Psychedelic Medicines and Drugs: A Comprehensive Guide

As interest in psychedelic-assisted therapies grows, understanding these substances' histories, effects, and potential therapeutic benefits becomes essential for anyone seeking alternative treatments for complex conditions such as PTSD, depression, and anxiety.

Psychedelics, historically used for spiritual and therapeutic purposes, are gaining renewed interest in the scientific community due to their unique ability to profoundly alter perception, mood, and cognitive processes. These comparative tables list the most common psychedelics, including ketamine, MDMA, psilocybin, ayahuasca, LSD, mescaline, and DMT, examining their mechanisms of action, therapeutic uses, and the legal landscape governing their clinical use.

Classification

Substance

Purpose

Ketamine

Dissociative anesthetic

MDMA
(3,4-Methylenedioxymethamphetamine)

Empathogen-entactogen

Psilocybin

Serotonergic psychedelic

Ayahuasca

Psychedelic brew containing DMT

LSD

(Lysergic Acid Diethylamide)

Serotonergic psychedelic

Mescaline

Phenethylamine psychedelic

DMT

(Dimethyltryptamine)

Tryptamine psychedelic

Chemical Structure

Substance

Chemical Structure

Ketamine

C13H16ClNO

MDMA
(3,4-Methylenedioxymethamphetamine)

C11H15NO2

Psilocybin

C12H17N2O4P

Ayahuasca

Primary active ingredient is DMT (C12H16N2)

LSD

C20H25N3O

Mescaline

C11H17NO3

DMT

C12H16N2

History of Use

Substance

History of Use

Ketamine

Developed in the 1960s for anesthesia; more recently used to treat depression.

MDMA
(3,4-Methylenedioxymethamphetamine)

Synthesized in 1912; used as a psychotherapeutic tool in the 1970s; became popular as a recreational drug in the 1980s.

Psilocybin

Used traditionally in religious and spiritual contexts; studied scientifically in the 1960s.

Ayahuasca

Used for centuries in South American shamanic practices.

LSD

Synthesized in 1938 and popularized in the 1960s counterculture.

Mescaline

Used traditionally by Native Americans for spiritual and religious purposes.

DMT

Used traditionally in various indigenous Amazonian rituals; found naturally in several plant species.

Subjective Effects

Substance

Subjective Effects

Ketamine

Dissociation from reality, altered perception, and tranquility under clinical settings.

MDMA
(3,4-Methylenedioxymethamphetamine)

Increased empathy, emotional warmth, and euphoria.

Psilocybin

Altered visual and auditory perceptions, sense of connectedness, mystical experiences.

Ayahuasca

Intense visual hallucinations, emotional revelations.

LSD

Distortions in sensory perception, profound psychological insights, altered sense of time.

Mescaline

Visual hallucinations, altered consciousness, euphoria, and profound introspection.

DMT

Short-acting but intense visual and auditory hallucinations, profound emotional shifts.

Mechanism of Action

Substance

Mechanism of Action

Ketamine

Blocks NMDA receptors in the brain, affecting glutamate, a neurotransmitter.

MDMA
(3,4-Methylenedioxymethamphetamine)

Increases the release of serotonin, dopamine, and norepinephrine.

Psilocybin

Agonist at serotonin receptors, particularly in the prefrontal cortex.

Ayahuasca

Contains DMT, which acts as a serotonin receptor agonist.

LSD

Serotonin receptor agonist, particularly affecting the 5-HT2A receptor.

Mescaline

Acts primarily on serotonin receptors.

DMT

Binds to serotonin receptors, similar to other psychedelics.

Therapeutic Uses

Substance

Therapeutic Uses

Ketamine

Treatment-resistant depression, acute management of pain.

MDMA
(3,4-Methylenedioxymethamphetamine)

PTSD, potentially anxiety and other mood disorders.

Psilocybin

Treatment-resistant depression, end-of-life anxiety, addiction.

Ayahuasca

Studied for depression and addiction.

LSD

Experimental treatments for anxiety, depression, and PTSD.

Mescaline

Investigated for therapeutic potential in treating addiction and facilitating psychological exploration.

DMT

Currently under research for various psychiatric conditions.

Regulatory Status

Substance

Regulatory Status

Ketamine

FDA-approved for anesthesia; used off-label for depression.

MDMA
(3,4-Methylenedioxymethamphetamine)

Schedule I in the USA; undergoing clinical trials for PTSD.

Psilocybin

Schedule I in the USA; granted Breakthrough Therapy designation by the FDA for depression.

Ayahuasca

Not regulated as a medicine; illegal in many countries.

LSD

Schedule I in the USA.

Mescaline

Controlled substance in many countries, with no mainstream medical use approved.

DMT

Schedule I in the USA.

Side Effects (Clinical Setting)

Substance

Side Effects (Clinical Setting)

Ketamine

Nausea, dizziness, dissociation, elevation in blood pressure.

MDMA
(3,4-Methylenedioxymethamphetamine)

Nausea, mild anxiety, jaw clenching, transient increase in heart rate.

Psilocybin

Mild anxiety, headache, altered sensory perception.

Ayahuasca

Nausea, vomiting (commonly referred to as "purging"), intense emotional upheaval.

LSD

Minimal physiological toxicity; potential for flashbacks.

Mescaline

Typically mild, including headache and nausea.

DMT

Minimal when used in controlled settings; primarily psychological effects like altered sensory perception and emotional intensity.

Side Effects (Casual / Abuse)

Substance

Side Effects (Casual / Abuse)

Ketamine

Potential for abuse, long-term cognitive deficits, bladder issues.

MDMA
(3,4-Methylenedioxymethamphetamine)

Dehydration, hyperthermia, potential neurotoxicity, dependency.

Psilocybin

Psychological distress, potential for triggering psychiatric conditions.

Ayahuasca

Psychological distress, potential exacerbation of mental health issues.

LSD

Hallucinogen persisting perception disorder, paranoia, disorientation.

Mescaline

Can cause significant psychological distress and potential for panic.

DMT

Potential for frightening hallucinations, overwhelming fear, and confusion.

Find Out More

Outside of clinical research settings, ketamine remains the sole FDA-approved psychedelic therapy. Ketamine, and particularly ketamine infusion therapy, remains the most studied psychedelic medication and therapy.

Read our introduction to Psychedelic Medicine.

To understand more about the benefits of an anesthesiology-led practice, click here.

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