Serotonin, Psychedelics, & Depression

Updated: Jun 23, 2021

Serotonin is a true complex neuromodulator containing over 14 receptors within the serotonin system (1). Considering the role of serotonin on cognition, perception, and it is no surprise to learn that serotonin has a major role in more than a handful of major mental health illnesses such as anxiety, depression, OCD, PTSD, and even epilepsy (4).

SSRIs also known as selective serotonin reuptake inhibitors are currently the dominant treatment for depression and the number of people who take SSRI's regularly have exponentially increased year after year. Even with more and more people taking SSRI's to treat their symptoms of depression, we have not seen SSRI's impacting the prevalence of depression. Doctors and patients alike are now questioning the effectiveness, safety, and the current standards of treating chronic medical issues with pharmaceutical drugs.

Doctors, patients, and psychiatrists had a strong view that serotonin is the main culprit of depression however the relationship between the 2 is more than complex. Over the last decade groundbreaking work has demonstrated how genetic variations and pharmacological manipulations of the serotonin system interact significantly with environmental factors and the effects on mental health.

Human use of psychedelics research is limited due to the criminal drug policy reform from the 1960's - 1970's, and has only been seriously researched over the last decade-ish. LSD (acid), magic mushrooms), and dimethyltryptamine (DMT) are all considered serotonergic psychedelics and they all activate receptor type 5-HT2A & 5-HT2A receptor agonism is the pharmacological trigger that causes the psychedelic effects.

A psychedelic experience varies from the environment which the trip takes place as well as the intention and mind set of the individual going on the trip, as well as the people that they are surrounded with as well (1,4). Those in a psychedelic experience often experience Oceanic Boundlessness, a oneness with the universe as well as Dread of Ego Dissolution, a complete loss of subjective self identity (1,3).

Over the past decade or so there have been many small scale studies that suggest psychedelics combined with psychological support and music works well as a safe and effective way to treat a wide range of psychiatric disorders ranging from anxiety, depression, addiction, even quitting smoking with just one psychedelic therapy session and the therapeutic effects lasting for 3 weeks to several months (1,2).

An easy to understand model of therapeutic mechanisms of psychedelic treatments would help clinical research immensely and is currently being developed by scientists. One thesis is that serotonin causes individual responses, behaviorally and physiologically, to uncertainty. The receptors subtype 5-HT1A is responsible for basal control during uneventful conditions, by means of anxiety, emotion, and overall patience. The receptor subtype 5-HT2A is hypothesized to take over control from 5-HT1A during a crisis often caused by change in environment or series of occurrences. Based on probability, due to the lack of research, it is thought that 5-HT2A receptor stimulation relaxes prior assumptions or beliefs, is involved with cognitive, emotional, perceptual, and philosophical brain functions and allows a person to feel heightened sensitivity to context which makes it easier for them to create change within their brains chemistry (1).

The benefits of psychedelics in the medicinal world is just the beginning, and the effects classic psychedelics will have on society when its use is as widespread as SSRI's today will be interesting to watch unfold for sure.

REFERENCES 1. Carhart‐Harris RL, Nutt DJ. J Psychopharmacol 2017;31:1091‐120. [PMC free article] [PubMed] [Google Scholar] 2. Carhart‐Harris RL, Goodwin GM. Neuropsychopharmacology 2017;42:2105‐13. [PMC free article][PubMed] [Google Scholar] 3. Roseman L, Nutt DJ, Carhart‐Harris RL et al. Front Pharmacol 2018;8:974. [PMC free article][PubMed] [Google Scholar]


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