Prof. Talma Hendler Photo credit: Tel Aviv Medical Center (Ichilov).
New Study by Tel Aviv University and Tel Aviv Medical Center (Ichilov) reveals
Ketamine Relieves Pain Without “Disconnecting” Consciousness
- For the first time, researchers have shown that ketamine activates two separate mechanisms in the brain, one for pain relief and another for altering the state of consciousness.
- The findings may help in developing treatments that provide the benefits of ketamine while reducing its psychological side effects.
An imaging study in humans led by Tel Aviv University’s Institute for Psychedelic Research, in collaboration with TAU-affiliated Tel Aviv Medical Center (Ichilov), found that the pain relief provided by ketamine does not result from the sense of dissociation – a detachment from oneself, body or surroundings, induced by the drug. The findings, indicating that pain relief and the effect on consciousness are based on different brain mechanisms, may help in developing treatments that provide the benefits of ketamine while reducing its psychological side effects.
The study was led by Dr. Noam Goldway, under the supervision of Prof. Talma Hendler and Dr. Haggai Sharon of the Institute for Psychedelic Research at TAU’s Sagol School of Neuroscience, in collaboration with Tel Aviv Medical Center (Ichilov). The paper was published in Nature‘s prestigious journal Neuropsychopharmacology.
In recent years, mind-altering substances have moved from fringe culture to the forefront of medical research. MDMA is being studied as a treatment for post-traumatic stress disorder (PTSD); psilocybin – the substance found in magic mushrooms – is being studied primarily as a treatment for depression; and ketamine is also attracting considerable interest because of its effectiveness in treating pain and depression, and more recently PTSD as well. Yet alongside this great promise, one central question remains: Is the alteration in consciousness produced by these drugs a necessary condition for their therapeutic effect?
To explore this question, the researchers focused on ketamine, a drug known to relieve pain while also inducing dissociation – a temporary sense of detachment from one’s self, body, or surroundings. For years, physicians and researchers assumed that these two effects were connected: greater detachment makes the pain seem less intense or threatening.
The study included 37 healthy volunteers, both women and men. In two separate sessions, each participant received a ketamine infusion and a placebo infusion. During the experiment, and under the drug’s influence, the participants underwent functional magnetic resonance imaging (fMRI) and were exposed to controlled pain stimuli, reporting the intensity of both their pain and sense of dissociation.
Dr. Noam Goldway says that while ketamine reduced pain and increased dissociation, no connection was found between the two phenomena. Participants who experienced strong dissociation did not necessarily benefit from greater pain relief, and vice versa. In other words, the sense of detachment is not the mechanism through which ketamine reduces pain.
The brain scans reinforced this conclusion. Pain relief was accompanied by reduced activity in brain regions involved in pain processing, such as the insula and the anterior cingulate cortex, while dissociation was related to changes in a different brain network – the default mode network, involved, among other things, in processing the sense of self. This means that these are not merely two uncorrelated experiences, but two different brain mechanisms affected by the same drug.
Prof. Talma Hendler, Head of TAU’s Institute for Psychedelic Research, explains: “In recent years, there has been a lively scientific and clinical debate over whether the subjective experience produced by psychoactive drugs is an integral part of their therapeutic effect. Our study shows that, at least in the case of ketamine and pain relief, the answer is apparently no. We were able to show that the drug’s effect on pain is separate from its effect on consciousness – both behaviorally and in terms of brain activity. It is important to note that this cannot be generalized to other psychedelic drugs, such as magic mushrooms. In this case, the burden of proof still rests with us, the scientists.”
According to Dr. Haggai Sharon, Deputy Head and Medical Director of the Institute and a specialist in pain medicine, the study provides further evidence of the complexity of the brain’s representation of the pain experience and the many different ways in which the brain can regulate and alter it. This understanding may also have broad clinical implications. If we learn how to activate ketamine’s pain-relief mechanism without simultaneously inducing dissociation, it may be possible to develop future treatments that preserve the drug’s effectiveness while reducing the sense of detachment and other subjective side effects.
