#psychopharmacology

#psychopharmacology

Many situations contain irreducible uncertainty. No matter how many variables we try to control, we can't reduce uncertainty to zero. It's inherent in the messiness of life.

The condition, called recessive RNU2-2-related neurodevelopmental disorder, is associated with seizures and severe developmental delay in children less than a year-old, in areas such as speech and walking.

We found no evidence any form of cannabis is effective in treating anxiety, depression or post-traumatic stress disorder, which are three of the leading reasons for which cannabis is prescribed. The cannabis medications being administered in these studies were largely oral formulations, such as capsules, sprays or oils. In real life, people typically use smoked cannabis, and there is even less evidence of its effectiveness for mental health.

Dopamine is one of the most extensively studied neurotransmitters, chemicals that convey signals from cell to cell. It's the one with the highest profile outside neuroscience: often known as the 'pleasure chemical', it's depicted as the hit of reward that people get from recreational drugs or scrolling through social media. That's a gross simplification of what dopamine does; on that, researchers agree.

Some clinicians have an uncanny quality. A colleague describes herself and others with this instinct as "witchy"-a capacity to know things about patients they haven't said yet, to follow a stray association to a song lyric or a half-remembered cultural reference and arrive, reliably, at something the patient urgently needed to say but couldn't reach on their own. We see with artificial intelligence these intriguing possibilities for discovery, especially as connections that human beings never would see pop out of apparently unrelated data.

In the mid-1990s, child mental health researchers at top New York institutions injected grade-school boys with fenfluramine, also known as the diet drug "fen-fen," a substance that was later banned by the Food and Drug Administration, due to its links to valvular heart disease and pulmonary hypertension. The boys were all Black or Hispanic by design: Eligible participants were required to be African American or Hispanic because they were deemed to be at higher risk for developing disruptive behaviors.

Anyone living with schizophrenia understands the true limitations of current treatment options. Antipsychotics remain the single leading treatment for the disorder, and they are riddled with undesirable side effects. Weight gain, tardive dyskinesia, and excessive drowsiness are a few. Much research is devoted to expanding the range of medication options, and few academics have pursued other avenues. However, there is a possibility that treatment for schizophrenia can be approached through cellular methods if long-term research validates early signs of hope.

Yes, there has been a shocking lack of progress in developing transformative psychiatric medicine (We need new drugs for mental ill-health, 5 February), but this may be because in mental health, drugs are not always the answer (see, for example, Richard P Bentall's Doctoring the Mind). Huge progress has been made in the effectiveness of talking therapies for example, free effective treatment for post-traumatic stress disorder (PTSD) is available to all UK army veterans through the charity PTSD Resolution.

The standard explanation is that ketamine blocks NMDA receptors. These receptors bind glutamate, which is a chemical messenger found throughout the brain and body. By blocking NMDA receptors, ketamine increase "brain-derived neurotrophic factor" (BDNF), a protein which I refer to as "Miracle-Grow for the brain." BDNF promotes neuroplasticity-which is the growth of new connections (synapses) in the brain. This has traditionally been viewed as the primary mechanism responsible for ketamine's therapeutic benefits. But ketamine does so much more!

Statistics show that about one-third of people with depression achieve remission-meaning their symptoms are gone-with traditional antidepressant medications. This matched my experience treating people, and I had grown to accept that this was as good as it gets. Although I wasn't thrilled with the fact that many people continued to struggle with significant symptoms of persistent depression, it seemed this was as good as we could do.

Every day, many thousands of parents across the U.S. face the difficult question of whether to place their child or teenager on a psychotropic medication. Receiving a diagnosis of a mental disorder can be scary and confusing, for the youth as well as their parents/caretakers. What is ADHD? Depression? Anxiety? OCD? Bipolar? What are the available treatments? Do we have to use medications to treat the symptoms?

Before treatment began, participants underwent neuroimaging. Instead of relying on a single modality, the researchers fused structural connectivity (how regions are physically wired) with functional connectivity (how regions co-activate at rest). The goal was not to throw every possible feature at a black box, but to learn a constrained pattern-what the authors call structure-function "covariation"-that carries the most predictive signal for outcome. In other words, the model tries to find the smallest set of connections that meaningfully forecasts symptom change.

That sounds impressive; however, the devil is in the details that the popular media completely ignored. For example, only 11 of those studies were focused on depression. The authors concluded that exercise had a medium effect on depression. It is impossible to know how a "medium" effect compares with drug therapy since the studies were not head-to-head comparisons. The study also reported that exercise benefited many other health conditions, including HIV or kidney disease, various mental disorders, and cancers.

A recent study published in Biological Psychiatry identified a distinct subtype of psychiatric illness marked by brain inflammation, one that cuts across traditional diagnoses and may explain why standard treatments fail for some people (Tang et al., 2025).This new brain imaging study offers an interesting clue. It turns out that across different psychiatric disorders, some people show clear signs of brain inflammation, visible on scans and confirmed through immune system tests.

That question may sound provocative, but it has fascinated scientists for decades. Despite the billions of dollars spent each year on antidepressant drugs, a striking body of research suggests that much, and possibly all, of their benefit may come not from chemistry, but from expectation: the simple belief that the pill will help. 1,2 That phenomenon has a name: the placebo effect.