Thu Mar 21

Elon Musk says ketamine can get you out of a ‘negative frame of mind’. What does the research say?

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

X owner Elon Musk recently described ^[1] 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 ^[2] 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 ^[3] that has not responded to at least two other types of treatments.

Ketamine is thought to change chemicals in the brain ^[5] 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 ^[6].

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 ^[7].

The US Food and Drug Administration approved ^[8] 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 ^[9].

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 ^[10].

Researchers have been investigating ketamine for depression for 30 years. SB Arts Media/Shutterstock ^[11]

The first clinical trial results were published in 2000 ^[12]. 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 ^[13], post-traumatic sress disorder ^[14] obsessive-compulsive disorder, eating disorders and for reducing substance use ^[15], with generally positive results.

One study in a community clinic ^[16] 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 ketamine research ^[18] conducted in the past 30 years found only 22 ketamine studies involving a total of 2,336 patients worldwide. In comparison, in 2021 alone, there were 1,489 studies being conducted on cancer drugs ^[19].

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 ^[20] was approved ^[21] by the Australian Therapuetic Goods Administration (TGA) in 2021. It must be administered under the direct supervision ^[22] of a health-care professional, usually a psychiatrist.

Spravato dosage ^[23] 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 ^[24] between A$600 and $900 ^[25] 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 ^[26] 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 ^[27].

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 ^[28].

Information about deaths due to ketamine is limited. Those that are reported are due to accidents or ketamine combined with other drugs ^[29]. No deaths have been reported in treatment settings ^[30].

Reducing stigma

Depression is the third leading cause of disability worldwide ^[31] and effective treatments are needed.

Seeking medical advice about treatment for depression is wiser than taking Musk’s advice on which drugs to use ^[32].

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.