Hallucinogens/Psychedelics
Psilocybin
* LSD
* Mescaline
* DMT (Ayahuasca)
* MDMA
* PCP
* Ketamine
produce changes in perception, mood, and cognitive processes.
Psychedelics and Serotonin
the chemical structure of 2 very common classical psychedelics, Lsd. And Psilocybin, are very similar to that of serotonin.
So you can see the tryptamine Molecules in the red here, and it’s consistent across all 3 chemical structures,
. So this similarity allows psilocybin and Lsd as well as other psychedelics to bind and activate serotonin receptors in the brain which really leads to its psychoactive effects.
Psychedelics also do a number of other things in the brain. They’ve been shown to increase neural plasticity, to increase neural pathways, to be able to help reduce rigidity of thinking and rigid thinking patterns which we’ve seen a lot of medical conditions, like depression, Ocd and addiction
and anxiety as well. They also have been shown to increase brain drive, neurotropic factor, which is another factor which often we can see benefit for depression out. Some other antidepressants do that as well.
, actually decrease what we call a activity in the default mode network
whatever we’re daydreaming, we’re never just thinking about sort of what’s present in front of us. We’re often thinking forward, and we’re thinking backwards. We’re thinking about something that happened. We’re thinking about something that could happen. That’s your default Mode network just in full action. Never kind of in the present moment.
And what psychedelics do is they actually calm the default moe network, and it can really quiet it so that you can just really be present and go inwards, and really have some really insightful moments
Psilocybin
- Produced by psilocybin mushrooms (eg. Psilocybe cubensis)
- Naturally occurring prodrug → converted rapidly in body to psilocin
- Route of administra=on: po, tea, iv
- Onset of ac=on: 10-40mins; dura=on 2-6hrs
- Dose: 10-50mg (10-50g fresh mushrooms, 1-5g dried)
- Most common therapeu=c dose: 25mg
- Serotonin 2A receptor (5-HT2AR) agonist
it increases serotonin effects in the brain so being an agonist, it
finds in place of serotonin, with really no
little to no effect on the production, release or re-uptake of serotonin. It does affect other serotonin subtypes as well. But the 2, a receptor is a strongest and definitely what we think is most likely link to the psychedelic effect
Psilocybin
*Effects:
Physical: pupil dilation, inc/dec HR, hypo/hypertension (caution!), nausea
*Psychological: disorientation, lethargy,
*Good trip= giddiness, euphoria, joy, connected to others, nature, and universe
*Bad trip=depression/anxiety/paranoia (inc. risk if used with other drugs/alcohol,
if used during emotional low, or in unsupportive environment)
*Potential long-term changes in personality of user (openness, spiritually active)
>1yr; reduced psychological distress, suicidal ideation/planning/attempts
Sensory: radiant colors, altered sense of /me, animated
sensory experiences
Psilocybin
ADR
clinical use
- ADR: impairment of mental
functioning, psychosis,
flashbacks/ ‘hallucinogen
persisting perception
disorder’ (HPPD) (rare) - No fatal overdoses.
Agitation can be treated
with benzodiazepines/
supportive care - Clinical Uses: MDD, anxiety,
end of life distress, tobacco
cessation, alcohol use
disorder, OCD, migraines,
etc.
LSD
- “acid”, “blo?er”, “heavenly blue”, “lucy in the
sky with diamonds” - Pharmacology: binds to most serotonin
subtypes (cross-acGvaGon), increases
glutamate in cerebral cortex, and enhances
dopamine (D2) signaling - Pharmacokine/cs: onset of acGon 30-40 min,
duraGon of acGon 8-12 hours, metabolized by
CYP 450, excreted by kidneys
Lysergic acid diethylamide
LSD
route
dose
fx
- Route of administra6on: po, SL (“bloMers”), iv (less
common) - Typical dose: 40-500µg
- Effects:
- Physical: pupil dilaTon, reduced appeTte,
wakefulness, others more varied - Psychological: similar to psilocybin
- Sensory: similar to psilocybin
“The psilocybin experience seems to be
warmer, not as forceful and less isolating.
It tends to build connections between
people, who are generally much more in
communication than when they use LSD.”
LSD
ADR
clinical use
- ADR: Similar to psilocybin
- Clinical uses: alcohol withdrawal, depression, anxiety (preliminary)
Mescaline
- “blue caps”, “buQons”, “cactus”
- Occurs naturally in the San Pedro cactus, the
Peruvian torch, the Bolvarian torch catus, the
Peyote cactus and other species of cac=. - Long history of use in Mexico and South America.
- Pharmacology: 5-HT2A/5-HT2C receptor agonist
- Usual Dose: 200–400mg of mescaline sulfate or
178–356mg of mescaline hydrochloride - 76mm buMon=25mg mescaline
- Routes of Administra;on: PO
Mescaline
pk
fx
adr
clinical use
- Pharmacokinetics: Onset 45-90min;
peak 4-6hr; duration 8-14hr.
Metabolized via liver and others.
Likely broken down by MAO. - Effect: Similar to LSD and psilocybin +
energetic/stimulating - ADR: Similar to LSD and psilocybin
- Clinical Uses: Alcohol use disorder,
depression
Ayahuasca
N,N-dimethyltryptamine (DMT)
- Obtained from the vine Banisteriopsis caapi, and used for
ritual purposes by Indigenous populations of the Amazon. - Often combined with the leaves of the shrub Psychotria viridis.
- This preparation contains the psychedelic 5-HT2A receptor agonist N,N- dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with
monoamine-oxidase-inhibiting properties from B. caapi. - Route of administration: oral ingestion (tea), inhaled, IV
- Pharmacology: DMT= 5-HT(2A/1A/2C) agonist; β-carbolines=
reversibly inhibit MAO to prevent breakdown of DMT orally
and allowing its absorption and access to the CNS. - Pharmacokinetics: fast/intense onset and duration with
inhaled or IV (5-15 minutes), duration in a tea with β- carbolines ~3 hours. Drug-drug interactions- dangerous with
any drugs that increase serotonin (serotonin syndrome).
Ayahuasca
N,N-dimethyltryptamine (DMT)
fx
adr
clinical use
- Effects: similar to other psychedelics; highly visual.
- ADR: similar to other psychedelics.
- Clinical Uses: substance use disorders, depression, anxiety.
Potential therapeutic tool by enhancing self-acceptance
and allowing safe exposure to emotional events.
Ecstasy (MDMA)
Methylenedioxymethamphetamine
- “love drug”, “E”, “XTC”, “Adam”, “X”,
“Molly” - S=mulant proper=es, capsules or tablets,
club drug (raves, dances) - Onset within 30-60mins, dura=on of
ac=on 4-6 hours - Supplemental dose use clinically
- Trus=ng, loving, and warm feelings
toward others - Stronger sensa=ons (esp. touch)
Ecstasy
(MDMA)
pharmacology
pk
adr
clinical use
- Pharmacology: potent reuptake
inhibitor of presynap=c 5
-HT, DA, and
NE - Usual dose: 50
-150mg - Pharmacokine;cs: metabolized in liver;
CYP450
-2D6 involved - ADR: jaw clenching, anxiety, GI
disturbances, increased vitals, swea=ng - Clinical uses: PTSD + more to come
Jaw-clenching
q
PCP or
Ketamine
Phencyclidine
- “angel dust” (PCP), “special K”, “jet”, “green”
(ketamine) - Stimulant, depressant, hallucinogenic,
anesthetic, analgesic - Route of administration: PO, smoked, IV * Dissociation from surroundings, time
distortions - ADR: paranoia, extremely aggressive behavior,
confusion, slurred speech, muscle rigidity - Long
-Term: speech problems, depression,
memory loss, violent behavior, flashbacks,
syndrome similar to schizophrenia, strong
cravings - Clinical Uses: treatment
-resistant depression +
additional under investigation (ketamine only)
Abuse potenFal and toxicity (psychedelics)
- Abuse Poten+al
- Does not cause physical dependence or withdrawal
- Introspec/ve, mys/cal, and spiritually meaningful effects vs. pleasureble/euphoric
- Repeated use over several days may reduce effect of drug
- Toxicity
- Lower than commonly used substances (alcohol and tobacco)
- Acute psychological distress, panic reac/ons, or psychosis when used in
unsupervised seNng - Not recommended in individuals with a history or family history of psychosis, mania, or
borderline personality disorder - Persistent changes in mood or cogni/on (rare)
- Very low overdose risk
Drug InteracFons (psychedelics)
- Antidepressants (such as SSRIs and MAO-Is):
- Increased risk of serotonin syndrome (++ Ayahuasca)
- Reduced psychedelic effect
- Antipsychotics:
- Reduced psychedelic effect
- Increased risk of adverse events
- CYP 450 Interactions:
- CYP 2D6: psilocybin, ayahuasca,
MDMA - CYP 3A4: MDMA
- QT Prolongation
