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What You Need to Know About Using Cannabis If You Take Tricyclic Antidepressants

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Tricyclic antidepressants (TCAs) are a class of medication prescribed for depression and anxiety when first-line antidepressants (usually SSRIs) like sertraline (Zoloft) and escitalopram (Lexapro) do not work. They can have sedative effects, which are increased when mixed with cannabis. Potential interactions between cannabis and TCAs include:

  • Increased heart rate (tachycardia).
  • High blood pressure.
  • Increased risk of anxiety, panic attacks, or even heart attack.

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What Are Tricyclic Antidepressants?

Tricyclic antidepressants are second-line medications used to treat depressive symptoms. They are typically prescribed when first-line antidepressants are ineffective for severe depression and anxiety disorders.

Examples include:

  • Amitriptyline (Elavil, Endep)
  • Amoxapine (Asendin)
  • Desipramine (Norpramin)
  • Doxepin (Sinequan, Adapin, Quitaxon)
  • Imipramine (Tofranil)
  • Nortriptyline (Pamelor)
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil)

Potential Benefits and Risks of Mixing Cannabis and Tricyclic Antidepressants

It is best not to mix cannabis and TCAs, as there are several possible drug interactions and negative side effects. Moreover, cannabis and cannabinoids like cannabidiol (CBD) and tetrahydrocannabinol (THC) desensitize the liver enzyme cytochrome P2C19 (CYP2C19), thereby inhibiting the metabolization of several classes of antidepressant medications and increasing the likelihood of adverse effects.

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Potential Benefits

Potential Risks

Combining cannabis and TCAs increases the risk of several negative side effects, like:

  • Dry mouth
  • Slight blurring of vision
  • Constipation
  • Problems passing urine
  • Drowsiness
  • Dizziness
  • Weight gain
  • Excessive sweating (especially at night)

Mixing TCAs with cannabis can increase heart rate and blood pressure to dangerous levels, sometimes requiring a visit to the emergency department (ED).

TCAs are contraindicated for bipolar disorder, as it is more likely to trigger a manic episode or rapid cycling than other depression drugs.

What to Do If You Need to Use Both Tricyclic Antidepressants and Marijuana

Those who require TCAs may need to stop cannabis use. Some may prefer medical cannabis over TCAs, which can have negative side effects like dry mouth, blurring of vision, drowsiness, sedation, weight gain, constipation, and excessive sweating. Neither should TCAs be mixed with other antidepressants like monoamine oxidase inhibitors (MAOIs) nor SSRIs.

The Bottom Line

TCAs are a second-line treatment for depression and anxiety prescribed when other treatment methods (exercise, improved diet, herbal medicines) and antidepressants, usually SSRIs, do not work. However, they can have several negative side effects, so many may prefer to try cannabis and phytocannabinoid-based medications instead. TCAs and medical cannabis should not be mixed.

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