Effects of 5HTP on the Injured Human Spinal Cord

This study will assess how the serotonin precursor, 5-HTP, alter nervous system excitability and motor function in individuals with spinal cord injuries of differing chronicity and severity. Participants will visit the lab on 4 separate occasions where they will be administered four different drugs in a randomized, double-blinded, placebo-controlled crossover design.

This study will assess for the first time the effects of 5-HTP on neural excitability utilizing a combination of neurophysiological and functional testing in subacute motor complete (AIS A/B), chronic motor complete (AIS A/B) and chronic incomplete (AIS C/D) SCI participants. To reduce peripheral side effects such as nausea, these supplements will be co-administered with carbidopa which inhibits the action of peripheral AADC, thereby ensuring that 5-HTP can effectively cross the blood brain barrier prior to being broken down. The neurophysiological outcomes will allow for the determination of the mechanistic actions of each pharmacological agent on different pathways/sites within the central nervous system in three different patient populations with varying degrees of lesion severity and will for the determination of whether increased Amino Acid Decarboxylase (AADC) expression and therefore the efficacy of this approach is correlated to lesion severity and/or chronicity. Importantly, the use of functional testing will allow for the determination of whether these often-reported neurophysiological changes translate to improvements in muscle activation patterns and kinematics during cycling.

The effects of 5-HTP will be assessed across three different participant groups: i) subacute (6 months-1 year) AIS A/B SCI individuals, ii) chronic (\>2 years post injury) AIS A/B SCI individuals and iii) chronic AIS C/D SCI individuals.. In a placebo-controlled, randomized crossover design, participants will receive i) 50 mg 5HTP combined with 50 mg carbidopa, ii) 100 mg 5-HTP combined with 50 mg carbidopa, iii) 50 mg carbidopa only or iv) placebo. Ten participants will be recruited in each group. Participants will visit the lab on four separate occasions, separated by at least 72 hours.

Eligibility Criteria:
Inclusion Criteria:

* participants must have suffered trauma to the spinal cord at least six months ago or longer

Exclusion Criteria:

* individuals with damage to the nervous system other than to the spinal cord
* pregnant and/or breastfeeding women
* alcoholic participants
* history of seizure/epilepsy
* history of suicidal thoughts or behaviors
* known or suspected allergy to the medication ingredients
* cardiovascular disease including history of heart attack or heart rhythm irregularities
* coronary artery disease
* reduced liver function or disease
* reduced kidney function or disease
* lung disease
* comatose or depressed states due to CNS depressants
* endocrine dysfunction
* blood dyscrasias or blood related disease
* bone marrow depression
* hypocalcemia
* history of stomach ulcers
* wide angle glaucoma
* phenylketonuria
* history of tumors
* uncontrolled heart problems
* unstable psychiatric or mental disorder

Participants taking:

* monoamine oxidase inhibitor therapy
* serotonergic antidepressants
* tricyclic antidepressants
* any type of serotonergic agonist
* dopamine D2 receptor antagonists
* amphetamine
* CNS depressants
* levodopa
* lithium
* anti-hypertensive drugs
* iron salts
* metoclopramide
* phenothiazine medication