How Does Marijuana Impact Antidepressants? | A Guide

Apr 15, 2024

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How does marijuana impact antidepressants? Mixing marijuana and antidepressants is complex and the current research is limited. With an increase in usage of both marijuana and antidepressants, it comes as no surprise that patients are increasingly wanting to learn more about the interaction between the two. This article explores these intricacies in an explanation on how using marijuana impacts antidepressants. 

TABLE OF CONTENTS

How Does Marijuana Impact Antidepressants

The Effects of Marijuana on Antidepressant Efficacy

Types of Antidepressants and Their Interaction with Marijuana

SSRIs: The Interaction with Cannabis

SNRIs, MAOIs, and Tricyclic Antidepressants: The Interaction with Cannabis

MAOIs: The Interaction with Cannabis

Tricyclic Antidepressants: The Interaction with Cannabis

Potential Risks and Side Effects of Combining Marijuana with Antidepressants

Conclusion

How Does Marijuana Impact Antidepressants

Patients are increasingly interested in learning about how does marijuana impact antidepressants. Common questions include:

  • Is smoking marijuana safe while on an antidepressant?
  • Can I smoke weed while on Lexapro? 
  • What will happen if I smoke and take an antidepressant?

The answer, in short, is that there isn’t currently enough research to say with certainty, and in all cases, whether using marijuana while on an antidepressant is safe. There seem to be many contributing factors, such as the class of antidepressant and individual genetic differences. We will explore these factors more in this article.   

Before we dive in, what’s even more crucial than determining whether smoking weed is safe while on an antidepressant is the recommendation for patients to consult their psychiatrist or mental health professional. It is essential that your provider is informed about the frequency and amount of marijuana you consume, so they can offer the most current and evidence-based advice. A quality provider will not shame or judge you for using marijuana but can offer objective recommendations based on your treatment plan. At A Better Day Psychiatry, our providers are knowledgeable about the interactions of marijuana and antidepressants.

The Effects of Marijuana on Antidepressant Efficacy 

Cannabis does have the potential to influence the effectiveness of antidepressants. 

There is ample research showing that cannabis has an inhibitory action on an enzyme called cytochrome P450. The Cytochrome P450 enzyme is in the liver and it plays a crucial role in metabolizing various substances, including medications such as antidepressants. In other words, using marijuana can lead to an increase of an antidepressant in your system as the Cytochrome P450 is not eliminating the antidepressant as rapidly as it should. 

Marijuana can also interact differently with different types of antidepressants. 

Types of Antidepressants and Their Interaction with Marijuana

Different classes of antidepressants interact uniquely with cannabis. Research indicates this varies widely among SSRIs (Selective Serotonin Reuptake Inhibitors), SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), MAOIs (Monoamine Oxidase Inhibitors), and Tricyclic Antidepressants —with each class having unique considerations when combined with marijuana use.

SSRIs: The Interaction with Cannabis

Selective Serotonin Reuptake Inhibitors are the most commonly prescribed antidepressants. They include:

  • Fluoxetine (Prozac).
  • Sertraline (Zoloft).
  • Escitalopram (Lexapro).
  • Paroxetine (Paxil).
  • Fluvoxamine (Luvox).
  • Citalopram (Celexa).

SSRIs work by increasing the levels of the neurotransmitter, serotonin, in the brain by blocking its reuptake. This enhances serotonin’s effects on mood regulation and emotional well-being. 

As mentioned above, cannabis use can lead to rising levels of antidepressants in your system, as they are not being metabolized as efficiently. This combination has the potential to lead to serotonin syndrome, which can be a life-threatening condition that occurs when there is an excess of serotonin in the body. When serotonin levels become too high, it can lead to a range of symptoms, ranging from mild to severe (seizures and coma). While rare, mixing substances like SSRIs and marijuana increases the risk of serotonin syndrome. Due to the possibility, mental health professionals are unlikely to recommend taking cannabis while on an SSRI. 

Due to the limited research, and thus doctors’ limited knowledge, you will likely be told the possible risks and what to look out for if you do choose to consume cannabis while on an SSRI. 

While surprising, the truth is that there is not enough research and data that supports to what extent individuals can safely use cannabis while on an SSRI. #evidencebasedcare

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Research is limited as:

  • There are few studies that report real-world adverse reactions while using cannabis.
  • Current studies have small sample sizes, which can undermine the validity of research findings.
  • Of the research we do have, evidence shows there can be differences in interaction even within antidepressant classes (so some SSRIs, like Prozac, may interact with weed differently than other SSRIs).   

To extrapolate, a study done in 2021 suggests that cannabis use while taking an SSRI increases panic attacks. However, it should be noted that this was a case study of one single individual adolescent. Further research needs to be conducted to corroborate if this finding holds true with a larger sample size. 

In another study published in the Journal of Clinical Psychopharmacology, cannabis use seemed to minimally effect the metabolism of sertraline and fluoxetine but has a significant impact on the metabolism of Citalopram. This shows that even with drugs in the same medication class, the interaction with cannabis can vary. 

Having limited research on the topic of whether marijuana is safe to consume while on an antidepressant is the main reason why medical health professionals likely won’t (can’t) tell you with decisiveness what is safe or not. They simply do not know, and out of an abundance of caution they will likely recommend proceeding with caution. 

SNRIs, MAOIs, and Tricyclic Antidepressants: The Interaction with Cannabis

SSRIs have, to date, garnered the most attention in the research about the interaction between antidepressants and marijuana. However, there are other classes of antidepressants we will briefly discuss. 

H4 SNRIs: The Interaction with Cannabis

Serotonin-Norepinephrine Reuptake Inhibitors, as the name suggests, target both serotonin and norepinephrine levels. By blocking the reuptake of both serotonin and norepinephrine, SNRIs increase the levels of both neurotransmitters in the brain. Common SNRIs include: 

  • Venlafaxine (Effexor).
  • Duloxetine (Cymbalta).
  • Desvenlafaxine (Pristiq).

Similarly to SSRIs, there is the possibility of serotonin syndrome if taking both the SNRI and cannabis. As mentioned, the research is scant. 

There is some indication that Duloxetine (Cymbalta) does interact with cannabis. Interestingly, for some people it can lead to an increase of Cymbalta in the system (thereby increasing the risk of serotonin syndrome). In others though, cannabis seems to decrease the levels of Cymbalta, meaning the antidepressant would be less effective. This study highlights the lack of clear data and also shows the variation from person to person, due to genetics and biology, that is possible. 

With findings incomplete, researchers suggest using caution when pairing cannabis with an antidepressant. The limitations in research is why most medical practitioners will not be comfortable telling you what is or is not safe but can discuss current research and possible impacts of combining marijuana and SNRIs. 

MAOIs: The Interaction with Cannabis

Monoamine Oxidase Inhibitors (MAOIs), work by inhibiting the activity of the enzyme monoamine oxidase, which is responsible for breaking down neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain. By blocking this enzyme, MAOIs increase the levels of these neurotransmitters, which can help alleviate symptoms of depression. MAOIs are not first line antidepressant medications as they have been shown to cause adverse effects when interacting with many other medications and foods. Common MAOIs include:

  • Phenelzine (Nardil).
  • Tranylcypromine (Parnate).
  • Isocarboxazid (Marplan).
  • Moclobemide (Manerix).
  • Selegiline (Emsam).

They are occasionally used when an individual hasn’t responded well to the more common medications, like SSRIs. Again, there is very little research on the interaction of MAOIs and cannabis, which doesn’t give providers enough information to make conclusive recommendations. While there is no direct evidence linking the use of MAOIs and marijuana to adverse effects, individuals are not recommended to use marijuana while on an MAOI, as the potential interaction risk is high.

Tricyclic Antidepressants: The Interaction with Cannabis

Tricyclic antidepressants (TCAs) work similarly to SNRIs as they inhibit the reuptake of the neurotransmitters serotonin and norepinephrine in the brain. This leads to increased levels of these neurotransmitters in the synaptic cleft. They are also not typically prescribed unless an individual has not responded well to SSRIs and/or SNRIs. Common TCAs include:

  • Amitriptyline (Elavil).
  • Nortriptyline (Pamelor).
  • Imipramine (Tofranil).
  • Desipramine (Norpramin).
  • Doxepin (Sinequan).
  • Clomipramine (Anafranil).

As you’re probably expecting, the research is limited on the interaction between TCAs and cannabis. 

In a widely discussed study published in the Journal of the American Academy of Child and Adolescent Psychiatry, the researchers found that using marijuana while taking a tricyclic antidepressant may have contributed to delirium and an abnormally fast heartbeat. However, it should be noted that there were limitations in this study. Specifically, the sample size was only four adolescent males aged 15 to 18. This demonstrates the need for more thorough research on the interaction between cannabis and Tricyclic antidepressants to understand the interaction in greater depth. 

Due to the possibility of adverse reactions, psychiatrists and other mental health professionals are likely not able to make conclusive recommendations on whether using Tricyclic antidepressants and marijuana is safe. They will only be able to discuss this current research and inform you of the potential risks, which is discussed in the next section. 

Key Takeaway: 

Mixing marijuana with antidepressants can be a gamble, affecting medication efficacy and potential adverse effects. Knowing the risks and how different antidepressants interact with cannabis is key to making informed decisions about your treatment plan.

Potential Risks and Side Effects of Combining Marijuana with Antidepressants

The research on interactions between antidepressants and cannabis is limited. Therefore, knowledge of potential risks and adverse reactions are also limited and comes from a smattering of small studies. To review, current literature has found that using cannabis while on an antidepressant can potentially lead to adverse reactions including: 

As with many medications, there are genetic differences in how individuals react and respond. Some people may not have any symptoms when mixing antidepressants and cannabis, while others could have adverse reactions. For providers, it’s not worth the risk, since so little is still known about the interactions. 

Finally, it should be noted there are also studies that support the notion that reducing cannabis intake can improve symptoms of anxiety, depression, and sleep quality. Though again, more research is warranted, this is another reason why clinicians are unlikely to recommend cannabis usage. 

Conclusion

To summarize, cannabis does interact with some antidepressants, but the research is far from clear. More studies are needed to clarify the interaction cannabis can have on antidepressants, and fully answer the question on how does marijuana impact antidepressants.

Significant interactions seem to occur somewhat rarely, but until more conclusive research comes out it is unlikely your medical provider will be able to offer you precise information on cannabis usage and safety while taking an antidepressant. More likely, your provider will be able to discuss the current research, any new research, and the limitations in knowledge that ultimately make it impossible to give you a definitive answer. This isn’t to say you shouldn’t be talking to your provider about your marijuana usage though. It is very important for your provider to be informed and aware of the frequency and amount of marijuana you use, so they can offer you the most up-to-date and evidence-based information, including what risks or symptoms to be aware of if you are using. 

Above all, your provider should be non-judgmental and objective in their discussion on the risks of combining antidepressants with marijuana. The providers at A Better Day Psychiatry can answer your questions about the interactions with cannabis on antidepressants and the risks. For more information and guidance on marijuana and other drugs, reach out to us today. 

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