Antidepressants and CBD oil can and do interact, but there seems to be little dependable data available on the topic. It appears that CBD oil and antidepressants interact through the body’s metabolizing system, and they both have a neurologic effect with possible interactions in some neural pathways. Let's dive a bit deeper and untangle this connection.
Let’s start with the body’s metabolizing system.
One of the body’s essential processes is to eliminate foreign compounds or xenobiotics. One of the main sites of drug metabolism is the liver. When we take in food or medicine, it gets broken down in the stomach and small intestine before compounds extracted from the food are taken to the liver for detoxification. After metabolism, they are distributed throughout the body via the circulatory system.
The metabolic process in the liver is complex, so it’s sufficient to know that the cytochrome P450 system, or CYP450, is involved in the first phase of this process. CYP450 comprises a family of enzymes or proteins that are found throughout the body but are highly concentrated in liver cells or hepatocytes. These enzymes are primarily responsible for the degradation and elimination of drugs in the body. 
Why Is it Important to Know about the CYP450?
It is important to know about this topic because of what is commonly referred to as drug-drug interaction. CYP-mediated drug interactions can cause either supra- or subtherapeutic levels of a drug in your system, and, in some cases, its effect can be lethal. Certain medicines should never be taken simultaneously, and your doctor will usually alert you to it.
With CBD, this interaction is not necessarily always a bad thing, though. For instance, cannabidiol has been shown to increase the potency of clobazam, an anti-epilepsy drug, which means that the drug dose doesn’t need to be very high. This augurs well for epilepsy patients who battle adverse side effects common to high-dose clobazam. 
However, what is the case with CBD and depression treatment, as well as drug-drug interaction?
Antidepressants and CBD Oil Interactions
Well, for starters, all antidepressants are metabolized in the liver by the CYP450 system with known drug interactions. Similarly, CBD as a compound is a potent inhibitor (agonist) specifically of the CYP2C19 pathway in the CYP450 system. That’s bad news, right? Maybe not…
The good news is that currently there seems to be little evidence of clinically significant interaction between antidepressants and CBD oil. As it stands, the only compound in cannabis that should be monitored for possibly severe interactions with antidepressants is tetrahydrocannabinol or THC.
THC, while also healthy, is the psychoactive element that causes the “high” marijuana is known for. Usually, it’s a pleasant sensation, but THC is unfortunately also known to cause psychosis in some individuals, especially if overused and in high doses. Furthermore, THC binds to endocannabinoid receptors mainly found in the brain with pronounced neurologic action. Antidepressants also access neural pathways for treatment, so interaction with THC is highly possible.
In contrast, CBD seems pretty safe. However, it is important to note that some people could be either hypersensitive or non-responsive to antidepressants because of specific enzyme polymorphism. In very simple terms, “polymorphism” means that some individuals are genetically disposed to metabolize antidepressants differently and should probably take greater care when using CBD products concurrently. 
Also, you need to be aware of CBD’s neurologic effects if you take a selective serotonin reuptake inhibitor (SSRI) such as Prozac, Luvox, or Zoloft.
CBD Oil and Neural Pathways
In a 2010 research paper published in the British Journal of Pharmacology, CBD has been shown to induce anti-anxiety and antipsychotic effects in animal subjects, mediated by the activation of 5-HT1A receptors. Why is this significant? SSRIs are involved in similar neural pathways, and while there’s no hard evidence that taking CBD oil with this class of antidepressants is harmful, caution is probably well advised. 
This study points to good news, though, because it and plenty of other research seem to suggest that CBD oil, especially in higher doses, has distinct antidepressant and anxiolytic properties.
This could mean that you should be able to switch from pharmaceutical antidepressants to CBD oil to manage depression and anxiety. This could be preferable, especially because CBD oil is safe to take and has almost no chronic or harmful side effects.
It is inadvisable that you switch treatment on your own, though, so be sure to consult with your prescribing doctor first.
Let’s look at more studies that support the notion that CBD oil could be a good replacement for antidepressants.
CBD Oil for Anxiety and Depression
Numerous pre-clinical and clinical studies indicate that CBD shows therapeutic action in a significant number of psychiatric disorders, including depression and anxiety. Anxiety tends to present in the majority of those diagnosed with depression as well, so CBD’s action against both is nothing but great news.
A small, placebo-controlled human study published in 2003 using functional neuroimaging to investigate how CBD’s anxiolytic effects are centrally mediated demonstrates that “CBD significantly decreased subjective anxiety and increased mental sedation, while placebo did not induce significant changes.” The authors conclude that CBD’s anti-anxiety properties were brought about by action in the limbic and paralimbic areas of the brain. These areas include parts of the brain associated with emotional regulation and fear responses. 
Another review, Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders (2012), supports the notion that CBD action is 5-HT1A-mediated in key areas of the brain and adds that “5HT1A receptors modulate responses to stressful stimuli and are proposed to mediate the effects of antidepressant drugs.” In other words, CBD has the same effects as pharmaceutical medicine for depression, according to the authors.
Exposure to prolonged and catastrophic stress is a key causative factor in depression. The authors of the same review noted that “one of the first studies that indicate the presence of antidepressant-like properties in CBD, focused on its ability to prevent the autonomic and behavioral consequences of inescapable stress.” Rats were injected with high doses of CBD and later submitted to restraint stress for an hour. Their stress responses were then tested, and these were shown to be significantly reduced due to the CBD. 
Yet another 2014 review of studies of animal models using CBD as an anxiolytic and antidepressant compound concluded “...that CBD exhibited anti-anxiety and antidepressant effects in animal models discussed...Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.”
However, thorough research into CBD’s action against depression is still in its baby steps, and successful treatment is largely anecdotal. There is clearly a need for more robust, clinically significant investigation, into especially the mechanisms of CBD’s therapeutic action in mood disorders. 
How to Take CBD Oil With Antidepressants
- If you are already on antidepressants and wish to take CBD oil concurrently or make a switch to use it exclusively, first visit your doctor for recommendations. This might especially be necessary for those on SSRIs, as immediate antidepressant dose adjustment might be needed.
- If you are on medication on top of antidepressants, such as beta blockers (high blood pressure meds), blood thinners, and the like, don’t take CBD oil without consulting your doctor first. In low concentrations, CBD might not have any noticeable effect, but therapeutic doses (for depression and anxiety) are usually high and could interact negatively with these medications.
- Then, make sure that the CBD oil you take is of high quality with low THC content. High doses of this other cannabinoid could interact badly with antidepressants.
- Also, start with a small dose of CBD oil, and increase slowly over a period of time.
For most, CBD oil and antidepressant interactions are not likely to be a problem, and CBD could possibly replace antidepressants as a successful treatment. As stated, so far research suggests that CBD has an excellent safety and side effect profile in general, but more study is needed to confirm how it works against depression in humans.