Evidence Based This post has 76 references
4.6 /5
8

10 Drugs Claimed to Increase Motivation

Written by Puya Yazdi, MD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Matt Carland
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Matt Carland, PhD (Neuroscience) | Written by Puya Yazdi, MD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

SelfHacked has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. We believe that the most accurate information is found directly in the scientific source.

We are dedicated to providing the most scientifically valid, unbiased, and comprehensive information on any given topic.

Our team comprises of trained MDs, PhDs, pharmacists, qualified scientists, and certified health and wellness specialists.

All of our content is written by scientists and people with a strong science background.

Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. Our science team must pass long technical science tests, difficult logical reasoning and reading comprehension tests. They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again.

Our goal is to not have a single piece of inaccurate information on this website. If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please leave a comment or contact us at [email protected]

Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number “[1+, 2+, etc...]” means that the information is found within the full scientific study rather than the abstract.

What are "Smart Drugs"?
//

Motivation to start and complete tasks is essential for mental health and success. Many diseases are marked by a lack of motivation, which can prevent people from living at their fullest. In this article, we discuss medical drugs and other compounds that have been reported to have an effect on motivation.

Disclaimer: This article is not a recommendation or endorsement for any of the substances or drugs mentioned throughout this post. Several of these compounds are pharmaceutical medications and have only been FDA-approved for the treatment of certain specific medical conditions, and most can only be safely and legally taken by prescription and with oversight from a licensed medical professional. Additionally, many other substances mentioned below are purely investigational, and have not yet been proven or officially approved for effectiveness in increasing motivation in healthy human users. Our goal is solely to inform people about the science behind these compounds’ effects, biological mechanisms, and potential health applications. None of the information in this post should ever be used to replace conventional medical care or treatment — and always be sure to discuss any new supplements or medications with your doctor first!

Drugs That May Affect Motivation

SelfHacked does not endorse or recommend taking these or any drugs. This post was written for informational purposes alone: these are widely-used drugs and pharmaceutical medications, and we feel that people should be aware of their uses, the evidence behind them, and their potential drawbacks.

None of the information in this post should ever be used to replace conventional medical treatment.

INSUFFICIENT EVIDENCE:

No drug has ever been approved by the FDA for the specific purpose of increasing motivation in healthy people. The studies below are investigational and are not conclusive enough to be considered sufficient evidence for use. Do not take any drug without a doctor’s recommendation.

1) Amphetamines

Amphetamines are a specific family of drugs that share a common molecular structure, which also gives them similar effects.

Medically speaking, these drugs are most commonly prescribed to treat ADHD, as well as sleep-related disorders, such as narcolepsy [1].

One of the main mechanisms of amphetamines is to stimulate the release of dopamine in several important regions of the brain. They can also further increase dopamine activity by inhibiting the “reuptake” of dopamine back into neurons, which increases the length and intensity of neural stimulation by dopamine [2, 3].

These dopamine-related mechanisms are most likely where these drugs get their “stimulating” effects from — which includes some effects directly related to motivation.

Due to the effects of stimulant drugs on motivation, they are sometimes used by doctors to treat other neurological and psychiatric diseases that feature motivation-related symptoms, such as apathy [4]. However, these are “unofficial,” or “off-label,” uses of these medications.

Nonetheless, even though they are widely used by doctors to treat a number of common health conditions, amphetamines are not without their dangers. For example, amphetamines can be highly addictive and potentially neurotoxic — especially when they are abused illegally, or used in any way other than prescribed and directed by a qualified medical professional. This is one of the main reasons why amphetamines should never be taken without the ongoing supervision from a doctor [5].

Additionally, many people who abuse amphetamines illegally do so due to the widespread — but mistaken — belief that they can “enhance cognition” (i.e. that they are “nootropic” compounds).

For example, healthy university students who have reported abusing Adderall commonly reported effects such as [6]:

  • Increased “energy” (both physical and mental)
  • Enhanced mood or overall sense of well-being
  • Increased “drive” to complete a task or achieve a goal
  • Increased interest and emotional investment in their work

However, evidence is lacking for any so-called “beneficial” effects of amphetamines on cognitive abilities in human users. In fact, research currently suggests that people who abuse amphetamines are most likely just mistaking these drugs’ general “stimulating” effects for “cognitive benefits,” when it is not actually the case that these drugs are actually changing or enhancing cognition in any significant way [4].

Adderall / Dextroamphetamine

Adderall is a pharmaceutical drug containing a combination of amphetamine salts (25% levoamphetamine, 75% dextroamphetamine). It is commonly used by doctors to treat ADHD and narcolepsy [1].

In addition to its effects on attention and wakefulness in patients diagnosed with these medical conditions, it is also believed that Adderall may directly influence how people experience motivation. For example, Adderall has been reported to increase the rate at which people decide to perform a high-effort, high-reward task, instead of choosing an easier task with lower rewards. This finding has been taken to imply that Adderall may directly influence how a person estimates the value of potential rewards, which may be why it appears to enhance overall motivation [4].

Methylphenidate (Ritalin)

Methylphenidate — more commonly known as the pharmaceutical drug Ritalin — is another amphetamine-based stimulant medication commonly prescribed for ADHD and narcolepsy. Like Adderall, the primary mechanisms of methylphenidate are to stimulate the release of dopamine, as well as inhibit its “reuptake” from neural synapses [2, 3].

These dopamine-based mechanisms are believed to primarily target the brain’s reward system, thereby influencing motivation [7].

Several clinical studies of ADHD patients taking methylphenidate have reported that these patients often experience improvements in cognitive functions such as attention (which are often impaired in ADHD). Such patients also often report feelings of increased motivation [7, 8].

However, these benefits have only been directly confirmed among human patients with actual diagnosed psychiatric conditions, such as ADHD — and there is little evidence for any significant “cognitive benefits” in healthy people who abuse Ritalin or other amphetamines illegally, outside of a medical setting [4].

2) Other Stimulants

Modafinil

Modafinil is a wakefulness-promoting, non-amphetamine stimulant drug that is most commonly used for treating excessive sleepiness and other fatigue-related health conditions.

Like amphetamines, Modafinil is also widely abused by otherwise-healthy people who believe it acts as a “nootropic,” or “cognitive-enhancing” drug [4].

In fairness, some evidence does exist to suggest that Modafinil could possibly affect cognition in healthy human users. For example, a few early studies have associated Modafinil with potentially enhanced cognitive performance, creative thinking, and increased motivation (increased “task enjoyment”) in healthy individuals, compared to inactive placebo treatments [9, 10, 11].

However, other studies have reported that Modafinil — like amphetamines — may not actually enhance cognition per se. Rather, the general “stimulating” effects of Modafinil may simply cause people to over-estimate their true cognitive ability, in turn causing them to believe that their cognition has been enhanced even when it is not [11].

Potential Mechanisms of Modafinil

Although the exact mechanisms of modafinil are not known for certain, some researchers have proposed that Modafinil may weakly inhibit dopamine reuptake transporters, thereby leading to increased amounts of active dopamine throughout the brain. However, this theory is controversial, and has not yet been fully proven or validated [12, 13].

Some other researchers have suggested that Modafinil may act primarily by increasing the levels of other neurotransmitters, such as norepinephrine, serotonin, and the histamine neuropeptide orexin [12].

All in all, more research will be needed to fully understand the exact mechanisms behind Modafinil’s effects in animals and humans.

Adrafinil

Adrafinil is a discontinued, non-FDA approved wakefulness-promoting stimulant drug, formerly used in France to promote alertness, attention, wakefulness, and mood — especially in the elderly [14].

As you may be able to guess from their similar names, Adrafinil is chemically and molecularly related to (i.e. is a chemical “analogue” of) Modafinil [14].

According to some preliminary research in humans and animals, Adrafinil has been reported to increase motivation [14, 15]. It may also increase libido, as well as have some effects on learning and memory ability [15, 16].

Additionally, some early evidence from one animal study has reported that Adrafinil reduced depression-related behaviors in mice, potentially suggesting a mood-related effect [17]. However, this finding would have to be confirmed by studies in human populations before any solid conclusions could be made.

Potential Mechanisms of Adrafinil

Not much is known for certain about the biological mechanisms of Adrafinil.

Some researchers believe that it may share many of its effects and mechanisms with Modafinil, although this is largely theoretical, and based mostly on the chemical and molecular similarities between the two compounds [14].

Additionally, some early evidence suggests that Adrafinil may be different from Modafinil in its ability to target a variety of neurotransmitters, such as norepinephrine (noradrenaline), glutamate, and GABA [14].

All in all, much more research needs to be done to determine how Adrafinil works, and what its potential effects and mechanisms might be.

3) Nicotine

NOTE: Nicotine is a harmful and addictive compound. The FDA has warned that nicotine use interferes with the development of the teenage brain, and increases the risk of complications during pregnancy and birth, regardless of the method of delivery (cigarettes, e-cigarettes, patches, chewing tobacco, etc.). We strongly recommend against using nicotine for any reason.

Nicotine is a highly-addictive drug that is most commonly ingested by smoking cigarettes. However, it can also be consumed in other forms, such as vaporizing devices, snus, and nicotine patches, gums, or lozenges.

It is a potent stimulator of the sympathetic nervous system, which is responsible for activating the body’s “fight-or-flight” response. It is believed to act primarily on nicotinic acetylcholine receptors, although it may also influence other important neurotransmitter systems, including dopamine [18, 19, 20, 21, 22].

Due to these mechanisms, nicotine is commonly reported to have “stimulating” effects, including increased motivation and reward-driven behavior. However, these are not “benefits” per se, as it is actually these same mechanisms that cause the drug to be addictive in the first place [23, 24, 25]!

Nonetheless, some researchers have suggested investigating some potential “therapeutic” uses of nicotine in treating certain physical and mental health conditions, such as [20]:

  • Alzheimer’s disease
  • Parkinson’s disease
  • ADHD
  • Depression/Anxiety
  • Schizophrenia

However, it is important to note that these potential applications are still in a very early stage of research, and are currently mostly theoretical. Additionally, they concern the specific biological effects of just nicotine by itself — and they do not suggest any “benefits” related to smoking or other conventional forms of nicotine consumption!

In general, the so-called “potential benefits” of nicotine do not outweigh the many severe and well-known health risks associated with smoking and other forms of nicotine use! Nicotine has not been officially FDA-approved for any medical use or other application, and is unlikely to ever become approved, due to its association with so many health-damaging behaviors (such as cigarette smoking).

4) Semax

Semax is an experimental drug originally developed in Russia for the prevention and treatment of circulatory disorders. It has also been claimed to act as a “nootropic,” or “cognitive enhancer,” although the evidence in support of this use is rather weak.

Additionally, Semax has not been extensively studied, and little is known about its efficacy or overall safety in human users. For this reason, Semax has not been approved by the FDA for any specific medical application or other use.

According to one preliminary study, patients with motor neuron disease reported experiencing significant increases in motivation and elevated mood after being administered an intranasal solution of Semax for 20 days [26].

Additionally, one animal study has reported that semax improved food motivation in rats that were isolated from birth (an animal model of early-life stress) [27].

However, semax has only been studied in animal models, or human patients with specific health conditions — and so its effects in healthy human users are unknown and scientifically unverified.

What little we know about semax’s effects in ordinary human users is limited to subjective reports from nootropics users posted online. Therefore, the following information is purely anecdotal, and should not be considered scientifically valid.

According to these subjective anecdotes, healthy users of semax have reported a number of potential effects including:

  • A general “stimulating” effect, reportedly similar to small doses of Adderall
  • Increased interest in or enthusiasm for work
  • Reduced fatigue / increased perceived energy
  • Increased social motivation
  • Decreased procrastination

Similarly, due to the lack of clinical studies, the potential side-effects of semax in healthy human users is mostly unknown. What little we know also comes from subjective user reports. Some of the unwanted side-effects that have been reported by semax users online include:

  • Feeling “overstimulated”
  • Increased anger
  • Hair loss / hair thinning (alopecia)
  • Headaches
  • Anxiety

However, it is worth noting that many of the reported side-effects have come from users who used either relatively high doses, or relatively stronger forms of semax (such as NA-semax, NA-semax-amidate) [28].

Potential Mechanisms of Semax

Due to a lack of research, the biological mechanisms of semax are largely unknown. However, some researchers have proposed a few possibilities, such as:

  • Stimulating the release of serotonin [29]
  • Enhancing the release of dopamine (when combined with D-amphetamine) [29]

LACKING EVIDENCE (Animal & Cell Studies Only):

5) Pregnenolone

Pregnenolone is a hormone that the body uses as one of the main “ingredients” (metabolic precursors) for producing a number of other important hormones such as testosterone, progesterone, cortisol, and estrogen [30, 31, 32].

The FDA states that pregnenolone is a new unapproved drug since it is not generally recognized as safe and effective for the labeled uses among experts.

According to one preliminary animal study in rats, one of the effects of pregnenolone may be to stimulate the release of dopamine throughout the reward system of the brain. These effects, in turn, have been associated with potential improvements in mood and motivation [33].

Additionally, another animal study reported that pregnenolone injections improved reward learning in rats, further suggesting a dopamine-related mechanism of action for this hormone’s effects [34].

Similarly, pregnenolone sulfate was reported to counteract some of the learning, memory, and motivation-related deficits produced by blocking NMDA receptors in mice [35].

While the mechanisms behind pregnenolone are still being actively researched, some studies have suggested a few potential mechanisms:

  • Pregnenolone may directly stimulate the release of dopamine [33, 36]
  • It may also enhance the ability of other substances, such as morphine and other opioids, to trigger dopamine release [33]
  • According to one cell study, pregnenolone may also “indirectly” stimulate dopamine release via its interactions with NMDA receptors [37]
  • Pregnenolone may also stimulate the release of other major neurotransmitters, such as acetylcholine, which has in turn been associated with increased neurogenesis, which could theoretically play a role in mood- and motivation-related benefits [38]
  • It may also increase levels of other important steroid hormones, such as allopregnanolone, which has been linked to neuro-protective effects such as reduced inflammation, increased myelination of neurons, and reduced cell death (apoptosis). However, whether these potential benefits have any effect on motivation remains unclear [39]

However, while some of these early findings are promising, no clinical studies have yet been conducted to investigate the effect of pregnenolone on motivation in healthy human users, and more research will be needed.

6) Bromantane / Ladasten

Bromantane is an experimental drug originally developed in Russia in the 1980’s. According to some preliminary research it is considered an “actoprotector,” which is a term used to describe compounds that (supposedly) increase physical and mental performance without significantly stressing the body [40].

However, relatively little research has been done on this drug, and not much known is currently known for certain regarding its overall safety and efficacy in healthy human users. Nonetheless, some early research has reported a few potential motivation-related effects.

Based on some very preliminary research in animals and cell cultures, bromantane (and other related drugs derived from a compound called adamantane) may have a variety of “stimulant-like” effects, similar to those of amphetamines and other stimulant drugs. Hypothetically, this could include motivation-related effects, although this possibility has not yet been directly tested in animals or humans [41].

Due to a lack of research, the mechanisms of bromantane remain unclear. However, some researchers have suggested a few possibilities, such as:

  • Stimulating the release of dopamine in certain key reward-related brain regions, such as the striatum [41]
  • Increasing overall dopamine levels by inhibiting its “reuptake” by neurons [41]
  • Increasing the production of dopamine in the brain, whether by increasing the levels of some of the main “building blocks” (metabolic precursors) of dopamine (such as tyrosine hydroxylase, L-DOPA, and the amino acid decarboxylase), or by activating certain genes related to the creation (synthesis) of dopamine [42, 43]
  • Reducing oxidative stress, which has been linked to motivational deficits and psychological disorders [44, 40, 45]

Theoretically, these mechanisms could affect motivation, although this specific effect has not yet been directly tested [41]. Therefore, these findings should be taken with a grain of salt until much more research is done on this experimental drug.

Additionally, not much is known about the potential addictiveness or possible side-effects of this drug in humans. Although the authors of some early studies have claimed that bromantane does not appear to have any major risks [40], these conclusions are based on very limited data. Much more extensive research — including large-scale trials in healthy human users — would be needed to properly establish whether or not this drug is actually safe to use, and what its exact effects might be.

7) Selegiline (L-Deprenyl)

NOTE: Selegiline has only been investigated for the purpose of increasing motivation in animals, or in treating certain symptoms of neurological disorders in human patients. Clinical data on the use of this drug in healthy humans is lacking, and there is therefore no evidence of any beneficial or therapeutic effects in healthy human users.

Selegiline — also known as L-Deprenyl — is a pharmaceutical drug that has been FDA-approved for the treatment of Parkinson’s disease and depression. Selegiline is also sometimes used “off-label” to treat ADHD [46].

Selegiline has shown some potential to counteract some of the cognitive deficits commonly seen in patients with neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease.

Additionally, one animal study has reported that selegiline may increase motivation in dogs [47]. However, this effect has not been investigated in humans.

While many different specific mechanisms may be involved in its effects, overall it is believed that selegiline’s effects come primarily from higher levels of dopamine, serotonin, and noradrenaline throughout the brain. Specifically, this may be due to selegiline’s ability to inhibit MAO-A and MAO-B, two of the main enzymes responsible for “breaking down” (metabolizing) dopamine and other major neurotransmitters throughout the brain [48, 49, 50, 51, 52].

Because dopamine is highly involved in motivation, there has been some speculation that selegiline use could cause increased levels of motivation, similar to how traditional stimulants (such as amphetamines) are commonly abused [53, 54, 55]. However, specific human studies on this potential effect are lacking.

Additionally, the concern over possible misuse of selegiline for its potential stimulant-like effects has led to it being classified as a banned substance for athletes by the World Anti-Doping Agency (WADA) [56, 57].

8) Tianeptine

Tianeptine is an experimental drug that is believed to have some notable anti-depressant and anti-anxiety (anxiolytic) effects. It was originally developed in France in 1989, and has been approved for medical use in some countries. However, tianeptine has not been officially approved by the FDA for medical use in the US, due largely due to concerns about its potential for addiction.

According to some early research in animals, tianeptine has been reported to partially prevent some of the memory- and motivation-related deficits that occured in rats subjected to chronic stress [58].

However, no clinical studies have investigated tianeptine’s effects in humans, so it is unclear whether it might have similar effects in human users.

Potential Mechanisms of Tianeptine

While the mechanisms behind tianeptine’s effects are not yet clear, some preliminary studies suggest that it may act by:

  • Stimulating dopamine release, and/or increasing the number of D2 and D3 dopamine receptors throughout the brain [59]
  • Preventing stress-induced changes in long-term potentiation (LTP), a critical biological process involved in synaptic plasticity [60]
  • Affecting the levels of the excitatory neurotransmitter glutamate, or influencing its activity [61]
  • Stimulating certain opioid receptors, such as mu-opioid receptors [62]

Racetam Drugs and Motivation

Racetams are a family of experimental drugs that are widely touted as “nootropics,” or “cognitive enhancers.”

On the whole, these drugs are relatively under-studied, and not much direct evidence supports the claims that they can enhance cognition.

Additionally, clinical studies in humans are especially lacking — so their safety and potential side-effects in healthy human users are relatively unknown.

Nonetheless, there are many specific types of racetams, and some preliminary research has looked at the potential of a few of them to affect motivation and other related processes.

LACKING EVIDENCE (Animal & Cell Studies Only):

9) Phenylpiracetam (Phenotropil)

Phenylpiracetam, an experimental racetam drug sometimes marketed or prescribed under the name Phenotropil, is a more potent phenyl-based derivative of piracetam.

According to one animal study, it may induce a variety of “stimulant-like” effects in mice [63]. Additionally, some scientists have noted some potential “anti-depressant” effects (also in mice) [63].

Some other animal studies have noted a variety of effects potentially related to motivation (such as increased exploratory behavior, or enhanced “operant conditioning”). However, the potential relevance of these findings to humans are difficult to interpret, as they all look at very specific forms of animal behavior that don’t necessarily have clear or direct analogues to human behavior [64, 63, 65].

According to a single study in human patients, phenylpiracetam has been reported to potentially counteract some of the common symptoms of brain injuries, such as impaired motor coordination and attention [66].

However, the potential effects of this drug in healthy human users has not been directly investigated.

Relatedly, very little is known about phenylpiracetam’s potential biological mechanisms. Some researchers have suggested that it may act by selectively inhibiting dopamine transporters, which could hypothetically increase overall dopamine levels and activity throughout the brain [67, 68].

Nonetheless, this research is still in a very early stage, and not many solid conclusions can be made based on the highly preliminary data available so far.

10) Oxiracetam

Oxiracetam is another experimental racetam drug that may have some motivation-related effects.

Although its potential effects have not been extensively studied in humans, some preliminary research suggests that it may help counteract impairments in cognitive function and reaction time in human patients with neurodegenerative conditions, such as dementia [69].

However, despite its reputation as a “cognitive enhancer,” there is no strong or direct evidence that it enhances cognitive function in healthy human users.

According to some preliminary animal studies, oxiracetam has also been reported to potentially affect motivation by:

However, these findings have only been reported in animals, and so it’s still unclear whether any of these effects might also apply to humans — and much more research will be needed before oxiracetam could ever be recommended or officially approved for this purpose.

Potential Mechanisms of Oxiracetam

Similarly, the lack of extensive research on oxiracetam means that its mechanisms are still unknown. However, based on some very preliminary studies (mostly in animals), some researchers have proposed a few possible mechanisms, such as:

  • Enhancing AMPA glutamate receptors in brain cells, which may help increase motivation [74, 75].
  • Increasing acetylcholine in the brain, a major neurotransmitter that is important for mediating arousal and many other aspects of overall mood [73, 76].

Nonetheless, much more additional research will be needed to confirm these early hypotheses, as well as to understand their relevance to healthy human users of oxiracetam.

Further Reading

Takeaway

Motivation is an extremely important psychological process that is regulated by many key systems in the brain — especially dopamine and the reward system.

Low motivation is also a hallmark of many physical and mental illnesses, such as depression.

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

Click here to subscribe

RATE THIS ARTICLE

1 Star2 Stars3 Stars4 Stars5 Stars
(16 votes, average: 4.56 out of 5)
Loading...

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.