Sigma-1 receptor and intracellular effects

Chris Masterjohn, PhD, Founder and Scientific Director of mito.me, explains why SSRI withdrawal is mitochondrial dysfunction and what to do about it.

This is not medical advice, diagnosis, or treatment.

29 million Americans and about 5-10% of the world's population are on SSRIs, which have become the first-line treatment of depression.

These can cause sexual dysfunction and emotional blunting in up to half of people, an unclear incidence of sleep disruption, and a rare risk of suicidality, self-harm, and new-onset psychosis.

On the other hand, 20-50% of people who go off experience SSRI discontinuation syndrome.

This can involve irritability, anxiety, mood problems, crying, dread, suicidal ideation, insomnia, nightmares, excessive dreaming, lethargy, fatigue, headache, tremor, sweating, anorexia, flu-like symptoms, nausea, vomiting, diarrhea, pain, numbness, tingling, feeling like something is crawling on the skin, electric shocks running through the brain or body, rushing noises, visual traces (seeing something persist when it is no longer there, or seeing moving objects leaving illusory streaks of light behind them, etc), dizziness, light-headedness, "brain zaps," vertigo, confusion, difficulty concentrating, amnesia, genital hypersensitivity, and premature ejaculation.

A closely related problem is post-SSRI sexual dysfunction (PSSD), which can cause total inability to feel the penis for males or for females the genitals and nipples, loss of sexual pleasure, weak orgasms, decreased libido, erectile dysfunction, and premature ejaculation. PSSD is often associated with general anhedonia, apathy, and poor mood.

In this video, Masterjohn maintains that the reason there are no good solutions to these problems is because we have completely misunderstood the role of serotonin and SSRIs.

Serotonin's role is to help mitochondria adapt to changing demands for oxygen-based energy production.

SSRIs enhance some of the mechanisms, and interfere with others. They enter the cell and stimulate independent mechanisms of mitochondrial stress adaptation, but in doing so they turn a cyclical and rhythmic pathway into a constantly stimulated one, creating mitochondrial dependence and making mitochondria vulnerable to new-onset dysfunction upon withdrawal. Once they make it to the mitochondria itself, the SSRIs act as mitochondrial toxins.

Scientific references for everything covered in the video can be found in this series:

https://chrismasterjohnphd.substack.com/p/prozac-is-a-performance-enhancing

At the bottom of each article is a link to the next one.

0:30 SSRI Side Effects

1:00 SSRI Discontinuation Syndrome and PSSD

11:33 The Problem With Primary Care Doctors and Psychiatrists

14:56 The Reason We Don't Have Good Solutions Is Because We Don't Understand the Problem

16:22 Prozac Is a Performance-Enhancing Drug

18:40 Depression and Altitude

19:36 The Truth About Serotonin

25:10 How Serotonin Helps Us Breathe

30:05 Hypoxia Explains Why Serotonin Is So Abundant In the Gut

33:55 Serotonin, Melatonin, and the Mitochondria

35:50 Serotonin and Light

39:25 Intermittent Hypobaric Hypoxia Training

42:56 SSRIs Are Whole-Body, Primarily Non-Brain, Non-Neuronal, Mitochondrial Drugs

44:00 SSRIs and Birth Defects

46:37 SSRIs Deplete Serotonin

48:50 SSRIs Distort the Sigma-1 Receptor From a Cyclical to a Constant Activation

51:10 Different SSRIs Promote Different Ratios of Mitophagy and Mitochondrial Biogenesis

54:00 Going Off SSRIs Causes New-Onset Mitochondrial Dysfunction

58:30 Slow and Hyperbolic Tapers

1:02:10 What to Do About SSRI Withdrawal Mitochondrial Dysfunction

Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondrial test Mitome.

Do You Have Hidden Mitochondrial Dysfunction?

Mitochondrial dysfunction is one of the earliest signs of aging and chronic disease—and most people don't know they have it. Mitome is the first at-home test that measures your cellular energy directly and gives you a personalized roadmap to optimize energy, slow aging, and protect against disease.

Find it here at mito.me