Ketamines Show Promise With Opioid Treatment

Ketamine is a drug long used for anesthesia. Depression is a disorder that is very hard to treat in some people. There are limited numbers of medications doctors can use at present. Research is now showing that for some people, ketamine use is helping with their depression.


Ketamines antidepressive effects require activation of opioid receptors in the brain. This finding may alter how new antidepressants are developed and given in an effort to avoid opioid dependence. Initially, it was thought the drug impacted the glutamate system. It was that belief that prompted the drugs’ use to treat depression. It has also led to the development of glutamate-blocking medications to be used as antidepressants. There is an interaction between depression, pain, and opioid addiction and this connection have provided researchers with the opportunity to develop treatment approaches that can influence the most important public health crisis today.

The research was conducted at Stanford University School of Medicine and has been published in The American Journal of Psychiatry. Ketamine was first developed in the 1960s and has been used for decades as anesthesia for surgery. It has been a side effect of hallucinations thus has also been illegally used as a recreational drug. The FDA (food and drug administration) has not approved this medication to be used for depression but some doctors have utilized it ‘off-label’ as an immediate acting antidepressant.

The Stanford researchers wanted to see if Ketamine also activated the opioid system. Researchers moreover found this medication could work with treating OCD (obsessive-compulsive disorder) in a similar method of morphine. They further felt that this study may explain why Ketamine works so quickly; it activates the brains opioid receptors. Psychiatry has long used opioids, barbiturates, and stimulants to treat depression; new treatments need to be explored (Williams et al, 2018).

Ketamine has been designed as a dissociate anesthetic. In recent years, this medication has been used as a low-dose treatment for moderate to severe and chronic pain. And while its use is showing promise, it does have side effects such as hallucination; drug high, nausea-vomiting, and hypertension. The study found that when a group of patients was given a bolus of Ketamine as opposed to placebo, morphine, or fentanyl in the ER department, it was just as effective against pain with a lower risk of cardiopulmonary complications. This study found an inconsistent view of the efficacy of Ketamine for pain relief. But they also agree the use in pain relief seemed to depend on the type of pain.

Ketamine was found most effective for postoperative pain-reducing the amounts of opioids needed. It also showed the effectiveness in the ER for other types of pain; though its usefulness is rather limited. The effect of this medicine for pain relief is limited for postoperative pain. Attempts to use Ketamine in other settings showed limited success. Why it shows this kind of divergent effect on other pain is unknown. They also have stated that further research is needed to learn why it responds as it does to such a limited type of pain (Jonkman et al, 2017).

Depression is one of the most common psychiatric conditions. Symptoms can be so debilitating they can adversely affect the quality of life. Even with all the medications at the doctors’ disposal, there are still a number of depression patients that are not helped with conventional treatments. A discovery of treatment to combat depression is essential. Many patients with depression do not respond to the medications currently available for treatment. It is imperative that depression research looks to find compounds that target non-monaninergic modulutations. Ketamine has been by far the most studied within the past two decades.

This has propelled a wide range of research into other agents. The evidence is building for Ketamines potential use as a rapid-acting antidepressant. In addition, Ketamines may provide a model for understanding the mechanisms behind rapidly acting antidepressants that could, in turn, lead to a discovery of novel compounds to treat depression. As the data suggests several experimental compounds do fail to separate from placebo in terms of effectiveness. Many studies lack the use of a suggest therapy arm. From a research point of view, the placebo effect itself remains a topic under active investigation. Recent data suggests that opioid system is likely implicated in the formation of placebo antidepressant effects.

Indeed, discovery is needed to determine the neurobiological underpinnings of placebo responses. Despite past disappointments, great caution needs to be taken with the excitement of as many compounds fail after being initially promising. Perseverance and a deeper understanding of how to distinguish negative from uninformative studies will be crucial for the continued discovery of newer medications (Ionescu & Papakostas, 2017).


Therapeutic medications for the treatment of depression have serious limitations, particularly delayed the onset and low rate of effectiveness. Ketamine has proven effective for treatment against suicidal ideation. Deleterious effects of depression are compounded by the lack of fast and effective treatment regimens. Currently available medications are effective in about two-thirds of patients and there is a significant therapeutic time lag of weeks to months. This time lag is especially troublesome in the population at increased risk for suicide.

This underscores the need for the treatment of depression and the impact of new rapid-acting antidepressant agents. Subanesthetic Ketamine has seen a therapeutic response within a few hours that lasts approximately seven days. In addition, the discovery of Ketamine and related agents hold tremendous promise for rapid effective treatment of depression. However, there are still several critical problems needed to be overcome; but the future of novel rapid-acting antidepressants is looking very bright. As drugs are currently being tested, and with continued efforts, there is hope that there will soon be a number of novel rapid and effective choices for treatment of depression and the possibility that these could target the underlying cause of the illness (Duman, 2018).

While not approved by the FDA (food and drug administration) for use other than anesthesia and analgesic for use in certain procedures, it has been showing promise as a treatment for co-morbid pain, depression, and substance use disorders (SUD). The effectiveness of this drug has been shown in both depressive and pain disorders; lasting three to four weeks after discontinuing Ketamine. And although the drug has the potential for abuse when used recreationally, its lasting effects without daily use has shown promise for patients with SUDs.

Decreased opiate craving in patients with SUD may be related to Ketamines effects on reducing opiate-induced hyperalgesia. This makes Ketamine a drug to help decrease opiate medication use and help alleviate symptoms of withdrawal. The use of Ketamine to treat co-morbid pain, depression, and SUDs is a relatively new concept. And as evidence of its effectiveness continues to accumulate, doctors are coming to recognize there are uses for it other than ER and OR. Because Ketamine can be obtained illicitly, doctors need to use caution when using this medication in populations that are being treated for pain and addiction. Ketamine has a less potent effect on opioid receptors than drugs like oxycodone or fentanyl. And Ketamine overdose can be treated with the use of naltrexone if needed (Ettensohn, Markay, & Levine, 2018).

Work Cited
Duman, R.S. (2018). Ketamine and rapid-acting antidepressants: A new era in the battle against depression and suicide. F1000 Research Faculty Review. Doi:10.12688/f1000research.14344.1

Ettensohn, M.E.; Markey, S.M.; Levine, S.P. (2018). Considering ketamine for the treatment of comorbid disorders. Psychiatric Annals, 48(4).doi:10.3928/00485713-20180312-02

Ionescu, D.F. & Papakostas, G.I. (2017). Experimental medication treatment approach for depression. Translational Psychiatry. Doi:10.1138/tp.2017.33

Jonkman, K. et al. (2017). Ketamine for Pain. F1000 Research Faculty Review. Doi:10.12688/f1000research.11372.1

Williams, N.R.; Heifets, A.F.; Rodriguez, C.; Schatzberg, A. F. (2017). New Research: Ketamine Activates Opioid System to Treat Depression. American Journal of Psychiatry. American Psychiatric Association.