The Dangers of Combining Zoloft and Weed

Medical professionals urge caution when combining Zoloft (sertraline) with marijuana because both substances affect the central nervous system. Drug interaction references note that using multiple psychoactive or sedating substances can increase impairment in attention, judgment, and coordination , leading to unpredictable effects.

Zoloft was the 11th most most commonly prescribed medication in the U.S. with over 42 million prescriptions in 2023. Meanwhile, marijuana use has steadily increased for both medical and recreational purposes. As the overlap grows, clinicians and drug-interaction resources have raised concerns about combining antidepressants like Zoloft with cannabis. To understand why doctors advise caution, it helps to first understand how both substance affect the user.

How Zoloft Works to Treat Depression and Anxiety

Zoloft is the brand name for sertraline, a selective serotonin reuptake inhibitor (SSRI) that increases serotonin levels in the brain. Widely prescribed since it received FDA approval in 1999, Zoloft reduces symptoms of major depressive disorder, panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and severe social anxiety disorder. Zoloft is even approved for treating OCD in children 6 to 17 years of age. Over 14.4% of adults aged 40–59 take antidepressants, according to the Centers for Disease Control (CDC), with sertraline being the most common antidepressant. People with depression, OCD, PTSD and anxiety disorders have abnormally low levels of serotonin due to receptors preventing the release of the neurotransmitter into the brain.

Doctors don’t fully understand all the biological factors involved in depression and anxiety, but SSRIs like Zoloft are designed to increase serotonin availability in the brain by limiting its reuptake.

Side Effects and Timeline for Relief

Zoloft doesn’t start relieving depression anxiety right away. Most people taking Zoloft report feeling better after 3 to 4 weeks of being on the drug. Initial side effects of Zoloft that usually resolve within several weeks include:

• Nausea (but not vomiting)
• Agitation (the sudden increase of serotonin can make some people feel jittery)
• Shakiness
• Insomnia or sleepiness
• Feeling tired or slightly drowsy during the day
• Feeling more anxious than usual

Risks and Warnings for Zoloft Use

Although Zoloft helps millions of people cope with depression and anxiety disorders, it can also cause serious side effects that require emergency treatment. In 2004, the FDA put warnings on all SSRIs about the risk of suicidal ideation in people taking these medicines. However, research indicates that children and adolescents are most at risk for suicidal thoughts due to “peculiar responses” to antidepressants early in their treatment. There’s no definitive evidence, though, that Zoloft or other SSRIs lead some individuals to attempt suicide.

What Happens When You Smoke or Consume Marijuana?

The brain’s endocannabinoid system contains thousands of receptors that are activated by THC and other chemicals in marijuana. Because this endocannabinoid system oversees appetite, memory, mood and pain relief, using marijuana intensifies the endocannabinoid system’s regulation of pain, mood, etc. In addition, THC is a psychoactive chemical that alters your mental, physiological and emotional states.

Like Zoloft, marijuana doesn’t affect everyone the same way. The most common side effects of THC include:

Depending on the grade and type of weed smoked, side effects could be minimal or could cause such severe reactions that the user seeks emergency medical treatment.

Self-Medicating by Mixing Zoloft and Cannabis

A lot of people understandably think that marijuana, or one of its derivatives, such as CBD oil, can reduce the negative side effects of SSRIs. In the real world, this most often takes the form of people using cannabis and antidepressants at the same time or mixing Zoloft and cannabis products. It’s also common for marijuana users to conceal their use of cannabis from the doctor prescribing them Zoloft. The U.S. Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS) has tracked both the recreational use of marijuana and people who are trying to self-medicate with it and found a significant risk of adverse events.

There’s still a lot to learn about the Zoloft-marijuana interaction. One potential problem is that marijuana can interfere with how the body metabolizes Zoloft, which reduces its effectiveness and could lead a doctor to increase the dose if ignorant of the patient’s marijuana use. It’s also possible that Zoloft, as an SSRI, can work against the depressive or relaxing effects of the marijuana, making that less effective, too, and encouraging heavier use.

Supporting these concerns, a peer-reviewed pharmacology review examining SSRI and cannabinoid interactions found that THC and cannabidiol (CBD) can inhibit enzymes involved in metabolizing sertraline. Using modeling and FDA adverse event data, the study states that cannabis compounds may increase sertraline concentrations and raise the likelihood of side effects such as dizziness, fatigue and gastrointestinal symptoms, particularly in younger patients.

Always tell your doctor about any drugs you take, including marijuana and related cannabis products. Self-medicating with street drugs is almost never safe to do without medical supervision, and the results can have inconsistent or even paradoxical effects.

3 Potentially Dangerous Zoloft-Cannabis Interactions

1. Higher Risk of a Bad Reaction to Zoloft

Cannabis has been shown to inhibit liver enzymes needed to metabolize Zoloft. This means the body doesn’t disperse and eliminate Zoloft like it should, leaving a higher-than-normal level of Zoloft in the bloodstream. Consequently, any adverse reaction to Zoloft a person may have had in the past could reemerge as an aggravated reaction.

2. Too Much Serotonin

Both marijuana use and Zoloft use can affect serotonin levels. Marijuana has been shown to interact with serotonin signaling, whereas Zoloft dosage works to dictate how much serotonin the brain receives. When people combine sertraline with weed, the interaction can disrupt normal serotonin signaling, increasing the risk of excessive serotonin-related effects (which may include vomiting, agitation, severe headache, confusion, fast heartbeat and muscle twitching).

3. Compromised Therapeutic Response

With sertraline and marijuana counteracting each other’s effects on the brain and body, doctors and their patients won’t know if Zoloft is actually helping them feel better. Additionally, people who use pot while taking Zoloft may come to the conclusion that Zoloft isn’t working and stop taking it altogether. This could worsen their depression and anxiety and lead them to rely more on weed to relieve symptoms of their mental illness.

What Happens When You Combine Sertraline and Weed?

There are limited studies directly examining interactions between sertraline and marijuana. While no formally established drug-drug interactions between sertraline and marijuana, clinicians caution that the combination can still pose risks due to overlapping effects on brain chemistry and medication metabolism.

Individual responses can vary widely. For some people, THC may intensify anxiety, panic symptoms, or intrusive thoughts, particularly in those taking sertraline for panic disorder or OCD. Because reactions are highly individualized, the effect of combining the two can be difficult to anticipate.

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Why Doctors Are More Concerned Today About the Dangers of Combining Zoloft and Weed

The recent legalization of both recreational and medicinal marijuana has significantly increased the number of people in the United States who use weed and take antidepressants. Prior to 2010, only a handful of states had legalized medicinal or recreational pot. Compounding that fact is the recent uptick in doctors writing prescriptions for Zoloft and other antidepressants due to the stress of the COVID-19 pandemic worsening rates of depression, anxiety and psychiatric disorders.

People who mix Zoloft with weed may not be at risk for an overdose, but they are at risk for exacerbating symptoms of their depression, anxiety, OCD or panic disorder. Additionally, smoking pot and taking antidepressants can disrupt brain chemistry in ways researchers are only beginning to uncover.

Take the First Step Toward Healing With FHE Health

Zoloft has been clinically proven to help people cope with depression and anxiety. But when the inability to stop smoking pot interferes with the ability of Zoloft to treat mental illness, it may be time to seek help for a marijuana problem. Call FHE today if you or someone you know is struggling with a mental illness and combining antidepressants with weed.

FAQs About Mixing Zoloft and Marijuana

References

• Sertraline Prescriptions – https://clincalc.com/DrugStats/Drugs/Sertraline
• Drug Interactions between cannabis and Zoloft – https://www.drugs.com/drug-interactions/cannabis-with-zoloft-2758-0-2057-1348.html?professional=1
• Sertraline approved for children https://kids.iocdf.org/what-is-ocd-kids/how-is-ocd-treated/medication-for-pediatric-ocd/
• Drug Interactions between marijuana and anxiety meds- https://www.vice.com/en_ca/article/vvq5vy/we-asked-experts-what-really-happens-when-you-mix-weed-with-anti-anxiety-meds
• Pharmacology review examining SSRI and cannabinoid interactions – https://pmc.ncbi.nlm.nih.gov/articles/PMC8307883/