely to the monoaminergic system. This includes the monoaminergic (or catecholamine) neurotransmitters. Monoamines help to transmit neuronal transmisions in the nervous system and are a vital part of the brain’s metabolism as well as being intricately linked to various emotional states. Monoamines in the body are one of two types, the catecholamines or the indolamines. Epinephrine, norepinephrine and dopamine are considered catecholamines while serotonin is believed to be an indolamine.
The catecholamines and the indolamine serotonin are an important part of learning, memory and mood. The catecholamines (epinephrine, norepinephrine, dopamine) are endogenously biosynthesized (created inside the body from amino acids, which are the basic building blocks of proteins). Proteins are produced within the body in chains of the 20 amino acids. These amino acids and proteins act like machine code for your body and brain.
Most nootropics are considered psychostimulants, which means they stimulate the brain and often have a positive effect on mood and cognition. Many drugs for ADD/ADHD and Parkinson’s are in the psychostimulant class. There are multiple theories on the biological basis for depression which includes the Serotonin hypothesis, the monoamine hypothesis and the catecholamine hypothesis. In the NCBI study “Depression: the case for a monoamine deficiency,” the monoamine hypothesis is described as predicting the underlying pathophysiologic basis of depression. According to the theory, a depletion in the levels of serotonin, norepinephrine and/or dopamine in the Central nervous system is blamed. These neurotransmitters are considered to have a close relationship to mood imbalances or “affective disorders.”
The three main monoamine neurotransmitters (dopamine, norepinephrine and serotonin) definitely seem linked to many cases of depression.
Neurotransmitters are the basic chemical messengers for the brain. All voluntary and involuntary activity that is carried through the central nervous system (both sympathetic and parasympathetic or autonomic nervous system) are responsible for regulating your breathing, heart beat and your various mental and emotional states. Psychostimulants primarily operate through monoaminergic pathways.
According to the catecholamine hypothesis of affective disorders (mood imbalances such as depression, mania, anxiety and bipolar disorder) some, or perhaps all depression is associated with a deficiency or relative decrease in the amount of catecholamines in the brain, particularly norepinephrine (one of the fight or flight neurotransmitters) which is responsible for alertness and vigilance, possibly a reason why sluggishness and anhedonia accompanies serious clinical depression. Finally, the serotonin theory of depression has been widely enforced by the efficacy of certain selective serotonin reuptake inhibitors. Not all patients are respondent to the SSRI class which seems to be evidence that the catecholaminergic and monoaminergic theory of depression may have a greater bearing in some cases of treatment resistant depression.
Several nootropics, cognitive enhancers and other supplements have an affect on the monoaminergic system that can have an effect on both mood and memory. Today we’ll be talking about mucuna pruriens (velvet bean) extract (l-dopa, a precursor to dopamine), caffeine and theanine (and the caffeine/theanine synergy), phenethylamine and the Ayurvedic memory tonic and mood balancer Bacopa monnieri (also known as Brahmi).
L-dopa is an amino acid that is a direct precursor to dopamine. After the oral ingestion of l-DOPA on a somewhat regular or chronic level, greater bio-availability has been noted which could lead to a sort of reverse tolerance or greater sensitivity to it’s effects. Regular dosages in the range of 500mg have been associated with increased levels of growth hormone in persons with hypopituitarism. L-dopa is most often sourced from the velvet bean (mucuna pruriens) and has been shown to elevate dopamine and norepinephrine levels, improve mood, focus and motivation as well as improve stress response and libido. It is recommended in a range of 500-1000mg per day.
Caffeine is the most popular and widely used psychoactive in the world today. Many people won’t even begin their day without at least a cup. Caffeine works primarily due to the fact that it is shaped like the adenosine molecule. Adenosine is the chemical that is produced and spills out when the body and brain have done work in order to signal tiredness. Caffeine is also a mild monoaminergic inhibitor and has action as a psychostimulant through those pathways as well as affecting GABA (our brain’s natural stress regulating neurotransmitter and the primary inhibitory compound made in the brain) and the adrenergic catecholamine Norepinephrine.
A meta-review taking into account 23 human studies published between 1998 and 2006 reported a significant trend of overall positive benefits associated with low to moderate caffeine usage (within the range of 37.5 and 450mg per day). Increased vigor and physical endurance, reaction time, cognitive function, alertness and vigilance and mood were most often cited as positive improvements. 100mg of caffeine is about the amount of two moderate strength cups of tea or a moderate strength 8 oz. cup of coffee. The maximum daily intake was capped at 450mg for a 70kg person (around 140 pounds) or about 5 double shots espresso (assuming 80mg in the 2 ounce shot). Greatest efficacy was observed in users who ingested around 37.5 to 450mg a day. Side effects were fairly mild in most cases (nausea, sleep disturbance) and more prevalent towards the top range of the therapeutic window (around 400mg/daily).
L-theanine is an extract that is found in teas and in highest concentration in green tea. Theanine is a GABAergic amino acid that is found only in the tea flower and the Guayusa. GABA is the primary inhibitory neurotransmitter and is responsible for quieting an over-firing nervous system. Theanine containing compounds have long been an important part of Chinese traditional medicine. Theanine has been shown to be a focusing and relaxing compound as well as having a neuro-protective and cardio-protective effect, possibly reducing the risk of ischemic stroke.
Theanine, like phenethylamine has a “hybrid agonist” quality. The serotonergic and dopaminergic effect of l-theanine could be at the base of some of it’s memory and mood enhancing potency. In the article “The combined effects of L-theanine and caffeine on cognitive performance and mood” in the journal Nutritional Neuroscience. published August, 2008 the researchers state that “Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus.”
Theanine and caffeine were both shown to separately have some effect on baseline mood and cognitive performance but the co-administration seems to potentiate a sort of synergy in its effect on cognitive performance, mood and memory.
The combination of caffeine and theanine and resulting synergy resulted in faster simple reaction time, faster numeric processing, improved working memory, reaction time as well as improve sentence verification accuracy. The combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. Reports of tiredness or headache experienced with either alone were also greater in the case of co-administration.
β-phenylethylamine is another important key to the monoaminergic system. Like l-DOPA and, to a lesser degree, caffeine, phenethylamine (or PEA) is a psychostimulant dopamine agonist that forms the background of many other stimulating chemical compounds. PEA is released with chocolate or cacao ingestion and is one of the “love compounds” in the brain. It has been theorized to be useful as an adjunct therapy in cases of addiction or obsession. Craving reduction through dopamine agonists is common but comes with possible dangers. Many dopamine agonists are, by their nature, addictive to some degree themselves. Dopamine agonists like l-dopa and PEA seem. This situation seems to be mitigated in certain circumstances by the introduction of “mixed-agonists” working on the catecholamine dopamine and the indolamide serotonin. Mixed agonists working on serotonin and dopamine are theorized to be effective at combatting cravings in alcohol and cocaine addiction. PEA is itself a mixed agonist.
A concern with PEA and other strong MAO inhibitors is the danger of what is known as “cheese syndrome” known to occur in persons who ingest cheese (especially aged cheeses like blue cheese) which have a high tyramine content. Chocolate can also enhance this potentially dangerous effect which may result in heightened blood pressure. Phenethylamine is known as a trace amine and thus binds at TAAR (trace amine associated receptors) or TA receptors.
Bacopa monnieri, or Brahmi as it is referred to in the ancient Indian Ayurvedic practice has long been prescribed in folk medicine to improve memory and balance mood, relieve anxiety as well as having other noted nootropic benefit. It is an adaptogen and believed to have a calming and balancing aspect. Like phenethylamine and theanine, it acts on both dopaminergic and serotonergic routes. It’s primary mechanism of action appears to be involved with promotion of neuronal transmission. This occurs through the promotion of dendrite growth, the nerve endings that form the branches that reach toward the synaptic gap. The tightening of the neural net through greater number of connected neurons improves the transmission of neuronal communication. In addition to all this bacopa (or Brahmi) is a brain antioxidant and long touted a rejuvenative compound. Common side effects include gas, nausea, cramps, bloating or diarrhea that is more likely when taken on an empty stomach.
Peak Nootropics “Mood and Memory” stack contains 100mg l-theanine, l-dopa, caffeine and phenethylamine. Remember to always check with your primary care practitioner before embarking on any new supplementation regimen especially if you’re currently under a doctor’s care or taking any over the counter or prescription drugs for any pre-existing condition.