Substance P (SP) is one of the chemicals that link the skin, the immune system, the brain, and the nervous system into one smoothly functioning organism. It’s categorized as a neurotransmitter because it relays information between these systems. Kinda like a chemical messenger.

Wikipedia describes SP as “a key first responder to most noxious/extreme stimuli (stressors), i.e., those with a potential to compromise biological integrity. SP is thus regarded as an immediate defense, stress, repair, survival system.”

As part of the body’s defense mechanism, substance P is vital for survival. Animal studies show that rats without functioning SP signaling die of infections much sooner than healthy rats as they cannot effectively fight off these infections. Without SP, the communication channels between the brain and different parts of the body are broken, and the brain has difficulty directing the immune system to where it’s needed. So SP is vital for your survival, but in some cases, it can also cause problems. And acne is one of those problems.

Among other things, substance P is involved in the perception of pain and injury, including emotional pain. SP is secreted from various places in the body, such as the skin, joints, muscles, and the brain. Similarly, SP receptors are spread throughout the body. However, they are especially prevalent in the areas of the brain that regulate emotions. The skin is also dotted with SP receptors.

Substance P is considered a central stress neurotransmitter. It is one of the chemicals that initiate the body’s healing, immune, and inflammatory responses. Let’s say you receive an injury to the skin. At the site of the injury, the nerve cells secrete SP (and other neurotransmitters). This activates the stress response, which triggers the release of inflammatory chemicals and alerts the immune system so that the immune system can clear the injured area and healing can take place.

The problem with SP is that it can make a mess of the skin. Cell culture studies show that substance P can:

• Increase the growth rate of sebum-producing sebocyte and keratin-producing keratinocyte cells
• Enlarge the sebaceous glands and increase sebum production
• Increase keratin production
• Stimulate inflammation in skin cells

If these results are confirmed in living humans, it means that substance P directly influences all of the proximal causes of acne. Research so far points to substance P as a factor in skin conditions. Although it’s generally accepted that the sebaceous glands don’t interact with the nervous system and that stress and other emotions have no effect on them, this may not be the case in acne-prone skin. At least one study found substance P receptors and nerves in and around the sebaceous glands in acne-prone skin but not in healthy skin. Sebaceous glands in acne-prone skin also contain enzymes for degrading substance P, a strong indicator that SP regularly interacts with them.

A Swedish study provides a glimpse into how much SP affects the skin. The researchers injected SP into the skin of psoriasis patients and healthy controls. The SP injection triggered psoriatic flares even in people not prone to getting psoriasis. Interestingly, a 2016 review looked at case studies of psoriasis patients who had suffered nerve damage. The authors found 11 reported case studies where psoriasis cleared completely as a result of nerve damage. Furthermore, regeneration of the nerves caused psoriasis to return.

Can SP do the same for acne? We don’t know yet, but the evidence we have now certainly doesn’t rule out the possibility.

Substance P may also turn out to be one of the chemical links between emotions and skin health. Research has shown that SP is involved in emotional control, and the three emotions it’s linked to are anxiety, depression, and stress. Not surprisingly, these are the three emotions familiar to many acne sufferers.

Substance P is secreted during stressful situations

Both animal and human studies show SP is secreted during stressful and anxiety-producing situations. For example, one study looked at people with little to no experience in parachuting and what happens to them before and after taking a tandem parachute jump. Jumping out of a plane would constitute an anxiety-producing situation for many people, and indeed, the data showed that the individuals with higher levels of anxiety also had higher SP levels in their blood.

Another study looked at the effects of war stress. During the 1991 Gulf War, Iraq launched Scud missiles toward Israel, and researchers took the rare opportunity to study the effects this had on the people in Israel. Again, they found that heightened anxiety levels go hand in hand with increased SP levels in the blood.

Other studies show that this is a two-way street. A 2002 study looked at the effects of SP on mood and sleep. The participants slept a few nights in a sleep lab where their emotional state and sleep quality were monitored. The researchers administered SP injections to the participants and stepped back to see what happened. They found that SP triggered a classic stress response. It significantly increased heart rate and blood pressure, and also caused skin flushing and feelings of heat. It also significantly worsened mood for participants and disturbed their sleep patterns. An increase in cortisol levels was also noted.

Animal studies offer further proof of the role of SP in anxiety and fear responses. For example, when the SP receptors in the brain are blocked, prey animals show much less fear and anxiety in the presence of predatory animals.

Finally, SP may also be involved in depression. Depressed people show higher levels of SP, and at least some studies show antidepressants reduce SP levels. Ongoing studies are also looking at the possibility of using SP receptor blockers as antidepressants, with some research showing promising yet somewhat mixed results.

Clearly there’s a case to be made for SP’s involvement in emotional control, and if we simplify things a bit, we can phrase it like this: the more anxiety, depression, and stress you feel, the more substance P you have in your blood. After reviewing the SP’s connection to skin health, it’s easy to see how this connection between SP and emotions could potentially cause problems in the skin. Note that this is far from a proven fact, but it should be enough to warrant a serious effort to tackling stress and other negative emotions.

I want to caution that it’s not the emotions per se that are the problem. Emotions are, to some extent, only a response to substance P levels in the brain, and the real problem lies in perception. SP is secreted in response to emotionally stressful or anxiety-producing stimuli. However, what is stressful for one person can be relaxing for another; it all depends on how you perceive the situation. A shift in perception can change how you react to any given situation. The power of perception in creating emotions is something we will explore further in a later section.