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Anandamide as a Marker of Human Disease

Mauro Maccarrone, PhD
JAMA. 2008;300(3):281-282. doi:10.1001/jama.2008.26
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To the Editor: In their Research Letter, Dr Habayeb and colleagues1 showed that plasma levels of the endocannabinoid anandamide (N-arachidonoyl-ethanolamine) were approximately 3-fold higher in women in a miscarriage group compared with those in a live birth group and thus were associated with the outcome in patients presenting with threatened miscarriage. This observation extends previous findings that in peripheral blood mononuclear cells, low levels of fatty acid amide hydrolase, the enzyme that metabolizes anandamide, were associated with subsequent miscarriage in women with uncomplicated early pregnancies.2 On this basis, the authors suggest that measurement of anandamide levels may have the potential to improve the prediction and counseling of women at risk of miscarriage.

Defective fatty acid amide hydrolase expression (with increased anandamide levels compared with healthy controls) has been observed in peripheral blood mononuclear cells from persons of reproductive age with presymptomatic and symptomatic Huntington disease3 and multiple sclerosis.4 In addition, increased plasma anandamide levels have been reported in women with anorexia nervosa or binge-eating disorder.5

It is unclear to what extent an altered content of anandamide in peripheral blood mononuclear cells contributes to its overall plasma concentration. However, the biochemical alterations that underlie an unbalanced anandamide content are different in various disease conditions.1 5 For example, in spontaneous abortion, increased plasma anandamide levels are paralleled by a marked decrease of activity and expression of fatty acid amide hydrolase in peripheral blood mononuclear cells,2 whereas in Huntington disease increased anandamide levels in peripheral blood mononuclear cells are associated with decreased activity (but not expression) of fatty acid amide hydrolase.3 In multiple sclerosis, increased anandamide levels in peripheral blood mononuclear cells are associated with decreased activity and expression of fatty acid amide hydrolase and with an increase in the activity of the anandamide-synthetase N-acylphosphatidylethanolamine phospholipase D.4

Taken together, these data suggest that altered blood levels of anandamide may be a broad marker of human disease, although the underlying biochemical alterations might offer the opportunity for a differential diagnosis of each disease condition. Further studies should be conducted to ascertain the potential of plasma anandamide as more than a predictor of pregnancy outcome in women.

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Habayeb OM, Taylor AH, Finney M, Evans MD, Konje JC. Plasma anandamide concentration and pregnancy outcome in women with threatened miscarriage.  JAMA. 2008;299(10):1135-1136
PubMedCrossRef
Maccarrone M, Valensise H, Bari M,  et al.  Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage.  Lancet. 2000;355(9212):1326-1329
PubMedCrossRef
Battista N, Bari M, Tarditi A,  et al.  Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's Disease mutation in peripheral lymphocytes.  Neurobiol Dis. 2007;27(1):108-116
PubMedCrossRef
Centonze D, Bari M, Rossi S,  et al.  The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis.  Brain. 2007;130(pt 10):2543-2553
PubMedCrossRef
Monteleone P, Matias I, Martiadis V, De Petrocellis L, Maj M, Di Marzo V. Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa.  Neuropsychopharmacology. 2005;30(6):1216-1221
PubMedCrossRef

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Habayeb OM, Taylor AH, Finney M, Evans MD, Konje JC. Plasma anandamide concentration and pregnancy outcome in women with threatened miscarriage.  JAMA. 2008;299(10):1135-1136
PubMedCrossRef
Maccarrone M, Valensise H, Bari M,  et al.  Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage.  Lancet. 2000;355(9212):1326-1329
PubMedCrossRef
Battista N, Bari M, Tarditi A,  et al.  Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's Disease mutation in peripheral lymphocytes.  Neurobiol Dis. 2007;27(1):108-116
PubMedCrossRef
Centonze D, Bari M, Rossi S,  et al.  The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis.  Brain. 2007;130(pt 10):2543-2553
PubMedCrossRef
Monteleone P, Matias I, Martiadis V, De Petrocellis L, Maj M, Di Marzo V. Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa.  Neuropsychopharmacology. 2005;30(6):1216-1221
PubMedCrossRef
July 16, 2008
Osama M. H. Habayeb, MBBS; Anthony H. Taylor, PhD; Justin C. Konje, MD
JAMA. 2008;300(3):281-282.
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