Antidepressant drugs that modulate the neurotransmitters serotonin and norepinephrine can often take up to 6 weeks to produce substantial response. This delayed response phenomenon is one of the most commonly cited flaws of the SSRI’s and related drugs. There are, however, other classes of drugs that are known to produce much more rapid relief of even the most severe depressions. Dopaminergic stimulants such as amphetamines as well as opiates like morphine are quite possibly the most powerful and fast acting antidepressants available. Their fast action lies in the modulation of the dopamine and opiate receptor complexes. Unfortunately, due to issues of tolerance and abuse potential, amphetamines and opiates are tightly controlled and not widely prescribed for depression.

So, if the key to a quick antidepressant response lies within the dopamine and opiate systems, are there any natural supplements that have the ability to upregulate these systems? This is where DLPA comes in. DLPA plays an important role in providing the building blocks for dopamine and phenylethylamine (the body’s natural amphetamine) and has the ability to greatly increase the action of our endorphins (the body’s natural morphine).

DLPA, is a 50:50 mixture of the D and L isomers of phenylalanine. It was found to be as effective as the tricyclic antidepressant imipramine in relieving depressive symptoms (17), can be used to treat ADHD (18) as well as potentiate opiate analgesia (16).

L-Phenylalanine, the form that is found in most foods, is an essential amino acid that can be converted into L-tyrosine (the precursor to norepinephrine and dopamine, for more info see David Tolson’s article on Tyrosine). But unlike L-tyrosine, L-phenyalanine is a direct precursor to phenylethylamine (PEA). L-phenylalanine is converted to PEA at a rate similar to that of L-tyrosine to dopamine (1). PEA acts as an endogenous amphetamine in the brain that promotes energy, elevates mood, and favors aggression (2).A deficit of PEA is implicated in ADHD and depression while too much PEA might be a part of schizophrenia (3). When administered with the MAOI l-deprenyl, PEA improves mood similar to amphetamine but without tolerance (9).

L-phenyalanine is readily absorbed across the brain-blood-barrier (4), and while there is conflicting evidence to as whether increases in dietary phenylalanine leads to increased levels of PEA in the brain (5,6), L-phenylalanine can improve mood and relieve depression when orally administered alone (7) and with the MAOI l-deprenyl (8).

D-phenylalanine has similar nutritional value to L-phenylalanine (10) and can lead to increases in PEA, though a different pathway than the L enantiomer (11). What makes the D-phenylalanine remarkable is its ability to inhibit the enzyme enkephalinase and prevent the degradation of endorphins (13). Endorphins induce analgesia (pain relief) and probably play a role in DLPA’s mood enhancing effects. Although D-phenylalanine appears to be ineffective by itself for reducing chronic pain (14), it can greatly pontentiate the pain relieving effects of both acupuncture and narcotic drugs such as morphine (15,16).

Dosages of DLPA used in most studies are usually considered very modest (200mg/day), and effective dosages are probably more in the range of 1g a day or more (19). Dosages should be divided up over the course of the day and taken in between meals. To treat depression, DLPA can be used alone or with l-deprenyl. For augmented pain relief, one can combine DLPA with prescribed narcotics. Those suffering from PKU (phenyketonuria) or schizophrenia should avoid DLPA supplementation as it might exacerbate the condition.