Since ketamine was first synthesised in 1956, its effects have been extensively studied. Today, it is widely used as a general anesthetic, for short-term sedation, and for managing chronic pain conditions like complex regional pain syndrome (CRPS) and neuropathic pain when other treatments fail. New ketamine trials may grow and further legitimise its use.
Beyond its medical use, ketamine has a long history of recreational use, particularly in the UK, where it is known as a ‘party drug’ due to its dissociative and hallucinogenic effects, finding popularity in club scenes and rave culture – contributing to its widespread notoriety.
More recently, ketamine has globally expanded its legitimacy for mental health treatments. It was approved in the US in 2019 for treatment-resistant depression, successfully keeping patients in remission for up to 16 weeks after. A publicly-funded clinical trial in the UK is exploring its application for treating Alcohol Use Disorder (AUD), which would be a global first. Additional research is also ongoing into ketamine’s potential to treat depression in people with anorexia nervosa when existing treatments have had limited success.
Depression & anorexia nervosa ketamine trials
Current treatment for anorexia nervosa involves a multidisciplinary approach, including medical care to stabilise health, nutritional rehabilitation to restore weight through structured meal plans, and psychotherapy, such as enhanced cognitive behavioural therapy (CBT-E) and family-based therapy (FBT), to address disordered thoughts and behaviours. Ketamine is a new tool within the medical arsenal.
While no medication directly treats anorexia, selective serotonin reuptake inhibitors (SSRIs) may be used for co-occurring depression or anxiety. The EDEN Project (kEtamine for DEpression with anorexia Nervosa) will administer either oral ketamine or a placebo twice weekly for six months to 60 adults with a diagnosis of persisting anorexia and treatment-resistant depression, with initial doses being supervised. Participants will also receive psychoeducation sessions to enhance the treatment’s effects. The study is looking to evaluate ketamine’s feasibility, tolerability, and impact on depression, anorexia, and its impact on quality of life.
EDEN project’s trial manager, Dr Johanna Keeler, emphasised to TalkingDrugs the point that differentiating ketamine’s medical use from its recreational abuse is a crucial challenge for researchers:
“This is very important, particularly in psychiatric populations where abuse might be a particular risk. For example, ketamine has been used (usually as IV) in people with alcohol use disorder, where this might be an even greater risk. It is important to consider whether ketamine is appropriate to prescribe to the patient in consideration of their own medical/psychiatric history”.
“In eating disorders, substance misuse and alcohol use disorder is more common with bulimia-like presentations than anorexia-like presentations (where it is relatively infrequent). Nevertheless, in studies researchers may take several measures to mitigate the likelihood of abuse and also to monitor abuse.”
Alcohol use disorder trial
The MORE-KARE (Multicentre Investigation of Ketamine for Reduction of Alcohol Relapse) trial is designed to investigate whether ketamine delivered with psychotherapy can reduce relapse rates in individuals with AUD. This combination is exploring the hypothesis that ketamine may alter the brain’s response to cravings and enhance therapeutic engagement, making it easier for individuals to break addiction patterns.
Ketamine-assisted psychotherapy involves administering ketamine in a controlled setting while a trained therapist guides the individual through the psychoactive experience. Researchers believe ketamine’s dissociative effects can disrupt habitual thought patterns linked to addiction, opening patients’ mental “door” to new perspectives on their behaviours. This approach can be targeted to reduce cravings, ease withdrawal, and promote lasting change through the combined effects of the medication and therapeutic support.
Benefits & limitations of ketamine therapy
Ketamine presents distinct advantages over conventional psychiatric medications. Unlike SSRIs, which take weeks to show effects, ketamine provides rapid relief. SSRIs increase serotonin levels in the brain by blocking its reabsorption and are commonly used to treat depression, anxiety, OCD, and PTSD. Examples include fluoxetine and sertraline.
“It is thought that ketamine can open a window of neuroplasticity in which change / new learning may be more possible. Therefore for people who are ‘stuck’, this might be something that helps them,” as Dr Keeler explained.
For eating disorders, ketamine may also have a more favourable side-effect profile, “as appetite increase and weight gain is not a side effect of ketamine – which often puts people off taking other medications,” she added.
However, ketamine’s effects are short-lived, requiring repeated dosing over treatment periods. It is also not 100% effective for all patients, and who best benefits from this treatment is still being discovered.
“People need close monitoring,” Dr Keeler explained. “Some people may also find the subjective effects [of ketamine] distressing depending on the dosage – particularly people who are already very anxious to start with”.
Dr. Keeler hopes that if ketamine proves effective for anorexia nervosa, it could be offered as a second-line treatment for those unresponsive to conventional therapies.
Implications for addiction treatment & policy
If this trial proves ketamine’s effectiveness for AUD, it could transform addiction treatment approaches. Traditional therapies for substance use disorders have struggled to demonstrate their long-term efficacy: cognitive-behavioural therapy (CBT) may be limited in maintaining long-term abstinence, and 12-step programmes have mixed results in keeping people within recovery programmes. More solutions are needed, and so far ketamine’s profile seems to fit our medical needs. Clinical trial success could prompt more research and legitimacy for its mainstream use, reinforcing the value of individualized, holistic, and alternative approaches.
Ketamine’s use in psychiatric treatment remains controversial, particularly given its recreational reputation and legal status. While its role as an anaesthetic is well established, its application in mental health care are still growing. Dr Keeler noted, ‘I would say ketamine isn’t in need of “legitimising” itself in the context of its medical use i.e., as an anaesthetic, as this appears to be not disputed – it is more its use in low doses for psychiatric purposes that seems to generate a lot of controversy, although more so in mainstream media than in the medical world’, believing that better safeguards and monitoring can help increase confidence in its use.
Ketamine research’s future may be at risk
In the UK, ketamine has come under increased political attacks, which may risk its future applications. In January 2025, the British Home Office requested a specialist review of ketamine’s legal status, seeking to potentially reclassify it as a Class A substance due to its increased use and societal harms. Currently a Class B drug, reclassification may challenge future research efforts, making it much more difficult to access the substance for investigations.
“[We] hope that this will take some time before they make the decision”, Dr Keeler said to TalkingDrugs. “[t]his isn’t necessarily a barrier to conducting the study since we have used other Class A substances with a license for research purposes, for example psilocybin. So in short, we will get to that bridge when we get to it.”
These clinical trials mark a significant milestone, potentially setting a new standard for treating substance dependencies. If they and others continue to show positive outcomes, they may fuel policy reforms, promoting a more open, evidence-based approach to psychedelic-assisted therapy. As their evidence grows, the public perception of ketamine may shift from its recreational risks to its wider therapeutic applications.
Ketamine, however, must first survive these years, where its connection to high-profile deaths like Matthew Perry’s and political narratives against drug use, have made its promising future fragile. As research progresses, it will be crucial to navigate these tensions, ensuring that its medical potential is not overshadowed by stigma or reactionary policies.
