The Science of CBD: Interactions with the 5-HT1A Receptors

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There’s a lot of hype flying around in the CBD industry these days. Everywhere you look, you see companies doing their best to make fanciful legal claims about the benefits of CBD without stepping on the toes of the U.S. Food and Drug Administration (FDA) or other regulatory agencies. In the midst of these attempts to bill CBD as a panacea, it’s easy to lose sight of the science that made medical professionals and entrepreneurs alike interested in CBD in the first place.

The truth is that there’s nothing magical about the benefits of CBD. The potential usefulness of this substance as a healing tool is rooted in scientifically-demonstrated mechanisms of action that allow CBD to modulate and transform processes in your body that could lead to or worsen physiological or psychological effects if left unchecked. In this series of articles, we’ll explore the various mechanisms of action that science has determined CBD uses to exert its benefits, and we’ll start our exploration of the science of CBD with a thorough look at how this non-psychoactive cannabinoid interacts with the 5-HT1A receptors.

What Are the 5-HT1A Receptors?

If you don’t know what a 5-HT1A receptor is off the top of your head, you aren’t alone. Even most players in the CBD industry would be stumped if pressured to rattle off the relationship between these neuroreceptors and the CBD molecule; the majority of CBD entrepreneurs are simply exploiting the “Green Rush,” and they couldn’t care less about how CBD actually works. Here at CBGenius, however, we do things a little differently, and we believe that clearly and accurately stating exactly how CBD works builds more trust than deceptive marketing and hype could ever hope to.

The 5-HT1A receptor, also known as the serotonin 1A receptor, is the most abundant form of serotonin receptor in the body. Therefore, this neuroreceptor modulates the action of serotonin, which almost everyone knows plays a role in your mood and mental well-being. What you might not know, however, is that serotonin also modulates your blood pressure, heart rate, and appetite. In fact, this single neurotransmitter is responsible for modulating dozens of different critical processes in your body, and increased activation of the 5-HT1A receptors is associated with a wide variety of health benefits.

Definition of Terms

Before we proceed, it’s important to define some of the scientific terms I’ll be using throughout the rest of this article:

  • Agonists and antagonists: In pharmacology, which is the study of how drugs interact with the body, the terms “agonist” and “antagonist” are used to describe the way that different molecules interact with neuroreceptors. An agonist is a molecule that stimulates the activity of a neuroreceptor, and an antagonist is a molecule that blocks or reduces the activity of a neuroreceptor.
  • Autoreceptors and heteroreceptors: Neuroreceptors, such as 5-HT1A receptors, are always embedded into the walls of cells. Autoreceptors only interact with neurotransmitters, hormones, and other signal transmitters that are produced within the confines of their cells, but heteroreceptors interact with signal transmitters that are produced by other cells. 5-HT1A autoreceptors generally serve as serotonin-reducing agents; they inform your cells when they are producing too much serotonin. On the other hand, 5-HT1A heteroreceptors, which are also known as postsynaptic receptors, increase levels of serotonin when they are stimulated.
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Can your 5-HT1A receptors make you happier?

How Do Your 5-HT1A Receptors Impact Your Health?

While the 5-HT1A receptors in your body are involved in a wide variety of physiological processes, the greatest attention has been given to the impact of these receptors on psychological conditions. For instance, scientific inquiry has firmly established that the 5-HT1A receptors play a critical role in the development of depression and anxiety1; while increased activation of these receptors appears to reduce the symptoms of these all-too-common conditions, decreased activation makes anxiety and depression worse.

There’s also evidence suggesting that the 5-HT1A receptors may be involved in the development of psychotic disorders2 like schizophrenia. More and more research indicates that serotonin plays a key role in psychosis3, and it appears that, overall, increased activation of the 5-HT1A receptors leads to increased mental health and stability.

Further Benefits of 5-HT1A Receptor Activation

Science has discovered a wide variety of potential benefits of increased 5-HT1A receptor activation. We’ll list them all here for your reference:

  • Vagus nerve stimulation: The Vagus nerve controls the parasympathetic nervous system action in your heart, lungs, and digestive tract.
  • Fatigue reduction: Research shows that increased 5-HT1A activation may reduce the symptoms of chronic fatigue syndrome (CFS)4.
  • Increased sociability: This effect could be related to the increased production of oxytocin and dopamine caused by 5-HT1A receptor activation.
  • Increased sexual arousal: 5-HT1A activation increases sex drive and arousal in both men and women.
  • Increased learning capacity: 5-HT1A activation appears to increase the production of acetylcholine in the prefrontal cortex, which seems to lead to increased learning ability.
  • Increased dopamine production: The apparent benefits of 5-HT1A for schizophrenia and Parkinson’s disease could be explained by the increased dopamine production this neuroreceptor stimulates.
  • Decreased aggression: By reducing dysphoric perceptions, increased 5-HT1A activation lowers the threshold for triggering angry and violent behaviors.
  • Decreased food intake: Anxiety and depression increase the chances of obesity, and increased endorphin production may help explain the observed ability of 5-HT1A activation to reduce food intake.
  • Decreased cardiovascular stress: 5-HT1A stimulation reduces your heart rate and blood pressure, which takes strain off your heart.
  • Decreased drug use: Increased 5-HT1A activation decreases drug-seeking behaviors.
  • Decreased impulsivity: By stimulating better mental clarity and improving decision-making, increased 5-HT1A activation reduces your tendency to engage in risky behaviors.
  • Decreased nausea: This effect may make increased 5-HT1A activation useful in reducing the side effects of chemotherapy and other nausea-inducing treatments.
  • Decreased pain: Studies indicate that increased 5-HT1A activation decreases mild sensations of pain5. In addition, opioid receptors and 5-HT1A receptors work hand in hand to reduce pain, so increased stimulation of the 5-HT1A receptors should numb overall pain sensations6.

Potential Detriments of 5-HT1A Receptor Activation

Increasing the activation of your 5-HT1A receptors isn’t all sunshine and rainbows. While activation of these receptors causes much more good than harm, there might be some side effects of increased 5-HT1A receptor activation:

  • Penile erection inhibition
  • Increased sleep time before the engagement of REM sleep
  • May interfere with certain forms of learning
  • May reduce physical activity
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Can CBD take your 5-HT1A activation to the next level?

Does CBD Interact with the 5-HT1A Receptors?

All signs indicate that CBD has a robust interaction with the 5-HT1A receptors in your nervous system. Since the discovery of CBD, scientists have been keenly interested in mapping the mechanisms of action of this cannabinoid, and one of the first-discovered potential mechanisms by which CBD exerts its beneficial effects was this cannabinoid’s apparent interaction with the 5-HT1A receptors.

If true, interaction between CBD and the 5-HT1A receptors would go a long way toward explaining the beneficial effects that millions of CBD users around the world have reported. As it turns out, hypothesizing that CBD interacts with the 5-HT1A receptors isn’t just shooting in the dark; a number of studies have been performed that support this potential mechanism of action of CBD.

Studies on CBD and the 5-HT1A Receptors

Here are a few of the most prominent examples of scientific research that has been done into the potential interaction of CBD with the 5-HT1A receptors:

1. Agonistic Properties of Cannabidiol at 5-HT1a Receptors

This 2005 study7 in the journal Neurochemical Research appears to confirm the wildest hopes of proponents of the theory that CBD interacts beneficially with the 5-HT1A receptors. The authors of this study report that “CBD is shown to displace the agonist, [3H]8-OH-DPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner,” which means that it moves a less-effective agonist out of the way at 5-HT1A receptors to exert more powerful effects.

The authors go on to confirm that “CBD acts as an agonist at the human 5-HT1a receptor,” and they conclude that this research demonstrates “that CBD is a modest affinity agonist at the human 5-HT1a receptor.” While a single study on its own doesn’t tell us much about the effects of a substance, the fact that independent researchers determined that CBD acts as an agonist at the 5-HT1A receptors is highly promising and merits further research.

2. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats

The facilitators of this animal study8 entered into their research with the preconception that either stimulation of the endocannabinoid system or the 5-HT1A receptors may be responsible for the previously-reported anxiolytic and antipsychotic effects of CBD. Upon the conclusion of their research, the study’s authors concluded that their results “suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT1A receptor-mediated neurotransmission.”

This study relates in detail how CBD appeared to reduce heart rate in rats exposed to restraint stress, and that “CBD attenuated the increased anxiety behaviour caused by a previous exposure to restraint.” Most importantly, however, their research showed that these beneficial effects of CBD could be stopped by WAY100635, which is a 5-HT1A receptor antagonist.

If a 5-HT1A antagonist stops the anxiolytic effects of CBD, then this evidence supports the theory that CBD acts as a 5-HT1A activator or agonist. The authors of this study conclude by saying that “the present findings indicate that CBD, by activating 5-HT1A receptors, can attenuate physiological and behavioural responses to restraint stress. This finding raises the possibility that CBD could be useful for treating psychiatric disorders thought to involve impairment of stress-coping mechanisms, such as depression and post-traumatic stress disorder.”

3. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats.

This study9 investigated studied the potential interaction of CBD with 5-HT1A receptors at a certain specific site within rat brain anatomy called the dorsolateral periaqueductal gray or dlPAG. The authors concluded that their results “suggest the CBD interacts with 5HT1A receptors to produce anxiolytic effects in the dlPAG.” While the scope of this study was limited, it provides further support for the idea that CBD exerts an agonistic effect at the 5-HT1A receptors.

4. Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism.

This 2005 study examined the potential of cannabidiol to reduce the extent of cerebral infarction10, which is a lack of blood flow to the brain that causes part of the brain tissue to die. The authors of this study knew ahead of time that CBD appeared to reduce the intensity of cerebral infarction, but they weren’t sure how cannabidiol helped with this condition by increasing cerebral blood flow (CBF).

By the conclusion of their research, however, the authors were convinced that “the neuroprotective effect of cannabidiol may be related to the increase in CBF through the serotonergic 5-HT1A receptor.” These results provide even more evidence for the 5-HT1A-activating effects of CBD.

5. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.

This mouse study examined the potential mechanisms behind CBD’s reported anti-depressant effects11. The authors found that “CBD exerts fast and maintained antidepressant-like effects,” and they also discovered that “[b]oth antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade.”

These results indicate that a blockade at the 5-HT1A receptors, which is a chemical mechanism that blocks the activation of these receptors, stopped the anti-depressant effects of CBD, thereby indicating that CBD interacts directly with the 5-HT1A receptors. The authors conclude that their “findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.”

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What’s the Best Way to Use CBD to Stimulate the 5-HT1A Receptors?

Now that you’re familiar with the science behind CBD’s interaction with the 5-HT1A receptors, you’ll need to understand the best ways to use this beneficial cannabinoid to increase this neuroreceptor’s activation to the fullest extent possible. Here are the basics of how to use CBD to boost your mood, reduce psychiatric conditions, and improve your overall health and well-being via 5-HT1A activation:

1. Oral Administration

This route of administration may be the most effective way to enjoy the reported 5-HT1A-activating effects of CBD over an extended period. While oral administration of CBD reduces its overall bioavailability, or the ability of your body to absorb this compound, it also delays the release of cannabidiol. Extended-release mechanisms ensure that you’ll experience the benefits of CBD over a significant duration, which means that oral administration gives cannabidiol the best-possible chance to stimulate your 5-HT1A receptors over the course of a few hours or even a whole day.

Here at CBGenius, we offer a variety of options for oral route administration of CBD. If you want an option with 0% THC, you might prefer our Lemon Lime Mint CBD Oil – 750mg CBD Isolate. If you’d prefer to experience the full benefits of the entourage effect with full-spectrum hemp oil, however, our Full-Spectrum Hemp Oil – 1500mg might be a better choice. Better yet, we now offer a Full-Spectrum CBD-Plus Oil Elixir – 1500mg that combines the benefits of hemp seed oil, full-spectrum hemp oil, and CBD isolate in one super-charged product.

2. Pulmonary Administration

While pulmonary administration of CBD doesn’t last as long as oral administration, this method of using CBD delivers more potent immediate effects. If you’re suffering from an anxiety attack or another type of acute psychological or physiological condition, inhalation of this cannabinoid may be the best way to experience the reported 5-HT1A-boosting effects of CBD.

You can use a CBGenius Flavored Prefilled 200mg CBD Vape Cartridge to deliver CBD directly into your bloodstream via the alveoli in your lungs. With flavor options like Strawberry Cream, Vanilla Banana Berry, Lemon Lime Mint, and Apple Pie, this high-end and affordable CBD-rich hemp oil product is designed to fit the tastes of every CBD vape liquid connoisseur.

3. Topical Administration

Topical administration of CBD is likely the least-effective way to use this substance to boost the activity of the 5-HT1A receptors. These receptors are most concentrated in the brain, and any CBD that you administer locally via transdermal absorption only uptakes into your bloodstream in tiny concentrations.

If you want to boost the effects of the 5-HT1A receptors in other parts of your body, however, topical administration might be an effective choice. Topical products like our CBGenius CBD Infused Hand & Body Lotion 1000mg CBD deliver a water-based CBD formula directly to the underlying tissues at the area of administration, which can result in more potent effects in a localized area of your body.

CBD and the 5-HT1A Receptors: The Bottom Line

To sum it all up, the main factors worth consideration after reviewing the evidence I’ve put together are:

  1. The 5-HT1A receptors are keenly involved in a vast array of different physical processes;
  2. Increasing the activation of these receptors appears to improve your overall physiological well-being, and increased 5-HT1A receptor activation also appears to directly combat anxiety and depression;
  3. CBD appears to be an incredibly potent 5-HT1A agonist, which means that it increases the effects of this neuroreceptor;
  4. Therefore, the evidence suggests that CBD may improve your health and well-being in all the same ways that 5-HT1A activation, in general, makes you healthier and happier.

Increased 5-HT1A activation would explain a lot of the anecdotal testimony that has been collected regarding the beneficial effects of CBD. In addition to decreasing anxiety and depression, CBD also appears to reduce the sensation of pain, and it also shows promise as an addiction treatment. Far from being mysterious and vague, the potential benefits of CBD are highly specific, and understanding more about the interaction of this cannabinoid with your 5-HT1A receptors begins to lift the veil off the misinformed marketing jargon that’s rampant in the CBD industry and clarifies the exact scientific mechanisms of action by which this non-psychoactive cannabinoid exerts its reported healing effects.

As we continue our “Science of CBD” series, we’ll explore all the potential mechanisms of action of this beneficial cannabinoid in detail. Increased activation of the 5-HT1A receptors isn’t the only specific beneficial mechanism of action of CBD that science has illuminated; far from it. As you’ll discover, the benefits of CBD aren’t just based on snake-oil claims and animal studies; there are clear and distinct mechanisms by which this cannabinoid interacts with your neurochemistry and physiology to deliver incredible results. Stick with me as I continue to unveil the science behind CBD and explain why CBGenius products deliver the most science-based CBD benefits on the planet.


  1. 5-HT1A receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function
  2. 5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies
  3. The Role of Serotonin in Schizophrenia
  4. Genetic evaluation of the serotonergic system in chronic fatigue syndrome.
  5. Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception
  6. μ-Opioid and 5-HT1A receptors heterodimerize and show signalling crosstalk via G protein and MAP-kinase pathways.
  7. Agonistic properties of cannabidiol at 5-HT1a receptors.
  8. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats
  9. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats.
  10. Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism.
  11. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.