Psychedelic Drugs Flashcards
Cards partially sourced from lecture, partially from textbook
Psychedelics
Class of psychoactive substances that produce
changes in perception, mood and cognition (as well as physiological changes). The term psychedelic literally means “mind expanding.”
Classical psychedelics are relatively safe in comparison to other ‘street drugs.’ Psychedelics show some promise as theraputic agents.
US Controlled Substances Act
Classified drugs into 5 schedules depending on the potential for abuse. (Schedule V is lowest, Schedule I is highest)
Alcohol and THC are not scheduled in Canada
Classical (Serotonergic) Psychedelics
Psilocybin, LSD, DMT, Mescaline
Structural similarities to serotonin
Partial agonists
Activate serotonin 5-HT2A receptors as a primary mechanism
Activate other subtypes of serotonin (5-HT) receptors as well
Which serotonin receptors are ionotropic, which are metabotropic? Especially important to know 5-HT(2A)
All serotonin receptors are metabotropic except for 5-HT(3), which is ionotropic. Thus classical psychedelics primarily function on the metabotropic 5-HT(2A) receptors.
Head-twitch response
When psychedelics are administered, the rodent “head twitch” increases. High predictive validity for effects in humans
Classical Psychedelics
Activation of 5HT2A Receptor Signaling
- Canonical signalling pathway
- Excitatory,
Come back to this later :(
Non-Classical Psychedelics
Ketamine, MDMA (molly)
Structurally dissimilar
Don’t activate serotonin 2A receptors as a primary mechanism
‘Good’ psychedelic effects
Feelings of transcendence, profoundness, sacredness, positive mood
‘Bad’ psychedelic effects
Negative thoughts, loss of control, hallucinations, panic, mood swings, overheating
Psilocin (psilocybin)
The psychoactive constituent in hallucinogenic (“magic”) mushrooms of the Psilocybe genus. Causes visual hallucinations.
Lysergic Acid Diethylamine (LSD)
A highly potent classical psychedelic drug.
LSD reaches peak absorption after:
60 minutes
Half-life of LSD, and how long its pharmalogical effects can last
Half-life: 3 hours
Effects can last as long as: 8 hours
N,N-dimethyl tryptamine (DMT)
Hallucinogenic compound found in certain South American plants and produced in small amounts endogenously (within the body). DMT appears to serve as an agonist for sigma-1 receptors.
Mescaline
Found in the peyote cactus. Causes visual hallucinations.
Ketamine
A non-classical psychedelic, a dissociative anesthetic. Low-dose ketamine has robust antidepressant effects with a single dose (hrs to weeks). Has shown potential for transdiagnostic issues too (PTSD, substance use disorder, pain).
MDMA (aka Molly or Ecstasy)
- Mixed stimulant-psychedelic drug used recreationally
- Increases dopamine, serotonin (5HT), and norepinephrine
- Can cause euphoria, hence street name “ecstasy” (note though, that ecstasy does not always refer to MDMA)
- Also called an empathogen because it increases sociability and feelings of empathy
- Shows some efficacy in treatment of PTSD
MDMA is absorbed through the [answer] and metabolized in the [answer]
Absorbed through the gastrointestinal tract, and metabolized in the liver
Deficiencies in the [answer] enzyme lead to accumulation of MDMA in the body, which prolongs effects of the drug and increases the probability of adverse effects.
CYP2D6 enzyme
MDMA’s elimination half-life:
9 hours
The two ways that MDMA alters serotonin neurotransmission
- MDMA inhibits serotonin transportation into synaptic storage vesicles (prevents the storage of serotonin).
- MDMA reverses serotonin membrane transporters, expelling unstored serotonin that was not catabolized into the synaptic cleft.
Both these mechanisms increase extracellular brain serotonin levels.
How MDMA enhances extracellular levels of dopamine in the brain:
MDMA, like amphetamine, inhibits dopamine entry into storage vesicles, and reverses the dopamine membrane transporter direction, allowing higher extracellular levels of dopamine to be present.
Chronic administration of MDMA can result in:
Serotonin neuron loss and cognitive deficits
Which gender exhibits a greater sensitivity to MDMA?
Women exhibit a greater sensitivity to MDMA.
Phencyclidine (PCP)
A dissociative anesthetic also known as angel dust. A noncompetitive antagonist for glutamate NDMA receptors. Glutamate can still bind to an NDMA receptor that PCP is binded to, but PCP will prevent ions from passing through the receptor. The most abused dissociative anesthetic.
Would be considered a non-classical psychedelic.
Phencyclidine’s elimination half-life after absorption
18 hours (but can be as long as 51 hours)
Phencyclidine pharmacodynamics
Affects serotonin, dopamine, acetylcholine and glutamate neurotransmission
Serotonin: Enhances serotonin levels by inhibiting reuptake of serotonin and functioning as a 5-HT2A receptor
Dopamine: Enhances dopamine levels by reuptake inhibition, and is a partial agonist for D2 receptors
Acetycholine: A non-competitive antagonist for nicotinic receptors and an antagonist for muscarinic receptors
Glutamate: Antagonist for glutamate NDMA receptors, interferes with long-term potentiation (memory forming)
Also activates opioid kappa receptors
Phencyclidine’s effects
Depends on the dose:
Low doses: Cause CNS depressant effects, a drunken-like state, numbness in fingers and toes
Moderate doses: Cause numbness throughout the body, memory impairment, reported out-of-body experiences
High doses: Produce psychostimulant effects, cause a “rush,” arousal, and sympathetic nervous system activation. High doses can also cause severe adverse effects, like catalepsy (rigidity) and other symptoms similar to schizophrenia
Do dissociative anesthetics cause dependence?
They seldom cause dependence due to infrequent dosage. When dependence occurs, it is usually psychological in nature (cravings and/or feeling lethargic and depressed). Dissociative anesthetics rarely produce physical dependence.
Dextromethorphan
An opioid receptor drug and cough suppresant that can cause psychedelic effects in high doses. Found in the cough syrup Robitussin, recreational high dosage of dextromethorphan is called robo-tripping.
Also mentioned in the opioids deck.
Salvinorin A/Salvia divinorum
A kappa opioid receptor agonist that causes psychedelic effects.
Scopolamine and atropine
Muscarinic receptor antagonists (they block cholinergic receptors in the parasympathetic nervous system). Found in deadly night shade/belladonna.
