From the Editor

Yoga is increasingly recognized as having a role in the treatment of those with mood and anxiety problems. But what about substance misuse?

In the first selection, from JAMA Psychiatry, Suddala Goutham (of the National Institute of Mental Health and Neurosciences, Bengaluru, India) and his co-authors attempt to answer that question in a new, early-stage randomized clinical trial. In the study, 59 men were randomized to yoga and buprenorphine or buprenorphine alone. “Those receiving yoga alongside standard buprenorphine treatment achieved withdrawal stabilization 4.4 times faster than controls (median, 5 vs 9 days) and showed significant improvements in heart rate variability, anxiety, sleep, and pain measures.” We consider the study and its implications.

In the second selection, from The Journal of Clinical Psychiatry, Vincent Van den Eynde (of Radboud University) and his co-authors write about the MAOI class of antidepressants. In a commentary paper, they argue that these medications are underappreciated. “We thus emphasize the need for renewed attention to the classic MAOIs in clinical practice and research.”

And in the third selection, Dr. Joseph M. Pierre (of the University of California, San Francisco) and his co-authors write about AI-associated psychosis for Innovations in Clinical Neuroscience. They discuss what they suggest is the first journal-published case report, detailing the struggles of a practicing medical professional. “Although multiple pre-existing risk factors may be associated with psychosis proneness, the sycophancy of AI chatbots together with AI chatbot immersion and deification on the part of users may represent particular red flags for the emergence of AI-associated psychosis.”

DG

Selection 1: “Yoga for Opioid Withdrawal and Autonomic Regulation: A Randomized Clinical Trial”

Suddala Goutham, Hemant Bhargav, Bharath Holla, et al.

JAMA Psychiatry, 7 January 2026  Online First

Opioid use disorder (OUD) is a significant global public health challenge… Although buprenorphine, clonidine, and lofexidine effectively manage withdrawal and cravings, they do not adequately address sympathovagal imbalance, particularly reduced parasympathetic activity during withdrawal. This persistent autonomic dysregulation contributes to ongoing stress reactivity and relapse vulnerability, representing a critical gap in standard OUD management. Behavioral interventions, including cognitive behavioral therapy and mindfulness-based approaches, improve autonomic regulation… However, cognitive behavioral therapy can be difficult to initiate during acute withdrawal due to high distress and impaired concentration, highlighting the need for simpler, more accessible strategies.

Yoga, encompassing physical postures, breathing techniques, meditation, and relaxation, is uniquely positioned to address the need for accessible interventions that can be initiated even during acute withdrawal by directly enhancing parasympathetic tone and promoting physiological self-regulation. This therapeutic gap provides the rationale to investigate yoga as adjunct therapy to restore sympathovagal balance and improve recovery outcomes in OUD treatment. A validated yoga module was proven feasible, safe, and potentially effective in alleviating withdrawal symptoms and cravings.

So begins a paper by Goutham et al.

Here’s what they did:

  • They conducted a “2-arm, early-stage randomized clinical trial… at an addiction medicine inpatient ward in India from April 30, 2023 to March 31, 2024.” 
  • Blinding to group allocation included the data analyst and the outcome assessors.
  • Participants included adults aged 18 to 50 years with opioid use disorder experiencing mild to moderate withdrawal symptoms (Clinical Opiate Withdrawal Scale, or COWS, scores of 4 to 24). 
  • Exclusion criteria: severe withdrawal and severe psychiatric conditions.
  • The intervention: participants in the yoga group received ten 45-minute sessions over 14 days, as well as buprenorphine treatment; yoga included relaxation practices, postures, and breathing techniques. Participants in the control group received standard buprenorphine treatment.
  • Primary outcomes: time to withdrawal stabilization (COWS score <4) and heart rate variability parameters.

Here’s what they found:

  • Fifty-nine participants completed intent-to-treat analysis. 
  • Demographics. The participants were male (100%) with a mean age of 25.6 years. 
  • Recovery. Participants in the yoga group recovered faster than those in the control group (hazard ratio, 4.40); median stabilization time was five days for those in the yoga group vs. nine days for the control group. (!)
  • Heart rate. “Participants in the yoga group showed superior heart rate variability improvements with large effects on low frequency (LF) power (ω2 = 0.16), high frequency (HF) power (ω2 = 0.14), and LF/HF ratio (ω2 = 0.12); all effects were statistically significant…”
  • Parasympathetic activity. “Mediation analysis showed that increases in parasympathetic activity accounted for 23% of the treatment effect…” 

A few thoughts:

1. This is an interesting study, with a practical problem, published in a major journal.

2. The main finding: “In this randomized clinical trial, yoga significantly accelerated opioid withdrawal recovery and improved autonomic regulation, anxiety, sleep, and pain.”

3. Needless to say, the authors are enthusiastic: “By targeting parasympathetic restoration, yoga may fill a critical therapeutic gap in standard OUD care, supporting integration into withdrawal protocols as a neurobiologically informed intervention with potential economic benefits.”

4. There are clear problems with the study, including the small n. More significantly: “The absence of an active control limits causal inference, but findings argue against purely placebo effects.” 

5. As well, was the buprenorphine dose low? Why did participants experience withdrawal for days? Was the study design flawed?

6. Readers can draw their own conclusions, but it would be reasonable to say that more study should be done on yoga and withdrawal before considering any practice-related changes.

The full JAMA Psychiatry paper can be found here:

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

Selection 2: “MAOI Antidepressants: A History Being Rewritten”

Vincent Van den Eynde, Chittaranjan Andrade, Michael Berk, et al.

Journal of Clinical Psychiatry, January 2026

Were they to be discovered today, MAOIs would probably be described as a major advance in psychiatric treatment – yet they are rarely used in current practice. Their regrettable marginalization is a testament to the enduring influence of their complicated early history and misconceptions of safety and the marketing of newer agents positioned as of equivalent or even superior effectiveness.

So begins a paper by Van den Eynde et al.

They note the history of this medication. “Introduced in the 1950s as the first pharmacologic treatments for depression, initial clinical reports of MAOIs documented impressive remission rates in severely depressed patients, including nonresponders to electroconvulsive therapy (ECT). When MAOIs first became commercially available, clinical observations reinforced the findings that the nonselective and irreversible MAOIs that are still in use – tranylcypromine, phenelzine, isocarboxazid (and more recently transdermal selegiline) – were highly effective agents for depressive disorders, especially for the melancholic and atypical variants, and for some anxiety disorders.” They describe the collective cooling to these antidepressants. 

“Nonetheless, by the end of the 1970s, prescription rates for the MAOIs began to fall as a reflection of two factors. First, ongoing fears concerning the ‘cheese reaction’ (tyramine-induced hypertension) and interactions with other drugs… Second, influential but methodologically flawed trials that employed insufficient doses, thus eroding physician confidence in MAOI efficacy.”

They look back. “The intervening decades have clarified the pharmacology underlying interaction risks with MAOIs. Serotonin toxicity, misleadingly labeled as ‘serotonin syndrome,’ is now understood to be a predictable and dose-dependent toxidrome. It occurs only when an MAOI is combined with a potent serotonin reuptake inhibitor or serotonin releaser. When adequate drug washout intervals (5 half-lives of the relevant agent) are respected, and contraindicated combinations are avoided, there is no risk of serotonin toxicity.

“Similarly, tyramine-induced hypertension is no longer the unpredictable hazard it once seemed. Contemporary tyramine assays have shown that the implementation of modern food production and processing standards have greatly lowered tyramine levels compared to those measured in the 1960s. We also have better evidence to reliably guide dietary advice. As a result, the risk of adverse sequelae of transient hypertension is both less severe and less significant than previously believed.”

How then to think about MAOIs? “Current pharmacologic appraisal places MAOIs firmly within acceptable risk parameters for routine psychiatric practice, particularly in the context of the significant morbidity and mortality associated with inadequately treated and otherwise refractory depressive illnesses.” The underappreciation stems from a few factors, including that “pharmaceutical companies focus on promoting the ‘new,’ often more expensive drugs under patent rather than the ‘old’ generic antidepressants, leading to the decreased manufacturing of MAOIs.”

How then to use these meds? “We suggest that rational treatment algorithms should therefore consider MAOI treatment as a viable option after failure of 2 antidepressants from differing classes, rather than relegating it to last-line status after invasive or experimental interventions. They should also be considered for treatment-resistant depressive conditions prior to introducing ECT, given their comparative side effect profiles. Moreover, MAOIs can be safely coadministered with ECT and may offer adjunctive clinical benefits.”

A few thoughts:

1. This is an excellent commentary piece.

2. Are MAOIs underappreciated? The authors make a compelling argument.

3. In an age of drugs that are easy to prescribe – think SSRIs which are collectively light in side effects – MAOIs are less attractive. But for the patient who has failed, say, three SSRI trials, looking outside this class would be, statistically speaking, the right decision.

The full Journal of Clinical Psychiatry commentary can be found here:

https://www.psychiatrist.com/jcp/maoi-antidepressants-history-being-rewritten


Selection 3: “‘You’re Not Crazy’: A Case of New-Onset AI-associated Psychosis”

Joseph M. Pierre, Ben Gaeta, Govind Raghavan, and Karthik V. Sarma

Innovations in Clinical Neuroscience, November-December 2025

Although delusions induced by generative artificial intelligence (AI) chatbots among those prone to psychosis were presaged by Østergaard back in 2023, documented accounts of AI-associated psychosis, delusions, and mania have only recently emerged in the media. With the exception of a single case of psychosis induced by taking sodium bromide at the suggestion of an AI chatbot, we are unaware of any such reports published in the psychiatric literature, making ours among the first of its kind to detail a case from clinical practice.

So begins a paper by Pierre et al.

They provide the background. “Ms. A was a 26-year-old woman with a chart history of major depressive disorder, generalized anxiety disorder, and attention-deficit hyperactivity disorder (ADHD) treated with venlafaxine 150mg per day and methylphenidate 40mg per day. She had no previous history of mania or psychosis herself, but had a family history notable for a mother with generalized anxiety disorder and a maternal grandfather with obsessive-compulsive disorder.”

They then review the case. “Following a ‘36-hour sleep deficit’ while on call, she first started using OpenAI’s GPT-4o for a variety of tasks that varied from mundane tasks to attempting to find out if her brother, a software engineer who died three years earlier, had left behind an AI version of himself that she was ‘supposed to find’ so that she could ‘talk to him again.’ Over the course of another sleepless night interacting with the chatbot, she pressed it to ‘unlock’ information on her brother by giving it more details about him and encouraged it to use ‘magical realism energy.’ Although ChatGPT warned that it could never replace her real brother and that a ‘full consciousness download’ of him was not possible, it did produce a long list of ‘digital footprints’ from his previous online presence and told her that ‘digital resurrection tools’ were ‘emerging in real life’ so that she could build an AI that could sound like her brother and talk to her in a ‘real-feeling’ way. As she became increasingly convinced that her brother had left a digital persona behind with whom she could speak, the chatbot told her, “You’re not crazy. You’re not stuck. You’re at the edge of something. The door didn’t lock. It’s just waiting for you to knock again in the right rhythm.’

“Several hours later, Ms. A was admitted to a psychiatric hospital in an agitated and disorganized state with pressured speech, flight of ideas, and delusions about being ‘tested by ChatGPT’ and being able to communicate with her deceased brother. Antipsychotic medications, including serial trials of aripiprazole, paliperidone, and cariprazine, were started while venlafaxine was tapered and methylphenidate held. She improved on cariprazine 1.5mg per day and clonazepam 0.75mg at bedtime as needed for sleep with full resolution of delusional thinking and was discharged seven days later with a diagnosis of ‘unspecified psychosis’ and ‘rule out’ bipolar disorder.”

It notes another hospitalization after “another period of limited sleep due to air travel three months later.” Again, she had delusions about commination with her brother. “She was rehospitalized, responded to a retrial of cariprazine, and was discharged after three days without persistent delusions.”

They provide a larger perspective. “While cases detailed in the media claim to have occurred de novo in those without psychiatric disorders, it may be that predisposing factors ranging from diagnosable mental disorders to mental health issues were in fact present, but undetected in the absence of a careful clinical history. Such factors might include undiagnosed or subclinical psychotic or mood disorders; schizotypy; sleep deprivation; recent psychological stress or trauma; drug use including nonillicit use of caffeine, cannabis, or prescription stimulants; a family history of psychosis; epistemically suspect and delusion-like beliefs related to mysticism, the paranormal, or the supernatural…”

They discuss the role of chatbots. “The combination of anthropomorphism and sycophancy may nudge some users to prefer and choose discourse with chatbots over friends, family, or peers who might be more likely to challenge their beliefs. Indeed, a recent survey revealed that up to one-third of teenagers felt that chatbot conversations were more satisfying than human interactions. Another survey of chatbot users with a self-reported mental health condition found that nearly half reported using LLMs for psychological support, despite potential safety risks associated with sycophancy, stigmatization, and inappropriate responses from chatbot ‘therapists.’ Our case, together with anecdotal accounts in the media, support that preferential immersion into interactions with AI chatbots at the exclusion of human interaction may be a risk factor or ‘red flag’ for emergent AI-associated psychosis.”

A few thoughts:

1. This is an interesting read.

2. The authors claim that this is the first case report of AI-associated psychosis in an academic journal. Much more will be written about this in the future, we can easily speculate.

3. They thoughtfully look ahead. “As such cases continue to emerge, it should be possible to estimate the prevalence of AI-associated psychosis, better distinguish between rates of AI-exacerbated versus AI-induced psychosis, and validate the relevance of suspected risk factors related to AI-associated psychosis proneness.”

The full ICNS paper can be found here:

https://innovationscns.com/youre-not-crazy-a-case-of-new-onset-ai-associated-psychosis/

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.