The short answer is, probably not! But there are variables and nuances to consider.
The question of combining antidepressants and microdosing is a common one. A significant portion of individuals is attracted to the practice because of the reported benefits of microdosing in reducing symptoms of depression. Many are hoping to utilize microdosing to avoid, reduce, or stop taking antidepressant medications.
While an extensive dive into the science of why psychedelics are effective in the treatment of depressive symptoms is beyond the scope of this article, it is important to note that most psychedelic medicines work by binding to serotonin receptors in the brain and triggering a process of neuronal avalanching similar to a domino effect of intense neural network activity in the brain. This mechanism is similar to how many modern anti-depressant pharmaceuticals, namely SSRIs function by binding these receptors.
Overstimulation of the serotonin receptors can be risky and in extreme cases, serotonin overload can lead to a fatal condition called "serotonin syndrome". Therefore, it is generally not recommended to mix most psychedelic medicines with pharmaceutical anti-depressants. With that said, the serotonin boost from a true microdose is most likely not sufficient to cause serious risk, instead, in most cases, combining anti-depressants with microdosing nullifies the benefits of the microdose and produces no tangible effects.
Although most antidepressants present a counter-interaction, there are categories of anti-depressants that do not and can be safely combined with the microdosing practice under the care of a psychiatrist. Many clients choose to work closely with their physician to safely engage in the microdosing practice as a means to reduce or eliminate anti-depressant medications. Not all individuals are good candidates for this approach.
Below is a brief overview of different types of antidepressants and potential risk factors in combination with the most commonly microdosed substances of psilocybin and LSD:
Can I microdose on SSRIs?
Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for depression among a variety of other mental health conditions. Prozac, Lexapro, and Zoloft belong to this category, amongst others.
Since this class of medications functions by modifying serotonin absorption in the brain, theoretically, the combination with psychedelics can run the risk of serotonin syndrome although no reported cases were identified in our research. New research is beginning to emerge that challenges this understanding. Until we develop a better understanding of how this class of drugs interacts with psychedelics, it is recommended to avoid the combination or solely engage under professional care.
Can I microdose on SNRIs?
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are a class of antidepressants that function by boosting both serotonin and norepinephrine levels in the brain. Similar to SSRIs, we do not yet fully understand how they interact with psychedelics. Cymbalta and Effexor XR are two examples of drugs in this class.
According to anecdotal reports, they are more likely to reduce the effects of psychedelics than to cause serious harm. If you are currently taking SNRIs and considering working with psychedelics, it is best to ensure you do so under professional care and guidance.
Can I microdose on MAOIs?
Monoamine Oxidase Inhibitors (MAOIs) are a class of drugs sometimes prescribed for depression. They increase the levels of monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) by preventing their breakdown in the brain. Nardil and Parnate are two of the most commonly prescribed MAOIs.
Since MAOIs also function to alter serotonin levels in the brain, it is not recommended to combine them with large doses of psychedelics. Like SNRIs, combination with a microdose will most likely produce no tangible effects.
Can I microdose on NRIs or NDRIs?
Norepinephrine Reuptake Inhibitors (NRIs) and Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs) are a class of medications commonly prescribed for depression and anxiety. They function by increasing the levels of norepinephrine (+ dopamine in NDRIs) in the brain. Wellbutrin, Strattera, and Ritalin are common examples.
We do not know how NRIs and NDRIs interact with psychedelics. Psilocybin does not interact with norepinephrine and dopamine receptors while LSD does, therefore, theoretically, there can be different risk factors for combining this class of drugs with these two commonly used psychedelic substances. However, until we better understand the counter-interaction mechanisms for each, it is best to avoid combining psychedelics with this category of pharmaceuticals.
Can I microdose on TCAs or TeCAs?
Tricyclic Antidepressants (TCAs) and Tetracyclic Antidepressants (TeCAs) are older classes of antidepressants that are not commonly prescribed. They function by boosting the levels of serotonin and norepinephrine in the brain. Anafranil, Elavil, and Norpramin are the most commonly prescribed medications in this class.
In addition to increasing serotonin and norepinephrine levels, this class of drugs also impacts a wide range of activities in the brain and the cardiovascular system making them especially risky in combination with psychedelics. TCAs and TeCAs should not be combined with psychedelics.
Can I microdose on SMSs or SARIs?
Serotonin Modulators and Stimulators (SMSs) and Serotonin Antagonists and Reuptake Inhibitors (SARIs) are a class of antidepressants that work to increase serotonin levels in the body by both stimulating and inhibiting various serotonin receptors. Desyrel and Trintellix are examples of this class of drugs.
While SSRIs and SNRIs often interact with one or two serotonin receptors, SMSs and SARIs are designed to target as many as 15 different serotonin receptors making their counter-interactions unpredictable and risky. It is therefore not recommended to combine psychedelics with this class of drugs.
Can I microdose on Lithium?
Lithium is a salt and not categorized as an anti-depressant, however, it is sometimes prescribed for bipolar and major depressive disorders. We do not fully understand how Lithium works but there are reports of serious counter-interactions with psychedelics resulting in seizures.
Combining psychedelics with Lithium can have extremely dangerous consequences and must be avoided at all costs.
Can I microdose if I recently stopped taking antidepressants?
If you've recently stopped taking antidepressants, you might be wondering if you can benefit from microdosing. Depending on the type of anti-depressant, dosage, and length of time on the medication, you will likely need a period of reset and detox to restore the serotonin receptors back to a state where microdosing will be effective. While each case is unique generally speaking, for every year on antidepressant medications, you will need to account for two months to restore the brain. There are however integrative detox protocols that can accelerate this process.
Customized detox protocols, alternatives to many pharmaceuticals for mental health, and expert-crafted Personalized Microdosing Protocols for mental health and performance are available through Microdose Guru's vetted network of practitioners. You can book a free consultation to learn more.
As outlined above, combining antidepressants with psychedelics can be risky but in some cases under appropriate medical and expert supervision, it can be done safely. More clinical research is needed to better understand how each of these drugs interacts with various psychedelic substances.
While we have some limited understanding of psychedelic interactions with antidepressants, nearly all of our insights are limited to larger doses of psychedelics. Microdosing practice due to its consistency of administration and low dosage is likely to have very distinct implications when combined with different classes of antidepressant drugs.
It is imperative to note that any changes to anti-depressant medication doses or combined with any mood-altering substances whether microdose, minidose, or macrodose must be done under the direct care of a licensed psychiatrist. Luckily, as the field of psychedelic therapy continues to grow, there are more and more psychiatrists with an open mind willing to work in conjunction with psychedelic medicines and allow their patients to safely explore these alternative options.