Oleamide: Nootropic Benefits, Uses, Dosage, & Side Effects

Oleamide is a fatty acid amide found naturally in the human plasma and is primarily known for enhancing sleep.

The physiological benefits don’t just stop there, they also include mood modulation, depression treatment, and neuroprotection.

In this comprehensive guide, we’ll lay out the science behind oleamide, its mechanisms of action, prospective benefits, and practical considerations for its use as a supplement.

What Is Oleamide?

Oleamide (cis-9-octadecenamide) is a fatty amide that belongs to the class of lipids known as biomolecules.

It was first found in human plasma and later research showed that it accumulated in cerebrospinal fluids during sleep deprivation.

It is also present in foods like olive oil, avocado, nuts (almonds and macadamia), and seeds (pumpkin and sunflower).

Oleamide consists of oleic acid (a monosaturated omega-9 fatty acid) and ammonia, which combine to provide a strong antidote for sleep disorders.

This ability to regulate sleep is just one aspect of the cognitive-enhancing property of oleamide. It also promotes relaxation, improves memory, and reduces anxiety disorder.

Additionally, it exhibits neuroprotective properties, acting as an antioxidant that shields neurons from oxidative stress.

Besides that, it possesses anti-inflammatory properties, reducing inflammation by inhibiting pro-inflammatory cytokines.

Besides the advantages for the brain, oleamide has other physiological benefits like improving cardiovascular health and enhancing digestive functions.

What are the Benefits of Oleamide for Cognitive Enhancement?

Oleamide offers various cognitive benefits, including enhancing memory and mood. Its effects on sleep regulation and neuroprotection pave the way for improvements in overall cognitive function.

How Does Oleamide Improve Sleep?

Oleamide enhances the effects of GABA, the primary inhibitory neurotransmitter in the brain, leading to increased relaxation and sleepiness.

A study demonstrated that oleamide administration significantly reduced sleep latency and increased total sleep time.⁽¹⁾

Another study showed that oleamide increased non-rapid eye movement (NREM) sleep by 41% and rapid eye movement (REM) sleep by 13%, indicating a substantial improvement in both sleep stages.⁽²⁾

Furthermore, oleamide administration leads to increased levels of serotonin in the brain, which is associated with improved sleep patterns and reduced time to fall asleep.⁽³⁾

How Does Oleamide Support Memory?

Oleamide supports memory through its modulation of endocannabinoid receptors.

It binds to cannabinoid receptors, particularly CB1, which are abundant in brain regions associated with memory, such as the hippocampus.⁽⁴⁾

A study found that oleamide administration increased long-term potentiation (LTP), i.e. longer signal transmission between neurons, by 25% in oleamide-treated participants, indicating improved synaptic strength and memory potential.⁽⁵⁾

Additionally, oleamide exhibits antioxidant properties that protect neurons from oxidative stress, a factor that can impair memory and cognitive function.

Can Oleamide Enhance Mood and Reduce Anxiety & Depression?

Oleamide enhances mood and reduces anxiety and depression by modulating serotonin and dopamine signaling, which are key neurotransmitters involved in mood regulation.

A study showed serotonin levels in the prefrontal cortex were elevated by 20-30% in oleamide-treated participants showing calming effects.⁽⁶⁾

Oleamide also exhibits anxiolytic-like effects, promoting relaxation which helps reduce anxiety levels.⁽⁷⁾

Another study implicates oleamide in providing antidepressant-like effects in participants with chronic depression disorder.⁽⁸⁾

Can Oleamide Treat Neurodegenerative Disorders?

Oleamide has shown promise in the treatment of neurodegenerative disorders due to its neuroprotective properties.

One of the ways it does that is by reducing oxidative stress, which is a major contributor to neuronal damage in neurodegenerative diseases like Alzheimer’s and Parkinson’s.

A study showed that oleamide administration reduced the levels of oxidative markers by 35% in the brain. This reduction in oxidative stress was associated with a decrease in amyloid-beta plaques, which are characteristic of Alzheimer’s pathology.⁽⁹⁾

Oleamide also helps with chronic inflammation in the brain by inhibiting pro-inflammatory cytokines, thereby reducing the pace of neurodegenerative disorders.

One comprehensive study classified oleamide as one of the endogenous compounds that can combat various neurodegenerative disorders, like Alzheimer’s and Parkinson’s disease, multiple sclerosis, etc.⁽¹⁰⁾

How to Dose Oleamide for Cognitive Benefits?

Oleamide should be taken orally, typically in capsule or powder form.

Take oleamide 30-60 minutes before bed to improve sleep, and consider cycling use (e.g., 5 days on, 2 days off) to prevent tolerance.

The recommended dosage of oleamide can vary depending on the individual and the intended use.

However, based on available research and anecdotal reports, typical dosages range from 10 mg to 150 mg per day.

The onset of oleamide’s effects can vary depending specific benefit being sought. Generally, you can expect 30-60 minutes for sleep-inducing effects to set in.

Moreover, the duration for other effects like anxiety reduction, memory enhancement, and neuroprotection may take between a few hours to several weeks of consistent use.

Does Oleamide Have Any Safety Concerns?

Although oleamide is generally well-tolerated, it still may not be suitable for everyone. Some users may experience adverse effects.

What Are the Common Side Effects of Oleamide?

Common side effects of oleamide may include:

• Drowsiness
• Grogginess
• Vivid dreams
• Gastrointestinal discomfort
• Headache
• Dry mouth
• Changes in appetite

It’s worth noting that these side effects are typically mild and often subside with continued use or dose adjustment.

Can Oleamide Interact with Medications?

Oleamide can potentially interact with certain medications, particularly those that affect neurotransmitter systems or sleep-wake cycles.

Possible interactions include:

1. Sleep medications may lead to excessive sedation
2. Anxiolytics could cause increased drowsiness or other side effects
3. Antidepressants may induce serotonin syndrome
4. Blood pressure medications could lead to invariable blood pressure
5. Anticoagulants affect excessive blood thinning
6. Cannabinoid receptor agonists may lead to adverse effects on endocannabinoid system

Who Should Avoid Oleamide?

While oleamide is safe for most individuals, certain groups should exercise caution or avoid its use:

• Pregnant or breastfeeding women
• Children and adolescents
• Individuals with liver or kidney disease
• People with sleep disorders
• Individuals with mood disorders
• People taking multiple medications
• Those with a history of substance abuse
• People with hormone-sensitive conditions

Is Oleamide Safe for Long-Term Use?

Yes, because as an endogenous compound naturally present in the body, oleamide is less likely to cause significant adverse effects compared to synthetic drugs over time.

Some users may develop tolerance to oleamide, requiring higher doses over time, and while it is not physically addictive, psychological dependence on sleep or relaxation can occur.

A review noted that oleamide appears to have a good safety profile but emphasized the need for more long-term studies to fully assess its safety for extended use.⁽¹¹⁾

How Does Oleamide Compare to Other Supplements?

Understanding how oleamide compares to other supplements can help individuals make informed decisions about their cognitive enhancement and sleep improvement strategies.

What Are the Key Differences Between Oleamide and Other Sleep Aids?

Research says that oleamide has similar sleep-promoting effects to other sleep aids, but each case may differ based on its potency or ability of side effects.

Oleamide differs from other sleep aids in several key aspects:

1. Melatonin: Oleamide enhances GABA activity, while melatonin mimics the sleep hormone to regulate the sleep-wake cycle
2. Valerian Root: Both increase GABA for relaxation, but valerian root focuses on improving sleep quality
3. Magnesium: Both affect GABA receptors; magnesium also supports sleep via NMDA
4. Chamomile: Uses apigenin to bind to benzodiazepine receptors for a mild sedative effect, oleamide has long-lasting effects
5. 5-HTP: Oleamide modulates GABA and serotonin, 5-HTP converts to serotonin and melatonin for sleep and mood regulation

How Does Oleamide Stack Against Other Nootropics?

The variability in comparison of oleamide with other nootropics is as follows:

• L-Theanine: It reduces stress and improves focus using GABA, dopamine, and serotonin effects
• Bacopa Monnieri: It enhances memory through improved neuron communication
• Rhodiola Rosea: It acts as an adaptogen to reduce fatigue and boost mental performance
• Piracetam: It enhances cognitive function and memory by increasing neuroplasticity and acetylcholine uptake
• Ashwagandha: It reduces stress and anxiety by balancing cortisol levels and enhancing cognitive function

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2. Huitrón-Reséndiz, Salvador, et al. “Effect of oleamide on sleep and its relationship to blood pressure, body temperature, and locomotor activity in rats.” Experimental neurology 172.1 (2001): 235-243.↩
3. Mendelson, Wallace B., and Anthony S. Basile. “The hypnotic actions of the fatty acid amide, oleamide.” Neuropsychopharmacology 25.1 (2001): S36-S39.↩
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