Bridging the Gap:
Antidepressants have been around for over 70 years now and have been the go to for people suffering from a range of mental health issues. Up until recently, they’ve had a solid reputation, but in recent years, questions have begun to arise. Turns out, not everyone’s thrilled with the side effects that come along for the ride with these meds. Furthermore, traditional antidepressants like selective serotonin reuptake inhibitors (SSRI) are nowadays seen more as band aid solutions that don’t really solve the root cause of mental health ailments.
People are craving for treatments that dig deeper and last longer. This desire has fueled the fire behind the psychedelic renaissance—a movement that’s picking up steam and offering a ray of hope for those suffering from these terrible mental health conditions. More and more people are looking to psychedelics as alternatives to their use of traditional antidepressants.
One of the core components of our mission here at Mind Mend is to help tackle the growing mental health crisis. We understand that psychedelics have the potential to alleviate the suffering of millions. However, we’re also aware that traditional antidepressants do still have a role to play. We very often get questions from people currently on antidepressants about how psychedelics could fit in with their treatment.
This article will cover everything you need to know about the interactions between psychedelics and antidepressants. We’ll start by exploring some of the basics around the interactions of antidepressants within the brain and the serotonergic system and follow it up with an explanation of the current best practices around psychedelic use for those currently on antidepressants.
Blunting of Psychedelic Effects by Antidepressants
SSRIs (like Zoloft) and SNRIs (like Cymbalta) are types of medications used for conditions like depression and anxiety. They work in the brain by affecting certain chemicals called neurotransmitters, which are key in controlling our mood.
Here’s a simple breakdown of what they are and how they work.:
- SSRIs focus on serotonin, a neurotransmitter that helps regulate mood.
- SNRIs work on both serotonin and another neurotransmitter called norepinephrine, which also plays a role in mood and emotion.
Normally, after these neurotransmitters do their job in the brain, they get reabsorbed, or “taken back up,” into brain cells. What SSRIs and SNRIs do is block this reabsorption process. So, instead of being reabsorbed, serotonin and norepinephrine stay around longer in the spaces between brain cells.
By preventing their reuptake, these medications increase the levels of serotonin and norepinephrine in the brain. This boost can help improve mood and alleviate symptoms of depression and anxiety receptors. Though not fully characterized, two leading theories attempt to explain this phenomenon.
1. Downregulation of Key Serotonin ReceptorsÂ
Chronic SSRI/SNRI use may cause downregulation of serotonin 2A (5-HT2A) receptors in the brain. Psychedelics like LSD and psilocybin rely on stimulating 5-HT2A receptors to produce their signature subjective and hallucinogenic effects. Downregulation means there are fewer receptors for psychedelics to bind to, resulting in muted effects.
2. Blockade of Serotonin Release
Psychedelics like LSD and psilocybin bind to and activate the serotonin 2A receptor, leading to their psychedelic effects. SSRIs and SNRIs interact with the same receptor, except they block its activity rather than activating it. This competitive binding and interference with normal serotonin signaling can dampen psychedelic effects.
Here you can see the degree of similarity in the chemical structures of LSD, psilocin and serotonin
While more research is needed to truly understand these effects, there is anecdotal evidence and some clinical data indicating that combining most SSRIs or SNRIs with psychedelics like psilocybin and LSD results in experiences that are significantly blunted or altogether absent.Â
Safety Implications of Combining Antidepressants and Psychedelics
A common instinct when psychedelic effects are blocked is to take very high doses in hopes of overriding the interference. Although psychedelics like psilocybin and LSD have a very good safety protocol from a physical perspective, dramatically increasing doses could raise psychological risks like anxiety, confusion, or even traumatic experiences.
Additionally, combining antidepressants with psychedelics that have monoamine oxidase inhibitor (MAOI) properties (such as ayahuasca) is extremely hazardous and should be avoided. However, neither LSD or psilocybin possess clinically relevant MAOI properties at normal doses.
Overall, current evidence doesn’t indicate any physical safety risk specifically from combining SSRIs or SNRIs with LSD or psilocybin. The main concerns are blunted/blocked effects and potential psychological harms if very high psychedelic doses are used to compensate.
Reflect Carefully Before Changing Medication Regimens
- Are you currently in a stable and healthy place mentally, emotionally, and physically to handle challenges that may emerge when discontinuing antidepressants? Tapering these medications can sometimes destabilize mood or anxiety symptoms. Make sure your symptoms are well-managed first.
- Do you have adequate support systems and resources in place? The process can be greatly eased by having professional support from your prescriber, therapist, or a psychedelic therapist. Surrounding yourself with understanding family and friends is also beneficial.
- How is your general life situation? Experiencing major unrelated stressors or upcoming life changes while undergoing this transition could be overwhelming. If you’re going through a particularly turbulent or crisis-prone period, it may be wise to postpone tapering or psychedelic exploration.
- Be mindful of past symptom history and sensitivity to medication changes. If you’ve had severe reactions when adjusting antidepressant doses in the past, extra caution is warranted.
Slow Tapering is Key for Antidepressant Discontinuation
For those reflecting deeply and feeling ready to proceed, the first step is to slowly taper your antidepressant under medical supervision. While providers sometimes recommend relatively quick tapers over 2-4 weeks, this is often too rapid, leading to intolerable withdrawal symptoms that derail efforts.
Some tips that can optimize success:
- Make small dose reductions between 5-25% near the end and when symptoms intensify. Larger cuts early on may be tolerated better.
- Consider using a compounding pharmacy for custom micro doses or specially formulated tapering strips.
- Be patient and compassionate with yourself through ups and downs. Expect some turbulence.
- Utilize additional therapies like psychotherapy, meditation, or exercise to ease the transition.
With close provider involvement, an extremely gradual taper, and using coping strategies, you can discontinue antidepressants safely. Again, we need to reiterate that this is not medical advice and that everyone’s situation is unique. Consulting your doctor and mental health professional is always the best approach.
Managing Return of Original Symptoms
Beyond withdrawal symptoms, another expected aspect of stopping antidepressants is possible return of the original underlying condition, whether that’s depression, anxiety, OCD, or another disorder. After all, antidepressants treat symptoms rather than addressing root causes.
This highlights the importance of having alternative treatment modalities lined up when discontinuing antidepressants. Psychedelic-assisted psychotherapy is one emerging option that has shown tremendous promise in conditions like treatment-resistant depression and end-of-life anxiety. Other options include transcranial magnetic stimulation, ECT, ketamine therapy, traditional psychotherapy, and natural supplements.
Washout Periods: How Long to Wait After Stopping Antidepressants
Once fully tapered off antidepressants, sufficient time must be allotted to ensure their clearance before using psychedelics. Waiting periods suggested by research studies are:
- For SSRIs and most SNRIs, a 2 week washout period is typically sufficient for the medication to be eliminated.
- For fluoxetine (Prozac), its long half-life requires waiting approximately 6 weeks after discontinuation to avoid potential interactions.
Following appropriate washout periods avoids safety concerns and allows your serotonin receptors to upregulate again, helping psychedelics work as intended. However, some people may choose to remain on certain antidepressants that are safer to combine with psychedelics, like bupropion or mirtazapine. If going this route, close monitoring is still prudent.
Open Provider Communication Facilitates Safe Navigation
Navigating the intersection of antidepressants and psychedelics like psilocybin or LSD requires nuanced understanding and open communication with your mental health providers. Following the best available evidence helps minimize risks and enhance outcomes.
Your prescriber or pharmacist can explain the unique considerations for your specific medications and doses. They can also supervise tapering regimens and support you through potential destabilization of symptoms during this transition. Checking for potential drug interactions using credible resources is prudent.
With knowledge, intention, and proper professional guidance, those on antidepressants can safely explore psychedelic healing when the time is right. While complex, this ceremonial dance between plant medicines and pharmaceuticals can be navigated gracefully.
