Psilocybin therapy in meth addiction—attitude of “leaning into the obstacle” drives recovery

Key Findings

💥 Ketamine eliminates 'exploding head syndrome' in chronic case

• A 75-year-old man with exploding head syndrome (hearing loud thunder-like sounds and experiencing lightning sensations during sleep) saw complete resolution after 6 months of sublingual ketamine treatment

• Episodes dropped from 3-4 times weekly to once every two weeks after just one month, and continued improving until only occasional sleep paralysis remained

• Previous treatments including gabapentin, valproic acid, and amitriptyline had all failed over 5+ years of this debilitating sleep disorder

🧠 Psilocybin preserves brain function in Alzheimer's mice without reducing plaques

• 5xFAD mice (an Alzheimer's model) receiving monthly psilocybin (0.5mg/kg) for 4 months showed improved memory, pattern recognition, and reduced depression-like behavior compared to untreated mice

• Brain analysis revealed significantly reduced neuroinflammation and increased production of new neurons in the hippocampus, along with better preservation of synaptic proteins

• Surprisingly, psilocybin didn't reduce the characteristic amyloid-beta plaques of Alzheimer's, suggesting it works through entirely different mechanisms than current drug approaches

🔬 Ibogaine shows 'matrix pharmacology' across multiple brain targets

• Researchers mapped ibogaine's complex effects across multiple neurotransmitter systems simultaneously, including serotonin, dopamine, and novel targets like organic cation transporter 2 (OCT2)

• The psychedelic and its metabolite noribogaine act as 'Synaptic Reuptake Inhibitors' (SynRIs), blocking both vesicular storage and reuptake of serotonin with similar potency—an uncommon dual action

• This 'matrix pharmacology' may explain why ibogaine doesn't cause the movement problems (catalepsy) seen with other drugs that block similar brain targets

🧪 Psilocybin reduces OCD symptoms through 'partial' psychedelic experiences

• 12 participants with treatment-resistant OCD described their single-dose psilocybin experiences, reporting that OCD symptoms actually interfered with the intensity of acute psychedelic effects

• Despite these 'partial' experiences with lower-intensity visual and emotional effects, participants still experienced meaningful reductions in obsessive-compulsive symptoms afterward

• The therapeutic changes appeared to work through mechanisms similar to evidence-based OCD therapies like exposure therapy and acceptance approaches

🎯 Ketamine's metabolite rescues brain translation pathways in Alzheimer's mice

• The ketamine breakdown product (2R,6R)-hydroxynorketamine (HNK) corrected abnormal gene expression patterns in APP/PS1 Alzheimer's mice after 14 days of daily treatment

• RNA sequencing revealed that HNK specifically rescued three pathways related to protein synthesis and RNA metabolism that were disrupted in the Alzheimer's model

• The metabolite also normalized inflammatory pathways and stress responses that were overactive in the disease mice compared to healthy controls

🧬 Chronic low-dose ketamine creates Alzheimer's-like brain changes in healthy mice

• Healthy mice given chronic ketamine treatment (35 days) developed gene expression patterns remarkably similar to those seen in APP/PS1 Alzheimer's mice, with over 700 overlapping gene changes

• While ketamine protected against memory problems from acute amyloid injection, chronic treatment in transgenic Alzheimer's mice showed no memory benefits and altered microglial brain cells in concerning ways

• The findings suggest ketamine induces an 'AD-like transcriptional signature' in normal brains, raising questions about long-term safety in patients at risk for dementia