Effects of oral dosing of PEA has been explored in humans, and include clinical trials for a variety of pain states, for inflammatory and pain syndromes. Daily doses range from 300 to 1200 mg per day. In a 2017 systematic meta-analysis involving 10 studies including data from 786 patients receiving PEA for pain-related indications and 512 controls, PEA was found to be associated with pain reduction significantly greater than observed in controls (P < 0.001). Positive influences have also been observed in dermal applications, specifically atopic eczema, which may be linked to PPAR alpha activation. 
In a 2015 analysis of a double blind placebo controlled study of PEA in sciatic pain, the Numbers Needed to Treat was 1.5. Its positive influence in chronic pain, and inflammatory states such as atopic eczema, seems to originate mainly from PPAR alpha activation. Since 2012 a number of new trials have been published, among which studies in glaucoma. PEA also seems to be one of the factors responsible for the decrease in pain sensitivity during and after sport, comparable to the endogenous opiates (endorphines).
From a clinical perspective the most important and promising indications for PEA are linked to neuropathic and chronic pain states, such as diabetic neuropathic pain, sciatic pain, CRPS, pelvic pain and entrapment neuropathic pain states. In a blind trial reported in a conference proceeding, patients affected by pain from synovitis or TMJ osteoarthritis (N=25, in total) were randomly assigned to PEA or ibuprofen groups for two weeks; the decrease in pain reported after two weeks was significantly higher for the PEA-treated group, likewise for improved masticatory function. In 2012, 20 patients with thalidomide and bortezomib induced neuropathy were reported to have improved nerve functions and less pain after a two-month treatment with PEA. The authors pointed out that although a placebo effect might play a role in the reported pain relief, the changes in neurophysiological measures clearly indicated that PEA exerted a positive action on the myelinated fibre groups. Sixteen men and fourteen women with two major types of neuropathic pain refractory to analgesic treatment—peripheral diabetic neuropathy (4 men, 7 women) or post-herpetic neuralgia (12 men, 7 women)—whose symptoms spanned eight pain categories ("burning", "osteoarticular", "piercing", etc.) who were under prior treatment with pregabalin were transferred to PEA, after which pregabalin treatment was gradually reintroduced; all were responding well after 45 days, and presented significant decreases in pain scores (without drug-drug interactions).
In 2013, a metareview was published on the clinical efficacy and safety of PEA in the treatment of the common cold and influenza, based on reports from six double-blind, placebo, randomized controlled trials, addressing PEA's proposed anti-inflammatory and retinoprotectant effects.
In 2019, significant increases in fatty acid amides including PEA, arachidonoylethanolamide, and oleoylethanolamide were noted in a Scottish woman with a previously undocumented variant of congenital insensitivity to pain. This was found to be a result of  a combination of a hypomorphic single nucleotide polymorphism of fatty acid amide hydrolase (FAAH), alongside a mutation of the pseudogene, FAAH-OUT. The pseudogene was previously considered to be non-coding DNA, FAAH-OUT was found to be capable of modulating the expression of FAAH, making it a possible future target for novel analgesia/anxiolytic drug development.
In 2020, PEA has been suggested as a drug that may prove beneficial for the treatment of lung inflammation caused by SARS-CoV-2 infection. A pharmaceutical company called FSD Pharma have entered PEA into a Phase 1 clinical trial under the name FSD-201, and has approval from the FDA for progressing to Phase 2a for this indication.