Zoloft and Weed: Interactions and Side Effects

Zoloft is a medication commonly prescribed to treat common mental health conditions, like depression and anxiety. 

According to the National Institute of Mental Health, it has been reported that around 9.7% of American adults aged 18 and above experience a depressive illness each year. In addition, it is reported that roughly 19.1% of adults aged 18 and above are affected by an anxiety disorder each year. 

Medical cannabis patients often turn to the plant for help with the same mental health conditions. According to our 2022 Annual Cannabis Conditions Report, which surveyed over 211,000 medical cannabis patients, roughly 19% of medical cannabis patients use cannabis for anxiety, and around 12% of medical cannabis patients use cannabis for PTSD. Considering these factors, it is important to assess the safety of concurrent use of prescription medications such as Zoloft and weed.

What is Zoloft?

Zoloft, also known as Sertraline, is a selective serotonin reuptake inhibitor (SSRI). SSRIs are a newer class of antidepressant drugs that work by stopping the body from reabsorbing serotonin, preventing the depletion of this vital neurotransmitter within the brain. Low serotonin levels are commonly associated with conditions like depression and anxiety.

Zoloft is FDA-approved for adults to take for the treatment of the following;

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Panic Disorder
• Posttraumatic Stress Disorder (PTSD)
• Premenstrual Dysphoric Disorder (PMDD), and
• Social Anxiety Disorder.

Zoloft is an extremely common prescribed medication. Between 2004 and 2020, prescriptions for Zoloft or Sertraline in the United States increased by 10 million. As of 2020, prescriptions in the United States for Zoloft or Sertraline land at 38.22 million.

Despite how often Zoloft is prescribed, it’s not without its risks. The most common side effects in adults treated with Zoloft include:

• Agitation
• Anxiety
• Diarrhea
• Change in sleep habits, including increased sleepiness or insomnia
• Fatigue
• Increased sweating
• Loss of appetite
• Nausea or indigestion
• Sexual problems
• Tremors

Zoloft, like most antidepressants, may also increase the risk of suicidal ideation in adults with major depression. In mild cases of  Zoloft overdose, it may result in a condition called serotonin syndrome. However, larger doses can result in more severe consequences and even death.

Research indicates that patients over 65 should be cautious of using Zoloft due to the high risk of adverse side effects, such as inappropriate antidiuretic hormone, which causes your body to retain water. This water retention can further lead to hyponatremia, an increase in sodium levels in the blood. These conditions are treatable if caught early, but severe cases can lead to loss of consciousness, hallucinations, coma, brain herniation, or death. Pregnant women are also advised to avoid Zoloft, which can cause heart defects and lead to prolonged hospitalization, tube feeding, and the need for respiratory support in infants.

Zoloft and Weed: How Do They Interact?

Zoloft and cannabinoids, such as THC and CBD, are metabolized by the CYP2C19 enzymes in the liver. Both CBD and THC are known to inhibit the CYP2C19 enzyme. This inhibition of the CYP2C19 enzyme can make it harder for the body to properly metabolize other drugs, such as Zoloft, which are also metabolized by the CYP2C19 enzyme. This enzyme interaction can lead to an increase in the levels of Zoloft present in a patient's system and can lead to an increase in adverse side effects such as; diarrhea, dizziness, and fatigue.^1,2,3

Based on the current data, more research is needed to determine the safety and efficacy of the concurrent use of Zoloft and weed. Individuals should consult their doctor before combining Zoloft and CBD or THC. 

What are the Potential Risks and Side Effects of Combining Zoloft and Medical Marijuana?

It can be extremely common to see varying responses to the safety of cannabis and Zoloft. Some online sources indicate no reported interactions, and others say individuals should be cautious when combining the two. 

So which is it?

THC and CBD have been found to inhibit the CYP2C19 enzyme, which is the same enzyme responsible for the metabolism of prescription medications like Zoloft. Research indicates that concurrent use of CBD and/or THC with Zoloft may lead to an increased concentration of Zoloft in the system, which can result in serotonin syndrome or other adverse side effects. 

According to the previously cited study by MacCallum et al., the combination of Zoloft and weed may lead to an increased risk of adverse side effects such as confusion, dizziness, drowsiness, and difficulty concentrating. For elderly individuals, concurrent use of Zoloft and weed may result in impaired thinking, judgment, and motor coordination. Overall, these findings line up with others that have found THC to have troubling interactions with SSRI medications.

Can Cannabis be a Substitute for Zoloft?

According to the NuggMD 2022 Annual Cannabis Conditions Report, which surveyed over 211,000 medical cannabis patients, 18.86% of patients use cannabis for anxiety, and 12.39% of patients use cannabis for PTSD. Because depression is not a qualifying condition for medical cannabis in most state programs, there aren’t a significant number of individuals who report depression as their reason for using cannabis. However, a survey done in 2022 consisting of just over 27,000 individuals found that 52% of respondents were using cannabis for anxiety, 40% were using cannabis for depression, and 17% were using cannabis for PTSD/trauma.⁴

Cannabinoids work in a number of ways that may help relieve symptoms of mental health disorders such as depression, anxiety, and PTSD. One of the ways cannabinoids have shown promise in alleviating symptoms of anxiety is through its modulation of GABA and Glutamate – important neurotransmitters associated with calming and exciting effects – via CB1 receptor interaction. Another is CBD’s ability to mediate the activation of the 5-HT_1A receptor, a serotonin receptor. 

It should be noted that limited clinical studies are available that detail the effectiveness of cannabinoids for anxiety. Studies that have been done relied on high doses of CBD, ranging from 300mg to 600mg per day, and have primarily focused on social anxiety. The average CBD tincture on the market can have up to 5,000mg per bottle; however, it is more likely to see tinctures with between 1,000mg and 2,000mg of CBD per bottle on the market.¹

Cannabinoids may play a role in the treatment of PTSD due to the high concentration of CB1 receptors found within the amygdala, hippocampus, and prefrontal cortex – regions of the brain associated with fear, memory, and logical reasoning.⁵ Thus, THC and the activation of these CB1 receptors within the brain may be important in what researchers consider to be the extinction of fear. Clinical evidence suggests that average THC levels of 49 mg demonstrated effectiveness in reducing symptoms of PTSD, but more research is needed.

Similar to the way CBD is thought to calm anxiety, cannabinoids may interact with the 5-HT1A receptor to alleviate symptoms of depression.⁶ Research has indicated that THC may have antidepressant effects when used in combination with CBD. Research has also demonstrated the potential of CBD as an antidepressant. Still, more research is needed to determine the efficacy and safety of using cannabinoids for depression, specifically THC, as it may lead to more depressive symptoms. In addition, high doses of THC, or even low doses in individuals sensitive to THC, may cause anxiety and paranoia.

More recently, the cannabinoid CBG is becoming more popularized as a cannabinoid with potential to alleviate symptoms of anxiety. A 2022 study by Russo et al. found that over half of their 127 participants were using CBG to treat anxiety symptoms, and about a third of participants were using it for symptoms of depression. Patients reported their conditions had improved since using CBG, and 44 percent of participants had no adverse effects. The adverse effects reported by participants included dry mouth, dry eyes, increased appetite, and feeling sleepy.²

Research on terpenes commonly found in cannabis has demonstrated that they may be acting synergistically with cannabinoids or on their own to relieve symptoms of depression and anxiety.⁷ Terpenes such as myrcene and linalool have demonstrated anti-anxiety effects, while limonene and pinene can make people more alert and energetic, boosting an individual's mood.³

Overall, while cannabinoids like THC, CBD, and CBG have demonstrated positive effects for individuals with anxiety, depression, and PTSD, more research is needed to determine their mechanism of action and their efficacy and safety in relieving symptoms. 

Long-term use of Zoloft or Sertraline may have negative effects like memory loss, weight gain, sexual dysfunction, and even an increase in suicidal thoughts.⁸ But stopping Zoloft suddenly is even more risky and can cause severe and dangerous withdrawal symptoms. 

Never attempt to replace Zoloft with cannabis without the support of a qualified doctor. Despite the commonly marketed benefits of THC and CBD, neither cannabinoid has been FDA-approved for the treatment of depression, anxiety, or PTSD. Self-medicating can lead to serious harm, especially when using SSRI drugs. If you use cannabis, and you are taking Zoloft or other SSRI drugs, tell your doctor so they can adjust your treatment to prevent dangerous interactions.

Zoloft and Weed FAQ

Is Zoloft addictive on its own?

Unlike some drugs, SSRIs like Zoloft are non-addictive and do not cause dependence when used correctly.

How does Zoloft interact with Delta 8?

Because delta 8 THC is an analog of delta 9 THC and acts on the same receptors, it is likely to interact with Zoloft in the same manner as Delta 9 THC.

Have there been any deaths from combining Zoloft and weed?

There have been no reported deaths from the concurrent use of Zoloft and weed; however, the risk of death may increase if an individual adds alcohol to the combination.

How long should I wait to ingest weed after taking Zoloft?

Individuals should consult with their doctor to discuss the concurrent use of cannabis and its safety with a prescription medication.

When should I see a doctor?

Individuals should seek medical attention immediately if they experience any of the following side effects: suicidal thoughts, manic episodes, hallucinations, seizures, tense muscles, fainting, or a combination of these effects. Do not take Zoloft and cannabis without first talking to your doctor as it can lead to unsafe drug interactions.

References

1. MacCallum CA, Lo LA, Boivin M. “Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations. European Journal of Internal Medicine. 2021;89:10-18. doi:https://doi.org/10.1016/j.ejim.2021.05.002
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2. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. ­­­­­­Cannabinoid metabolites as inhibitors of major hepatic CYP450 enzymes, with implications for cannabis-drug interactions. Drug Metabolism and Disposition. 2021;49(12):DMD-AR-2021-000442. doi:https://doi.org/10.1124/dmd.121.000442
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3. Vaughn SE, Strawn JR, Poweleit EA, Sarangdhar M, Ramsey LB. The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations. J Pers Med. 2021;11(7):615. Published 2021 Jun 29. doi:10.3390/jpm11070615
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4.  Leung J, Chan G, Stjepanović D, Chung JYC, Hall W, Hammond D. Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada. Psychopharmacology (Berl). 2022;239(5):1509-1519. doi:10.1007/s00213-021-06047-8
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5.  Sarris J, Sinclair J, Karamacoska D, Davidson M, Firth J. Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review. BMC Psychiatry. 2020;20(1). doi:https://doi.org/10.1186/s12888-019-2409-8
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6.  Russo EB, Cuttler C, Cooper ZD, Stueber A, Whiteley VL, Sexton M. Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms. Cannabis and Cannabinoid Research. 2021;7(5). doi:https://doi.org/10.1089/can.2021.0058
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7.  Ferber SG, Namdar D, Hen-Shoval D, et al. The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders. Current Neuropharmacology. 2020;18(2):87-96. doi:https://doi.org/10.2174/1570159x17666190903103923
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8.  Sayyah M, Eslami K, AlaiShehni S, Kouti L. Cognitive Function before and during Treatment with Selective Serotonin Reuptake Inhibitors in Patients with Depression or Obsessive-Compulsive Disorder. Psychiatry J. 2016;2016:5480391. doi:10.1155/2016/5480391
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The information in this article and any included images or charts are for educational purposes only. This information is neither a substitute for, nor does it replace, professional legal advice or medical advice, diagnosis, or treatment. If you have any concerns or questions about laws, regulations, or your health, you should always consult with an attorney, physician or other licensed professional.