X owner Elon Musk recently described using small amounts of ketamine “once every other week” to manage the “chemical tides” that cause his depression. He says it’s helpful to get out of a “negative frame of mind”.

This has caused a range of reactions in the media, including on X (formerly Twitter), from strong support for Musk’s choice of treatment, to allegations he has a drug problem.

But what exactly is ketamine? And what is its role in the treatment of depression?

It was first used as an anaesthetic

Ketamine is a dissociative anaesthetic used in surgery and to relieve pain.

At certain doses, people are awake but are disconnected from their bodies. This makes it useful for paramedics, for example, who can continue to talk to injured patients while the drug blocks pain but without affecting the person’s breathing or blood flow.

Ketamine is also used to sedate animals in veterinary practice.

Ketamine is a mixture of two molecules, usually referred to a S-Ketamine and R-Ketamine.

S-Ketamine, or esketamine, is stronger than R-Ketamine and was approved in 2019 in the United States under the drug name Spravato for serious and long-term depression that has not responded to at least two other types of treatments.

Ketamine is thought to change chemicals in the brain that affect mood.
While the exact way ketamine works on the brain is not known, scientists think it changes the amount of the neurotransmitter glutamate and therefore changes symptoms of depression.

How was it developed?

Ketamine was first synthesised by chemists at the Parke Davis pharmaceutical company in Michigan in the United States as an anaesthetic. It was tested on a group of prisoners at Jackson Prison in Michigan in 1964 and found to be fast acting with few side effects.

The US Food and Drug Administration approved ketamine as a general anaesthetic in 1970. It is now on the World Health Organization’s core list of essential medicines for health systems worldwide as an anaesthetic drug.

In 1994, following patient reports of improved depression symptoms after surgery where ketamine was used as the anaesthetic, researchers began studying the effects of low doses of ketamine on depression.

The first clinical trial results were published in 2000. In the trial, seven people were given either intravenous ketamine or a salt solution over two days. Like the earlier case studies, ketamine was found to reduce symptoms of depression quickly, often within hours and the effects lasted up to seven days.

Over the past 20 years, researchers have studied the effects of ketamine on treatment resistant depression, bipolar disorder, post-traumatic sress disorder obsessive-compulsive disorder, eating disorders and for reducing substance use, with generally positive results.

One study in a community clinic providing ketamine intravenous therapy for depression and anxiety found the majority of patients reported improved depression symptoms eight weeks after starting regular treatment.

While this might sound like a lot of research, it’s not. A recent review of randomised controlled trials conducted up to April 2023 looking at the effects of ketamine for treating depression found only 49 studies involving a total of 3,299 patients worldwide. In comparison, in 2021 alone, there were 1,489 studies being conducted on cancer drugs.

Is ketamine prescribed in Australia?

Even though the research results on ketamine’s effectiveness are encouraging, scientists still don’t really know how it works. That’s why it’s not readily available from GPs in Australia as a standard depression treatment. Instead, ketamine is mostly used in specialised clinics and research centres.

However, the clinical use of ketamine is increasing. Spravato nasal spray was approved by the Australian Therapuetic Goods Administration (TGA) in 2021. It must be administered under the direct supervision of a health-care professional, usually a psychiatrist.

Spravato dosage and frequency varies for each person. People usually start with three to six doses over several weeks to see how it works, moving to fortnightly treatment as a maintenance dose. The nasal spray costs between A$600 and $900 per dose, which will significantly limit many people’s access to the drug.

Ketamine can be prescribed “off-label” by GPs in Australia who can prescribe schedule 8 drugs. This means it is up to the GP to assess the person and their medication needs. But experts in the drug recommend caution because of the lack of research into negative side-effects and longer-term effects.

What about its illicit use?

Concern about use and misuse of ketamine is heightened by highly publicised deaths connected to the drug.

Ketamine has been used as a recreational drug since the 1970s. People report it makes them feel euphoric, trance-like, floating and dreamy. However, the amounts used recreationally are typically higher than those used to treat depression.

Information about deaths due to ketamine is limited. Those that are reported are due to accidents or ketamine combined with other drugs. No deaths have been reported in treatment settings.

Reducing stigma

Depression is the third leading cause of disability worldwide and effective treatments are needed.

Seeking medical advice about treatment for depression is wiser than taking Musk’s advice on which drugs to use.

However, Musk’s public discussion of his mental health challenges and experiences of treatment has the potential to reduce stigma around depression and help-seeking for mental health conditions.

Clarification: this article previously referred to a systematic review looking at oral ketamine to treat depression. The article has been updated to instead cite a review that encompasses other routes of administration as well, such as intravenous and intranasal ketamine.

Julaine Allan, Associate Professor, Mental Health and Addiction, Rural Health Research Institute, Charles Sturt University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Anorexia nervosa is a severe mental health disorder where people fear weight gain. Those with the disorder have distorted body image and hold rigid beliefs their body is too big. They typically manage this through restricted eating, leading to the serious medical consequences of malnutrition.

Anorexia has one of the highest death rates of any mental illness. Yet there are currently no effective drug treatments and the outcomes of psychotherapy (talk therapy) are poor. So we’re desperately in need of new and improved treatments.

Psilocybin, commonly known as magic mushrooms, is one such novel treatment. But while it shows early promise, you won’t see it used in clinical practice just yet – more research is needed to test if it’s safe and effective.

What does treatment involve?

The treatment involves the patient taking a dose of psilocybin in a safe environment, which is usually a specifically set up clinic. The patient undergoes preparation therapy before the dosing session and integration therapy after.

Psilocybin, extracted from mushrooms, is a psychedelic, which means it can produce altered thinking, sense of time and emotions, and can often result in hallucinations. It also has the potential to shift patients out of their rigid thinking patterns.

Psilocybin is not administered alone but instead with combined structured psychotherapy sessions to help the patient make sense of their experiences and the changes to their thinking. This is an important part of the treatment.

What does the research show?

Research has shown improved effects of psilocybin-assisted psychotherapy after one or two dosing sessions, a couple of weeks apart. Most research to date has targeted depression.

Psilocybin has been found to increase cognitive flexibility – our ability to adjust our thinking patterns according to changing environments or demands. This is one of the ways researchers believe psilocybin might improve symptoms for conditions such as depression and alcohol use disorder, which are marked by rigid thinking styles.

People with anorexia similarly struggle with rigid thinking patterns. So researchers and clinicians have recently turned their attention to anorexia.

In 2023, a small pilot study of ten women with anorexia was published in the journal Nature Medicine. It showed psilocybin-assisted psychotherapy (with 25mg of psilocybin) was safe and acceptable. There were no significant side effects and participants reported having valuable experiences.

Although the trial was not a formal efficacy trial, 40% of the patients did have significant drops in their eating disorder behaviour.

However, the trial only had one dosing session and no long-term follow up, so further research is needed.

A recent animal study using rats examined whether rigid thinking could be improved in rats when given psilocybin. After the psilocybin, rats gained weight and had more flexible thinking (using a reversal learning task).

These positive changes were related to the serotonin neurotransmitter system, which regulates mood, behaviour and satiety (feeling full).

Brain imaging studies in humans show serotonin disturbances in people with anorexia. Psilocybin-assisted psychotherapy is showing promise at modifying the serotonin disturbances and cognitive inflexibility that have been shown to be problematic in anorexia.

Research with animals can provide unique insights into the brain which can sometimes not be investigated in living humans. But animal models can never truly mimic human behaviour and the complex nature of chronic mental health conditions.

What’s next for research?

Further clinical trials in humans are very much needed – and are underway from a research team at the University of Sydney and ours at Swinburne.

Our trial will involve an initial 5mg dose followed by two subsequent doses of 25mg, several weeks apart. An initial low dose aims to help participants prepare for what is likely to be a new and somewhat unpredictable experience.

Our trial will examine the usefulness of providing psychotherapy that directly addresses body image disturbance. We are also investigating if including a family member or close friend in the treatment increases support for their loved one.

Data from other mental health conditions has suggested that not everyone sees benefits, with some people having bad trips and a deterioration in their mental health. So this treatment won’t be for everyone. It’s important to work out who is most likely to respond and under what conditions.

New trials and those underway will be critical in understanding whether psilocybin-assisted psychotherapy is a safe and effective treatment for anorexia, and the optimal conditions to improve the patient’s response. But we are some way off from seeing this treatment in the clinic. One of the big issues being the cost of this intervention and how this will be funded.

Susan Rossell, Director Clinical Trials and Professor Cognitive Neuropsychiatry Centre for Mental Health and Brain Sciences, Swinburne University of Technology and Claire Finkelstein, Clinical Psychologist and PhD candidate, Swinburne University of Technology

This article is republished from The Conversation under a Creative Commons license. Read the original article.