Jun 17, 2026 · 41 min · 13 segments
In the first episode of Season 5 on the *Neuroethics of Psychedelics*, we speak with Godfrey Pearlson about the science of psychedelics, what these substances…
Godfrey PearlsonGuest
Lavinia UscatescuHost
Okay, so maybe a useful way to approach that important question is just to start off with some basic definitions.
So there are a number of terms that are Similar and therefore confusing, but let's briefly go through them just to unpack them for listeners.
So if we describe a substance as psychoactive, it just means that it's a chemical that affects perception or mood or consciousness or cognition or behavior, just in a broad sense.
So many substances are psychoactive like alcohol or tobacco or Valium or sleeping pills or antidepressants.
They're used for recreational purposes because taking them produces pleasant effects as well as psychoactive effects.
Psychedelic drugs are also psychoactive, but they have prominent, peculiar effects of ego dissolution.
lose your identity and blend with your surroundings in the universe and profound sensory distortion and the sensation of immersion that you're completely immersed within the experience and you can't really pull yourself out of it and then there are drugs that are described as hallucinogenic and that's a subclass of psychedelics that just produce strong hallucinations That's usually reserved for LSD or psilocybin or mescaline or other classic psychedelic drugs, most of which act on serotonin receptors in the brain.
There's this 60s term of psychotomimetic, meaning drugs that mimic psychosis.
And that's an inaccurate term that we should probably avoid, but people drag that up.
Having got those definitions out of the way, back to your question of why some substances alter brain activity and others don't.
One is physical and biological factors, and the second is psychological and social factors.
So the biology is that in order to protect our vulnerable brains from outside potentially damaging chemicals in the environment that we might inhale or eat.
There's a blood-brain barrier, which is literally a barrier that's physical that protects the brain by blocking many substances from entering.
And the only molecules that can cross it are either fat soluble, like cannabis, or small, like alcohol, or have specific transport mechanisms that drag them across the blood-brain barrier or they're molecularly compatible so that they can cross the barrier and fit into neuroreceptor sites like little keys into little locks in the brain.
So there are dozens, many dozens of neuroreceptors that it uses to do that, each of which has its own receptor sites.
So cannabinoids have their own set of receptor sites that we can talk about.
Okay, so maybe a useful way to approach that important question is just to start off with some basic definitions.
So there are a number of terms that are Similar and therefore confusing, but let's briefly go through them just to unpack them for listeners.
So if we describe a substance as psychoactive, it just means that it's a chemical that affects perception or mood or consciousness or cognition or behavior, just in a broad sense.
So many substances are psychoactive like alcohol or tobacco or Valium or sleeping pills or antidepressants.
They're used for recreational purposes because taking them produces pleasant effects as well as psychoactive effects.
Psychedelic drugs are also psychoactive, but they have prominent, peculiar effects of ego dissolution.
lose your identity and blend with your surroundings in the universe and profound sensory distortion and the sensation of immersion that you're completely immersed within the experience and you can't really pull yourself out of it and then there are drugs that are described as hallucinogenic and that's a subclass of psychedelics that just produce strong hallucinations That's usually reserved for LSD or psilocybin or mescaline or other classic psychedelic drugs, most of which act on serotonin receptors in the brain.
There's this 60s term of psychotomimetic, meaning drugs that mimic psychosis.
And that's an inaccurate term that we should probably avoid, but people drag that up.
Having got those definitions out of the way, back to your question of why some substances alter brain activity and others don't.
One is physical and biological factors, and the second is psychological and social factors.
So the biology is that in order to protect our vulnerable brains from outside potentially damaging chemicals in the environment that we might inhale or eat.
There's a blood-brain barrier, which is literally a barrier that's physical that protects the brain by blocking many substances from entering.
And the only molecules that can cross it are either fat soluble, like cannabis, or small, like alcohol, or have specific transport mechanisms that drag them across the blood-brain barrier or they're molecularly compatible so that they can cross the barrier and fit into neuroreceptor sites like little keys into little locks in the brain.
So there are dozens, many dozens of neuroreceptors that it uses to do that, each of which has its own receptor sites.
So cannabinoids have their own set of receptor sites that we can talk about.
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