With books like Michael Pollan’s, “How To Change Your Mind” you’ve probably grown curious about the therapeutic use of psychedelics and you’re not alone. Medical professionals are noticing the promise psychedelics have on those suffering from depression, PTSD, and other mental health conditions. But could the therapeutic benefits of psychedelics be ineffective for those who need them the most? Patients on antidepressants may face a drawback when seeking psychedelic treatment.

How antidepressants work

Seldomly, do those on antidepressants have a clear comprehension of how their prescriptions work. This is likely due to the many indefinite possible causes of depression. However, understanding how antidepressants affect the brain is essential in realizing the significance of potential interactions between antidepressants and psychedelics.  

Common Antidepressants

The most common antidepressants are reuptake inhibitors. Reuptake naturally occurs when neurotransmitters are reabsorbed back into the nerve cells. Categorizing a reuptake inhibitor as the catalyst that stops this from happening by allowing the neurotransmitter to stay within the space between the nerves called the synapse. Increasing the number of neurotransmitters within the synapse may enhance interactions between the nerve cells, strengthening the circuits within the brain that control mood, stress-response, and emotions. 

SSRIs or selective serotonin reuptake inhibitors, are the most frequently prescribed antidepressants including but not limited to citalopram, paroxetine, Prozac, and sertraline. They target selective serotonin hence its name, by inhibiting the serotonin transporter, otherwise known as SERT, through keeping it in the synapse in order to increase serotonin production. Some newer SSRIs like vortioxetine target not only SERT but other serotonin receptors as well to relieve major depression. 

Analogous to SSRIs, SNRIs or Serotonin and norepinephrine reuptake inhibitors, block the reuptake of serotonin. However, they also inhibit norepinephrine, a stress hormone, and neurotransmitter. Common SNRIs include duloxetine, venlafaxine, and desvenlafaxine. Creating a class of its own, Bupropion is an NDRI or Norepinephrine and dopamine reuptake inhibitor, which affects the reuptake of norepinephrine and dopamine.

Other Antidepressant

SARIs like nefazodone and trazodone, work in a twofold manner by blocking the reuptake of serotonin but also through inhibiting serotonin particles released in a synapse from connecting at certain unfavorable receptors and instead, redirect them to other receptors that can assist nerve cells inside mood circuits to function optimally.

Less Common Antidepressants

Amongst the first to be developed and used in treatment for depression, Cyclic antidepressants or Tricyclics and Tetracyclics, are a subclass of antidepressants that block the reabsorption of serotonin and/or epinephrine and norepinephrine as well as other neurotransmitters. They are less common due to their possible side effects. Monoamine oxidase inhibitors or MAOIs, block the effects of Monoamine oxidase, a natural enzyme that breaks down serotonin, epinephrine, and dopamine causing a potential increase in these neurotransmitters. 

So how does this relate to psychedelics?

Due to the nature of antidepressants and psychedelics, both treatments may work in similar or adverse ways causing undesirable effects upon interaction.

Classic Psychedelics

Similar to some antidepressants, classic psychedelics like LSD, Psilocybin, DMT, and MDMA work by affecting the serotonin receptors. This is why when most antidepressants and psychedelics interact, the efficacy of the psychedelic may change and could potentially be unsafe. A chart curated by psychopharmacologist Benjamin Malcolm, displays the most readily available information on interactions between antidepressants and psychedelics. Synthesis, a legal psilocybin retreat in Amsterdam, due to the safety of their guests, do not permit those who are currently on SSRIs and are unable to accept clients who have previously been on SSRIs or any other prescription medication in the past 42 days. This is common amongst several psychedelic supported treatment centers due to the unknown possible reactions certain antidepressants may cause. 

MDMA, otherwise known as ecstasy, is a synthetic substance that modifies mood and perception. The interactions between the serotonin system and MDMA are the most clinically researched of any other psychedelic. MDMA tends to attach to some of the same targets as SSRIs. A 2007 study showed rats pretreated with SSRIs had a blunted response to MDMA treatment. Correspondingly, based on anecdotal reports, SSRIs may diminish the effects of MDMA and may even contribute to an undesirable hangover. However, it’s important to note that pre-existing factors, including previous serotonin imbalance prior to taking antidepressants, could potentially be the culprit. 

MDMA has shown promise in the treatment of PTSD as well as anxiety and depression. In 2017, the FDA approved MDMA for Phase III clinical trials in the U.S. to treat PTSD, which is one of the final trials before a substance becomes legally approved for therapeutic use. The Multidisciplinary Association for Psychedelic Studies (MAPS) funded these clinical trials. Research has shown that half of PTSD sufferers also have a major depressive disorder. This is concerning when considering half of those who suffer from PTSD are also suffering from depression where if they are prescribed antidepressants, it may cause patients’ unable to reap the therapeutic benefits of MDMA. Equally, taking MDMA while on MAOIs may cause serotonin syndrome, a rare and potentially life-threatening occurrence that takes place when high levels of serotonin accumulate. This can cause unpleasant symptoms that range from mild shivering, confusion, seizures, diarrhea, and in extreme cases, it can even be fatal.  

Ayahuasca

Ayahuasca is a South American psychedelic brew, made from Psychotria Viridis leaves and Banisteriopsis caapi vine. Because the brew contains MAOI, there are several medical and dietary restrictions that must be adhered to before use. This is one of the many reasons why dieta, a dietary contract between the journeyer and the plant medicine, is typically involved with Ayahuasca treatment. Due to the risk of serotonin syndrome, researchers have suggested heeding with caution when considering Ayahuasca and possible interactions. Similar to Psilocybin retreats, Ayahuasca retreat centers typically refuse to administer treatment to those on SSRIs or request tapering off SSRIs at least 6 months prior to treatment.

Tapering off antidepressants

Simply discontinuing the use of antidepressants may sound like an easy solution but doing so can cause antidepressant withdrawal and even contribute to a relapse in depression. Symptoms may include anxiety, insomnia, headaches, nausea, flu-like effects, and a return of depression and suicidal thoughts. Experiencing this withdrawal seems like an unlikely route to potentially have a blunted reaction to treatment.

Ketamine has proven to be a great solution

Despite the dispiriting reports about potential interactions with antidepressants and most psychedelics, ketamine treatment  may offer a light at the end of the tunnel. A commonly used dissociative anesthetic, ketamine, also known as “Special K”, shows promise in the treatment of depression and pain management. 

Unlike most psychedelic studies, research has found ketamine to be an effective replacement for those taking antidepressants. In 2019, the FDA approved esketamine for treatment-resistant depression, Esketamine (brand name Spravato) is a distant cousin of ketamine. Moreover, ketamine has shown the ability to treat depression after a single dose and has proven to have lasting success while antidepressants’ efficacy typically takes months upon regular use. Esketamine, an FDA approved nasal spray, as well as ketamine infusions and lozenges, are turning this well-known party drug into short-term effective treatment for those suffering from chronic pain and mental illness.

Although, it’s important to remember there is still more research that needs to be done on the interactions of psychedelics and antidepressants. The information that is available on this basis primarily originates from anecdotal evidence and case reports. More research is needed in order to fully understand the possible therapeutic benefits of psychedelics and how antidepressants may interact with them.

References

Bhandari, Smitha. “How Antidepressants Work: SSRIs, MAOIs, Tricyclics, and More.” WebMD, WebMD, 27 June 2019, www.webmd.com/depression/how-different-antidepressants-work#1.

Carhart-Harris, Robin L. “Serotonin, Psychedelics and Psychiatry.” World Psychiatry : Official Journal of the World Psychiatric Association (WPA), John Wiley & Sons, Inc., Oct. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6127802/.

Evans, Dave, et al. “Can You Take Psychedelics With Antidepressants?” The Third Wave, 9 July 2019, thethirdwave.co/psychedelics-antidepressants/.

Malcolm, Benjamin. “Antidepressant and Psychedelic Combinations: A Guide to Risks & Discontinuation Times.” Spirit Pharmacist, Spirit Pharmacist, 10 May 2019, www.spiritpharmacist.com/blog/2019/5/10/antidepressant-and-psychedelic-combinations-a-guide-to-risks-amp-discontinuation-times.

If you connected with the above write-up, are curious, and need some guidance, psychedelic medicines such as Ketamine can really support this process of healing, self-discovery, and purpose. Click below to find out more.

Author: Bre Jenkins

Bre Jenkins, a certified health coach, previously worked in mainstream wellness before shifting her focus to energy healing and psychedelic medicine to support deep healing and personal expansion. She is certified in Reiki levels 1, 2, and 3, as well as Inner Dance and Psychedelic Integration. Her work has been featured in major publications, and she is also a significant voice in the psychedelics space, contributing to renowned psychedelic companies such as Doubleblind Mag, Third Wave, The Ancestor Project, and more.