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Cambridge University Science Magazine
We are all aware that toxins cause damage to our body though many people subject themselves to toxic substances such as alcohol and nicotine regularly. Despite this, it is perhaps surprising that one of the most potent poisons known to science is regularly used by beauticians and prescribed in hospitals across the world.

Clostridium botulinum bacteria produce a set of toxins which affect nerve cells, or neurons. These so-called neurotoxins cause paralysis by blocking the signals neurons release onto muscle cells. Specifically, they cut protein complexes which are responsible for the release of neurotransmitters, the chemicals which signal to the muscle to contract. The resulting weakness affects the muscles controlling respiratory function and may prove fatal if medical help is not provided. Despite its foreboding nature, this toxin is often used in a clinical setting and is known under a different moniker: Botox.

The negative effects of botulinum intoxication have not marred its reputation in the cosmetics sector. The Aesthetic Society reports that Botox injections have remained the most popular non-invasive cosmetic practice since 1999, with over 1.7 million cosmetic injection procedures completed in 2019 in the US alone. Intramuscular injections of Botox ensure the toxin stays local to the site of injection. The resulting muscle weakness lasts between 3-6 months – a temporary effect which can have favourable, rather than deadly, consequences. Used as an aesthetic aide, Botox is heralded to create a youthful appearance, smoothing wrinkles in the face which are caused by muscle contractions.

Aside from its prominent cosmetic use, Botox has also proven useful in treating a number of medical conditions. In fact, the use of Botox in a clinical setting began in the 1980s, 20 years before cosmetic application became widespread. It can alleviate a variety of symptoms, including management of muscle hyperactivity disorders, misalignment of the eyes and excessive sweating. Botox has also been shown to be effective against chronic headaches and migraines. While our understanding of migraines is not complete, the pain they cause is thought to be due to inflammation around nociceptive (pain-sensing) neurons. Stimulation of these neurons by inflammatory substances causes increased neurotransmitter release from these nerve terminals. This causes sensitisation of neurons, increasing the transmission of nociceptive signals from the periphery to central systems. Botox impedes this sensitisation by reducing the release of neurotransmitters from peripheral neurons.

The effects of Botox extend beyond the physical and neurological. It is well-established that facial Botox recipients lack control over emotional expression. Recently, research has shown Botox may also affect perception, as well as portrayal of emotion. This is suggested in studies in which recipients of Botox injections have reduced ability to identify facial expressions in photos presented to them. This is thought to be due to interference with a process known as emotional proprioception. Proprioception is our sense of limb location and body position. For example, you know if your arm is raised in the air without having to physically see it above your head. This is mediated by feedback from our muscles to the brain. We assume our emotions dictate our facial expression; you smile when happy and frown when sad. However, by smiling or frowning, your muscles also indicate to the brain that you are happy or sad. In this way, your expression can affect your emotion. A forced smile, regardless of genuine happiness, improves how entertaining a viewer rates a film or TV program. This bi-directional interaction between muscles and emotional state is referred to as the facial feedback hypothesis. Facial feedback helps us to understand our own emotions, but may also help in the perception of the emotions of others. When we interact with someone, we subtly mimic their facial expression on our own face. The combination of facial mimicry and facial feedback means that feedback from our muscles can be used to comprehend the emotions of the people we speak to. If this hypothesis is true, the paralytic effects of Botox will disrupt this feedback.

The phenomenon of facial feedback is now being tested as a potential therapy for people with severe mental health disorders. Major Depressive Disorder is an extremely prevalent illness, affecting millions of people around the world. Several studies suggest that when Botox is injected into the glabellar region between the eyebrows of depressed patients, they show significant improvements in depression scores compared to pretreatment values when tested around 6-8 weeks following injection. The paralysis of the corrugator muscle is thought to reduce the proprioception of negative facial expressions, and therefore reduce perception of negative emotion. Although research is more in the preliminary stages, a recent study has suggested Botox may also be an effective treatment against untreated bipolar disorder.

Arguments remain as to whether Botox is actually effective in psychiatric treatment; a product of our limited understanding of facial feedback and the interaction between emotion and mental health. This is exacerbated by a myriad of studies which have weak results, low sample sizes, and authors with conflicts of interest. As with many mental health medications, the story is not black and white. Proponents of Botox dispute naysayers, arguing for its use on the basis that we should care if something works, rather than how it works. Similar doubts surrounding Botox could be applied to current mental health medications. For example, serotonin selective reuptake inhibitors, a common class of antidepressant, are still subject to intense scrutiny, with studies suggesting the drug has limited effectiveness against depression, poor withdrawal responses and causes an assortment of side effects. As we are yet to fully understand the aetiology or causes of complex mental health disorders, it is perhaps foolish to expect a full understanding of their remedies. Compared to other treatments, Botox is relatively cheap and causes very few unpleasant side effects; there are few safety concerns associated with its use. It may be used in combinatorial approaches to reduce the dosage of medication patients take or in cases where people who have not responded to other medication and therapies. However, it is clear larger and more in-depth patient studies need to be completed to further determine the effectiveness of treatment.

Lauded by some as the ‘miracle toxin’, Botox is often seen in a scornful light by general society. Although the native toxin is causative of death, this unsavoury opinion pertains to Botox’s cosmetic applications; reserved for the rich and vain. This unfortunate reputation does a disservice to the benefits of its use and ignores its true value. It is a sad truth that people feel it is necessary to undergo procedures to appear more youthful, but this should be perceived as a reflection of the unrealistic beauty standards imposed upon us. Even if the potential benefits to self-esteem are ignored, Botox has many other benefits. While it is overambitious to claim the discovery of a ‘miracle’ cure, the clinical use of Botox in neuromuscular conditions alone should merit a favourable stance towards Botox in society. Additional interest in its use as an alleviant of chronic pain and a part of combinatorial mental health therapies indicate that a reappraisal in our view towards Botox is long overdue.

Emily Birt is a third year Natural Sciences student at Girton College, University of Cambridge. She is specialising in Neuroscience with a project focusing on the neuroendocrine regulation of reproduction and fertility. She is the social media officer for the Girton College Natural Sciences Society and secretary for Cambridge University Show Choir. Illustration by Marida Ianni-Radi.