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Opioid Addiction: RNA Biology, Brain Inflammation & Psychedelic Therapy
This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.com
Wide release: February 19, 2026. Not medical advice.
TOPICS DISCUSSED:
* Gene regulation basics: DNA transcribes to RNAs, including non-coding types like microRNAs that inhibit mRNA translation into proteins, influencing up to 60% of the proteome.
* Non-coding RNAs in neuroplasticity: MicroRNAs and circular RNAs regulate synaptic changes, with activity-induced ones like miR-485-5p linked to rapid responses in drug cue memory and addiction reinforcement.
* Opioid addiction models: Rats self-administer heroin or fentanyl via levers, showing compulsive seeking; fentanyl’s higher potency drives faster learning but similar long-term effects to heroin when doses are equated.
* Differences between opioids: Heroin and fentanyl both activate mu-opioid receptors for euphoria and dopamine release, but fentanyl lingers longer; no major behavioral differences in seeking once potency is matched.
* Psilocybin’s effects on addiction: A single psilocybin dose post-abstinence reduces heroin-seeking in rats by dampening neuroinflammation in brain regions like the nucleus accumbens and prefrontal cortex.
* Brain Inflammation: Opioids induce pro-inflammatory changes via cytokines like IL-17A and pathways like TNF-alpha, leading to glial activation and blood-brain barrier leaks; psilocybin counters this.
* MicroRNA biomarkers: Blood microRNAs reflect gene expression patterns tied to disease states, with potential to predict opioid relapse risk, treatment response, or neonatal withdrawal severity non-invasively.
* Future research: Ongoing work links psilocybin’s serotonin 2A activation to anti-inflammatory gene changes, plus human studies on microRNAs for personalized addiction treatments.
ABOUT THE GUEST: Stephanie Daws, PhD is an associate professor at Temple University in the Center for Substance Abuse Research and Department of Neurosciences, where she researches mechanisms of drug-seeking behavior with a focus on opioids and psychedelics.
RELATED EPISODE:
* M&M 2 | Psilocybin, LSD, Ketamine, Inflammation & Novel Psychedelic Medicines | Charles Nichols
Listen or watch on your favorite platform:
* Audio version: [Apple] [Spotify] [Elsewhere]
* Video version: [YouTube]
* Support M&M if you find value in this content.
PRACTICAL TAKEAWAYS:
* For those in recovery, discuss medication options like buprenorphine or methadone with providers, as individual responses vary and biomarkers may one day guide choices.
* Be aware of fentanyl’s extreme potency in street drugs, which heightens overdose risk.
* Explore emerging psychedelic therapies under medical supervision, as psilocybin shows promise in reducing drug cravings via plasticity and inflammation modulation.
SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.
View all episodes
By Nick JikomesThis is a free preview of a paid episode. To hear more, visit mindandmatter.substack.com
Wide release: February 19, 2026. Not medical advice.
TOPICS DISCUSSED:
* Gene regulation basics: DNA transcribes to RNAs, including non-coding types like microRNAs that inhibit mRNA translation into proteins, influencing up to 60% of the proteome.
* Non-coding RNAs in neuroplasticity: MicroRNAs and circular RNAs regulate synaptic changes, with activity-induced ones like miR-485-5p linked to rapid responses in drug cue memory and addiction reinforcement.
* Opioid addiction models: Rats self-administer heroin or fentanyl via levers, showing compulsive seeking; fentanyl’s higher potency drives faster learning but similar long-term effects to heroin when doses are equated.
* Differences between opioids: Heroin and fentanyl both activate mu-opioid receptors for euphoria and dopamine release, but fentanyl lingers longer; no major behavioral differences in seeking once potency is matched.
* Psilocybin’s effects on addiction: A single psilocybin dose post-abstinence reduces heroin-seeking in rats by dampening neuroinflammation in brain regions like the nucleus accumbens and prefrontal cortex.
* Brain Inflammation: Opioids induce pro-inflammatory changes via cytokines like IL-17A and pathways like TNF-alpha, leading to glial activation and blood-brain barrier leaks; psilocybin counters this.
* MicroRNA biomarkers: Blood microRNAs reflect gene expression patterns tied to disease states, with potential to predict opioid relapse risk, treatment response, or neonatal withdrawal severity non-invasively.
* Future research: Ongoing work links psilocybin’s serotonin 2A activation to anti-inflammatory gene changes, plus human studies on microRNAs for personalized addiction treatments.
ABOUT THE GUEST: Stephanie Daws, PhD is an associate professor at Temple University in the Center for Substance Abuse Research and Department of Neurosciences, where she researches mechanisms of drug-seeking behavior with a focus on opioids and psychedelics.
RELATED EPISODE:
* M&M 2 | Psilocybin, LSD, Ketamine, Inflammation & Novel Psychedelic Medicines | Charles Nichols
Listen or watch on your favorite platform:
* Audio version: [Apple] [Spotify] [Elsewhere]
* Video version: [YouTube]
* Support M&M if you find value in this content.
PRACTICAL TAKEAWAYS:
* For those in recovery, discuss medication options like buprenorphine or methadone with providers, as individual responses vary and biomarkers may one day guide choices.
* Be aware of fentanyl’s extreme potency in street drugs, which heightens overdose risk.
* Explore emerging psychedelic therapies under medical supervision, as psilocybin shows promise in reducing drug cravings via plasticity and inflammation modulation.
SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.