Mechanism of Action
DLPA is a 50/50 mixture of both isomers. L-Phenylalanine is hydroxylated to L-tyrosine, then further to dopamine → norepinephrine → epinephrine. D-Phenylalanine is proposed to inhibit enkephalinase — an enzyme that breaks down endogenous endorphins — thereby prolonging natural pain relief.
Evidence
Evidence predominantly dates from the 1970s-80s. Beckmann (1979) showed DLPA as non-inferior to imipramine for depression in a small double-blind trial. For pain relief via enkephalinase inhibition, there is mechanistic plausibility but no modern RCTs. Overall: historically interesting but replication is lacking.
Safety
Contraindicated in phenylketonuria (PKU). Do not combine with MAO inhibitors or levodopa. May cause headaches, nausea, or anxiety in sensitive individuals. Generally well-tolerated in studies.
Dosage
500–1000 mg per day on an empty stomach. Avoid evening doses (stimulating via dopamine pathway).