What is Ketamine?

Historically, ketamine has been used as an anesthetic agent, however it has more recently started to play a big role in treating symptoms of depression and in catalyzing psychotherapeutic change.

Video: What Ketamine Actually Does to your Brain

4:34

In this video, you will learn about the neurotransmitter that is most impacted by ketamine.

Molecular Structure of Ketamine

Ketamine is a derivative of PCP mixed with one of two or both optimal isomers.

Video: Isomers

2:05

Ketamine contains one of two optimal isomers or a mixture of them both. In this video, you will learn more about the molecular structure of isomers to provide some additional context.

The molecular structure of ketamine as a whole is C13H16ClNO and its chemical name is 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone. As a result of the different isomers that can be used to create ketamine, ketamine has three molecular structures:

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The S-(+) enantiomer is trademarked as esketamine which is more potent with stronger analgesic properties than the others and used as an anti-depressant: (2S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one (Domino, 2010; Matveychuk et al., 2020; NCBI, 2022a; NCBI, 2022b; NCBI, 2022c).

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R-(-) enantiomer which is not typically used: (2R)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one (Domino, 2010; Matveychuk et al., 2020; NCBI, 2022a; NCBI, 2022b; NCBI, 2022c).

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The racemic mixture is typically used for anesthesia and ketamine-assisted therapy: 2-(2-chlorophenyl)-2-[deuterio(methyl)amino]cyclohexan-1-one (Domino, 2010; Matveychuk et al., 2020; NCBI, 2022a; NCBI, 2022b; NCBI, 2022c).

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Off-Label Indications

Unlike many other psychedelic medicines, ketamine is legal in most areas of the world as anesthesia for surgery (Psychedelic.support, n.d.). Esketamine is also approved by the FDA for the treatment of the symptoms of depression (Rush et al., 2022). All other uses of ketamine are considered off label in Canada, the United States, and other countries. Ketamine has been used as an analgesic, anti-obsessional, and antidepressant medicine.

Ketamine in Mental Health Treatment

Ketamine is used in two primary ways to treat mental health conditions. This certification pathway will primarily focus on ketamine-assisted therapy rather than ketamine as an antidepressant.

Ketamine as an Anti-Depressant

Ketamine has antidepressant properties (among other mechanisms), and it can be administered repeatedly over time at a low dose to relieve the symptoms of depression (Psychedelic.support, n.d.).

Ketamine-Assisted Therapy

During ketamine-assisted therapy, clients participate in Preparation, Medicine, and Integration Sessions.

Advantages

This form of treatment is cheaper than ketamine-assisted therapy.

Advantages

Ketamine-assisted therapy uses ketamine as a way to stimulate neuroplasticity, promote openness, and enhance a client’s ability to meaningfully engage with the therapeutic process in an attempt to reach the source of the client’s mental health condition in order to treat the condition (Hasler, 2020; Dore et al., 2019). Despite its dissociative effects, ketamine may allow for increased access to felt states and repressed emotions or memories (Ceban et al., 2021). Clients are therefore more supported emotionally through this therapy.

Disadvantages

To take advantage of its antidepressant properties, it typically requires repeated administration of ketamine as the effects can last for up to two weeks (Psychedelic.support, n.d.). The primary focus of this treatment is to relieve the symptoms of depression. As a result, talk therapy is not typically integral to this treatment approach. In addition, possible adverse effects of long-term and cumulative ketamine administration require further research (Hasler, 2020; Marcantoni et al., 2020).

Disadvantages

This form of treatment is more expensive because of the time required to be spent with health professionals.

References

Ceban, F., Rosenblat, J. D., Kratiuk, K., Lee, Y., Rodrigues, N. B., Gill, H., . . . McIntyre, R. S. (2021). Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders. CNS Drugs, 35(9), 925-934. https://doi.org/10.1007/s40263-021-00846-5

Domino, E. F. (2010). Taming the ketamine tiger. Anesthesiology, 113(3), 678-684. https://doi.org/10.1097/ALN.0b013e3181ed09a2

Dore, J., Turnipseed, B., Dwyer, S., Turnipseed, A., Andries, J., Ascani, G., . . . Wolfson, P. (2019). Ketamine assisted psychotherapy (KAP): Patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. Journal of Psychoactive Drugs, 51(2), 189-198. https://doi.org/https://doi.org/10.1080/02791072.2019.1587556

Hasler, G. (2020). Toward specific ways to combine ketamine and psychotherapy in treating depression. CNS Spectr, 25(3), 445-447. https://doi.org/10.1017/S1092852919001007

Marcantoni, W. S., Akoumba, B. S., Wassef, M., Mayrand, J., Lai, H., Richard-Devantoy, S., & Beauchamp, S. (2020). A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019. J Affect Disord, 277, 831-841. https://doi.org/10.1016/j.jad.2020.09.007

Matveychuk, D., Thomas, R. K., Swainson, J., Khullar, A., MacKay, M. A., Baker, G. B., & Dursun, S. M. (2020). Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol, 10, 2045125320916657. https://doi.org/10.1177/2045125320916657

National Center for Biotechnology Information (2022a). PubChem Compound Summary for CID 182137, Esketamine. https://pubchem.ncbi.nlm.nih.gov/compound/Esketamine.

National Center for Biotechnology Information (2022b). PubChem Compound Summary for CID 3821, Ketamine. https://pubchem.ncbi.nlm.nih.gov/compound/Ketamine.

National Center for Biotechnology Information (2022c). PubChem Compound Summary for CID 644025, (R)-Ketamine. https://pubchem.ncbi.nlm.nih.gov/compound/R_-Ketamine.

Psychedelic.support (N.d.). Little book of psychedelics. https://psychedelic.support/education/free-courses/

Rush, B., Marcus, O., Shore, R., Cunningham, L., Thomson, N., and Rideout, K. (2022). Psychedelic Medicine: A Rapid Review of Therapeutic Applications and Implications for Future Research. Homewood Research Institute. https://hriresearch.com/research/exploratory- research/research-reports/