Scientists find ketamine’s surprising effect on depression

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Ketamine, a psychoactive drug, has shown remarkable and rapid relief for individuals suffering from severe depression in various studies.

However, one significant issue has been present in these studies: participants can often tell whether they received ketamine or a placebo due to ketamine’s distinctive effects, including its psychedelic or dissociative properties.

Even in blinded trials where participants are unaware of their treatment, the psychedelic effects of ketamine can reveal its presence.

A Creative Approach

A recent study by researchers from Stanford Medicine aimed to overcome this challenge.

They devised an innovative solution to hide ketamine’s psychedelic effects by administering the drug during routine surgery when participants were under general anesthesia.

The study involved 40 participants with moderate to severe depression, and both researchers and clinicians were blinded to the treatments. The true nature of the treatments was revealed two weeks later.

The researchers were surprised to find that both the group that received ketamine and the group that received a placebo experienced a significant improvement in depression symptoms. This outcome contradicted their expectations.

Dr. Boris Heifets, the senior author of the study, expressed his surprise when some patients who had received the placebo reported life-changing improvements in their condition.

One day after treatment, both groups saw a roughly 50% reduction in their depression severity scores, as measured by the Montgomery–Åsberg depression rating scale (MADRS).

Interpreting the Findings

The unexpected results of the study have led to more questions than answers.

The researchers found it unlikely that the improvements were solely due to the surgeries and general anesthesia because depression typically does not improve after surgery and can sometimes worsen.

Instead, the researchers believe that participants’ positive expectations played a crucial role in the effectiveness of ketamine.

Participants who improved more in their depression scores were more likely to believe they had received ketamine, even when they had not.

This suggests that preexisting positive expectations for ketamine may have influenced their perceptions.

The Power of Expectations

This phenomenon is often referred to as expectancy bias or the placebo effect. The psychological factors at play in a treatment can be incredibly influential.

Positive expectations, hope, and interactions with healthcare professionals can significantly impact a person’s response to treatment.

Dr. Heifets emphasizes that the takeaway from the study should not be that ketamine is “just a placebo.” Labeling it as such oversimplifies the complexity of the placebo effect and does not negate the real struggles of individuals with depression.

There is a physiological component to the placebo effect, likely involving the brain’s μ-opioid receptors, which process pain.

Exploring the Role of Psychedelic Experiences

The study results also suggest that the psychedelic experience may not be essential for ketamine’s therapeutic benefits, although it may contribute to more positive expectations.

The researchers speculate that non-hallucinogenic psychedelic analogs could potentially offer similar benefits without inducing psychedelic effects.


In conclusion, the study’s surprising findings highlight the intricate relationship between hope, medication, and the human mind.

Ketamine’s effectiveness in treating depression may involve a blend of pharmacological effects and the psychological impact of positive expectations. This study underscores the importance of understanding and harnessing the power of hope in healthcare.

If you care about depression, please read studies that vegetarian diet may increase your depression risk, and Vitamin D could help reduce depression symptoms.

For more information about health, please see recent studies that ultra-processed foods may make you feel depressed, and these antioxidants could help reduce the risk of dementia.

The research findings can be found in Nature Mental Health.

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