When antidepressants were first introduced in the mid-20th century, they were a breakthrough in pharmaceuticals. Nearly 70 years later, antidepressants are still an important piece of the mental health puzzle. But for thousands of people, these little pills aren’t enough.
The statistics on depression are startling. Depression is the most common mental health disorder in the US, and some 21 million people suffer daily. Of the people who take antidepressants, 30% won’t respond to treatment. Of those that do, a startling 80% will have symptom relapse within five years. 1
But what other options do people suffering from depression, particularly treatment-resistant depression, have? Historically, the answer has always been: not much. But today, thanks to a combination of changing laws and attitudes and a building consensus of scientific research, there’s another, perhaps unexpected option – ketamine.
What is ketamine treatment?
Ketamine treatment for depression may be one of the biggest leaps forward in mental healthcare in decades.
Ketamine is best known for its use as an anesthetic, both in humans and animals, and is commonly used in emergency departments and operating rooms around the world today. But at subanesthetic levels, ketamine can produce powerful mind altering effects. Ketamine is often thought of as a psychedelic, but it is important to note that it does not behave like a typical psychedelic. Ketamine works in complex ways, interacting with many receptors in the brain, of note, it does not have a preference for the serotonin 2A (5-HT2A) receptor like classic psychedelics.
At the right dose, ketamine can cause a dissociative experience. These experiences are commonly described like out-of-body experiences, sometimes where the user reports to be watching themselves as a third person. These effects made the drug popular in the music and clubbing communities, but when used in a controlled, guided setting, the effects can be profoundly transformative.
- The first randomized trial of ketamine for depression took place in 2000, where researchers found a single dose of ketamine could decrease depressive symptoms in just 72 hours. 2
- In 2019 the FDA approved a ketamine-based nasal spray to treat depression that does not respond to other therapies.
- A 2022 study of 22 patients with treatment-resistant depression found a 42% reduction in depressive symptoms with ketamine infusions. 3
Depression and psychedelics
Psychedelics have a profound effect on consciousness because they increase neuroplasticity. Neuroplasticity is your brain’s ability to adapt; to use, grow, and form new neural pathways.
When you’re young, your brain is highly neuroplastic; it’s how you learn to interpret and navigate the world. But we can lose this ability as we age, and our brains suffer the consequences. It was once thought that we couldn’t replace the neuron connections lost, but recent studies have shown that’s not the case and “psychedelics induce molecular and cellular adaptations related to neuroplasticity.” 4 5
Ketamine can change the way you think, helping you break out of negative thought loops and explore parts of your mind that are normally blocked off. Depression can actually reduce the brain’s connections and excitability, so increasing your brain’s neuroplasticity is also thought to help restore balance to the brain and combat depression. 6 7
Why ketamine and cannabis are different
Cannabis is a popular choice of self-medication for people with depression, but it doesn’t help everyone. Depression and cannabis use is an area of scientific interest with a sizable amount of studies, but they have mixed results. There is a correlation between people with depression and people who use cannabis, but it’s not always a positive link.
In fact, several studies have suggested cannabis could be a contributing factor to worsening depressive symptoms, finding that “cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders.” 8 9
The variability in results is due to several factors, including the chemical composition of the cannabis used, the unique endocannabinoid of the person consuming, and a handful of other factors like tolerance, mindset, and genetic predisposition.
“Though hope remains for using cannabinoids to treat depression, in human studies THC has often been more associated with depressive behavior. Most existing research does not support the use of THC in combating depression and there is very limited data for other cannabinoids.” said Dr. Codi Peterson, PharmD, Chief Scientific Officer at the Cannigma.
The results of ketamine treatment aren’t nearly as variable. A 2022 study of 1247 people using at-home ketamine-assisted therapy found that 62% of participants reported a 50%+ improvement in depressive symptoms. 10
“Research on ketamine on the other hand has been extremely encouraging, especially as it relates to the onset of effects.” Dr Peterson added. “In severe depression, a rapid acting medication can be a literal lifesaver. The use of ketamine for depression is best optimized as part of an integrated health and wellness plan, which should be planned with a healthcare professional.”
How ketamine treats depression
Typical antidepressants like SSRIs (selective serotonin reuptake inhibitors) primarily act on the serotonin system, but ketamine acts on the glutamate system, specifically blocking the N-methyl-D-aspartate (NMDA) receptor, the primary mechanism responsible for synaptic plasticity and memory function. 11
By blocking NMDA receptors, ketamine triggers a chain reaction that leads to promotion of brain connectivity, especially in the excitatory part of the brain. These connections can help disrupt negative thought patterns and can help with developing supportive habits. Some scientists also believe that ketamine can help reverse brain changes caused by stress, helping you build a more resilient brain. 12
Ketamine also works quickly; many patients report a reduction in depressive symptoms within hours or days, versus the weeks or even months it can take antidepressants to provide benefit. However, the effects can wear off after 7 – 10 days, and most people require multiple treatment sessions to sustain the results.
Ketamine for depression is typically taken in one of four ways; sublingually, nasally, intramuscularly, or intravenously. Intravenous (IV) and intramuscular (IM) ketamine, as well as the nasal ketamine, must be administered in a clinic setting by a doctor, while oral can be taken at home.
Using ketamine to treat your depression
Despite ketamine’s impressive early results, it’s not a miracle drug. It works best for patients as a part of a comprehensive mental health treatment plan, one that includes preparation, therapy, and integration. And if you’re interested in starting such a plan, Nue Life Health is an interesting option.
Nue Life is a telemedicine company that provides ketamine experiences for people with treatment-resistant depression and other mental health conditions. The company offers two treatment plans; a 4-week plan and a 16-week plan.
The process is surprisingly simple – fill out an intake form and see if you qualify for participation. Once approved, you’ll register and meet with a medical provider who gets to know your medical history, your concerns, and your aims for the program.
From there, you’ll receive oral ketamine lozenges in the mail. The starting dose of the lozenges range from 150-200mg of ketamine, depending on your comfort level, and previous psychedelic experiences. A typical ketamine experience can last between 30 and 120 minutes, depending on the dosage, and may feel like floating or a sense of weightlessness. You may see vibrant images, past memories, or have what feels like a spiritual experience.
But this program offers more than just the ketamine itself. Each experience is supported by the Nue Life app, where you can access custom playlists designed to facilitate your ketamine sessions. You’ll also have telemedicine sessions with your provider, group integration sessions for digesting your experience, and health coaching, to support your overall wellness goals.
Though this treatment isn’t yet covered by insurance, Nue Life aims to keep the program affordable so everyone who needs help can access it. The cost for ketamine treatment depends on your program; the 4-week program includes six ketamine experiences for $1,399 while the 16-week program includes 18 ketamine experiences for $2,999. Financing is available so you don’t have to front the entire cost at once.
Nue Life is available in:
- New York
Mental health treatment options have come a long way in the past few decades, but traditional options are not effective enough. For some, SSRIs or cannabis provide relief to keep the worst depressive symptoms at bay. But if you’re searching for a different way to treat your depression, Nue Life ketamine therapy provides a chance to create a better relationship with yourself. Their program is affordable, discreet, and can be done from the comfort of your own home. Who could you be if you felt better?
This article was sponsored by Nue Life, and all scientific references were reviewed by Dr. Codi Peterson. The Cannigma has not evaluated the products and services mentioned, nor does promotion equal endorsement or recommendation.
- Beyeler A. Do antidepressants restore lost synapses?. Science. 2019;364(6436):129-130. doi:10.1126/science.aax0719
- Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9. PMID: 10686270.
- Dai, D., Miller, C., Valdivia, V. et al. Neurocognitive effects of repeated ketamine infusion treatments in patients with treatment resistant depression: a retrospective chart review. BMC Psychiatry 22, 140 (2022). https://doi.org/10.1186/s12888-022-03789-3
- Fuchs E, Flügge G. Adult neuroplasticity: more than 40 years of research. Neural Plast. 2014;2014:541870. doi: 10.1155/2014/541870. Epub 2014 May 4. PMID: 24883212; PMCID: PMC4026979.
- de Vos Cato M. H., Mason Natasha L., Kuypers Kim P. C.Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry V12 2021 DOI: 10.3389/fpsyt.2021.724606 https://www.frontiersin.org/article/10.3389/fpsyt.2021.724606
- Albert PR. Adult neuroplasticity: A new “cure” for major depression? J Psychiatry Neurosci. 2019 Mar 1;44(3):147-150. doi: 10.1503/jpn.190072. PMID: 31038297; PMCID: PMC6488487.
- Zhang FF, Peng W, Sweeney JA, Jia ZY, Gong QY. Brain structure alterations in depression: Psychoradiological evidence. CNS Neurosci Ther. 2018 Nov;24(11):994-1003. doi: 10.1111/cns.12835. Epub 2018 Mar 5. PMID: 29508560; PMCID: PMC6489983.
- Lev-Ran, S., Roerecke, M., Le Foll, B., George, T., McKenzie, K., & Rehm, J. (2014). The association between cannabis use and depression: A systematic review and meta-analysis of longitudinal studies. Psychological Medicine, 44(4), 797-810. doi:10.1017/S0033291713001438
- Hser YI, Mooney LJ, Huang D, Zhu Y, Tomko RL, McClure E, Chou CP, Gray KM. Reductions in cannabis use are associated with improvements in anxiety, depression, and sleep quality, but not quality of life. J Subst Abuse Treat. 2017 Oct;81:53-58. doi: 10.1016/j.jsat.2017.07.012. Epub 2017 Jul 29. PMID: 28847455; PMCID: PMC5607644.
- Thomas D. Hull, Matteo Malgaroli, Adam Gazzaley, Teddy J. Akiki, Alok Madan, Leonardo Vando, Kristin Arden, Jack Swain, Madeline Klotz, Casey Paleos, At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression: Findings from a large, prospective, open-label effectiveness trial, Journal of Affective Disorders, V 314, 2022, https://doi.org/10.1016/j.jad.2022.07.004.
- Li F, Tsien JZ. Memory and the NMDA receptors. N Engl J Med. 2009;361(3):302-303. doi:10.1056/NEJMcibr0902052
- Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13. PMID: 29532791; PMCID: PMC5999402.
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