Dr. Grey AI

Oleamide

Oleamide is an endogenous fatty acid amide produced naturally in the brain, accumulating during sleep deprivation. It induces sleep and modulates cannabinoid receptors (CB1). Structurally derived from oleic acid with nitrogen group. Animal studies show potent sleep-inducing effects via GABAergic potentiation and endocannabinoid system modulation. NO human clinical trials. Found in dark chocolate. May interact with anandamide degradation. Research limited to preclinical - cannot recommend for supplementation.

Quick Answer

What it is

Oleamide is an endogenous fatty acid amide produced naturally in the brain, accumulating during sleep deprivation. It induces sleep and modulates cannabinoid receptors (CB1).

Key findings

  • Grade C: Sleep Induction
  • Grade D: Endocannabinoid Tone
  • Grade D: GABAergic Neurotransmission

Safety

  • It accumulates endogenously in cerebrospinal fluid during sleep deprivation, and its mechanism involves GABAergic potentiation, serotonergic modulation, and endocannabinoid system interaction.
  • The effect may involve serotonin receptor modulation and cannabinoid receptor interaction.
ℹ️ Quick Facts: Oleamide

Quick Facts: Oleamide

  • Best Evidence:Grade D
  • Conditions Studied:2
  • Research Outcomes:9
  • Key Effect:Age-Associated Memory Impairment and Cognitive Decline (AAMCD)
Outcomes by grade:
A0
B0
C1
D8
2 conditions · 9 outcomes

Detailed Outcomes

|
C
Sleep Induction
In multiple rodent models, oleamide consistently induced sleep, reduced sleep latency, and increased sleep duration. It accumulates endogenously in cerebrospinal fluid during sleep deprivation, and its mechanism involves GABAergic potentiation, serotonergic modulation, and endocannabinoid system interaction. No human clinical trials have been conducted.
large↑Improves
D
Endocannabinoid Tone
In vitro and animal studies show oleamide inhibits fatty acid amide hydrolase (FAAH), the primary enzyme degrading anandamide and other endocannabinoids. Oleamide also produces vasorelaxant effects via a novel cannabinoid receptor in rat mesenteric arteries, and FAAH-knockout mice show enhanced sensitivity to oleamide in behavioral tasks.
moderate↑Improves
D
GABAergic Neurotransmission
In vitro electrophysiology studies demonstrate oleamide stereoselectively potentiates GABA(A) receptor currents and enhances benzodiazepine-sensitive GABA receptor activity. It modulates inhibitory ionotropic receptors in mammalian CNS tissue, acting as a putative endogenous ligand for depressant drug sites.
moderate↑Improves
D
Locomotor Activity
In rodent models, oleamide reduced locomotor activity, consistent with its sedative and hypnotic properties. Effects on blood pressure and body temperature were also observed alongside locomotor suppression in rats.
moderate↓Improves
D
Serotonin Receptor Modulation
In vitro and animal studies show oleamide allosterically regulates 5-HT7 receptor binding properties and modifies 5-HT2 receptor-mediated behavior in rats. The serotonergic system appears to be involved in oleamide's sleep-inducing mechanism.
small↑Improves
D
Neuroprotection
In a single in vitro study, oleamide attenuated apoptotic cell death in cultured rat cerebellar granule neurons, suggesting potential neuroprotective properties. This finding has not been replicated or tested in vivo.
small↑Improves
D
Immune Cell Proliferation
A single in vitro study found oleamide inhibited lymphocyte proliferation, suggesting immunomodulatory properties. No follow-up studies have confirmed this effect in vivo.
small↓Worsens
D
Anxiety Symptoms
In rodent models, oleamide produced anxiolytic-like effects in both group-housed and socially isolated mice, with behavioral changes observed across multiple anxiety paradigms. The effect may involve serotonin receptor modulation and cannabinoid receptor interaction.
moderate↓Improves
D
Cognitive Function
In rodent studies, oleamide affected choline acetyltransferase activity and cognitive performance. However, FAAH-knockout mice showed disrupted working memory in water maze tasks with oleamide, suggesting dose- and context-dependent cognitive effects. Evidence is mixed and limited to animal models.
small↑Improves

Research Citations (28)

Oleamide: a fatty acid amide signaling molecule in the cardiovascular system?
(2007)
PMID: 17445087
Anxiolytic-like effects of oleamide in group-housed and socially isolated mice.
(2007)
PMID: 17521793
Neuropharmacological effects of oleamide in male and female mice.
(2007)
PMID: 17588682
Fatty acid amide hydrolase (-/-) mice exhibit an increased sensitivity to the disruptive effects of anandamide or oleamide in a working memory water maze task.
(2006)
PMID: 16352706
Vasorelaxant effects of oleamide in rat small mesenteric artery indicate action at a novel cannabinoid receptor.
(2006)
PMID: 16415907
Enhanced radiosensitization of p53 mutant cells by oleamide.
(2006)
PMID: 16580498
Oleamide: a member of the endocannabinoid family?
(2004)
PMID: 14691053
Effects of oleamide on choline acetyltransferase and cognitive activities.
(2003)
PMID: 12843655
The serotonergic system may be involved in the sleep-inducing action of oleamide in rats.
(2003)
PMID: 14615880
The sleep hormone oleamide modulates inhibitory ionotropic receptors in mammalian CNS in vitro.
(2002)
PMID: 11959801

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