Article written by
Dipak HemrajHead of Research and Education
Content reviewed by
Dr. Lewis JasseyMedical Director - Pediatric Medicine
Table of contents
Selective serotonin reuptake inhibitors (SSRIs) are prescription medications usually used to manage depression, anxiety, and other psychological conditions. Data suggests that marijuana use with SSRIs like es/citalopram and sertraline can increase the body’s concentrations, leading to adverse effects like dizziness, dry mouth, and sleeping problems. Drug Bank Online lists THC and CBD as having a moderate interaction with SSRIs like citalopram, escitalopram, and sertraline.
Medical cannabis may also be used to reduce antidepressant intake and manage the side effects that arise from its use, such as headaches, insomnia, and appetite loss. Depression is often comorbid with anxiety, which medical cannabis can help manage.
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What Are SSRIs?
SSRIs are antidepressant medications. Other classes of antidepressant medications include serotonin-noradrenaline reuptake inhibitors (SNRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), serotonin antagonists, and reuptake inhibitors (SARIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs).
Examples of SSRIs include:
- Citalopram (Cipramil)
- Escitalopram (Cipralex)
- Dapoxetine (Priligy)
- Fluoxetine (Prozac or Oxactin)
- Fluvoxamine (Faverin)
- Paroxetine (Seroxat)
- Sertraline (Lustral)
- Vortioxetine (Brintellix)
Uses and How They Work
SSRIs are a class of antidepressant medications that increase the neurotransmitter serotonin’s extracellular level and limit its reabsorption (reuptake) into the presynaptic cell. This increases the level of serotonin in the brain.
SSRIs have a strong affinity for the serotonin transporter and only a weak affinity for the norepinephrine and dopamine transporters. Different SSRIs have different mechanisms of action regarding sigma (σ) receptors. Fluvoxamine is an agonist of the σ1 receptor; sertraline is an antagonist of the σ1 receptor, and paroxetine does not significantly interact with the σ1 receptor.
There is no agreed-upon mechanism of action for SSRIs and other antidepressants, as mood disorders and brain chemistry are so complex. SSRIs may also take several weeks to take effect; some find that they do not work and may need to try other antidepressants. In the case of SSRIs, it is thought that they inhibit serotonin reuptake and let the neurotransmitter stay between the presynaptic and postsynaptic cell (the synaptic gap) for longer periods. This helps improve mood over time.
SSRIs are often prescribed for mood disorders like depression, post-traumatic stress disorder, eating disorders, and anxiety disorders like social anxiety disorder (SAD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and panic disorder. Antidepressants may also be prescribed for chronic pain, premature ejaculation, and stroke recovery.
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Potential Benefits and Risks of Mixing Cannabis and SSRIs
Cannabinoids in cannabis, including cannabidiol (CBD) and tetrahydrocannabinol (THC), inhibit the liver enzyme cytochrome P2C19 (CYP2C19), decreasing the metabolism of CYP2C19 substrates, including sertraline and es/citalopram. Cannabinoids also impact serotonin receptors, with CBD modulating serotonin transmission and THC activating serotonin receptors and inhibiting serotonin reuptake. This means that mixing cannabis and SSRIs can have potential benefits and risks.
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- There are reports of cannabis being useful for immediate relief of depression and depressive symptoms.
- Both THC and CBD can increase serotonin available in the brain, and CBD acts on 5-HT1A serotonin receptors in particular.
- Medical cannabis can help manage some side effects of antidepressant intake, such as headaches, nausea, appetite loss, insomnia, and GI upset.
- There is some evidence that medical cannabis may help reduce antidepressant intake.
- Some patients who find antidepressants intolerable may benefit from medical cannabis and CBD, with minimal risk of addiction.
- CBD has antipsychotic properties.
- Cannabis contains many mood-boosting and stress-busting terpenes, including pinene, limonene, and linalool.
- Dosage matters — as is the case for anxiety disorders, cannabis is a potent antidepressant in low doses and may worsen depression in high doses. High doses of THC may deplete serotonin levels, which may help explain why cannabis use for depression relief returns inconsistent results, especially when there are many misunderstandings surrounding dosing.
- Cannabis can impair the metabolization of various antidepressants, including SSRIs, TCAs, and MAOIs.
- Although rare, there are reports of serotonin syndrome (toxic levels of serotonin in the brain) due to combined cannabis and antidepressant use.
What to Do If You Need to Use Both SSRIs and Marijuana
Cannabis seems to interact more with some types of SSRIs than others. Many use both together with little harm, but it is worth remembering that adverse effects are still possible when the two are mixed. Many may need to reduce their antidepressant intake to reduce the chances of severe negative side effects, and some may need to stop antidepressant use entirely.
Why Mixing Cannabis with SSRIs Can Help You Feel Better
Some may find most relief from depressive symptoms by using a combination of SSRIs and medical cannabis when dosed appropriately. Some people may also find that cannabis can help mitigate some side effects of antidepressants.
The Bottom Line
Medical cannabis and the terpenes, cannabinoids, and flavonoids it contains have potent anti-anxiety and antidepressant effects. Those using cannabis may wish to reduce or replace antidepressant use to reduce the chances of negative side effects. Those who intend to use medical cannabis for depression ideally should do so under the supervision of a healthcare professional, where medications can be tapered more effectively.
Frequently Asked Questions
How does weed affect dopamine?
Cannabis has a complex relationship with dopamine and dopamine receptors. In the short term, cannabis can increase dopamine release, and repeated exposure over time can blunt dopamine receptors. This blunting can help protect against excess dopamine and can help manage PTSD as well. However, for others, blunting dopamine in this way may lead to more depressive symptoms as the brain’s reward system produces fewer pleasant sensations. More studies need to understand how cannabis interacts with dopamine receptors fully.
Does weed affect serotonin?
Weed, or cannabis, affects serotonin in many different ways, depending on the dosage and the ratio of cannabinoids you use. Low doses of THC may boost serotonin levels in the brain, whereas high doses of THC may deplete serotonin levels in the brain. CBD interacts with serotonin receptor 5HT1A and modulates serotonergic transmission. However, we know little about how cannabis and various cannabinoids interact with serotonin receptors, especially over a long period.