For patients with ADHD, stimulants are popular medications. But, according to the Substance Abuse and Mental Health Services Administration, around 1.2 million individuals in the United States use prescription stimulants for nonmedical reasons.  Generally, these drugs are addictive and may cause dependency when abused. Fortunately, there are stimulant alternatives that others may consider. But what are these natural stimulants and OTC? Are they as effective as the prescription ones?
This article provides information about natural and OTC stimulants, stimulant vs. depressant comparison, how these drugs work, and what may happen when they are combined.
What Are Natural Stimulants?
Natural stimulant alternatives are derived from plants and their roots. They are used to increase energy, reduce appetite, and improve mental clarity and focus. Although natural stimulants are made from plants, when used in large doses or excessively, they can become dangerous, resulting in severe effects of stimulants. According to a study from the Neural Plasticity journal, for those with ADHD, natural stimulants work by reducing the symptoms of the condition. 
Furthermore, natural stimulants can be purchased from the drug store, online, or even from supermarkets or grocery stores.
The most studied and most used natural OTC stimulant is caffeine. It can be found in many products, such as coffee, tea, and medicine. Although caffeine has its benefits, natural stimulants in coffee can adversely impact the body. According to the US Food and Drug Administration, adults should not drink more than 400 mg of caffeine daily. 
Because caffeine is a diuretic, it can cause severe dehydration in the body. Caffeine leads to caffeinism, a specific toxidrome when ingested in high amounts and for a long time. High doses of caffeine have been linked to deaths, specifically in people with existing heart disease.
Other herbal stimulants include the following:
- Huperzine-A – Also known as Hup-A, this is an alkaloid nootropic extracted from the Chinese Club Moss. It is a reversible acetylcholinesterase inhibitor and an NMDA receptor antagonist, which promotes long-term brain health and boosts short-term memory. 
- Lion’s Mane is the only herb stimulant mushroom proven to support brain health. It supplies unique nootropic support needed for synthesizing the Nerve Growth Factor. Lion’s Mane is one of the natural brain stimulant alternatives, a nootropic that increases the use of nerve growth factors in the brain, promoting healthy mood balance and cognitive function. 
- Gotu kola – The active ingredient in this herb stimulant is asiaticoside. It is reported that Gotu kola can improve mental clarity and focus, strengthen brain function, and decrease anxiety. 
- Kola nut – This is one of the foods that fall among the natural stimulants list containing caffeine which stimulates the central nervous system. Kola nuts are used to fight mental slowness and fatigue, making a person feel energetic and awake. 
- Rhodiola – This herb stimulant is one of the herbal stimulant alternatives used for centuries in Siberia to deal with physiological stress during the cold winter season. Salidroside, the main chemical in the plant, is believed to reduce mental fatigue, improve mental performance, and enhance physical capacity through free radical mitigation. 
- Guarana – This plant is packed with caffeine, and it is used for its ability to reduce fatigue. It also contains theophylline and theobromine, which have relaxing and stimulant effects. Compared to caffeine, guarana can provide better stimulant effects. 
- Oat straw – Green oat grass can enhance mental function and is long known as one of the herbal stimulants for energy. Eating oat straws increases the electrical activity in the brain’s left frontal-temporal area, leading to mental arousal, alertness, and a boost in cognitive performance. 
- Ashwagandha – This adaptogen, an herb stimulant, helps the body adapt to stress. Ashwagandha contains alkaloids, steroidal lactones, and saponins, which improve mental energy and reduce fatigue. 
- Bacopa – Much better when taken with ginseng, Bacopa is one of the herbal stimulant alternatives used for centuries in Ayurveda to improve mental function, but also for poor memory, in treating anxiety disorders, ADHD, and Alzheimer’s. It works by inhibiting an enzyme that leads to the degradation of acetylcholine and by increasing cerebral blood flow. 
- Ginseng – Ginseng is one of the foods that are all natural stimulants. This plant stimulates mental and physical activity in people who feel tired and weak and cancer patients. It improves cognition and the thinking process. 
- Maca – For those who need sexual stimulation, maca is very popular as it can increase performance, energy, and sexual desire. This is one of the foods that are natural stimulants that contain amino acids and fatty acids, which improve memory, athletic performance, and energy. 
- Cordyceps – This fungus can improve athletic performance, but it is also used as a tonic, immune stimulant, energy booster, and stamina enhancer. 
- Theobromine is the alkaloid that gives the cacao plant a bitter taste. It acts as a stimulant of the nervous system, boosting mood, brain function, and relaxation and giving a positive effect. It is also a more powerful cardiac stimulant compared to caffeine. 
- Yerba Mate – This evergreen tree is one of the natural stimulants which contain caffeine. It stimulates the brain, muscles, blood vessels, and heart, and provides energy, enhances memory, alertness, and mood. 
- Ginkgo Biloba – This plant is known to enhance memory. Ginkgo Biloba contains antioxidants, such as terpenoids and flavonoids, which protect against oxidative cell damage. The plant improves memory and thinking, boosts cognitive speed, and improves blood flow in the body.
- Capsaicin – This compound is present in hot red peppers. Apart from its stimulant effects, capsaicin also comes with analgesic effects. When taking this natural stimulant as an alternative to prescription stimulants, the right dosage should be computed based on a patient’s weight. 
- Omega-3 – Surprisingly, omega-3 is also considered one of the natural stimulants for patients with ADHD. According to a study from The Netherlands, omega-3 reduces hyperactivity and impulsivity. 
- Pine bark extract – This extract regulates the antioxidant levels of patients with ADHD. According to a study by psychiatrists from Slovakia, pine bark extract can reduce hyperactivity and improve the focus and concentration of individuals with ADHD. 
Although these natural stimulants offer many benefits when used for a long time or in excess, they can do more harm than good. That is why it is crucial to consult with a doctor before taking such herbal stimulants, as they can also interact with other OTC drugs or prescription medicines.
OTC Stimulants Alternatives
Stimulants can be purchased from a pharmacy only if the patient has a valid and legal prescription. However, although most CNS stimulants are prescribed stimulants, some OTC stimulants can still be obtained in the United States. Aside from pharmacies, some of these OTC medications can also be obtained online.
Generally, ADHD and stimulants go hand in hand, with the latter boosting the dopamine level to increase concentration and focus. Similarly, OTC stimulant alternatives are expected to provide the same effects.
Some of these over-the-counter uppers alternatives include the following:
- Cough and cold medicines that contain dextromethorphan (DM). According to a study from researchers from Thailand, prolonged and improper use of DM can cause dependence and addiction. 
- Caffeine-containing medicines such as Excedrin, Alka-Seltzer, and Panadol Extra.
- Diet pills
- Motion sickness pills that contain dimenhydrinate and diphenhydramine. According to research from the Frontiers in Pharmacology, these two substances are considered mild stimulants.
- Nasal decongestants that contain pseudoephedrine. According to research by pharmacologists from Poland, pseudoephedrine is also known as an energizer. 
Many people consider OTC uppers alternatives as harmless, but most of them include compounds of great concern, such as pseudoephedrine, phenylpropanolamine (PPA), or ephedrine. Many manufacturers producing and selling these drugs use claims that the FDA has not researched and evaluated. So, consumers are not adequately informed about the product’s possible dangers.
What CNS Stimulant Alternatives Were Available OTC in The Past?
For those looking for legit OTC stimulants that can be used as an alternative for mental health conditions such as ADHD, there are still options being written on the Internet. However, not all alternatives are still available. Three alternatives, pseudoephedrine, and ephedrine, were now removed from the market decades ago. But, these two, along with phenylpropanolamine, will be elaborated on for information purposes. 
The common stimulant alternatives (containing pseudoephedrine) treat allergic rhinitis and asthma. In the past, pseudoephedrine was frequently used in treatments for depression, asthma, or hypotension. However, due to their serious toxicity and side effects, these OTC uppers alternatives have been replaced by more selective, safer agents.
Phenylpropanolamine, or PPA, is a sympathomimetic agent with anorectic properties, usually found in decongestants, appetite suppressants, and other over-the-counter uppers. Several case reports have shown that PPA can cause intracranial hemorrhage and that appetite suppressants containing PPA might cause hemorrhagic strokes in women.  Due to these dangerous side effects, the FDA issued a warning, and phenylpropanolamine was removed from the US market in 2000.
Ephedrine was used as a decongestant and bronchodilator for many years to treat heart block, asthma, hypotension, narcolepsy, and depression. Nowadays, ephedrine is chemically synthesized, but traditionally it was used in its plant form as an herbal stimulant. As it is an adrenergic agonist, ephedrine enhances norepinephrine release from sympathetic neurons, elevating mood, decreasing appetite, and increasing heart rate and blood pressure.
In 2004, the FDA prohibited selling supplements containing ephedrine since they pose an unreasonable risk because of their potential health hazards. Today, ephedrine can still be legally obtained only in pure form (pure herb or tea). 
Natural And Over-the-Counter Stimulants For ADHD
Moving on, several natural stimulants and OTC psychostimulants still exist that individuals with Attention-Deficit Hyperactivity Disorder can use. These natural OTC stimulant alternatives do not work like stimulant drugs, but they still offer the same benefits. 
Some of these natural and over-the-counter stimulants for ADHD include the following:
- Ginkgo Biloba – This plant extract preserves the balance of dopamine, serotonin, norepinephrine, and acetylcholine in the brain, reducing impulsivity and improving attention span. According to studies by researchers from New York, Ginkgo Biloba can also be considered antidementia. 
- Bacopa Monnieri – The extracts of this plant interact with dopaminergic and serotonergic systems in the body, enhancing energy levels and alertness. According to a study from Thailand, this plant can effectively improve memory. 
- Caffeine – This is a CNS psychostimulant that increases the dopamine level in the brain. Caffeine also shrinks blood levels reducing the blood flow in the brain’s overactive regions and allowing for more stable and predictable communication in the brain.
- L-Theanine – This amino acid boosts the levels of glycine and GABA in the brain, reducing anxiety and stress and creating a state of calmness and relaxation. Based on studies from Scientific Reports, it was stated that L-theanine, even at low doses, can reduce hyperactivity. 
- Alpha GPC – This compound crosses the blood-brain barrier, increasing acetylcholine levels, the most important memory and learning neurotransmitter. In a randomized controlled trial from Los Angeles, it was reported that Alpha GPC could offer better stimulant effects than caffeine. 
- L-Tyrosine – This amino acid has the ability to be synthesized into dopamine and serotonin. Additionally, it is used in the production of noradrenaline and dopamine. Thus, by increasing dopamine levels in patients with ADHD, this amino acid can enhance mental cognition in episodes with uncontrollable, acute stress. 
- 5-HTP Supplements – These supplements increase serotonin levels, a neurotransmitter with an antidepressant effect. 5-HTP can boost mental energy, improve creativity, and rejuvenate concentration and focus. 
- Gamma-Aminobutyric Acid – Also known as GABA, this neurotransmitter helps the brain keep its equilibrium, reducing neurons’ erratic activity and excitability by countering Glutamate receptors. According to a study by pharmacologists from Brazil, GABA is involved in stimulant pathways. For those who are wondering how to get GABA, this can be acquired through supplements. 
Even though those mentioned above natural and over-the-counter stimulants for ADHD can be obtained without a prescription, a patient needs to consult with a doctor before use to avoid side effects and dangerous interactions.
What Is The Difference Between Stimulants and Depressants?
Stimulants and depressants are among the most commonly abused types of drugs. Because they are frequently discussed together, not everyone understands the difference between stimulants and depressants. So, what is the difference between stimulants and depressants? In essence, this comes down to how they impact the central nervous system. Stimulants increase their activity, while depressants reduce it. A stimulant vs. depressant comparison is made between prescription medications and street drugs.
Also known as uppers, these drugs allow the users to be more awake and energetic. Uppers are available in tablets, capsules, and powders.
Some of the commonly used stimulants include the following:
Users should be mindful of the dose as these drugs can also cause overstimulation. This is the reason why only medical doctors can decide on the dosage and frequency of use for these drugs.
Also known as downers, these drugs relax the muscles and are usually used to treat insomnia and anxiety. Generally, depressants work by slowing down the activity in the CNS. Unlike uppers, these downers are also available in injection form. 
Some of these drugs include the following:
It is important to note that even if someone has a prescription for a depressant or stimulant, there is still a risk of abuse and developing an addiction. Thus, patients using these medications are highly advised to take them correctly and accurately to avoid these complications.
Uppers and Downers Mechanism Of Action
Mechanism of action describes how stimulants and depressants work. Essentially, this explains the specific effects these medications have on the body. The MOA is central to both the therapeutic benefits of stimulants and depressants and the highs they can produce.
MOA In Different Body Systems
Both downers and uppers primarily interact with the central nervous system. Uppers impact the CNS by stimulating it or making it more active. Downers inhibit the actions of the CNS. Both stimulants and depressants impact other bodily systems through their impact on the CNS.
For example, interacting with the cardiac system, uppers will cause the heart rate to accelerate and the blood pressure to rise.  With depressants, the effect is the exact opposite. The cardiac system will slow, resulting in a slower pulse and lower blood pressure. They also both impact the digestive system; stimulants increase metabolism and even cause diarrhea, while depressants slow things down, making it easier to gain weight and experience constipation.
However, stimulants are not likely to change the respiratory system. Yet this is an effect of downers. In fact, respiratory depression is often the greatest risk associated with depressant use. 
MOA In The Brain
The core of the MOA of both stimulants and depressants is in the brain. Stimulants usually increase the activity of the brain chemicals dopamine and norepinephrine. In general, depressants increase the activity of gamma-aminobutyric acid (GABA), a chemical that inhibits brain activity. However, because each drug is different, their effects on brain chemicals can vary. 
Is Mixing Uppers and Downers Dangerous?
Mixing stimulants and depressants is absolutely dangerous. While it is easy to reason that using both upper and downer drugs balances each other out, it actually just places twice the stress on the body, pulling it from one extreme to the other. Then there are the potential drug interactions to account for, which can easily lead to an overdose. Abusing these drugs on their own is incredibly risky and potentially deadly; combining them only increases the chances of severe or fatal effects.
Effects Of Mixing Uppers And Downers
Mixing uppers and downers effects are seen in numerous bodily systems, resulting in terrible side effects. Generally, the mixing of these two classes of drugs is called polydrug use. Some potential and dangerous effects of using both stimulants and depressants are:
- Uppers can mask the signs of CNS depression, and downers can mask CNS excitement. The other can kick in and have deadly results as one wears off. Eventually, patients will be motivated to take too much. When the high of both drugs is masked by each other, the user can take more to try to feel something, resulting in an overdose. 
- The creation of deadly chemicals within the body is also one of the effects of mixing uppers and downers. For example, alcohol and cocaine come together to cause the body to produce cocaethylene, which is extremely toxic. 
- Stimulants cause dehydration, as do certain depressants. This can result in severe damage to vital organs. Remember, when the body experiences dehydration, the organs, especially the kidneys, are affected. 
- Stimulants tell the body to increase the pulse, while downers tell it to reduce it. This fluctuation can cause dysrhythmias and, ultimately, heart failure. 
- Mixing the two types of substances can create an illusion of control. This can make the user feel more confident than they should, resulting in injury.
Patients should not mix stimulants with depressive drugs without medical consultation. Only a doctor can set a prescription schedule and prescribe concurrent use of both. If a patient already uses any stimulants ordered by another doctor, it is important to notify this current physician prescribing downers.
Summarizing Prescription, OTC, and Natural Stimulants
Indeed, stimulants are effective medications that can treat and manage certain health conditions such as ADHD, anxiety, and insomnia. Moreover, aside from prescription stimulants, there are also natural and OTC stimulants that can be considered. Still, when taking these nonprescription ones, the right dosage should always be considered to avoid health complications, including overstimulation. Furthermore, it is common for some to take stimulants and depressants together. Unfortunately, mixing these two can cause dangerous effects, addiction, and dependency.
In case symptoms of addiction occur, seeking resources such as rehab centers would be of great help. Professional addiction specialists at these centers can inform patients about how to wean off these medications safely. Aside from this, patients can also choose between in-patient rehab programs and outpatient rehab programs. Any of these, together with a relapse prevention plan, would be an effective way to recover from the dangerous use of antidepressants.
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