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CBD and Wellbutrin: Can CBD Effectively Replace Wellbutrin?

Wellbutrin or Zyban – some of the brand names of antidepressants that you may be familiar with – contains Bupropion, an NDRI* medication often used to treat the major depressive disorder (MDD), motion sickness, insomnia, seasonal allergies, as well as to enable smokers to kick the butt!

If you’re reading this article it could mean one of two things:

  • You must be struggling with the side effects of Bupropion (or what you know as Wellbutrin), or
  • You are suffering from one of the above-mentioned conditions and are looking for a more side-effect-free way out.

And you’d be right in looking for a way out. After all, in either case, you must be aware of the wide range of severe effects that Wellbutrin (Bupropion) can cause.

Can CBD Replace Wellbutrin as an Effective Antidepressant?

There’s no denying that CBD (Cannabidiol) has been the rage for the past couple of years, with no sign of relenting!

From edible products to tinctures, from bath and beauty products to vape products, from capsules to topical balms, CBD seems to be everywhere. Marketed as a natural, holistic, safe, and effective way to manage a wide variety of health issues, CBD seems to be helping a lot of people.

While research is still on into how CBD impacts our system and the various ways it can help us, people from around the world have been singing praises of this natural substance – that happens to a close cousin of an intoxicating substance that gives people the marijuana “high”.

So, Can CBD work as an Antidepressant?

There’s been quite a bit of research on this for many years now.

Even though CBD works on our bodies quite differently from prescription drugs, it has proven to exhibit similar effects as an NDRI by interacting with the endocannabinoid system.

  • According to a 2017 study, published in the Frontiers in Pharmacology, CBD, “either acutely or repeatedly administered, induces plastic changes on the human brain”, quite similar to clinical antidepressants or atypical antipsychotic drugs.
  • Another 2018 study, conducted by the University of São Paulo and published in the Progress in Neuro-Psychopharmacology & Biological Psychiatry, found evidence of even small doses of CBD exhibiting “antidepressant-like effects”, depending on the level of serotonin in the body. This is quite similar to NDRIs, the effects of which are dependent on the body’s dopamine level.

What’s more, CBD not only encourages neurogenesis (i.e. formation of new brain cells) and cell regeneration but may also have neuroprotective properties – benefits that are not observed in NDRI use.

  • This is was exhibited in a 2013 study by the University of São Paulo, published in the Current Neuropharmacology. The focus of the research was to establish CBD’s relationship to neurogenesis and cell regeneration, which is believed to alleviate depression.
  • Additionally, a 2016 review, published in the Pharmacological Research, revealed that “CBD exhibits a broad spectrum of other possible therapeutic actions”, including anxiolytic, antipsychotic, antidepressive, and neuroprotective properties, which can address and treat a wide range of psychiatric and neurodegenerative disorders.

The reason why CBD (a cannabis extract) doesn’t behave the way cannabinoids, like THC, do is perhaps because it doesn’t directly bind with the endocannabinoid system. Instead, it interacts with the 5-HT1A neuroreceptor that, in turn,

  • A 2014 review, published in the CNS & Neurological Disorders-Drug Targets, tested CBD as an anxiolytic-like and antidepressant-like compound on animal models. The research confirmed that CBD indeed exhibits these properties. Additionally, the scientists also found evidence that CBD does not activate the neuroreceptors CB1 and CB2. Instead, it interacts quite well with the 5-HT1A neuroreceptor, which is involved in regulating the brain’s anxiety and depression mechanisms.

CBD doesn’t just interact with the Endocannabinoid System to influence the depressive mechanisms of the brain. Studies show that CBD has “complex pharmacology, with the ability to interact with multiple neurotransmitter systems involved in depression”, including the serotonergic, glutamatergic, and endocannabinoid systems.

  • This was established in a 2019 study, published in the Journal of Chemical Neuroanatomy. Besides, the scientists also found evidence of CBD inducing cellular and molecular changes in areas of the brain linked to depression, while also promoting neurogenesis in the hippocampus. Hippocampus, a section of the brain responsible for motivation, emotion, learning, and memory, is believed to shrink under the impact of chronic depression.

Most of the above studies point to CBD’s abilities to:

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  • Alleviate depression and anxiety,
  • Protect nerves from damage due to such neuropsychiatric disorders,
  • Enable the nerves to regenerate on a cellular level, and
  • Help patients recover from such conditions.

Fresh evidence has emerged that indicates towards CBD helping people recover from their depressive disorder, even when antidepressants fail.

CBD can even help people, who have been thrust into multiple substance abuse (due to chronic depression and social anxiety), give up their drug dependence without displaying any withdrawal symptoms.

This is what was seen in an adolescent, with multiple-substance abuse disorder (cannabis, Cocaine, Ecstasy, MDMA), severe depression, social phobia, and narcissistic personality disorder.

  • A February 2020 study, published in the Neuropsychiatrie, revealed how this 16.9-year-old patient recovered completely after 8 weeks of treatment with CBD. The patient was given CBD capsules, starting from 100 mg, which was gradually increased to 600 mg). Incidentally, the patient had earlier been unsuccessfully treated with antidepressants. While the patient was able to tolerate this new substance quite well, the CBD treatment helped stop the antidepressants the adolescent was put on. The patient’s depressive behavior, anxiety symptoms, including phobias, paranoia, and dissociation, were all gone too. So much so, the teenager was able to quit abusing illegal drugs, including THC, without exhibiting any signs of withdrawal.

The last, most recent human experiment proves that cannabidiol has the potential to replace antidepressants for good. It also seems to successfully prevent the typical symptoms of depression, anxiety, and related neuropsychiatric disorders even where prescription antidepressants fail.

Using CBD Alongside Wellbutrin: Possible Drug Interactions

While CBD may be able to successfully help patients overcome their dependence over other substances without themselves creating any substance dependence, can CBD be used while you’re still on antidepressants?

It is a widely known fact that ‘CBD tends to interact with a wide range of prescription drugs’, which when taken together can cause some severe adverse effects, including overdosing of the drug.

Reason: CBD is known to hinder or block the group of liver enzymes, known as Cytochrome P450 or CYP450, from metabolizing most prescription drugs. That’s because CBD, too, requires this enzyme to break down inside the body.

Naturally, this would increase the level of the drug in the body, thereby causing more severe side effects from the use of such prescription drugs with CBD. Often known as the “grapefruit effect”, this reaction is also observed when citrus fruits, like grapefruit, are consumed, while being on such prescription drugs, including most antidepressants.

Although specific research on Wellbutrin-CBD interactions is scarce, preliminary studies indicate that CBD can both block and increase the effects of a specific CYP enzyme – CYP2B6 – that is required to metabolize Bupropion.

Here are the facts:

  1. Wellbutrin (containing Bupropion) interacts with drugs that inhibit or induce CYP2B6’s function (as per Wellbutrin’s prescribing information).
  2. The “Prescribing Information” on Epidiolex® (100 mg/ml CBD), released by the US Food and Drug Administration (FDA), specifically mentions that this CBD product (approved by FDA in 2018) can potentially interact with Bupropion.

Additionally, we found only two separate studies that suggest that CBD could potentially interact with Bupropion.

  1. A 2019 study, “The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications”, published in the Journal of Clinical Psychopharmacology, mentions “The isoforms (subtypes of CYP450) CYP2D6, CYP2C19, CYP2B6, and CYP2J2 are inhibited by (both) THC and CBD.”
  2. Another July 2011 study, published in the Forensic Toxicology, indicated that CBD inhibits the CYP2B6 the most. The researchers were so convinced with the idea that CBD blocks CYP2B6, that they went on to investigate the differential rate of inhibition of CYP2B6 by CBD’s natural and synthetic derivatives (CBD-2′-monomethyl ether and CBD-2′,6′-dimethyl ether). The results revealed that CBD’s natural form is a more potent CYP2B6- inhibitor than its synthetic forms.

CBD over Wellbutrin: Is CBD The Best Option?

While CBD may be a good – safe and effective – replacement for antidepressants, it is not advisable to suddenly stop taking antidepressants – no matter what subtype it falls under.

One should always wean off it gradually.

Secondly, there are several risks involved in using CBD as an adjunct treatment along with NDRIs like Wellbutrin, as there is quite a bit of scientific proof of the two interacting in your body.

Thirdly, not everyone reacts to CBD in the same way. This is particularly true when it concerns complicated conditions like depression and anxiety. This is even more so when you combine CBD with other medications. Although someone using CBD, while being on Wellbutrin, may not exhibit any severe side effects, you may experience a few – if not numerous.

Fourthly, and most importantly, it’s best to always consult your doctor before trying out any new substance or making any changes in your existing medications. Additionally, if you must, it’s best to do so under the strict supervision of your doctor – preferably one who is acquainted with cannabis medicine.

Lastly, we would like to add that a lot of patients with depression have successfully been treated with CBD after giving up Wellbutrin – a potentially hazardous antidepressant. Their testimonials are available all over the internet – if you have the patience to look for them.


* NDRI: Norepinephrine and dopamine reuptake inhibitors (NDRIs) are antidepressant medications that block the action of specific transporter proteins, increasing the level of certain active mood-controlling neurotransmitters in the brain. This helps stabilize/modulate a person’s moods, emotions, behaviors, etc.

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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