The science

The Library

The practices at Halcyon are old. The research on them is newer, and growing. These are the studies we read and return to, each with a short note in plain language and a link to the original paper. We share them to inform, not to promise, and none of it is medical advice.

6 studies

Ketamine-Assisted Psychotherapy · Meditation

Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder

Grabski M, McAndrew A, Lawn W, et al.

American Journal of Psychiatry · 2022

This phase 2 trial tested whether ketamine, combined with talk therapy, could help people with severe alcohol use disorder stay abstinent. Ninety-six adults were randomly assigned, double-blind, to three weekly ketamine or saline infusions, paired with either mindfulness-based relapse prevention therapy or alcohol education. In this study, the ketamine groups had more days without alcohol at six months than the placebo groups, an average difference of about 10%, and the largest difference was between ketamine plus therapy and saline plus education. There was no significant difference in relapse rates, and the treatment was well tolerated. The authors describe it as a proof-of-concept study with wide confidence intervals, so the results need confirming in larger trials.

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Ketamine-Assisted Psychotherapy

Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy

Dore J, Turnipseed B, Dwyer S, et al.

Journal of Psychoactive Drugs · 2019

This paper describes Ketamine Assisted Psychotherapy (KAP), an approach in which ketamine is given alongside psychotherapy and its psychedelic qualities are treated as part of the therapeutic process rather than as unwanted side effects. The authors gathered demographic and outcome data from 235 patients across three private practices using similar methods, mostly without intravenous access. In this study, patients showed decreases in depression and anxiety, and the authors report the changes were especially notable for older patients and those with more severe symptoms. An honest limitation: this was an observational report from the treating practices themselves, with no control group or randomization, so it cannot show that KAP caused the improvements.

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Ketamine-Assisted Psychotherapy

Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression

Daly EJ, Trivedi MH, Janik A, et al.

JAMA Psychiatry · 2019

This phase 3 trial looked at whether continuing esketamine nasal spray helps people with treatment-resistant depression stay well after they improve. Of 705 adults enrolled, 297 who reached stable remission or stable response after 16 weeks of esketamine plus an oral antidepressant were randomly assigned, double-blind, to keep using esketamine or switch to a placebo spray while staying on their antidepressant. In this study, among those in stable remission, 26.7% relapsed on esketamine versus 45.3% on placebo, and among those in stable response, 25.8% versus 57.6%. Temporary altered taste, vertigo, dissociation, sleepiness and dizziness were the most common side effects. A limitation is that only people who had already done well on esketamine were randomized, so results may not apply to everyone.

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Ketamine-Assisted Psychotherapy

Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study

Popova V, Daly EJ, Trivedi M, et al.

American Journal of Psychiatry · 2019

This phase 3 trial, run at 39 outpatient centers, studied esketamine, a nasal-spray form related to ketamine, in adults with moderate to severe depression who had not responded to at least two antidepressants. Of 227 randomized participants, one group started esketamine twice weekly plus a new oral antidepressant, and the other started the new antidepressant plus a placebo spray, in a double-blind design. In this study, depression scores at day 28 improved more in the esketamine group, with a difference of about 4 points on the rating scale. Dissociation, nausea, vertigo, altered taste and dizziness were more common with esketamine and usually settled within 1.5 hours. A limitation is the short four-week window of the main comparison.

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Ketamine-Assisted Psychotherapy

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

Murrough JW, Iosifescu DV, Chang LC, et al.

American Journal of Psychiatry · 2013

This two-site randomized controlled trial tested a single intravenous ketamine infusion in 73 adults with treatment-resistant major depression. To make the comparison fairer, the control group received midazolam, an anesthetic that produces noticeable effects of its own, so participants were less able to guess which drug they had. In this study, depression scores 24 hours after the infusion were about 8 points lower on average in the ketamine group, and 64% of the ketamine group responded compared with 28% of the midazolam group. The authors themselves note an important limitation: more information on how long the response lasts, and on longer-term tolerability, was needed before routine clinical use.

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Ketamine-Assisted Psychotherapy

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Zarate CA, Singh JB, Carlson PJ, et al.

Archives of General Psychiatry · 2006

This small study from the National Institute of Mental Health asked whether a single dose of ketamine could lift depression quickly. Eighteen adults with depression that had not responded to earlier treatments took part in a randomized, double-blind, placebo-controlled crossover design, receiving one intravenous ketamine infusion and one placebo infusion a week apart. In this study, people improved within about two hours of ketamine compared with placebo, and the difference held through the following week. The day after the infusion, 71% met criteria for response and 29% for remission, and 35% kept their response for at least a week. An honest limitation: the sample was very small, there was no psychotherapy component, and the effect faded for most participants within days.

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