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Hemp Oil Extract and Palmitoylethanolamide (PEA) Synergize to Enhance Pain Relief

Most patients seeking pain relief rely on the following three families of drugs: opioids, gabapentinoids, and nonsteroidal anti-inflammatory agents (NSAIDs). These widely used drugs are associated with serious side effects.1 During the past decade there has been an increasing interest in cannabis-derived products for pain management with a better safety profile and adequate pain relief. However, we still know surprisingly little about the effectiveness of nonintoxicating cannabis-based products on pain—conventionally referred to as “industrial hemp.”

A new preclinical study using industrial hemp oil extract and PEA was recently published in the Pharmacological Research journal.2 The study assessed the efficacy of full-spectrum hemp oil extract alone or in combination with PEA in the acute and chronic pain models. PEA is a bioactive compound found in lipid extracts of foods, as well as our body.3,4 A large body of animal and human studies indicate that PEA produces safe and effective pain relief in a large number of chronic and acute pain conditions, for example, neuropathic, arthritic, headache, and low back pain.3,5,6

The results of this recent study suggest that hemp oil extract is modestly effective when administered alone in treating acute and chronic pain. Surprisingly, however, the extract strongly enhanced the analgesic effects of PEA such that the combination of the two compounds exerted greater-than-additive alleviation of pain-related behaviors in two mouse models of pain. This synergism is partially supported by hemp oil extract’s extending the life of PEA in the blood, and therefore prolonging its actions.


Hemp, CBD, and PEA

Why is this clinically relevant?

  • This study demonstrated that a combination of hemp oil extract and PEA is associated with greater-than-sum effect in alleviating acute and chronic pain behaviors.
  • Given the rising concern of opioid use disorders and their associated side effects, identifying promising alternative therapies without causing apparent undesirable effects is crucial.

View the Article 



  1. Varrassi G et al. Towards an effective and safe treatment of inflammatory pain: a delphi-guided expert consensus. Adv Ther. 2019;36(10):2618-2637.
  2. Tagne AM et al. Palmitoylethanolamide and hemp oil extract exert synergistic anti-nociceptive effects in mouse models of acute and chronic pain. Pharmacol Res. 2021:105545.
  3. Petrosino S et al. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br J Pharmacol. 2017;174(11):1349-1365.
  4. Schuel H et al. N-Acylethanolamines in human reproductive fluids. Chem Phys Lipids. 2002;121(1-2):211-227.
  5. Gabrielsson L et al. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016;82(4):932-942.
  6. Lo Verme J et al. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol. 2005;67(1):15-19.


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