CBD and Zoloft: what to know before using both

by Apoorva Shivankar, M.D

CBD and Zoloft

It’s quite evident by now that Cannabidiol (CBD) is an efficient mind-healer. It fights against almost every ailment that disturbs your mental peace including the most common anxiety, stress, pain, and depression.

But CBD is not the only one helping us here, we also know that a number of other prescription antidepressants like SSRIs (Zoloft), TCAs, SNRIs, MAOI’s are also well-established in treating such conditions.

What we don’t know is,

Does CBD oil interfere with Zoloft?

Is it safe to use this oil with Zoloft?

How will they perform together? 

Enhanced actions or increased risk?


On this page, we shall be dealing with the if’s and but’s of the concurrent use of CBD and Zoloft., the two well-known antidepressants.

Before we begin, a quick overview of what CBD and Zoloft are actually.

Cannabidiol (CBD)

Cannabidiol is extracted from industrial hemp, a variety of cannabis plant. In spite of the origin, these cannabis products are legal and won’t get you high as their content of psychoactive THC is strictly limited to <0.3%. CBD is already ruling the medical world due to its immense therapeutic potential benefitting almost every ailment right from skin acne to sleep disorders.

All this comes by virtue of its ability to modulate the most efficient homeostatic regulator of our body – THE ENDOCANNABINOID SYSTEM(ECS)- which regulates mood, cognition, stress, hunger, pain relief, sleep, boost the immune system, among many others via cannabinoid receptors and endogenous cannabinoids.

Any deviation from normal such as anxiety disorder, pain, sleep disorder, inflammation, depression, etc. are the after-effects of this ECS deficiency. CBD restores this deficiency by preventing the breakdown of endogenous cannabinoids and thus, keeps ECS working. In this way, cannabidiol restores the balance and relieves the symptoms of varied illnesses.


Zoloft is a popular, FDA-approved commonly prescribed antidepressant that contain the chemical Sertraline, an SSRI (Selective Serotonin Reuptake Inhibitors).

As the name suggests, they work by inhibiting the reabsorption of serotonin in the nerve cells and thereby increase/restore serotonin levels in the brain. This serotonin fondly referred to as the ‘Happy Hormone’, is a neurotransmitter/chemical messenger which transmits the mood-elevating signals between the neurons in the central nervous system.

It positively influences your overall mood, social behaviour, appetite, sleep, memory, mental health, and even sexual behaviour and hence, is a drug of choice to restore the interest in daily living in patients suffering from OCD, panic disorders, depression, severe premenstrual syndrome, etc.

The unfortunate part is that SSRIs come with a host of unwanted side-effects like nausea, vomiting, headache, nervousness, agitation, restlessness, dry mouth, diarrhoea, weight alterations, etc. However, what takes a great toll on SSRI use is the well-documented fact that some people using SSRI below the age of 25 years tend to experience suicidal thoughts.

To add to the agony, stopping the use of SSRIs can lead to withdrawal effects like nausea, lethargy, flu-like symptoms, uneasiness.

What do they have in common? 

Both CBD and Zoloft can:

  • treat anxiety, depression, memory defects, confusions.
  • promote a sense of calmness and relaxation to improve mental health.

This provokes the thought process that with an intention to maximize effectiveness.

Can you take CBD while on antidepressants?

  • It’s been advised to use SSRIs cautiously in patients with health issues like seizures, hypertension, kidney or liver disease, etc. Here the addition of CBD can be logical as apart from the antidepressant effect, CBD also exhibits strong anti-seizure, and blood pressure lowering benefits.

    Furthermore, CBD can even reduce inflammation and stress in the overall body especially in the liver and kidneys.

  • CBD being rapid-acting as compared to sertraline (takes weeks to show effect), can take care of the situation till the Zoloft effect sets in.

  • Plus, you enjoy some additional CBD benefits too like cosmetic gains, better immunity and many more.

  • Evidences suggest that CBD can lower the effective dose of Zoloft required and can even ease out SSRI withdrawal symptoms if needed.

But while thinking of these combination benefits, jumps in the concern:

Can taking together add on their adverse effects too?

Yes, as the positives, even the common negatives of CBD and sertraline (dry mouth, drowsiness, dizziness, and decreased concentrating ability) can add up validating above-mentioned question.

To confirm this, let’s dive deeper

Does CBD interact with SSRI?

With the available research on these antidepressants, we realized that the researchers have split opinions regarding the CBD oil - SSRI drug interactions.

Science says,

CBD is broken down by the Cytochrome P450 enzyme system in the liver. The same CytoP450 is also involved in the metabolism of several other drugs including SSRIs. Hence when taken together, they compete for the same.

In addition, studies have shown that CBD products while undergoing metabolism can competitively inhibit 3 enzymes of the cytoP450 family, thereby slowing down SSRI processing. Decreased/ Sluggish breakdown of SSRI leads to their accumulation in serum and may result in the following outcomes:

  • Even when consumed in lower doses, higher serum concentrations are achieved making SSRIs more potent.
  • Slower metabolism keeps the drug in circulation for a longer duration, decreasing the need of frequent dosing.
  • Accumulation can aggravate unwanted side-effects like increased dizziness, drowsiness, hypotension, nervousness, etc.
  • If SSRIs are taken in higher but acceptable amounts, the addition of CBD can land you up in extremely high serum levels resulting in Serotonin Overdose Syndrome characterized by agitation, confusion, dilated pupils, headaches, nausea, vomiting, rapid heart rate, diarrhoea, muscle twitching, tremors, heavy sweating, changes in blood pressure, etc.
  • It is also noticed that the elderly population might experience impairment in thinking, judgment, cognition and motor coordination when sertraline is taken alongside CBD.
  • On the flipside, it’s equally possible that higher quantities of Zoloft utilize the enzyme CytoP450, leaving very smaller amounts to degrade CBD. This can increase the potency as well as the duration of action of CBD or can precipitate overdose too.

Thus, the combination of Zoloft and CBD carry both positive as well as negative influences on the body.

Added confusion

There are few studies that nullify the interactions of these two medications stating that

  • CBD cannot inhibit the CytoP450 with regular doses. A much higher dosage is required to produce these drug interactions.
  • Though CytoP450 is the dominant sertraline degrading enzyme, there are many other minor enzymes involved in sertraline metabolism which can take over if CytoP450 is inhibited by CBD.

Taking into account all these varied possibilities of increased potency, longer duration of action, overdose toxicity, enhanced side-effects or no interaction at all, it is better to go with your doctor advice who will decide whether to go for or not to the combination based on your condition. Also, he will adjust the dose for you to minimise untoward effects and reap the best possible outcome.


We do have some tricks to share to avoid CBD and Sertraline adverse drug interactions while using both.

  • Adjust the Timing: Space out

You can use both CBD and Sertraline but with a significant time gap in between to avoid any excessive burden on CytoP450 at one stretch. This space-out time can be based on the half-life of the drug and will metabolize one drug at a time, facilitating the availability of enough enzymes for each of them and even skip the inhibitory effect.

  • Forms

Intravenous, sublingual tinctures, topicals or inhalational forms of CBD can directly reach the bloodstream bypassing the GI tract and liver, unlike oral CBD oil or pills. Hence, CytoP450 is spared for sertraline and the tussle for CytoP450 can be constrained.

What drugs should not be taken with CBD oil?

By competitively inhibiting the important liver enzyme, CytoP450, CBD oil can alter the metabolism of a number of other drugs. When taken with CBD, CBD and drug interactions result in decreased or increased drug absorption.

This altered absorption, in turn, may lead to reduced drug effects, or an increased risk of overdose toxicity and side effects. Owing to this, the health authorities strictly issued a ‘use with caution’ warning for taking CBD oil with some prescription medications like:

  • Blood thinners (warfarin)
  • Anti-seizure medications (clobazam, lamotrigine).
  • Antidepressants (fluoxetine, Prozac)
  • Antipsychotics (Benzodiazepines)
  • Cholesterol-lowering agents
  • Macrolide antibiotics (erythromycin, clarithromycin)
  • Cardiac medications, precisely calcium channel blockers, heart rhythm medication (amiodarone)
  • Thyroid medications (levothyroxine)
  • Oral Hypoglycaemic Agents (sulfonylureas, meglitinides)
  • Antihistamines
  • Antiretrovirals.

Final word

Mixing medications is no child’s play as by doing so we are messing up with the biochemical make-up of the body. With not much research data available, the results of taking both Zoloft and CBD together are still unpredictable.

They vary with the individual dosages, time gap, severity of symptoms and even bodily responses. So, to be on the safer side, we suggest to follow your doctor advice before combining these two drugs and follow the smart approach like spacing out the two medications and micro-dosing CBD.

It goes without saying,

  • Seek clean and safe tested products.
  • Start low go slow.
  • Watch for effects and side-effects.
  • Monitor, document, share your results and adjust the dosage accordingly with healthcare provider.
  • Re-titrate and reduce Zoloft dose by checking its effectiveness with CBD.
  • Avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you.


How long can CBD stay in human body?

It depends on patient’s weight, metabolism, dose and form of CBD products taken, its purity, etc. On average, CBD can stay for somewhere between 2-5 days in the users.

Is CBD oil a prescription medication?

No, it is available over the counter as a health food supplement.


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