Format

Send to

Choose Destination
J Pain. 2015 Aug;16(8):707-16. doi: 10.1016/j.jpain.2015.04.007. Epub 2015 May 7.

Diet-induced changes in n-3- and n-6-derived endocannabinoids and reductions in headache pain and psychological distress.

Author information

1
Section on Nutritional Neurosciences, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, University of North Carolina, Chapel Hill, North Carolina. Electronic address: chris.ramsden@nih.gov.
2
Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, University of North Carolina, Chapel Hill, North Carolina.
3
Center for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts.
4
Department of Neurology, Program on Integrative Medicine, University of North Carolina, Chapel Hill, North Carolina.
5
Nutrition Research and Metabolism Core, North Carolina Translational Clinical Sciences Institute, University of North Carolina, Chapel Hill, North Carolina.
6
Section on Nutritional Neurosciences, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
7
Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
8
Nutrition Department, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland.
9
Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.

Abstract

Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation-increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)-reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties.

TRIAL REGISTRATION:

ClinicalTrials.gov (NCT01157208) PERSPECTIVE: This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related conditions.

KEYWORDS:

2-arachidonoylglycerol; 2-docosahexaenoylglycerol; Endocannabinoids; docosahexaenoylethanolamine; headache; psychological distress

PMID:
25958314
PMCID:
PMC4522350
DOI:
10.1016/j.jpain.2015.04.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center