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L-DOPA (Levodopa) Uses, Dosage & Mechanism of Action

Written by Biljana Novkovic, PhD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Biljana Novkovic, PhD | Last updated:

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L-DOPA

The combination of L-Dopa (levodopa) and carbidopa is a prime treatment for Parkinson’s disease. L-Dopa is also under investigation for sleep & motivation. Plant-based L-Dopa supplements are also available, but studies on their benefits are sparse. Learn what the science says about the approved and investigational uses of L-Dopa here.

Disclaimer: Levodopa is prescribed, usually in combination with carbidopa to treat Parkinson’s disease. This post provides a summary of the information available in the scientific and clinical literature, along with a list of evidence-based complementary strategies.

The combination of levodopa and carbidopa (also known as SINEMET) should be used only with the prescription and supervision of a doctor. L-Dopa is classified and sold as a supplement, but anyone considering taking it should consult a doctor first.

What is L-DOPA (Levodopa)?

Definition

L-DOPA is an amino acid derivative also known as levodopa or L-3,4-dihydroxyphenylalanine. It is naturally produced in animals and plants. In humans, it is produced from the amino acid L-tyrosine [1].

It has been the prime treatment for Parkinson’s disease since the 1960s. It increases dopamine levels in the brain, which provides relief of Parkinson’s symptoms [2].

SINEMET (Carbidopa Levodopa)

L-DOPA is administered with carbidopa (also known as SINEMET) for the treatment of Parkinson’s disease. The combination is classified by the FDA as a drug.

Carbidopa prevents the conversion of L-DOPA into dopamine outside the brain. This allows more L-DOPA to reach the brain. As carbidopa does not cross the blood-brain barrier, L-DOPA is converted into dopamine in the brain, increasing dopamine levels [3].

L-DOPA (levodopa) is the direct precursor to the neurotransmitter dopamine. The levodopa carbidopa combination is an FDA-approved treatment for Parkinson’s disease.

Investigational Outlook

Some scientists think that the uses of L-DOPA may go beyond Parkinson’s disease in the future. At the moment, however, there is insufficient evidence to support the use of L-DOPA for any indication other than Parkison’s disease management. 

Such investigational uses of L-DOPA  include improved sexual function, mental alertness, motivation, sleep, pain relief, and weight loss. On the other hand, mixed effects were reported in depression, anxiety, and oxidative stress.

L-DOPA Supplements

L-DOPA can be obtained from multiple natural sources, the most popular one being the plant Mucuna pruriens.

In addition, some healthy people claim that L-DOPA has positive effects on their cognitive function and use it in supplemental form as a “smart drug.” No valid clinical trials have tested the nootropic effects and safety of L-DOPA in healthy volunteers, though.

However, L-DOPA may also cause side effects, including involuntary, abnormal muscle movements (dyskinesia) in patients with Parkinson’s disease.

Additionally, L-DOPA supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

L-DOPA supplements are usually made from the plant Mucuna pruriens. Early research points to their potential health benefits, but solid data are lacking. 

L-DOPA (Levodopa) Mechanism of Action

L-DOPA is a Dopamine Precursor 

L-DOPA is a direct precursor of dopamine – it is the compound that dopamine is made from. It gets converted to dopamine by the enzyme aromatic amino acid decarboxylase (AADC or AAAD), which is active both in the bloodstream and in the brain [1].

Pyridoxal 5’-phosphate (the active form of vitamin B6) is required for this reaction, in the form of pyridoxine [4].

Importantly, unlike dopamine (which is broken down before it can reach the brain), L-DOPA is able to cross the blood-brain barrier. This means that taking L-DOPA can increase dopamine in the brain, which is key in the fight against brain diseases, including Parkinson’s [5].

However, L-DOPA will not reach the brain if it is degraded into dopamine in the bloodstream. For this reason, it is prescribed in combination with carbidopa, which prevents L-DOPA breakdown in the circulation. This way, most of the L-DOPA a person takes gets into the brain unchanged [1].

L-DOPA mainly acts a dopamine precursor. Carbidopa prevents L-DOPA from being broken down before it reaches the brain.

L-DOPA May Affect Testosterone Levels

L-DOPA also has an effect on the levels of testosterone. It was shown to prevent the decrease in testosterone levels in a small study of 32 Parkinson’s disease patients. It also increased the levels of testosterone in rats. This effect may be due to the dopaminergic inhibition of prolactin, which prevents decreases in the levels of luteinizing hormone and testosterone [6, 7].

Potential Effects on Adrenaline/Noradrenaline

Subsequently, dopamine can generate adrenaline (epinephrine) and noradrenaline (norepinephrine) [8].

In fact, studies in rat and mouse show that administration of L-DOPA leads to a temporary increase in brain levels of noradrenaline [8, 9, 10].

However, a study in 36 young hypertensive patients showed no changes in blood plasma levels of noradrenaline after L-DOPA treatment [11].

As a dopamine precursor, much of the mechanism of effect of L-DOPA comes from dopamine. It may also maintain testosterone levels and generate additional epinephrine and norepinephrine.

L-DOPA Is Hypothesized to Affect Other Hormones

Apart from testosterone, L-DOPA can also affect a number of other hormones.

Of note, the effects are noted in women with polycystic ovarian disease, who have elevated androgen levels, and in obese patients. Both of these groups showed a reduced release of growth hormone in response to L-DOPA [12, 13].

In children, L-DOPA increases blood concentrations of adrenocorticotropin and growth hormone, which are released by the pituitary gland, and of cortisol, which is produced by the adrenal glands [14].

However, L-DOPA decreased the concentration of cortisol in a study with 12 Parkinson’s disease patients, possibly due to reduced levels of serotonin – a regulator of cortisol release [15].

L-DOPA may also increase blood levels of insulin [16, 17].

However, this effect was not shown in a study of 10 healthy subjects [18].

L-DOPA appears to interact with a number of hormones, including growth hormone, adrenocorticotropin, cortisol, and insulin. However, its relationship to these is not fully understood.

Approved Use of Levodopa Carbidopa (Sinemet)

1) As a Parkinson’s Disease Medication

L-DOPA is currently the most effective drug for the improvement of Parkinson’s disease symptoms. Parkinson’s disease is a movement disorder characterized by a range of motor symptoms that include slowness, rigidity, tremor at rest, postural instability, and shuffling gait. These symptoms are often accompanied by the appearance of cognitive and psychiatric problems [19].

A pathological hallmark of the disease is the dramatic reduction of dopamine and dopamine-responsive neurons in the brain, particularly in a crucial area that controls movement, called substantia nigra [20].

The benefits of L-DOPA are due to an increase in dopamine levels in the brain. Improved life expectancy has been shown in 176 patients treated for 12 years [21].

L-DOPA improves Parkinson’s motor symptoms such as slowness of movement, rigidity, and tremor, but not the non-motor symptoms. It is particularly useful as an early treatment before more extensive degeneration of dopamine neurons [19, 22].

An increase in brain noradrenaline levels may also explain the benefits of L-DOPA treatment in Parkinson’s disease, particularly in alleviating depression, reduced vigilance, and sleep impairment that is often associated with motor symptoms [23].

To avoid the negative effects of long-term use of L-DOPA, other drugs have been developed over the years [24].

However, L-DOPA remains the prime therapy for Parkinson’s due to a combination of factors. It [19]:

  • activates both D1 (DRD1) and D2 (DRD2) receptors
  • possibly activates adrenergic receptors (which bind adrenaline and noradrenaline)
  • has high efficiency (it takes less time to reach an effective dosage)
  • reduces the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)

A study in which 86 Parkinson’s disease patients took increasing doses of an L-DOPA inhalation powder showed rapid improvement of motor function after 4 weeks of treatment [25].

Furthermore, an analysis of 11 studies showed that, compared to therapies that avoid L-DOPA in favor of other drugs, the use of L-DOPA alone was a more efficient for the treatment of motor symptoms of Parkinson’s, with reduced risk of treatment discontinuation due to adverse effects [26].

A study including 60 Parkinson’s disease patients with and without dementia found that L-DOPA improved motor and cognitive function, although verbal attention and memory deteriorated, which may be due to fluctuations in attention [27].

In a rat model of Parkinson’s disease, this drug improved cognitive deficits and synaptic activity in the hippocampus, a critical area for learning and memory [28].

L-DOPA is used to treat Parkinson’s disease because it helps replace the dopamine that people with PD cannot produce. People tend to be prescribed L-DOPA for many years to slow the progression of the disease.

Effects of L-Dopa on Parkinson’s Disease Complications

While levodopa is prescribed to manage the most troublesome aspects of Parkinson’s disease, it also has benefits to other, less well known effects of the disease. There is little to no evidence that L-dopa improves these markers in people without Parkinson’s disease, however.

If you are having trouble with these conditions and you don’t have Parkinson’s, talk to your doctor about more appropriate means to manage them.

2) Testosterone and Libido

Treatment with L-DOPA significantly prevented the lowering of testosterone levels in early Parkinson’s disease in a study with 32 male patients, compared with untreated subjects. This may be due to dopamine’s ability to inhibit prolactin, a hormone which lowers the levels of luteinizing hormone and testosterone [6].

Of note, Mucuna pruriens, a natural source of L-DOPA (see below) increased testosterone levels in 75 infertile men aged 25 to 40 years [29].

Research in rats showed that oral doses of L-DOPA equivalent to 160 mg/kg in humans increased testosterone levels in the blood after 7 to 14 days. This effect is probably secondary to increases in the levels of luteinizing hormone [7].

Levodopa increased sexual interest in a study with 7 male patients with Parkinson’s disease [30].

The same effect was observed in a case report of a 64-year-old male patient and in a 57-year old male, both with Parkinson’s disease [31, 32].

In a study of 8 sexually impotent male patients, treatment with L-DOPA for 12 weeks increased libido in two patients [33].

In men, but not in women, a single consumption of L-DOPA increased the magnitude of a reflex regulated by preparation for motivated action (Achilles tendon reflex) in response to sexual stimulation [34].

Erectile Function

L-DOPA increased penile swelling (tumescence) in 12 subjects, who were 50 years old or older and had normal levels of androgen (testosterone is the main androgen in men). In addition, L-DOPA augmented maximum penile circumference in 9 subjects younger than 50 years [35].

Furthermore, a study with 8 sexually impotent patients showed that 12-week treatment with L-DOPA increased the frequency of spontaneous erection during the night. L-DOPA also increased penile erection in 6 patients [33].

Male Parkinson’s disease patients who take L-DOPA tend to develop sexual dysfunction at a lower rate than those who don’t.

3) Mental Alertness

In comparison with other dopaminergic medications for Parkinson’s disease, L-DOPA induced higher levels of alertness in 48 patients, whose nigh-time sleep and daytime wakefulness were measured over 2 days [36].

Also, in a Parkinson’s disease study, L-DOPA improved alertness in all 60 patients with and without dementia [27].

Improvements in alertness were also noted in a study of 6 subjects with periodic limb movements following two doses of L-DOPA given for 5 days each [37].

Of note, contradictory results have also been reported. A study with 10 healthy men indicated a decrease in alertness with L-DOPA [38].

L-DOPA increased alertness in multiple studies of Parkinson’s disease patients.

4) Weight and Body Fat Mass

Although scientists debate whether the weight loss in Parkinson’s disease is due to L-DOPA treatment, the aging process, disease mechanisms, or a combination of these factors, studies suggest that L-DOPA contributes to weight reduction in these patients.

Specifically, a study with 7 patients treated over 1-3 years with L-DOPA suggested that the weight loss in Parkinson’s could be due to the breakdown of fat that results from L-DOPA-induced higher blood levels of insulin. However, this effect may also be due to the aging process [17].

In another study with 56 subjects, including 28 Parkinson’s disease patients and 28 controls, L-DOPA contributed to weight loss in Parkinson’s [39].

L-DOPA is associated with reduced weight in Parkinson’s disease patients prescribed the drug.

5) Pain

L-DOPA has potential pain relieving properties. Treatment in patients with Parkinson’s disease showed that this drug reduced pain intensity in 8 of 14 patients with severe pain [40].

However, a different study with 17 Parkinson’s disease patients showed that, although some patients reported an improvement of pain with L-DOPA, objective measurements with sensory testing did not reveal pain reduction [41].

In sleep-deprived rats, which show decreased numbers of dopaminergic neurons in a crucial brain area responsible for pain control (periaqueductal gray matter), L-DOPA decreased pain sensitivity to a hot plate [42].

Research in mice showed that the pain-relieving effects of this drug occur after conversion to dopamine and are mediated by D2 receptors [43].

Taking L-DOPA appears to reduce pain intensity in Parkinson’s disease patients, though the effect is not universal.

Potential L-DOPA Uses With Insufficient Evidence

The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of L-DOPA for any of the below-listed uses. Remember to speak with a doctor before taking L-DOPA, and never use it in place of something your doctor recommends or prescribes.

6) Cognitive Function

People use nootropics (“smart drugs”) to try to improve cognitive function in healthy individuals. In this regard, 5 days of L-DOPA improved learning of new words in a study with 40 healthy humans [44].

Similar results were reported from a study with 22 healthy young adults taking L-DOPA, who showed improved word recall over five learning sessions and better recognition accuracy at a 1-month follow-up, compared to placebo [45].

Improvements in working memory and in long-term memory were also reported upon L-DOPA usage in a study with 18 healthy humans [46].

However, L-DOPA may impair memory in Parkinson’s disease patients depending on the status of their brain dopamine system and specific gene variations (polymorphisms) [47].

In addition, studies have shown highlighted the potential negative effects of taking L-DOPA. A study with 26 healthy young adults with normal cognitive function showed that a single-dose L-DOPA impaired stimulus-reward learning [48].

Similar findings were reported in another study with healthy participants, which demonstrated that single administration of L-DOPA decreased the ability to filter out distracting information (interference control) in 15 young subjects, but not in 13 older participants [49].

Single-dose L-DOPA also caused less efficient learning of stimulus-response associations in 40 healthy young adults [50].

The evidence for levodopa as a nootropic is mixed and insufficient. Larger and more robust human trials will be required to determine whether it is effective for this purpose.

7) Motivation

In an MRI study of 28 healthy adults, L-DOPA improved motivation by increasing brain activation related to punishment processing. The study also found that novelty seeking was associated with the observed effects on motivation [51].

L-DOPA also improved motivational deficits in Parkinson’s disease. A study with 23 patients and 28 controls showed increases in motivation in the patients [52].

Larger and more robust human studies will be required to determine levodopa’s role in increasing motivation.

8) Sleep Quality

In a study of 6 subjects with periodic limb movements, increasing doses of L-DOPA given over 2-week periods improved sleep, particularly in the first 3 hours [37].

In another study of sleep disturbances in ADHD with 35 subjects, L-DOPA reduced the time taken to fall asleep [53].

In macaques with Parkinson’s disease, treatment with this drug resulted in partial, but significant, improvement of all sleep parameters, including sleep episodes during the daytime, sleep fragmentation and sleep efficiency at nighttime [54].

However, reports of negative findings can also be found. In 32 Parkinson’s disease patients, L-DOPA did not improve any of the sleep variables analyzed, while the time spent awake increased [55].

The results of studies on L-DOPA and sleep have been mixed or contradictory; more human studies are required to determine levodopa’s role in sleep.

9) Vision

In a pilot trial with 33 children and adolescents with residual amblyopia (a condition often called lazy eye, in which the vision in one of the eyes is reduced even if using prescription glasses due to the brain favoring the other eye), L-DOPA/carbidopa treatment for 8 weeks improved visual acuity with no serious side effects [56].

In another study in 32 patients with optic nerve injury resulting from trauma (indirect traumatic optic neuropathy), treatment with L-DOPA for 1 month, and starting 6 days after trauma, improved visual acuity [57].

10) Addiction and Withdrawal

A study with 136 treatment-seeking cocaine-dependent subjects, showed that 12-week treatment with L-DOPA in combination with behavioral therapy increased cocaine-negative urine samples, evidencing reduced cocaine consumption, in comparison with placebo [58].

11) Schizophrenia

In a meta-analysis of 30 studies involving 716 patients, L-DOPA was found beneficial in the treatment of schizophrenia when added to a regimen with antipsychotic drugs (which bind to dopamine receptors), particularly in reducing negative symptoms, such as apathy, social withdrawal, and impaired attention [59].

These results seem promising, but more research is required to determine whether levodopa should be used alongside conventional therapies for schizophrenia.

Uses Lacking Evidence

No clinical evidence supports the use of L-DOPA for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

12) Immunity and Inflammation

Activation of the inflammatory response in the brain is one of the mechanisms proposed for L-DOPA-induced abnormal muscle movements (see below). Specifically, studies suggest that L-DOPA leads to chronic and abnormal activation of microglia and astrocytes, which disrupts the communication between neurons and synaptic activity [60].

In mice, L-DOPA increased immune response around transplants, despite administration of drugs that suppress the immune system [61].

Also in mice, this drug-induced rapid growth of specific immune cells (T lymphocytes) through a dopaminergic mechanism outside the brain [62].

In opposition, a study in mouse and human immune cells showed that L-DOPA released by active melanoma cells can inhibit the production of new lymphocytes (types of white blood cells) upon immune challenge [63].

These studies were performed in animals only and results were mixed; human trials will be required to confirm or refute this potential benefit.

Animal studies suggest a role for levodopa in modulating inflammation and immunity, but further research is required.

Natural Sources of L-DOPA

Mucuna Pruriens

Many plants naturally produce levodopa in quantities that may be enough to affect human health, though relevant clinical studies are lacking.

We advise strongly against supplementing with these plants without the recommendation and supervision of a doctor. Furthermore, never use any of these natural sources in place of medication prescribed for your doctor!

L-DOPA can be obtained from diverse natural sources, particularly Mucuna pruriens, commonly known as velvet beans or cowitch, and other members of the Mucuna family (Holtonii, Andreana, Aterrima, and Gigantean). Seeds of Mucuna pruriens contain an average of 4-7% levodopa, with the content of some samples as high as 9% [64, 65].

Read about Mucuna pruriens in this SelfHacked post:

Other Plants

Other natural sources include [66, 67]:

  • White bark acacia (Acacia leucophloea)
  • Tamarind (Tamarindus indica)
  • Dunchi fiber (Sesbania bispinosa)
  • Sword bean (Entada scandens)
  • Mountain ebony (Bauhinia variegata)
  • Sword jackbean (Canavalia gladiata)
  • Moth bean (Vigna aconitifolia)
  • Cowpea (Vigna unguiculata)
  • Zombi pea (Vigna vexillata)
  • Algarrobo (Prosopis chilensis)
  • Purple orchid tree (Piliostigma malabarica)
  • Maloo creeper (Phanera vahlii)
  • Jerusalem thorn (Parkinsonia aculeata)
  • Senna (Cassia floribunda)
  • Woolly senna (Cassia hirsuta)
  • Cocobolo (Dalbergia retusa)

Levodopa Carbidopa (Sinemet) Dosage

The oral dosage of L-DOPA with carbidopa (Sinemet) in Parkinson’s disease is usually 250 mg 2 to 4 times a day in the case of adults and teenagers. This may be increased up to 6000 mg (6 g) a day. Your doctor will determine the correct dosage if you are prescribed levodopa carbidopa for Parkinson’s disease [68, 69].

Individual doses will be different for each patient, and 3 to 4 months of treatment may be needed to establish a stable regimen [68].

Adjustment is frequently necessary when the effectiveness decreases as a result of long-term use in Parkinson’s disease. This can lead to abnormal, involuntary movements and rapid worsening of symptoms. Combining L-DOPA with other medications is an alternative strategy [68, 69].

To stabilize the levels of dopamine, L-DOPA may be prescribed along with drugs that inhibit dopamine breakdown, such as monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors [70, 71].

However, dopamine agonists should be avoided in late-stage Parkinson’s disease because they can cause hallucinations and psychosis [72].

Fragmentation of L-DOPA oral dosing, with L-DOPA administered up to 6 or 7 times a day at 3-hour intervals, can be an effective strategy, though with potential for delayed response [72].

In late-stage Parkinson’s, the substitution of regular with controlled-release and liquid formulations may help improve the therapeutic effect [72].

Doctors adapt levodopa carbidopa dosage depending on the patient and over time. This combination is available only with a doctor\s prescription.

Limitations and Caveats

As detailed in the above sections, L-DOPA may elicit opposite effects depending on a number of factors, such as dosage, inter-subjects differences, and the presence of a disease. Your healthcare provider will take these aspects into consideration before prescribing you the drug.

Further Reading

Takeaway

Levodopa, or L-DOPA, is a direct precursor to dopamine. It occurs naturally in the human body and in some plants. A combination of levodopa and carbidopa (Sinemet) is a first-line treatment of Parkinson’s disease, which is characterized by a loss of dopamine neurons.

In addition to directly treating Parkinson’s disease (reducing the progression of the disease; Parkinson’s currently has no cure), L-DOPA helps relieve many of the side effects of the disease, like sexual dysfunction, weight gain, pain, and mental difficulties.

New research suggests that L-DOPA has potential for other health purposes, including insomnia, schizophrenia, and addiction. Further research is required to determine whether it is effective in these cases, however.

About the Author

Biljana Novkovic

Biljana Novkovic

PhD
Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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