From the Editor
Cannabis for chronic pain? What about insomnia or seizures? Patients often ask about the therapeutic use of cannabis. And your patients aren’t the only ones thinking about it; more than one in four Americans have used cannabis for medicinal purposes. But what does the literature actually say?
In an impressive, new review paper just published in JAMA, Dr. Michael Hsu (of the University of California, Los Angeles) and his co-authors seek to answer that question. With 124 citations, they are thorough and thoughtful, drawing on studies, clinical guidelines, and more. They are also clear in their conclusion. “Despite the accumulation of new studies, evidence is insufficient for the use of cannabis or cannabinoids for most medical conditions.” We consider the paper and its implications.
In the second selection from The Lancet Psychiatry, Dr. Richard Braithwaite (of the Sussex Partnership NHS Foundation Trust) and his co-authors comment on ketamine for depression. Though some new studies have reported solid results comparable to ECT, they remain skeptical. “The claim that ketamine is equivalent to ECT is not supported by credible evidence. It is a narrative constructed on a foundation of a small number of inadequately designed trials and flawed meta-analyses.”
Is sobriety required for recovery from substance misuse? In a personal essay for The New York Times, writer Maia Szalavitz argues that it isn’t. She notes her own journey which has spanned 40 years. “In reality, most people who resolve addictions – including me – do not reject all substance use forever.”
DG
Selection 1: “Therapeutic Use of Cannabis and Cannabinoids: A Review”
Michael Hsu, Arya Shah, Ayana Jordan, et al.
JAMA, 26 November 2025 Online First
The term cannabis broadly refers to products derived from the Cannabis genus plant, and cannabinoids refers to active compounds found in cannabis, including synthetic forms. Cannabis contains many cannabinoids, including Δ9-tetrahydrocannabinol (Δ9-THC), which is a psychoactive compound that causes the high associated with cannabis, and cannabidiol (CBD), which is nonintoxicating… Of 27 169 adults, aged 16-65 years, participating in a 2018 survey conducted in the US and Canada, 27% reported lifetime use of cannabis or cannabinoids for medical purposes, including treatment of pain (53%)…
So begins a paper by Hsu et al.
They review FDA-approved uses, as well as unapproved ones.
Chemotherapy-Induced Nausea and Vomiting
“In 1985, the FDA approved dronabinol and nabilone for chemotherapy-induced nausea and vomiting. The 2024 American Society of Clinical Oncology (ASCO) guideline recommends that for adults with cancer receiving moderately or highly emetogenic antineoplastic agents (eg, carboplatin, oxaliplatin) who experience nausea and vomiting refractory to first-line and second-line treatment (eg, olanzapine, dexamethasone), clinicians may consider prescribing dronabinol or nabilone (moderate-quality evidence) or a quality-controlled oral 1:1 Δ9-THC to CBD extract… The overall strength of this conditional recommendation was weak.”
Appetite Stimulation in HIV/AIDS
“Dronabinol is FDA approved for treatment of HIV/AIDs-induced anorexia and may be considered for patients with persistent weight loss despite antiretroviral therapy, although supporting evidence is limited and of low quality. A 2018 meta-analysis of 192 adult participants with HIV in 2 RCTs reported that cannabinoids (2.5-mg dronabinol capsule or 3.95% Δ9-THC cannabis cigarette) had a moderate effect on increasing body weight (SMD, 0.57…), although the quality of evidence was very low.”
Seizures
“The FDA approved pharmaceutical-grade CBD as adjunctive therapy for seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years or older and for tuberous sclerosis complex in patients aged 1 year or older. The American Academy of Neurology and American Epilepsy Society support the use of FDA-approved CBD in combination with other antiepileptic medications for these childhood seizure disorders.A meta-analysis… reported that CBD compared with placebo had a moderate effect on reducing seizure frequency (SMD, −0.50…). Evidence remains insufficient to recommend cannabis or cannabinoids for treatment of epilepsy in adults.”
Chronic Noncancer Pain
“The International Association for the Study of Pain, the American College of Physicians (ACP), and the Canadian Rheumatology Association (CRA) recommend against use of cannabis or cannabinoids as first-line treatment for chronic noncancer pain due to limited evidence of benefit and well-documented risks. The ACP’s 2025 best practice advice suggests that nabiximols may be considered for patients whose neuropathic pain does not improve with first-line therapies (eg, tricyclic antidepressants, topical agents), based on moderate-certainty evidence. A meta-analysis of 4 RCTs and 733 adult participants with chronic pain (eg, neuropathic pain, osteoarthritis, fibromyalgia) reported that nabiximols improved pain severity compared with placebo…”
Spasticity Due to Multiple Sclerosis
“The American Academy of Physical Medicine and Rehabilitation 2024 consensus guidance suggests further study before recommending cannabis or cannabinoids for multiple sclerosis (MS)–related spasticity. Although currently not FDA-approved in the US, nabiximols is approved in several other countries including Canada, the UK, France, and Germany for MS-related spasticity unresponsive to first-line treatments… A 2024 systematic review and meta-analysis of 8780 adults with MS-related spasticity across 31 studies (both randomized and nonrandomized) reported that nabiximols had a large effect on improving spasticity symptoms on the numeric rating scale…”
Cancer Pain
“The 2024 ASCO guidelines state that there is currently insufficient evidence to recommend for or against use of cannabis or cannabinoids to treat cancer pain.”
Insomnia
“The 2022 World Sleep Society and Kaiser Permanente Insomnia guidelines do not recommend use of cannabis or cannabinoids for treatment of insomnia; the World Sleep Society cited insufficient supporting evidence and issued a weak recommendation against its use based on low-quality data.”
Dementia
“RCT evidence suggests that cannabis or cannabinoids have no effect on prevention or treatment of dementia, and there is currently insufficient evidence to recommend for or against the use of cannabis or cannabinoids to treat behavioral or psychological symptoms of dementia such as aggression.”
A few thoughts:
1. This is an excellent paper – relevant and concise – and published in a Very Big Journal.
2. The main finding in a sentence: “Evidence is insufficient for the use of cannabis or cannabinoids for most medical indications.”
3. Even the FDA-approved uses didn’t have great evidence. (!)
4. Complicating our work as physicians: many patients have been told otherwise. Indeed, private industry makes bold claims.
5. Past Readings have included selections on cannabis. In The American Journal of Psychiatry, Dr. Kevin P. Hill (of Harvard University) and his co-authors reviewed almost 850 papers and commented on cannabis and psychiatry. “There is little data indicating that cannabinoids are helpful in treating psychiatric illness, while there is considerable evidence that there is potential for harm in vulnerable populations such as adolescents and those with psychotic disorders.” That Reading can be found here:
For the record, Dr. Hill is the senior author of this JAMA paper, which can be found here:
https://jamanetwork.com/journals/jama/article-abstract/2842072
Selection 2: “Ketamine versus ECT for major depression: flawed evidence base”
Richard Braithwaite, Ana Jelovacc, Charles H. Kellner, et al.
The Lancet Psychiatry, 22 October 2025 Online First
Electroconvulsive therapy (ECT) has long been considered in the scientific literature to be the most effective treatment for major depressive episodes. Recently, this view has been challenged by claims that ketamine could be an equally effective alternative, based on multiple meta-analyses of head-to-head randomised controlled trials (RCTs). However, close scrutiny shows that this literature includes methodologically flawed trials and meta-analyses that threaten the integrity of evidence-based medicine and risk steering patients and clinicians towards what might be a less effective treatment.
So begins a Comment by Braithwaite et al.
They review the literature. “Six RCTs have compared ketamine with ECT: five used intravenous infusions of ketamine and one used intramuscular and oral preparations.” They note several problems: “There is marked patient heterogeneity across studies in terms of mean age, frequency of psychotic features, bipolarity, and comorbidities such as anxiety disorders. The primary design flaw in all but one of the six existing RCTs is the use of suboptimal ECT as a comparator. Most trials have arbitrarily capped the number of ECT sessions at insufficient levels – as few as three, six, or nine sessions – a practice that does not reflect how ECT delivery is dynamically adjusted according to patient response in the real world. In a meta-analysis comparing different forms of ECT, patients treated with brief-pulse ECT received a mean of 8.7 sessions, and those treated with ultrabrief-pulse ECT received a mean of 9.6 sessions. Thus, limiting the number of sessions to nine or fewer in ECT versus ketamine trials implies that the patients who require an above-average number of sessions will receive insufficient ECT. Consequently, this trial design fails to address the relevant research question of whether a course of ketamine is as effective as a course of ECT.”
They focus on the Anand et al. study published in The New England Journal of Medicine. They detail problems.
- Sessions and stimulation. “The study limited ECT to only nine sessions and was the only RCT to primarily use ultrabrief-pulse stimulation, a technique shown in a previous meta-analysis to be less effective than standard brief-pulse ECT.”
- Exclusions. “The trial excluded patients with psychotic features or bipolar depression and adults older than 75 years, all of whom are typically good candidates for ECT…”
- Selection. “The reported 20% remission rate for ECT was even lower than the disappointing rates seen in other trials with ultrabrief-pulse stimulation and probably reflects inappropriate patient selection criteria and the poor efficacy of this specific technique.”
“In contrast, the KetECT trial, the only well powered trial that allowed a more clinically appropriate course of up to 12 ECT sessions, found ECT to be superior to serial intravenous ketamine, achieving a 63% remission rate compared with 46% for ketamine (odds ratio 0.51…).”
They describe the unfortunate consequences, including the current Royal Australian and New Zealand College of Psychiatrists’ clinical guideline on ketamine concludes that there is “comparable” efficacy between ECT and ketamine. “Clinicians treating patients with serious depressive illness or in urgent need of treatment should not be led to believe that the evidence base for the efficacy of ECT and ketamine is comparable…”
A few thoughts:
1. This is a well-argued paper.
2. They raise good points about some of the past work.
3. As I’ve wondered before: Is part of the discrepancy in results owing to the biases of the study authors, a case of ECT versus ketamine camps?
The full Lancet Psychiatry comment can be found here:
https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00300-1/abstract
Selection 3: “I’m in Addiction Recovery and I Still Drink Wine”
Maia Szalavitz
The New York Times, 14 August 2025
Not long ago, Robert F. Kennedy Jr.’s history of heroin addiction alone would likely have disqualified him from being considered for a role like secretary of health and human services. Now, however, numerous successful authors, politicians, executives and celebrities talk openly about past substance use disorders. ‘Lived experience’ even confers additional authority.
But there’s a caveat to this acceptance. Recovery is still largely viewed as lifelong abstinence – not just forever avoiding the specific substances someone once relied on, but also typically steering clear of all nonmedical drugs besides caffeine and nicotine. Most public recovery stories – like Mr. Kennedy’s – are tales of total abstinence, often propelled by participation in 12-step programs like Alcoholics Anonymous.
In reality, most people who resolve addictions – including me – do not reject all substance use forever.
So begins an essay by Szalavitz.
“Though I am in recovery from heroin and cocaine addiction, I still occasionally drink alcohol and use marijuana without issue.” She argues that there are biases at play. “Still, few people are open about their ‘non-abstinent’ recovery. Many of us fear that if we disclose the occasional weed gummy or sauvignon blanc with friends, we will be viewed as still in active addiction, and face the stigma that comes with that.”
She notes the influence on drug policy. “It bolsters the continued dominance of abstinence-only rehabs and recovery housing, which deters many people who could benefit from seeking help. It enables most residential treatment and recovery homes to reject long-term use of the addiction medications like buprenorphine and methadone – the only treatments proven to cut opioid overdose deaths in half – based on the mistaken idea that taking them means a person isn’t really sober or in recovery.” She describes a new Executive order that proposes “defunding a wide range of harm reduction programs that help people use drugs more safely without requiring abstinence, including efforts that provide clean needles or supervised places to use drugs.”
Her own journey included total abstinence for years. “The rehab I attended taught that abstinence was essential and could be achieved only via lifelong participation in a 12-step program based on Alcoholics Anonymous – so I engaged enthusiastically. I attended 12-step meetings daily until around 1995. For seven years, I did not use recreational drugs beyond caffeine.”
“But then, I fell into a deep depression after a book I’d written was rejected – leaving me despairing and in debt. I’d previously resisted psychiatric medications because many 12-steppers derided them as ‘an easier, softer way’ that would interfere with the work of overcoming my ‘character defects.’ At that point, though, I felt I would relapse without additional help…Via Zoloft, I soon discovered that my base line state of dread and social anxiety could be relieved by the right drug, without self-destructive behavior. Over time, I began to find 12-step meetings less necessary.”
Substance is part of her life. “Nowadays, I cautiously use alcohol and cannabis – drinking wine with dinner, for example, or taking a weed gummy for sleep. But because I do not love those drugs in the all-consuming way I loved heroin and cocaine, moderation isn’t difficult. If I have more than around 2.5 drinks, I get the urge to stop – so I do. That never happened with my favorite drugs.”
She notes that her period of total abstinence was helpful. So were other things. “Another key to recovery is discovering the purpose that excessive drug use serves for you and finding healthier ways to achieve it. I used drugs primarily because I felt unlovable. In recovery, I learned that sensory and emotional overload were behind my difficulties connecting with people and that antidepressant medication and cognitive techniques could relieve my discomfort. Now social support, music and exercise ease stress for me, enabling me to live a meaningful life without an anesthetic.”
A few thoughts:
1. This is a thoughtful essay.
2. She is quite balanced: “not everyone can safely moderate – and swinging from a treatment system that overwhelmingly requires abstinence to one that supports only reducing harmful use would be unwise.”
3. Should the recovery toolkit include several tools?
4. As always, readers can draw their own conclusions.
The full New York Times essay can be found here:
https://www.nytimes.com/2025/08/14/opinion/non-sober-addiction-recovery.html
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.
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