Chronic pain is generally defined as pain that persists for more than three months, affecting millions of people worldwide. It can manifest in various forms, such as postoperative pain, cancer pain, orofacial pain (involving the head and mouth), and musculoskeletal pain (affecting bones, muscles, and tendons). A particularly challenging type is neuropathic pain, which is caused by damage or dysfunction in the nervous system. Neuropathic pain often presents as burning, stabbing, or electric shock sensations and can be caused by conditions such as diabetes, herpes, or nerve injuries. Unlike other types of pain, it does not respond well to standard treatments such as anti-inflammatories or opioids.
Managing chronic pain, especially neuropathic pain, remains a complex challenge. Although anti-inflammatory drugs such as ibuprofen or aspirin can help in cases of mild pain, they offer limited relief in more severe cases. For many patients, stronger medications such as opioids are necessary, but the risk of addiction and other negative side effects makes this option less than ideal. Many patients find themselves at a crossroads, faced with ineffective treatments or dangerous alternatives.
Ketamine: A Promising Option for Neuropathic Pain
An emerging option for treating chronic and neuropathic pain is ketamine, traditionally used as an anesthetic. In recent years, ketamine has gained attention for its ability to provide relief to patients suffering from intractable chronic pain. Its mechanism of action involves blocking N-methyl-D-aspartate (NMDA) receptors in the brain and spinal cord, which are involved in pain perception and memory.
Research has shown ketamine to be effective, especially when used in a controlled clinical setting. A study by Sigtermans and colleagues involved 60 people with chronic pain. Half received ketamine infusions, while the other half received a placebo. The results were remarkable: those who received ketamine experienced significant pain reduction during the first week, and the relief lasted up to 12 weeks. A recent literature review also found that ketamine treatment could provide pain relief lasting more than 30 days in people with neuropathic pain, although for now it appears that some types of neuropathic pain (such as complex regional pain syndrome) may respond better than others.
Ketamine and Mental Health
Beyond its properties for relieving physical pain, ketamine has also shown promise in treating the psychological effects of chronic pain. Mental health conditions such as depression and post-traumatic stress disorder (PTSD) often coexist with chronic pain. A study by Keizer and colleagues highlighted the comorbidity between PTSD and chronic pain, underscoring the importance of addressing both the physical and emotional aspects of these conditions. Therefore, it is likely that the therapeutic and pain-relieving effects of ketamine can be enhanced with ketamine-assisted psychotherapy (KAP), administered in a supervised setting and combined with psychological support.
Psychedelics and Neuropathic Pain: The Evidence
In addition to ketamine, researchers are exploring the potential of psychedelics in the treatment of chronic and neuropathic pain. Psychedelics such as psilocybin, LSD, and MDMA have long been stigmatized because of their classification as Schedule Y substances, meaning they are considered to have a high potential for abuse and no accepted medical use. However, evidence suggests that the potential for abuse of these substances is actually low, and recent studies suggest that psychedelics may offer innovative mechanisms for pain relief.
Although research is still in its early stages, there is evidence that psychedelics may provide analgesic (pain relief) benefits for various types of pain, such as cluster headaches, cancer-related pain, and limb pain. For example, a study by Castellanos reviewed the available evidence on psychedelic therapy and highlighted its potential to reduce pain sensitivity in these conditions. In addition, psychedelics have been shown to significantly improve psychiatric disorders such as depression and PTSD, which often accompany chronic pain.
Final thoughts
Ketamine-assisted psychotherapy has emerged as a powerful treatment option for chronic neuropathic pain, offering hope to patients who have exhausted traditional therapies. Its ability to modulate NMDA receptors allows for significant pain relief, while its potential to improve mental health outcomes further enhances its appeal. In addition, its psychedelic effects may be potentially useful in treating mental health issues that often exacerbate pain when used with appropriate therapeutic support.
As the stigma surrounding these substances begins to fade and more studies are conducted, they could become part of a broader strategy to relieve pain and support mental health.
There is still much to discover about pain itself, as new and ongoing research reveals previously unknown facts (such as gender differences in pain perception), but it seems clear that psychedelic medicine, combined with clear treatment guidelines and adequate psychological support, has the potential to improve the lives of people suffering from chronic and neuropathic pain.
Bibliography
- Sigtermans, M. J., et al. (2009). Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain, 145(3), 304-311. https://journals.lww.com/pain/abstract/2009/10000/ketamine_produces_effective_and_long_term_pain.10.aspx
- Guimarães Pereira JE, Ferreira Gomes Pereira L, Mercante Linhares R, Darcy Alves Bersot C, Aslanidis T, Ashmawi HA. Efficacy and Safety of Ketamine in the Treatment of Neuropathic Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of Pain Research. 2022 Apr;Volume 15:1011–37.
- Keizer, K., et al. (2020). Chronic pain and PTSD: A co-occurring burden. Journal of Pain Research, 13, 2567-2579.
- Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology [Internet]. 2018 Nov;142(142):143–66. Available from: https://www.sciencedirect.com/science/article/pii/S0028390818302296?via%3Dihub
- Castellanos, D. (2020). The emerging use of psychedelics in chronic pain management: A review of current literature. Journal of Psychedelic Studies, 4(2), 1-10.
- Niesters, M., Martini, C., & Dahan, A. (2013). Ketamine for chronic pain: Risks and benefits. British Journal of Clinical Pharmacology, 77(2), 357-367. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.12094
- Kooijman, M., et al. (2023). Psychedelics in pain research: Challenges and future perspectives. Journal of Psychopharmacology, 37(3), 250-262.
- Stratton H, Lee G, Mahdi Dolatyari, Ghetti A, Cotta T, Mitchell S, et al. Nociceptors are functionally male or female: from mouse to monkey to man. Brain. 2024 Jun 3.
