Opparounds

GH001 vs Placebo in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial

Cubała WJ, Bajbouj M, Bauer M, et al. · JAMA Psychiatry · June 2026

This phase 2b trial randomized 81 patients with treatment-resistant depression across 16 European sites to a single day of inhaled GH001 (mebufotenin, a synthetic 5-MeO-DMT-class "neuroplastogen") or placebo. MADRS scores improved substantially more with GH001 than placebo — a between-group difference of 15.5 points — and remission by day 8 was 57.5% with GH001 versus 0% with placebo, with no serious adverse events.

Read the paper →  doi:10.1001/jamapsychiatry.2026.0096

Does Congruence Between Therapist and Patient in Session-by-Session Bond Ratings Predict Change in Symptoms?

Falkenström F, Rubel JA, Stachelscheid A, Lutz W · Journal of Consulting and Clinical Psychology · July 2026

Analyzing 2,575 CBT patients across 82,641 sessions, this large-scale study tested a common supervision assumption: that therapist-patient agreement on session-by-session emotional-bond ratings predicts better outcomes. It didn't hold up.

Instead, outcomes were better when therapists rated the bond lower than the patient did, rather than the reverse — congruence itself carried no advantage.

Read the paper →  doi:10.1037/ccp0001017

Converting Paliperidone Palmitate Formulations Is Arithmetic, Not a Restart

Switching a stable patient from monthly to the three-month paliperidone palmitate formulation isn't a new-drug decision — it's a dose conversion with a fixed rule: the first PP3M injection is dosed at 3.5 times the patient's last stable PP1M dose, given at the time the next monthly injection would have been due, with a ±7-day window.

The conversion is only validated after at least four months of PP1M treatment, because that's the point at which the monthly formulation is presumed to have reached steady state — converting earlier introduces uncertainty the dosing table wasn't built for. The most common error isn't the math, it's the timing: teams often delay the switch appointment past the window "to be safe," which actually undermines the pharmacokinetic assumption the conversion relies on and can produce a trough dip mistaken for treatment failure. Get the conversion dose right and keep the window tight, and there's no reason to expect a gap in coverage.

Safety Behaviors Don't Just Coexist with the Fear — They Manufacture Its Survival

A safety behavior looks like coping — carrying anti-anxiety medication "just in case," always sitting near an exit, subtly avoiding eye contact during a feared conversation — but functionally it prevents disconfirmation. The feared catastrophe never happens, and the patient attributes that non-occurrence to the safety behavior rather than learning the catastrophe was never likely in the first place.

This is why exposure that permits safety behaviors underperforms exposure that systematically removes them: the exposure exists to generate a genuine prediction-error signal, and a safety behavior is precisely engineered to prevent that signal from landing. The clinical implication is to inventory safety behaviors as carefully as avoidance itself — patients often disclose the phobic situation readily but never mention the ritual that makes it tolerable.