Understanding Ketamine for Treating Depression: How Does it Work?

Is ketamine classified as an opioid?

Advancements in science and mental health have spurred the quest for alternative treatments for mental illnesses. You should know that there is no one-size-fits-all solution that works effectively for everyone, as each person reacts uniquely to medications and therapies. Consequently, esketamine has emerged as a groundbreaking alternative. This compound, an enantiomer of ketamine, has been extensively researched for treating treatment-resistant depression and has garnered FDA approval.

Within the realm of those exploring treatments for depression, a typical query arises: Is ketamine classified as an opioid? This question naturally extends to esketamine as well.

At GateHouse Treatment, our commitment lies in offering solutions to enhance the well-being of individuals grappling with mental disorders, including substance dependence. Beyond delivering treatment, we endeavor to keep our clients abreast of cutting-edge and contemporary approaches that can act as substitutes for their distress.

In this blog, we will explore ketamine and its derivative, esketamine, as viable options for addressing treatment-resistant depression. We will investigate their definitions and applications and tackle the pivotal query: Is ketamine indeed categorized as an opioid?

Discovering Ketamine

Ketamine, a substance that has intrigued the medical community since its discovery in the 1960s, has garnered attention for its dual potential—both as an anesthetic and as a possible treatment for mental health disorders. Synthesized initially by Dr. Calvin Stevens, this compound stood out due to its pharmacological distinctiveness. In contrast to other dissociative anesthetics like PCP, ketamine was recognized for its gentle nature, rapid effects, and minimal impact on respiratory function, rendering it a safer choice for anesthesia.

Discovering Ketamine

Despite its medical promise, ketamine drifted towards a recreational niche, overshadowing its therapeutic merits. It wasn’t until the 1990s that researchers, spearheaded by Dr. Robert Berman of Yale University, stumbled upon its unexpected antidepressant properties. Even at subanesthetic doses, ketamine demonstrated remarkable improvements in depressive symptoms, especially in individuals resistant to conventional therapies.

Since then, ketamine has been extensively studied in numerous clinical trials to assess its effectiveness and safety in various mental health conditions, including depression. The outcomes have been encouraging, prompting further exploration and earning recognition from both the medical community and the FDA.


Studies conducted at Yale Research Laboratories have unveiled that, beyond its anesthetic role, ketamine triggers the release of glutamate in the brain. This mechanism sets off a chain of events that facilitate the development of fresh neural connections, enhancing the brain’s adaptability and capacity to foster more positive thoughts and behaviors. This unique attribute represents a groundbreaking advancement in the realm of depression treatment, surpassing the limitations of conventional antidepressants.


Exploring Esketamine as an Innovative Treatment for Depression

Studies by the National Institutes of Health have delved into the impact of ketamine on the brain following prolonged exposure to chronic stress, a common trigger for depressive symptoms. Experiments on mice subjected to extended chronic stress revealed that ketamine treatment swiftly mitigated abnormal behaviors. Furthermore, ketamine promptly reinstated the synchronized activity of prefrontal neural circuits disrupted by chronic stress, facilitating the development of new functional dendritic spines.

Yale Medicine, at the forefront of ketamine research in the United States, reported on March 5, 2019, that the FDA authorized esketamine in nasal spray format as a novel treatment for major depression. Esketamine, a derivative of ketamine, has exhibited significant benefits for individuals grappling with treatment-resistant depression. Notably, a study indicated that 70% of patients with treatment-resistant depression who received intranasal esketamine demonstrated substantial improvements.

Dr. John Krystal, chief psychiatrist at Yale Medicine, emphasizes the unique mechanism of action of this medication, labeling ketamine as “the antidrug.” He elucidates, “Unlike traditional drugs such as valium, where the calming effect lasts only as long as the drug remains in your system, ketamine stimulates reactions in the cortex that facilitate the regeneration of brain connections. It is not the presence of ketamine in the body but the response it triggers that underpins its effects. This distinction is what sets ketamine apart as an antidepressant.

Is Ketamine an Opioid?

Understanding the disparity between ketamine and opioids is pivotal in grasping their pharmacological impacts and therapeutic potentials. Whereas opioids like morphine and codeine are derived from the opium poppy plant and primarily target opioid receptors in the brain, ketamine operates through an entirely distinct mechanism.

As a dissociative anesthetic, ketamine can modulate N-methyl-D-aspartate (NMDA) receptors. These receptors are vital to transmit and regulate nerve signals within the central nervous system. In contrast to opioids that predominantly influence the limbic system and brain stem, ketamine chiefly impacts the cerebral cortex and subcortical regions, including the glutamatergic and serotonergic systems.

Is Ketamine an Opioid?

Studies conducted by the National Library of Medicine have revealed that ketamine exerts effects at both the neurochemical and neurobiological levels. At the neurochemical level, ketamine instigates alterations in the release and reuptake of neurotransmitters such as glutamate and serotonin, which are integral to mood regulation and pain perception. Furthermore, neuroimaging investigations have demonstrated that ketamine can adjust functional connectivity among various brain regions, indicating a notable influence on brain structure and operation.

While ketamine and opioids may share specific analgesic attributes, they diverge fundamentally in their modes of action and pharmacological characteristics. Recognizing these distinctions is crucial for formulating more efficient and safer therapeutic approaches for managing pain and psychiatric disorders.

GateHouse Treatment: Empowering Long-Term Recovery with Comprehensive Support

At GateHouse Treatment, we recognize the hurdles that substance dependence and mental health challenges, such as depression, can present to you or your loved ones. This understanding drives us to offer a holistic approach to recovery customized to meet the unique needs of each individual.

Our array of programs encompasses alcohol detoxification, medication-assisted treatment, and care options spanning various levels of support, all meticulously crafted to offer assistance at every phase of the recovery journey.

If you find yourself in New England seeking immediate assistance for long-term recovery, please don’t hesitate to reach out to us at (855) 448-3588 or engage with one of our specialists online.

Here at GateHouse Treatment, we stand ready to furnish you with the care and direction necessary to embark on your path toward a life free from addiction and optimal mental well-being.

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