Scientists designed psychedelics that skip the heart-risk receptor entirely

Key Findings

⚡ Ketamine Dials Down the Brain's 'Bad News' Center

• In a randomized study of 70 healthy adults, a single 0.5 mg/kg ketamine infusion reduced activity in the lateral habenula — a structure involved in aversive learning — when participants encountered negative outcomes 24 hours later.
• Preliminary evidence also suggested that when aversive learning happened after the infusion, reduced habenula activity during learning was associated with weaker encoding of negative memories.

💊 For Ketamine in Anxiety Disorders, More Isn't More

• A crossover trial tested 0.5 and 1.0 mg/kg intramuscular ketamine across four internalizing disorders — treatment-resistant depression, PTSD, generalized/social anxiety, and OCD.
• Both doses produced robust effects at 24 hours compared to an active control, but the higher dose did not outperform the lower one at either 24 or 168 hours, suggesting an inverted-U dose-response curve that peaks around 0.5–1.0 mg/kg.

🐭 Psilocybin Restored Social Behavior in a Compulsive-Behavior Mouse Model

• Male mice bred to model compulsive behavior showed impaired social novelty investigation. A single 1 mg/kg psilocybin injection restored that behavior seven days later — an effect that was male-specific and did not appear in females.
• Only activation in the infralimbic region of the prefrontal cortex correlated with the behavioral rescue, while other reward-related brain regions showed no change.

🧠 Psychedelics May 'Reset' How the Hippocampus Frames Anxiety

• A review proposes that anxiety disorders involve a self-reinforcing loop: the hippocampus supplies anxiety-laden context that biases perception, which gets re-encoded, which reinforces the bias.
• Psychedelics may temporarily free cortical networks from that hippocampal context via serotonin receptor activity, while post-trip plasticity allows the hippocampus to integrate new, less aversive contextual frames — a proposed "resetting of the hippocampal buffer."

🎭 In OCD Trials, How You Relate to the Experience Predicts Response

• A qualitative study compared psilocybin responders and non-responders in treatment-resistant OCD and found that psychological processes — specifically surrender, disidentification from obsessive thoughts, and cognitive reappraisal — differentiated the two groups.
• Non-responders tended to resist or intellectualize the experience rather than allowing it to shift their relationship to their symptoms.

😮‍💨 Hyperventilation Breathwork Produced Psychedelic-Like States in Mental Health Professionals

• Forty-eight mental health clinicians participated in a high-ventilation breathwork workshop and reported altered states reaching intensity ranges comparable to moderate doses of serotonergic psychedelics.
• Participants rated perceived clinical potential as significantly higher than anticipated risks; trait openness and emotional breakthrough during the session predicted that positive assessment. Psychotic and dissociative disorders were flagged as contraindications.