Return to the Cognitive Enhancement Research Institute Home Page.
From the October 23rd, 1996 issue of Smart Drug News [v5n4]. Copyright (c) 1996, 1997. All rights reserved.
Smart Drug Update:
Several years ago, I received a frantic phone call from a subscriber with Tourettes syndrome. She had been using L-tryptophan for almost a decade to control the tics (muscle twitches) and involuntary vocalizations caused by her condition. With regular tryptophan use throughout the day, she was able to stay fully employed in a verbally demanding job. She loved the job but was running out of tryptophan. The FDAs ban on tryptophan had shut off her supply and she was frantic to find an alternative source. Fortunately, she was able to make a connection to a pharmacy in Canada and obtain it with a doctors prescription.
Tourettes syndrome is a neurological condition that causes motor uncoordination. Although popularly known for causing coprolalia (involuntary utterance of vulgar language) and echolalia (involuntary repetition of words spoken by others), Tourettes is really characterized by involuntary movements (tics) of all kinds. These movements may include uncontrollable blinking, facial grimaces, head jerking, muscle twitches, vocalizations, etc. While involuntary vocalizations may serve the interests of comedy screenwriters and stand-up comedians, they are a minor part of this complex and poorly understood condition.
While the causes of Tourettes syndrome are not known, the symptoms are known to be aggravated by dopaminergic stimulants. The dopaminergic nervous system deals with primitive drives and motivations (aggressiveness, territoriality, mating behaviors, emotional arousal, etc.). and it is counterbalanced, to a significant extent, by the serotoninergic nervous system. The serotoninergic nervous system uses the neurotransmitter serotonin, which can only be made from the essential amino acid tryptophan.
So tryptophan may function to increase serotonin levels and better maintain balance between serotoninergic neurons and dopaminergic neurons. This seems a reasonable mechanism considering the known sensitivity of serotonin synthesis to the availability of tryptophan. The first step in the synthesis of serotonon is the hydroxylation of tryptophan, and the tryptophan hydroxylase enzyme is typically only half saturated with substrate (tryptophan). Since tryptophan hydroxylation is the rate-limiting step (the bottleneck), serotonin production is strongly influenced by tryptophan availability.
In a recent study of identical twins, researchers at the National Institute of Mental Health (NIMH) have localized one aspect of Tourettes syndrome to the caudate nucleus, a region of the brain that is closely associated with control of voluntary movements, and obsessive and compulsive behaviors. To control for wide variability in brain development, the researchers studied five pairs of identical twins, in which one twin exhibited significantly worse Tourettes symptoms than the other.
The researchers then studied differences in the binding of radioactive iodobenzamide between the more-affected and less-affected twins. Iodobenzamide is a drug that selectively binds to dopamine D2 receptors. Single-photon emission computed tomography (SPECT) scans localized differences to the caudate nucleus. All of the twins with the more severe symptoms had heightened binding to caudate D2 receptors. The twins with the milder symptoms exhibited lesser binding.
Metabolic overactivity of the caudate nucleus would explain the sensitivity of Tourettes symptoms to dopaminergic stimulants. It may also account for the unusual constellation of behaviors typically associated with Tourettes syndrome. But most important, it provides a neuroanatomical and neurochemical mechanism by which tryptophan could exert an inhibiting influence on Tourettes behaviors.
As far as we know, tryptophan therapy for Tourettes syndrome has not yet been explored. However, Tourettes syndrome is quite similar in many respects to obsessive/compulsive disorders which do respond to tryptophan supplementation. This observation provides a ray of hope for individuals trying to cope with the symptoms of Tourettes syndrome.
Wolf SS, Jones DW, Knable MB, Gorey JG, Lee KS, Hyde TM, Coppola R and Weinberger DR. Tourette Syndrome: Prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science 273: 1225-7, 30 August 1996.