L-Dopa for ADHD
L-dopa (levodopa, L-3,4-dihydroxyphenylalanine) is an amino acid formed from tyrosine by tyrosine hydroxylase and is a precursor of dopamine, norepinephrine and epinephrine, among others.
Levodopa, unlike dopamine, norepinephrine and epinephrine, can cross blood-brain barriers. If L-dopa reaches the brain, it is converted there to dopamine and is thus a dopamine prodrug.
L-dopa is commonly used to treat Parkinson’s disease.
It has not yet been shown to be effective for the treatment of ADHD. Like dopamine agonists (amantadine), it does not significantly improve hypermotor skills, impulsivity or attention.1
One study found that the increased leg movements of ADHD sufferers during sleep were unaffected by L-dopa,2 even though restless legs are often treated with L-dopa.3
A survey revealed circumstantial evidence that in the rare cases of postsynaptic dopamine receptor hypersensitivity (DARSS), therapy with very low doses of levodopa (VLDT) of 0.5-1 mg/kg/day may also be helpful with respect to ADHD symptoms.4
Amphetamine drugs appear to increase L-dopa levels by activating tyrosine hydroxylase in the dorsal striatum and nucleus accumbens. However, this does not appear to occur via a change in the phosphorylation of tyrosine hydroxylase.5
Hässler, Irmisch (2000): Biochemische Störungen bei Kindern mit hyperkinetischen Störungen, Seite 87, 89, in Steinhausen (Hrsg.) (2000): Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen, 2. Aufl. ↥
Ferri, Bruni, Novelli, Picchietti, Picchietti (2013): Time structure of leg movement activity during sleep in attention-deficit/hyperactivity disorder and effects of levodopa. Sleep Med. 2013 Apr;14(4):359-66. doi: 10.1016/j.sleep.2012.12.012. PMID: 23415543. ↥
Scholz, Trenkwalder, Kohnen, Riemann, Kriston, Hornyak (2011): Levodopa for restless legs syndrome. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD005504. doi: 10.1002/14651858.CD005504.pub2. PMID: 21328278. ↥
Hoshino, Hayashi, Ishizaki, Kimura, Kubota, Nezu, Yasuhara (2021): Very-Low-Dose Levodopa Therapy for Pediatric Neurological Disorders: A Preliminary Questionnaire in Japan. Front Pediatr. 2021 Mar 4;9:569594. doi: 10.3389/fped.2021.569594. PMID: 33748036; PMCID: PMC7970027. ↥
Janenaite, Vengeliene, Bespalov, Behl (2017): Potential role of tyrosine hydroxylase in the loss of psychostimulant effect of amphetamine under conditions of impaired dopamine transporter activity. Behav Brain Res. 2017 Sep 15;334:105-108. doi: 10.1016/j.bbr.2017.07.028. PMID: 28750831. ↥