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Can CBD Replace Zoloft as an Antidepressant?

Depression has become a chronic problem among millions of people worldwide, with around 17.3 million adults suffering from at least one major depressive episode in the US in 2017, i.e. 7.1% of America’s adult population.

This spike in cases of depression and mental disorder has led to prescription antidepressants flooding the pharmaceutical market.

Zoloft is the brand name of one such antidepressant drug, known as Sertraline. This antidepressant is usually the first line of treatment for most patients, with anxiety, depression, panic attacks, premenstrual dysphoric disorder (PMDD), obsessive-compulsive disorders (OCDs), and post-traumatic stress disorders (PTSD), among others.

Belonging to a class of medications, called selective serotonin reuptake inhibitor (SSRI), Sertraline targets the chemical imbalances within the brains of such patients. It is said to boost the mental health of patients with depression.

But at what cost?

Studies indicate that Zoloft can cause certain unwanted side-effects, like dizziness, drowsiness, confusion, hallucinations, trouble concentrating, decreased libido, aggressiveness, diarrhea, fever, convulsions, among others. Some of Zoloft’s side-effects can even be life-threatening too!

Besides, if taken with certain medications (like blood thinners, non-steroidal anti-inflammatory drug/NSAIDs, etc.) or alcohol, Zoloft can further aggravate the individual’s condition.

Patients put on sertraline are also told to avoid activities that need mental alertness and focus, such as driving or operating heavy machinery.

That is why many patients voluntarily, or under their doctor’s guidance, move shift to CBD products. CBD is seen by many as a safer, more viable, potent, and an incredibly effective option over popping antidepressants.

Is CBD a Safe & Effective Alternative to Zoloft?

Cannabidiol, a cannabinoid and a chemical extract of cannabis plants, is unlike most other chemicals found in these plants.

For one, unlike its psychotropic sisters (like THC), CBD doesn’t cause intoxication, hallucinations, or dependence, and has no psychotropic properties.

Instead, anecdotal evidence points to CBD’s abilities to help people manage typical symptoms of depressive disorders. Several studies, too, have reinforced this understanding.

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These have given many patients on antidepressants a ray of hope, and several others a fresh lease of life!

Moreover, CBD doesn’t cause the kind of side-effects one may expect from antidepressants. It has been found to have a much safer profile than most prescription medications, illicit drugs, and other natural intoxicating substances, like marijuana, opium, etc.

So far, many have come to accept CBD as a better alternative for the treatment of depression.

But what is the scientific basis of such claims? Can CBD really help combat depressive disorders? Let’s find out what researchers have found out so far…

Can CBD Replace Zoloft?

CBD and prescription drugs behave quite differently in the human body. However, some studies have proven CBD’s efficiency in helping patients with depression just as much as Zoloft does.

  • A 2018 study, published in the Frontiers in Immunology, demonstrates how CBD could be a potential medication to treat depression. The researchers examined the clinical and experimental uses of CBD in this study and found proof of CBD’s anxiolytic and antipsychotic properties.
  • An earlier study, published in the Brazilian Journal of Psychiatry in 2008, had also come to the same conclusion. The researchers pointed out that studies on CBD for the past 45 years have shed new light on its “wide range of pharmacological effects, many of which being of great therapeutic interest…” However, they said more clinical trials were needed to confirm that.

Further studies revealed that CBD’s antidepressant-like effects have something to do with its interaction with the serotonin receptors in the brain – something that CBD has in common with Zoloft, which is a selective serotonin reuptake inhibitor.

  • According to a 2018 study, published in the Progress in Neuro-Psychopharmacology & Biological Psychiatry, CBD’s abilities to combat depression are linked to the positive effects it has on the serotonin receptors in the human brain and is directly “dependent on serotonin levels in the central nervous system”.

Certain studies have also turned to the rationale of using the endocannabinoid system as a potent target for addressing mood disorders.

  • A 2009 research, published in Trends in Pharmacological Sciences, studied the therapeutic potential of the endocannabinoid system (ECS) for developing anti-depressants. The study’s preclinical findings supported the idea of the “clinical development of agents” that inhibit the breakdown of endocannabinoids in the body for successful treatment of mood disorders, like depression.

Since we are on the topic of replacing antidepressants with CBD, some studies have shown that CBD behaves similarly to some antidepressants.

  • A 2010 study of the animal model, published in the British Journal of Pharmacology, established that CBD has more benefits than most antidepressants. According to the researchers of the study, it must have something to do CBD’s activation of 5-HT1A receptors.

However, these studies don’t directly confirm that CBD can replace Zoloft. We can only derive that the former has antidepressant effects. How far it will impact an individual with depressive disorders is another issue.

Nevertheless, proof of CBD’s antidepressant-like effects may be found in abundance in the public domain.

  • A 2014 review, published in the CNS & Neurological Disorders – Drug Targets, further confirmed CBD’s anti-anxiety and antidepressant effects in animal models. It added that CBD does not demonstrate the activation of neuroreceptors CB1 and CB2. Instead, studies show a “good interaction between CBD and the 5-HT1A neuro-receptor”.

Recent studies have further revealed that CBD promotes both rapid and sustained antidepressant effects in animal models.

  • According to a 2019 review, published in the Journal of Chemical Neuroanatomy, CBD has a complex pharmacology, making it a unique compound. The review shed light on a few such aspects of CBD:
    • CBD can interact with multiple neurotransmitter systems involved in depression, such as the serotonergic, glutamatergic, and endocannabinoid systems.
    • CBD can induce cellular and molecular changes in areas of the brain associated with depression neurobiology.
    • CBD also induces cell regeneration in the hippocampus – a part of the brain that controls moods, motivation, memory, and learning.

These studies are in no way exhaustive or conclusive. More randomized clinical trials need to be carried out to support the rationale that CBD can indeed replace strong prescription antidepressants, like Zoloft.

However, if we were to compare the pros and cons of the two – CBD and Zoloft – it may seem that a natural cannabinoid, which has a few side-effects, maybe a better option than such strong prescription drugs – even if the effects of the former may be slower than most drugs.

However, one should never stop Zoloft just to try out this new substance, without confirming it with a doctor first. Doing so may cause withdrawal symptoms, like irritability, nausea, dizziness, nightmares, and headaches.

Drug Interactions: Can CBD Be Taken Along With Zoloft?

While there are no exact studies on sertraline-CBD interaction, it is a derived understanding that combining the two may be risky, like in the case with most antidepressants.

According to some reputed sources, mixing the two may aggravate Zoloft’s side-effects, like dizziness, confusion, disorientation, etc.

Some, more vulnerable, groups of people, like the elderly and those with comorbidities, may experience additional effects, like impairment of thought and judgment, and lapses in motor coordination.

Here are a few facts we DO know about CBD-Zoloft interaction:

  • Zoloft is an SSRI that requires certain CYP450 enzymes, such as CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP2D6, to metabolize and reach the bloodstream.
  • Studies indicate that CBD could inhibit many, if not most, of these CYP enzymes, including CYP2C9, CYP2C19, CYP3A4, CYP2D6, among others.

This points to the possibility of CBD hindering the normal break down of Sertraline, leading to the drug remaining in the bloodstream for a longer period, wreaking more physical and psychological havoc.

However, some studies indicate that the interaction between the two is not significant enough to cause any serious damage.

  • According to a comparative study, published in the Drug Metabolism and Disposition in 2005, the blood concentrations of any two compounds, including sertraline, required to impact the functioning of the CYP enzymes involved is much more than the normal dosage prescribed, and, that multiple enzymes are involved in sertraline metabolism, suggesting that “there should be no single agent that could substantially alter the pharmacokinetics of sertraline”.
  • Another 2014 review, published in the Drug Metabolism Reviews, indicates that “CBD inhibition of major human CYP-450 isoforms reflect a low risk” of drug interactions…”.

These studies partially indicate that CBD and Zoloft may interact mildly and that this interaction may be manipulated by appropriately adjusting the dosage.

Parting Thoughts: CBD or Zoloft?

As CBD products gain popularity in America as a potent therapeutic agent for treating depression and other psychological disorders, more research is being conducted worldwide to better understand CBD’s properties and pharmacology.

While CBD has only a few, mostly mild and benign side-effects, this substance can still interact with other prescription drugs, like Zoloft, aggravating their side effects.

It’s also not wise to suddenly quit antidepressants – if you ARE on one. It’s better to consult with your doctor to find the best way to wean off them, that is, only if he considers it safe and apt for your specific pathology.

Ivan writes about Cannabis at The Cannabis Radar. He has a degree in Nutrition Sciences from University of Oklahoma Health Sciences Centre. He likes to spend his spare time reading to his daughter or spending time with his wife.

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