Drug Interaction – Psilocybin & Antidepressants

Psilocybin and antidepressants

At Essence, we are committed to empowering our visitors with reliable information and valuable insights into the realm of psychedelic research and mental health treatments. A crucial topic we address is the interplay between psilocybin and antidepressants. Our goal with this content is to provide education and awareness, enabling you to grasp the possible risks and nuances in this field. Please read on to learn more about this vital subject.

Psilocybin and Antidepressants

Antidepressants

Antidepressants are a broad category of medications used primarily to treat depression. They can also be effective in treating a range of other conditions, including anxiety and chronic administration of pain. These drugs work by altering the chemicals in the brain responsible for mood and emotional states.

Antidepressants operate by influencing the brain’s chemical messengers, primarily neurotransmitters like serotonin, norepinephrine, and dopamine. For example, Selective Serotonin Reuptake Inhibitors (SSRIs), an antidepressant, works by blocking the reuptake of serotonin in the brain, making more serotonin available to improve transmission of messages between neurons. Another type, Tricyclic Antidepressants (TCAs), increase the levels of norepinephrine and serotonin, and block the action of acetylcholine, which helps to balance mood and alleviate depressive symptoms. Meanwhile, Monoamine Oxidase Inhibitors (MAOIs) inhibit the activity of monoamine oxidase, an enzyme that breaks down serotonin and norepinephrine, thus increasing their levels in the brain and improving mood and emotional balance. Each of these mechanisms targets the complex neurochemical pathways involved in mood regulation, aiming to correct imbalances that contribute to depressive states.

Psilocybin

Psilocybin is a naturally occurring psychedelic compound produced by certain species of mushrooms, often referred to as “magic mushrooms”. This substance has been the subject of increasing scientific study due to its potential to significantly impact mental health conditions, including depression(or treatment resistant depression) and anxiety. Unlike antidepressants, which are taken regularly and work by adjusting brain chemistry over time, psilocybin offers a different approach. Psilocybin mushroom effects during and after the experience, produce profound changes in consciousness and perception, which can lead to rapid and lasting changes in mood and outlook. Psilocybin has shown promise for treatment resistant depression or major depression as well.

Psilocybin’s chemical composition is intriguing, with its molecular formula being C12H17N2O4P. This compound is a tryptamine alkaloid, structurally similar to the neurotransmitter serotonin and the psychedelic effects of psilocybin play a significant role in regulating mood, anxiety, and happiness. Please read more about Psilocybin use in depression treatment in “Single-Dose Psilocybin Treatment for Major Depressive Disorder – A Randomized Clinical Trial”.

Types of Antidepressants

Antidepressants come in several forms, most commonly SSRIs (Selective Serotonergic Reuptake Inhibitors), SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), and MAOIs (Monoamine Oxidase Inhibitors) etc.

SSRI’s

Selective serotonin reuptake inhibitors (SSRI’s) are the most commonly prescribed antidepressants.  They work by blocking the reuptake of serotonin, a neurotransmitter that helps regulate mood and emotional states. SSRIs include drugs like Prozac, Zoloft, Celexa, Paxil and Lexapro.

Specific variants are (generic name, brand name(s)):

  • citalopram (Celexa, Cipramil)
  • escitalopram (Lexapro)
  • fluoxetine (Prozac)
  • fluvoxamine (Luvox, Fevarin)
  • paroxetine (Seroxat, Paxil)
  • sertraline (Zoloft, Serlain)

SNRI’s

Serotonin-Norepinephrine Reuptake Inhibitors, or SNRIs, offer another avenue for treating depression by simultaneously affecting two critical neurotransmitters in the brain. This class of medication includes drugs like Effexor, Pristiq, Cymbalta and Savella.

Specific variants are (generic name, brand name(s)):

  • venlafaxine (Effexor)
  • duloxetine (Cymbalta)
  • desvenlafaxine (Pristiq)
  • atomoxetine (Strattera)
  • levomilnacipran (Fetzima)
  • milnacipran (Ixel, Savella, Impulsor)
  • sibutramine (Meridia)
  • tramadol (Ultram)

TCA’s

Tricyclic Antidepressants (TCAs) represent an older class of antidepressants that, despite the advent of newer medications, remain a critical option for certain patients due to their unique mechanism of action and effectiveness. Due to more side-effects they are mostly not the first choice.

Specific variants are (generic name, brand name(s)):

  • Amitriptyline (Elavil)
  • Desipramine (Norpramin)
  • Imipramine (Tofranil, Janimine)
  • Nortriptyline (Pamelor, Aventyl)
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil)
  • Clomipramine (Anafranil)
  • Imipramine (Tofranil, Janimine, Praminil)
  • Maprotiline (Ludiomil)

MAOI’s

Monoamine-oxidase inhibitors represent a traditional category of antidepressants, particularly the earlier versions. They exhibited a higher incidence of side effects, with some posing risks when consumed alongside tyramine-containing foods such as certain cheeses and sauerkraut.

Specific variants are (generic name, brand name(s)):

  • Hydrazine (antidepressant)
  • Isocarboxazid (Marplan)
  • Nialamide (Niamid)
  • Phenelzine (Nardil, Nardelzine)
  • Hydracarbazine
  • Tranylcypromine (Parnate, Jatrosom)
  • Bifemelane (Alnert, Celeport)
  • Moclobemide (Aurorix, Manerix)
  • Pirlindole (Pirazidol)
  • Toloxatone (Humoryl)
  • Rasagiline (Azilect)
  • Selegiline (Deprenyl, Eldepryl, Emsam, Zelapar)
  • Safinamide (Xadago)

Psilocybin and antidepressants

The intersection of psilocybin and antidepressants in mental health treatment marks a fascinating frontier in modern psychiatry, inviting a deeper exploration of their potential synergies and differences. While antidepressants work by altering brain chemistry over time, psilocybin can induce a powerful and immediate change in perception during the experience. Let’s delve into the interaction between Psilocybin and Antidepressants by taking a closer look.

How Does Psilocybin Work?

The intersection of psilocybin and antidepressants in mental health treatment marks a fascinating frontier in modern psychiatry, inviting a deeper exploration of their potential synergies and differences. While antidepressants work by altering brain chemistry over time, psilocybin can induce a powerful and immediate change in perception during the experience. Let’s delve into the interaction between Psilocybin and Antidepressants by taking a closer look.

Psilocybin interacts with the brain in a fascinating and complex way, primarily affecting the serotonin 2A receptor (5-HT2A). This receptor is responsible for regulating the flow of information between neurons, and its activation by psilocybin leads to changes in brain activity that give rise to altered states of consciousness. The effects of psilocybin can include enhanced introspection, increased emotional openness, and a sense of connection with others and the world around us.

Upon ingestion, psilocybin is quickly metabolized into psilocin, which then exerts its psychoactive effects by binding to serotonin receptors in the brain, particularly the 5-HT2A receptor. This interaction is thought to produce the profound changes in perception, mood, and thought associated with psilocybin use.

While the psychedelic experience is the intended outcome of psilocybin, there is much more to it. Extensive research has been conducted on the safety of psilocybin (as well as other psychedelics). The findings are promising: psilocybin exhibits low toxicity and does not result in organ damage or neuropsychological deficits.

During the course of the experience, certain physiological symptoms may manifest, including dizziness, weakness, tremors, nausea, drowsiness, paresthesia, blurred vision, dilated pupils, and heightened tendon reflexes.

How Antidepressants work?

We have already explored this topic above while introducing different types of Antidepressants in this article above.(Types of Antidepressants) In summary, antidepressants work by altering levels of neurotransmitters in the brain, particularly serotonin. This can help balance moods and emotions, alleviating symptoms of depression and anxiety.

Drug Interaction

The interaction between psilocybin and antidepressants is not fully understood, but it involves the shared pathway of serotonin regulation. When combined, these substances may alter the effects of one another in unpredictable ways. Since this topic is still a relatively new area of research, there were no reports or clear guidelines on the potential risks and benefits of combining psilocybin with antidepressants.

Serotonin Syndrome

Serotonin Syndrome is a potentially serious condition that can occur when levels of serotonin become too high, often as a result of interaction between medications that affect serotonin metabolism.

Symptoms include confusion, agitation, rapid heart rate, dilated pupils, muscle rigidity, heart rate and blood pressure, seizures. and in severe cases, it can be life-threatening.

During and after SSRI SNRI antidepressant treatment, it is crucial to monitor the interaction between these antidepressants and psilocybin, as combining these substances can significantly alter the efficacy and safety of both.

While rare, the combination of psilocybin and ssri snri antidepressant use may increase the risk of serotonin syndrome. Therefore, it is crucial for individuals using both substances to consult with your GP or psychiatrist before going on a retreat. They can (possibly) help you to discontinue the antidepressants before going on a retreat.

Attenuation of psilocybin mushroom(Decreased Effectiveness)

Effects of psilocybin combining with antidepressants can have the possibility of reduced drug effects. Some studies have suggested that certain antidepressants may interfere with the psychedelic experience, potentially dulling its effects. This could have implications for the therapeutic potential of psilocybin, as it may diminish any positive impact on mental health conditions such as depression and anxiety.

Prolonged Effects

Some antidepressants, particularly MAOIs, can inhibit the breakdown of psilocybin and prolong its effects. This could lead to longer-lasting psychedelic experiences, which may not be desirable for all individuals. It is therefore essential to discuss any ongoing medication use with a healthcare provider before embarking on a psilocybin journey.

Recommendations

In light of the complex interactions between psilocybin and antidepressants, navigating their combined use requires careful consideration and guidance from healthcare professionals.

  • Consult Your Healthcare Provider: Before considering the use of psilocybin, speak with your doctor or psychiatrist. They can provide personalized advice based on your current medication, mental health condition, and overall health.
  • Gradual Discontinuation: If recommended by a healthcare professional, patients should gradually reduce antidepressant medication(including their current ssri) under supervision to minimize withdrawal symptoms and potential side effects.
  • Wait Period: After discontinuing antidepressants, observe a wait period (as advised by your healthcare provider) before trying psilocybin. This period allows your body to clear the antidepressants and reduces the risk of interaction.
  • Monitor for Serotonin Syndrome: Be aware of the symptoms of serotonin syndrome, a condition that can occur from high levels of serotonin in the brain. Seek immediate medical attention if symptoms develop.
  • Start with a Low Dose: When first using psilocybin, consider starting with a lower dose to observe how your body reacts, particularly in the absence of antidepressants and to prevent any adverse events.
  • Professional Supervision: Consider participating in a psilocybin therapy session supervised by qualified professionals. This ensures a safe environment and immediate assistance if needed. Always consult your healthcare professional before discontinuing an antidepressant.
  • Follow-Up Care: Schedule follow-up appointments with your healthcare provider to discuss your experience and any changes in your mental health after discontinuation of antidepressants.
  • Educate Yourself: Research and understand both the potential benefits and risks associated with psilocybin use, especially in the context of mental health treatment.
  • Be Patient: Understand that mental health improvement is a gradual process, and the integration of experiences from psilocybin use into daily life might require time and support.

FAQ

Can I use psilocybin if I'm on antidepressants?

Consult with a healthcare provider as combining these two can lead to serious health risks.

What should I do If experience symptoms of Serotonin Syndrome?

Seek immediate medical attention if you suspect Serotonin Syndrome.

Are there safe ways to explore psilocybin therapy?

Yes, under the guidance of professionals and in legal settings.

References

For further reading and scientific research on the topic, please refer to the provided references or reach out to us. Our commitment is to bring well-researched, accurate information within your reach, fostering safe and informed choices in the landscapes of mental health and psychedelic therapy.

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    Carhart-Harris, R. L. (2019). How do psychedelics work? Current Opinion in Psychiatry, 32, 16-21. doi:10.1097/yco.0000000000000467
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    Johnson, M., Richards, W., & Griffiths, R. (2008). Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology, 22(6), 603–620. doi:10.1177/0269881108093587
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    Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268–283. doi:10.1007/s00213-006-0457-5
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    Halpern, J. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and Alcohol Dependence, 69(2), 109–119. doi:10.1016/s0376-8716(02)00306-x
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    Dos Santos, R. G., Bouso, J. C., Alcázar-Córcoles, M. Á., & Hallak, J. E. C. (2018). Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety and substance use disorders: a systematic review of systematic reviews. Expert Review of Clinical Pharmacology 11(9), 889 – 902. doi:10.1080/17512433.2018.1511424
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    Erritzoe, D., Roseman, L., Nour, M. M., MacLean, K., Kaelen, M., Nutt, D. J., & Carhart-Harris, R. L. (2018). Effects of psilocybin therapy on personality structure. Acta Psychiatrica Scandinavica. doi:10.1111/acps.12904
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    Arora, B., & Kannikeswaran, N. (2010). The serotonin syndrome—the need for physician’s awareness. International Journal of Emergency Medicine, 3(4), 373–377. doi:10.1007/s12245-010-0195-7Drug Interaction
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    https://jamanetwork.com/journals/jama/fullarticle/2808950