Agonists and antagonists are chemical messengers that affect the process of neurotransmission. They bind to specific receptor sites of neurotransmitters and this can affect brain function and behaviour. Ketamine is one antagonists of the receptor sites of the neurotransmitter, glutamate. In this post we’ll learn more about antagonists, how they work, how ketamine may help PTSD and a key study that demonstrates this.
Ketamine is a drug that has been around for decades. However, it’s primarily been used as an anaesthetic, by human doctors and veterinarians. But it’s showing promise as a treatment for depression. Because of this, some psychologists are wondering if it can also help to treat PTSD.
- Read More: Ketamine: An antagonist in the treatment of depression (link)
- Read More: Neural networks and synaptic pruning (link)
What is an antagonist?
Agonists and antagonists are chemicals that bind to the receptor sites of specific neurotransmitters. An antagonist binds to the receptor and then stops that neurotransmitter from binding and sending a signal.
Remember that the process of neurotransmission is a bit like a lock-and-key: the right neurotransmitters can only bind with the right receptor sites on the post-synaptic neuron (see image). Neurotransmitters bind to specific receptors and send signals to the next neuron.
Neurotransmitters have an effect by binding to receptor sites on the post-synaptic neuron. This is how the chemical and electrical signals are sent throughout neural networks in the brain.
Antagonists and PTSD
Glutamate is one neurotransmitter that has specific receptor sites that it binds to (one being NMDA receptor sites). Glutamate is an excitatory neurotransmitter, so when it binds to its receptor sites it sends a signal for the post-synaptic neuron to “fire.” But ketamine is an antagonist of the receptor sites for glutamate. So when ketamine binds to the receptor sites, it blocks the glutamate and prevents that neuron from firing (see Fig 2.)
Ketamine binds to glutamate receptor sites and blocks it from having an effect. Because glutamate is high in people with depression, this inhibitory effect of the antagonist ketamine could help treat depression.
Ketamine binds to glutamate receptor sites and blocks it from having an effect. Ketamine is an effective drug for people with depression because high levels of glutamate is common in people diagnosed with depression (read more). But is this the same in people with PTSD?
The evidence linking PTSD and glutamate is not as strong as it is with depression. In reality, the research is in the hypothetical stages. But there are three key reasons why some psychologists believe glutamate could be a key factor in PTSD (Holmes et al. 2017):
- Glutamate helps with the synaptic plasticity and memory formation: This is relevant because PTSD is a disorder characterized by memory-related symptoms like intrusive memories, flashbacks, nightmares and even memory loss.
- Glutamate neurotransmission is affected by stress: In particular, stress impacts the transmission of glutamate in the prefrontal cortex and the hippocampus – two important parts of the brain associated with PTSD.
- Ketamine (a glutamate antagonist) has shown to reduce PTSD symptoms: The logic here is that if you can affect glutamate neurotransmission and it reduces PTSD symptoms, then glutamate must play a role in PTSD somehow. The key study is summarized below.
IB Psychology Exam Tips:
- Remember that “agonists and antagonists” could be asked in SAQs only (not essays).
- The effects of ketamine on glutamate neurotransmission can be used to explain how neurotransmission (glutamate) and antagonists (ketamine) affect behaviour, biological treatments of PTSD (and depression), and research methods (true experiments)
Key Study: Ketamine in the Treatment of PTSD (Feder et al. 2014)
Aim: To test the effectiveness of ketamine on reducing the symptoms of PTSD (and depression).
Ketamine or midazolam was administered using an IV drip like the one in this image – patients lay for 40 mins while the drugs seep into their systems. (wikicommons).
Methods: This clinical drug trial was conducted in a hospital in New York City. 41 patients diagnosed with PTSD received either ketamine or midazolam (another anaesthetic sometimes used for anxiety). The drugs were given to participants using an IV drip. The study was repeated measures – they received both ketamine and midazolam but two weeks apart so the relative effects of both treatments could be assessed. To prevent order effects, the order of which drug they were given was randomized. The main measure of effectiveness was taken after 24 hours. To measure PTSD symptoms, the Impact of Event Scale – Revised version (IES-R) was used. To measure effects on depression the Montgomery-Asberg Depression Rating Scale (MADRS) was also used.
The study was double-blind, so neither the patient nor the person conducting the tests knew which condition the patient was in (however, the chief researchers would know).
Results: The results of the IES scores showed that ketamine was significantly more effective in reducing PTSD symptoms compared with midazolam.
A comparison of the effects of ketamine and midazolam. Note that low scores are a good thing, because they show fewer PTSD symptoms. (From Feder et al. 2014)
Test Yourself:
- What is an antagonist?
- How does ketamine affect the transmission of glutamate?
- Why might ketamine be effective in treating depression?
- What were the results of Feder et al.’s (2014) study?
Watch More: You can watch a clip of a War veteran discussing his experiences using ketamine in this clip from the Joe Rogan Podcast (Warning: Language)(Link).
References
Feder A, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: A randomized clinical trial. JAMA Psychiatry. 2014;71:681–688. (Link)
Holmes, S. E., Girgenti, M. J., Davis, M. T., Pietrzak, R. H., DellaGioia, N., Nabulsi, N., … Traumatic Stress Brain Study Group (2017). Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings of the National Academy of Sciences of the United States of America, 114(31), 8390–8395. doi:10.1073/pnas.1701749114. (Link)
Liriano, F., Hatten, C., & Schwartz, T. L. (2019). Ketamine as treatment for post-traumatic stress disorder: a review. Drugs in context, 8, 212305. doi:10.7573/dic.212305. (Link)
Travis Dixon is an IB Psychology teacher, author, workshop leader, examiner and IA moderator.