Oleamide is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the formula . It is the

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

derived from the

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

oleic acid Oleic acid is a fatty acid that occurs naturally in various animal and vegetable fats and oils. It is an odorless, colorless oil, although commercial samples may be yellowish due to the presence of impurities. In chemical terms, oleic acid is cl ...

. It is a colorless waxy solid and occurs in nature. Sometimes labeled as a fatty acid primary amide (FAPA), it is

biosynthesized Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme- catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve ...

from ''N''-oleoylglycine.

Biochemical and medical aspects

In terms of natural occurrence, oleamide was first detected in human plasma. It was later shown to accumulate in the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

during

sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either Chronic (medicine), chronic ...

and induces

sleep in animals Sleep is a biological requirement for all animals that have a brain, except for ones which have only a rudimentary brain. Therefore Basal (phylogenetics), basal species do not sleep, since they do not have brains. It has been observed in mammals, ...

. It has been considered as a treatment for mood and sleep disorders, as well as

cannabinoid Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

-regulated depression. In terms of its sleep inducing effects, it is speculated that oleamide interacts with multiple

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

systems. Some in-vitro studies show that ''cis''-oleamide is an agonist for the

cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cann ...

CB-1 with an affinity around 8 micromolar. However, given oleamide's relatively low affinity for CB-1 and uncertainty about the concentration and biological role of oleamide in-vivo, it has been argued that it is premature to classify oleamide as an

endocannabinoid Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

. At larger doses oleamide can lower the body temperature of mice by about 2 degrees, with the effect lasting about two hours. The mechanism for this remains unknown. Oleamide has been found to enhance PPARα-dependent increase in doublecortin, a marker of neurogenesis in the hippocampus Oleamide is rapidly metabolized by

fatty acid amide hydrolase Fatty-acid amide hydrolase 1 (FAAH) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide (AEA), an ''N''-acylethanolamine (NAE) in 1993. In humans, it is encoded by the gene ''FAAH''.; Function ...

(FAAH), the same enzyme that metabolizes

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

. It has been postulated that some effects of oleamide are caused by increased concentrations of anandamide brought about through the inhibition of FAAH. It has been claimed that oleamide increases the activity of choline acetyltransferase, an enzyme that is critical in the production of acetylcholine. Oleamide and analogues have been found to act as

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that ...

s of the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A, 5-HT_2C, and 5-HT_1A receptors and as

negative allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that a ...

s of the serotonin 5-HT₇ receptor.

Synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

s of oleamide acting as selective dual serotonin 5-HT_2A and 5-HT_2C receptor positive allosteric modulators, such as

JPC0323 JPC0323, also known as ''N''-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)oleamide, is a dual serotonin 5-HT2C and 5-HT2A receptor positive allosteric modulator related to oleamide. It showed negligible affinity for roughly 50other targets and ...

, have been developed.

Other occurrences

Oleamide has been found in ''

Ziziphus jujuba Jujube (UK ; US or ), sometimes jujuba, scientific name ''Ziziphus jujuba'', and also called red date, Chinese date, and Chinese jujube, is a species in the genus '' Ziziphus'' in the buckthorn family Rhamnaceae. It is often confused wit ...

'', also known as Jujube fruit. Synthetic oleamide has a variety of industrial uses, including as a

lubricant A lubricant (sometimes shortened to lube) is a substance that helps to reduce friction between surfaces in mutual contact, which ultimately reduces the heat generated when the surfaces move. It may also have the function of transmitting forces, ...

. Oleamide was found to be leaching out of

polypropylene Polypropylene (PP), also known as polypropene, is a thermoplastic polymer used in a wide variety of applications. It is produced via chain-growth polymerization from the monomer Propene, propylene. Polypropylene belongs to the group of polyolefin ...

plastics in laboratory experiments, affecting experimental results. Since polypropylene is used in a wide number of food containers such as those for

yogurt Yogurt (; , from , ; also spelled yoghurt, yogourt or yoghourt) is a food produced by bacterial Fermentation (food), fermentation of milk. Fermentation of sugars in the milk by these bacteria produces lactic acid, which acts on milk protein to ...

, the problem is being studied. Oleamide is "one of the most frequent non-cannabinoid ingredients associated with

Spice In the culinary arts, a spice is any seed, fruit, root, Bark (botany), bark, or other plant substance in a form primarily used for flavoring or coloring food. Spices are distinguished from herbs, which are the leaves, flowers, or stems of pl ...

products." Analysis of 44 products synthetic cannabinoid revealed oleamide in 7 of the products tested.

References

{{Serotonin receptor modulators 5-HT2A receptor positive allosteric modulators 5-HT2C receptor positive allosteric modulators Eicosanoids Endocannabinoids Fatty acid amides Hypnotics Lipids Lubricants Serotonin receptor allosteric modulators

Biochemical and medical aspects

Other occurrences

See also

References