Psilocybins & SSRIs
Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, often referred to as "magic mushrooms." It is known for its ability to produce profound alterations in perception, mood, and cognition.
When ingested, psilocybin is rapidly converted into its active form, psilocin, by the enzyme alkaline phosphatase. Psilocin is the primary compound responsible for the psychedelic effects. Psilocin primarily acts as an agonist at serotonin (5-HT) receptors, particularly the 5-HT2A receptor. It also affects other 5-HT receptor subtypes, such as 5-HT1A and 5-HT2C, but to a lesser extent. The 5-HT2A receptor is densely located in the prefrontal cortex, a region involved in mood, cognition, and perception. Activation of these receptors by psilocin leads to the characteristic psychedelic effects.
Selective serotonin reuptake inhibitors (SSRIs) are a class of medications commonly used to treat depression and anxiety disorders. They work by increasing the levels of serotonin in the brain, which is a neurotransmitter known to influence mood, emotion, and sleep.
Neurons in the brain communicate with each other through synapses, where neurotransmitters like serotonin are released from one neuron and bind to receptors on the next neuron. After serotonin has transmitted its signal, it is usually reabsorbed back into the presynaptic neuron through a process called reuptake. SSRIs block the serotonin reuptake transporter (SERT), preventing the reabsorption of serotonin back into the presynaptic neuron. This results in increased levels of serotonin in the synaptic cleft, enhancing its positive effects on mood and anxiety.
Examples of SSRIs:
- Fluoxetine (Prozac): Fluoxetine is one of the most well-known SSRIs. It is used to treat major depressive disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, and panic disorder.
- Sertraline (Zoloft): Sertraline is another widely prescribed SSRI used to treat depression, OCD, panic disorder, social anxiety disorder, and post-traumatic stress disorder (PTSD).
- Citalopram (Celexa): Citalopram is used primarily for treating depression. It is known for its tolerability and lower potential for drug interactions.
- Paroxetine (Paxil): Paroxetine is used to treat depression, panic disorder, social anxiety disorder, generalized anxiety disorder, and PTSD.
- Fluvoxamine (Luvox): Fluvoxamine is primarily used to treat OCD and has also been used for social anxiety disorder.
The combination of psilocybin and SSRIs presents a complex interplay due to their effects on the serotonin system. SSRIs increase serotonin levels in the brain, which can lead to receptor occupancy and potentially reduce the effects of psilocybin. This is due to competitive inhibition where serotonin and psilocin (the active metabolite of psilocybin) compete for the same receptors, particularly the 5-HT2A receptor. Chronic SSRI use can cause downregulation of serotonin receptors, meaning there are fewer receptors available for psilocin to bind to, further diminishing the psychedelic experience.
1. Higher Required Dosage of Psilocybin: Due to the diminished effects, individuals on SSRIs may need higher doses of psilocybin to achieve the desired psychedelic effects. Anecdotal evidence suggests that doses may need to be increased by 30-50%.
2. Reduced Negative Side Effects: Some studies have found that SSRIs did not significantly alter the positive mood effects, but can reduce the negative side effects associated with psilocybin, such as anxiety and adverse cardiovascular reactions. This effect is particularly noted with two weeks escitalopram (Lexapro) pretreatment.
3. Treatment potential: Another study involving patients with treatment-resistant depression showed that a single administration of psilocybin combined with SSRIs resulted in significant improvements in depressive symptoms without severe side effects.
Safety and Risks:
- Serotonin Syndrome: Although rare, combining psilocybin with SSRIs could theoretically increase the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin activity. Symptoms include agitation, muscle rigidity, fever, and seizures. The risk is considered lower with psilocybin compared to other serotonergic substances, but caution is still advised
- Increased Anxiety and Panic: While SSRIs are used to manage anxiety, their combination with psilocybin could lead to unpredictable emotional responses, including heightened anxiety and panic during the psychedelic experience.
- Altered Metabolism and Duration: SSRIs can alter the metabolism of psilocybin, potentially leading to prolonged or intensified effects in some individuals. This can result in a longer duration of action and unexpected side effects
- Tapering Considerations: To maximize the effects of psilocybin and minimize risks, some practitioners recommend tapering off SSRIs before psilocybin use. However, this should be done gradually and under control to avoid withdrawal symptoms and ensure safety.
It's also important to highlight that SSRIs are prescribed for managing psychological and psychiatric conditions. Introducing psychoactive substances during treatment with such medications generally diminishes the efficacy of the therapy, further destabilizes compromised neural systems, and elevates the likelihood of exacerbations and negative side effects.
Considering the above, we recommend treating this combination with great caution.
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