5-HT1A: The Serotonin Receptor


Most modern treatments for depression target the serotonin system, but they can take weeks to take effect. Is targeting 5-HT1A a better option?


The antidepressant drugs available today work by targeting the serotonin system, blocking the recycling of serotonin and keeping it in the spaces between neurons. This allows it to be active for far longer than it would be otherwise.

The issue with these drugs is that they take a long time to have any sort of obvious impact.

Often, it can take many weeks, and in that time, a patient’s frustration with side effects will grow as the desired effects of the medication are not yet being felt. A person wrestling with depression may be in a precarious mental state, and any additional time before the drugs kick in is potentially risky.

And who’s to say the drugs will work at all?

The patient may need to undergo a period of trial and error to find the correct medication for him or her, and any delays in identifying the necessary drug or dosage will only be detrimental to his or her care.

Scientists, therefore, are looking for new antidepressant mechanisms in an attempt to create more effective medication.

But could the gateway to a faster and more effective treatment for depression be in our brains all along?



Introducing The 5-HT1A Receptor


By targeting a specific serotonin receptor, it is thought that antidepressant drugs could work faster. And this specific receptor is called 5-HT1A.

Found on the surfaces of cells, receptors are proteins that bind with chemicals, causing a reaction by either opening a channel or starting a signal to make a neuron fire. What it ends up doing depends on the type of receptor as well as where in the brain it is located and on what type of cell.

The 5-H1TA receptor is found throughout the brain. Sometimes, it can be observed as an autoreceptor on a serotonin neuron. Other times, it is on other neurons in the cortex, where it can produce different effects. But it’s the receptor’s role as an autoreceptor that could be the game changer for antidepressants.

You see, most antidepressants are tasked with increasing the levels of serotonin available in the brain. This means that they hit the receptors more often. The dorsal raphe (the brain’s largest serotonergic nucleus, which provides a substantial proportion of the serotonin supply to the forwardmost part of the brain) uses 5-H1TA receptors as a means of gathering feedback. When the serotonin hits them, they signal that there’s enough serotonin, causing the raphe to rein in the release.

In a normal state, there’s absolutely no issue with this response. However, in a depressed state, this can limit the impact of antidepressants as it fights against the drugs. There may be more serotonin present due to the antidepressants, but there’s also less being released due to the 5-HT1A receptors.

Over time, the receptors will become desensitized, and the raphe will begin to release normal levels of serotonin, which, along with the antidepressants, will ensure there is more serotonin present, lifting the mood of the patient.

In theory, if the 5-HT1A receptors were immediately desensitized, then the antidepressants could get to work faster, increasing those levels of serotonin by preventing the usual feedback.



What Impact Does CBD Have on This Receptor?


Research conducted by the University of Sao Paulo in Brazil and by King’s College in London has revealed that, at high concentrations, CBD directly activates the 5-HT1A receptor.

The 5-HT1A receptor has been implicated in a number of processes, both biological and neurological in nature. This includes but is not limited to anxiety, appetite, addiction, pain perception, nausea, sleep, and vomiting. When the receptor is triggered, it will produce either an excitatory or an inhibitory response, depending on the chemical that has triggered it.

Activating the receptor using CBD produces the inhibitory response, therefore preventing the 5-HT1A receptor from signaling to slow down or stop the production of serotonin.



Related Uses for CBD


With the observed activation of the 5-HT1A receptor, it is believed that there are a number of possible advantages associated with the use of CBD. 

CBD has not been associated with any major side effects, further underlining it as an appealing strategy.

CBD isn’t known for producing feelings of euphoria. However, there is some evidence that points to its potential to enhance serotonin production. While the severely depressed will be unlikely to solve their depression via the use of CBD alone, the fact that CBD targets the 5-HT1A receptor as well as the CB1 and CB2 receptors suggests that it could facilitate serotonin improvement for certain individuals. And, unlike current antidepressants, which take weeks or months to take effect, studies suggest the impact of CBD-induced serotonin production could be felt almost immediately, meaning there is little need for daily administration.

There has been speculation that the use of CBD could actually be used simultaneously with “first-line” pharmaceutical agents. The likelihood of CBD interfering with these agents is minimal, so it could be used at the same time, taken on an “as required” basis.

While it is impossible to confirm that the use of CBD will reduce these symptoms in all users, most of the evidence seems to be positive.



What Does the Future Hold?


Coming to fully understand CBD’s impact on certain receptors, such as the 5-HT1A receptor, could help bolster medical marijuana’s reputation as a legitimate and effective solution.

That being said, there is a great deal of research to be carried out before we know for certain just how well cannabinoids can help inhibit these symptoms.

While there’s a long way to go, the early studies point to a promising future.


What do you think about utilizing the 5-HT1A receptor to improve antidepressants? Have you had any experience waiting for prescription antidepressants to kick in? Tell us about your experience with prescription antidepressants (or other remedies you’ve used to combat mood disorders) below. 


And, as always, feel free to ask us questions.