Clinic ketamine-assisted psychotherapy results published

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I’m excited to share my recent publication on ketamine-assisted psychotherapy done here in my clinic in Los Angeles. I partnered with a colleague at Stanford university, Boris Heifets, M.D., Ph.D., to help analyze all the data. It follows patients with depression (and often addiction as well) that I’ve treated over a period of up to 6 years, with combination intramuscular ketamine and psychotherapy that I provided, first in the initial phase of six sessions over a month, and then maintenance phase during this time (approximately monthly). As expected, over time people moved or discontinued treatment, but despite attrition we have enough long term data here to get a look at the good and the bad of ketamine over a long period of time. A few findings and thoughts:

  • ketamine assisted psychotherapy works well: around 80% of people respond, in terms of significant and meaningful improvements in depression

  • tolerance wasn’t a consistent finding; i.e. it continued to work well for many, for years

  • it’s mostly safe: nausea, sedation, and dizziness were most common. A minority of people had emesis (threw up) but anti-emetic medications helped.

  • addiction to ketamine is possible, and can be severe: One person with a history of polysubstance abuse went on to develop a ketamine use disorder, using to excess, losing their job, and suffering a number of other problems. This illustrates the intriguing duality of ketamine as a compound that can both treat depression addiction as well as cause it, and makes the case for keeping such ketamine-assisted psychotherapy as an in-office treatment.

Check it out at the links below. I’ve got a link to the paper as well as video talk I gave on it at the University of Oxford, UK, Ketamine international journal club.

You are what you eat

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The old addage, ‘you are what you eat’ has some scientific validity, at least from these preliminary findings. This study out of UC San Francisco examined an intervention which reduced peoples’ ultraprocessed food consumption, finding improvements in anxiety and depression symptoms. It’s a small study, and it’s not blinded, however it is consistent with broader findings about problems with unhealthy foods. Ultraprocessed foods are those containing ingredients you would not typically find at home, and are typically shelf stable. It’s no surprise that wonderbread that can survive the apocalypse isn’t good for you!

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2854373

Reducing Ultraprocessed Foods From the Diets of Patients With Depression
A Pilot Crossover Trial

D. Nyasha Chagwedera, MD, PhD; Eliana Kim, MD; Dorothy T. Chiu, PhD et al

JAMA Psychiatry

Epidemiological and observational studies show that an increased consumption of ultraprocessed food (UPF) is associated with an increased risk of developing depression and that this association is present in a dose-response manner.1-4 In addition to correlational studies, there are also plausible peripheral and central links between UPF and major depressive disorder (MDD), although no direct mechanistic link has been established. This crossover pilot study assessed the feasibility and acceptability of removing UPF from the diets of patients with MDD who eat a large percentage of UPF in their diets to establish the viability of pursuing this line of inquiry by carrying out clinical trials of the impact of manipulating UPF on MDD.

Can yoga help with opioid withdrawal?

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Yes, so it seems. A publication from earlier this year describes adding on a course of yoga onto buprenorphine (Suboxone) treatment for opioid use disorder. It was randomized and controlled, improving the rigor of the study over a single arm open label trial, but seemed to employ somewhat lower doses of buprenorphine. Still, the outcomes described, of lower anxiety, decreased time to cessation of opioid withdrawal symptoms, improved sleep, and improved pain, is compelling, especially that unlike medications yoga has very few “side effects.” Here, they did 10 guided yoga sessions of 45 minutes duration over the first 2 weeks of treatment. It sure does seem like controlled breathing and relaxation practices (such as yoga), are a useful addition to mental health, and these benefits likely also apply to other populations of people who are not in opioid withdrawal, but just depressed or anxious. Does it work? Try it out. I recommend yoga to most all of my patients.

Goutham S, Bhargav H, Holla B, et al. Yoga for Opioid Withdrawal and Autonomic Regulation: A Randomized Clinical Trial. JAMA Psychiatry. Published online January 07, 2026. doi:10.1001/jamapsychiatry.2025.3863

full text: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2843424

Psilocybin in alcohol use disorder and comorbid depressive symptoms

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Depression after alcohol detox is a big risk factor for relapse to drinking, so this study looked at psychedelic assisted psychotherapy with psilocybin (the active ingredient in magic mushrooms) to see if they could improve outcomes. Two groups were randomized; one group received a 25mg dose and the other got a placebo of 1mg which is an inactive microdose. A few different outcome measures were different between the groups: number of drinking days, craving scores, and relapse rates were all better in the 25mg group, suggesting psilocybin has a genuine effect in facilitating staying quit from drinking. Still, this is a small study, enrolling only 30 individuals, so as they say, more research needs to be done. Check out the link below for the full article. While psilocybin is still not available for medical use in the United States, it will likely be in the coming years at which point it’s worth considering. For now, ketamine assisted psychotherapy remains the only medically available psychedelic, which also has robust anti-addiction properties; confusingly, it also sometimes precipitates a ketamine use disorder, so it’s worth closely considering the risks and benefits, and working with an experienced clinician.

Luquiens A, Belahda D, Graux C, Igounenc N, Serrand C, Rochefort P, et al. Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial. Addiction. 2025. https://doi.org/10.1111/add.70152

full text: https://onlinelibrary.wiley.com/doi/10.1111/add.70152

psychedelics for addiction

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“The first major impact of a psychedelic experience in the 20th century in relation to addiction was that of Bill Wilson, the founder of Alcoholics Anonymous. He had an atropine-induced revelatory experience that he described as follows: “Suddenly the room lit up with a great white light. I was caught up in an ecstasy which there are no words to describe. It seemed to me in my mind’s eye, that I was on a mountain and that a wind not of air but of spirit was blowing. And then it burst upon me that I was a free man.” Bill’s psychedelic spiritual experience changed his life—through it he felt he was able to escape from the shackles of alcohol dependence, becoming permanently abstinent (for more details on the history of psychedelics, see Nutt, 2023).”
— Nutt et al.

Psychedelics, including more broadly, MDMA and ketamine, along with the classical psychedelics like LSD and psilocybin/psilocin, are being studied more and more as treatments for substance use disorders (ie, addictions). More studies means more data in support of their use, and already we are seeing such clinical trials demonstrating hopeful effects of ketamine on treatmnet of alcohol use disorder, opioid use disorder, cocaine use disorder, and cannabis use disorder. Use in these indications are still being studied, and it’s unclear how ketamine would be marketed given it’s a generic drug and being used off label. The limited data we have on the FDA approved ketamine product (esketamine nasal spray, AKA Spravato), suggests it is less effective than generic racemic ketamine, at least for treatment of depression. It is certainly much more expensive ($600-900 instead of $2-3). It is possible that a company will try to gain FDA approval for one of these indications, but then they would risk clinicians simply using generic ketamine off label, bypassing their formulation, and decreasing their profit potential. It makes me wonder if any company will actually invest in the work to carry out FDA trials for this.

Nutt DJ, Morgan C, Klaire S. A Perspective on Psychedelics as Treatments for Addictions. Journal of Studies on Alcohol and Drugs. 2024. 202485:5,583-588

full text: https://www.jsad.com/doi/full/10.15288/jsad.23-00032

Could soda be making your depression worse?

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Could soda be making your depression worse? Maybe, according to this new study published in JAMA Psychiatry, which looked at soft drink consumption and the gut microbiome in almost a thousand German people. The authors notes this effect has been observed elsewhere and seems to be absent in high sugar solid foods, so only occurs with consumption of high sugar liquids, like soda. Rodent models of depression show similar effects too, and this seems to be mediated by several different specific microorganisms that can disrupt the gut microbiome, leading to inflammation and more. In this study they linked it to Eggerthella, a bacteria found in the gut and associated with various illnesses like ulcerative colitis or abscesses. Even more interestingly, this depressive effect seemed only to occur in women. From a nutritional perspective, it is generally a good idea to steer clear of soft drinks, and instead aim for water. Coffee or tea is another option (and has a lot of health benefits), as long as you can avoid caffeine exposure in the afternoon so it does not disrupt sleep.

Edwin Thanarajah S, Ribeiro AH, Lee J, et al. Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations. JAMA Psychiatry. 2025;82(11):1095–1102. doi:10.1001/jamapsychiatry.2025.2579

full text: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2839019

Rolling stone article, "The Psychedelic Miracle"

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Earlier this month Rolling Stone published an article about the clinical use of psychedelics in underground clinics.*  It's an interesting read and delves in the motivations and experiences of a number of medical and allied professionals who opt to provide such agents as MDMA, ayahuasca, or magic mushroms (containing psilocybin) in unregulated settings.  That professionals will take on potential legal risk from practicing with these substances is a testament to their belief that they work, and something that is being gradually backed up by high quality scientific studies.  Several organizations are working on this process to formally medicalize these agents and bring them to legal clinical use, such as Hefter, MAPS, and others (see my resources page for links and more reading).  The available clinical data suggests that the classical hallucinogens such as psilocybin, LSD, and ayahuasca (which contains DMT) may have greater efficacy and duration of effect for depression and processing trauma, but it is hard to say concretely without further clinical trials, several of which are in the process due to the efforts of the above mentioned organizations.  Until that time, it seems that ketamine is the only clinically available (and legal) psychedlic available.  

*As as aside, Rolling Stone labels psychedelics as "miracle", which I am always hesitant to endorse as such.  The clinical trial data thus far shows large effect sizes and a relatively benign side effect profile, though with the caveat that these outcomes are carefully structured and take place in controlled medical settings.  As the article mentions, based on the authors personal account of several illicit psychedelic treatments, there can be significant personal turmoil during the healing and integration process; such treatments are not without their risks, and it is very likely that such treatments will not work for everyone.  There does, however, seem to be a correlation between subjects who achieve a mystical experience and better treatment outcomes, at least with the classical hallucinogens.  So perhaps it is more appropriate to term it "a miraculous experience"?

Link: http://www.rollingstone.com/culture/features/how-doctors-treat-mental-illness-with-psychedelic-drugs-w470673

JAMA Psychiatry, "A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders"

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Earlier this month JAMA Psychiatry published a consensus statement on ketamine for mood disorders (such as depression and bipolar depression) jointly written by a number of physicians from prominent academic centers across the United States.  While somewhat conservative in it's interpretation of available data, it is notable that academics who have been historically opposed to the clinical use of ketamine, seem to be gradually coming around and while not concretely endorsing its use, do seem to agree on ketamine being a viable treatment option.  As described in the article, plenty of data exists to support the short-term use of ketamine for depression, but the field is still developing in terms of high quality randomized controlled trials exploring ongoing maintenance treatment.  This is not uncommon in psychiatry--that medication treatments are studied for shorter periods of time--though as the data accumulates in favor of ketamine we will eventually see more such long-term studies.  Until that time, clinical experience, case studies, open label trials, and related treatments (such as maintenance ECT) guide the use of ketamine for maintenance of mood disorders.

YaleNews summary: http://news.yale.edu/2017/03/01/ketamine-eases-severe-depression-questions-dosage-duration-remain

JAMA Psychiatry article: http://jamanetwork.com/journals/jamapsychiatry/article-abstract/2605202

Genetics study develops our understanding of alcohol use disorder

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Interesting news for future potential treatments of alcohol use disorder:  a study in PNAS recently came out that points to a novel gene, and particular hormone, being involved in drinking behavior, β-Klotho and FGF21, respectively.  This is particularly interesting because it elaborates on our existing understanding of alcohol use disorder, and may offer a new molecular target for medications to disrupt drinking behavior.  The mainstay of substance use disorder treatment is a combination of psychosocial (such as psychotherapy and/or 12 step meetings, lifestyle changes) and biological treatments (like existing medications including naltrexone/vivitrol, acamprosate, disulfiram/antabuse).  With the current array of medications available, one--or a combination of several--works well for many folks, but more options, with potentially a better side effect profile, is always welcome.  

NBC story: http://www.nbcnews.com/health/health-news/gene-might-affect-how-much-you-drink-n689156

Article: http://www.pnas.org/content/early/2016/11/22/1611243113.abstract

Ketamine for depression (Washington Post article)

/ Wesley Ryan MD PC/

Ketamine has received a lot of publicity lately as a novel treatment for depression, and particularly because it seems to work when other treatment options have failed.   As a psychiatrist, it is particularly exciting for me to see a treatment that provides such a large magnitude of change (large effect size), works rapidly (on the order of hours typically), and is generally well tolerated by most folks who receive it.  What the article does not delve into are some of the treatment alternatives.  Ketamine treatments are largely modelled after electroconvulsive therapy (ECT) treatments, where several treatments are given in a burst to get people out of their depression, then followed up by periodic booster treatments.  While ECT has been around for many decades, use of ketamine for psychiatric indications (treatment of psychiatric diagnoses) is relatively new, being about a decade old.  Luckily, we have plenty of safety data from use of much higher doses of ketamine in anaesthesia, and it has proved remarkably safe.  When considering options for treatment resistant depression, many individuals are rightfully worried about the cognitive side effects of ECT such as memory loss and amnesia.  Ketamine, at least in the doses used in clinical treatment, does not seem to have such adverse effects.  While the benefits do appear to exceed the risks currently, it is important to monitor side effects and the growing scientific literature, as there is much remaining to learn about the long term used of ketamine for treatment of depression.  Still, at this point ketamine is an exciting new treatment option for patient and doctors alike.  Readers who are potentially interested in receiving such treatments are invited to browse my page on ketamine here.

Article:
https://www.washingtonpost.com/national/health-science/a-one-time-party-drug-is-helping-people-with-deep-depression/2016/02/01/d3e73862-b490-11e5-a76a-0b5145e8679a_story.html