Pharmacology of Psychedelics and Psychoactive Inhalants Flashcards
Differentiate delusions, hallucinations, and illusions, and identify which are most commonly caused by psychedelic drugs
Delusion: Fixed, false belief unresponsive to logic; Paranoia is a common manifestation
Hallucination: A false perception arising from internal stimuli; Creates a false reality
Illusion: A misperception of external stimuli; Distorts reality
Psychedelics rarely produce frank hallucinations at doses commonly used
Differentiate between classical psychedelics and dissociative psychedelics based upon their mechanism of action and clinical effects
Classical psychedelics: derivatives of phenethylamine, derivatives of tyramine
Dissociative pscyhedelics: phencyclidine, ketamine, muscimol
Derivatives of the structure of phenethylamine
mescaline, MDA, MDMA
Derivatives of the structure of tryptamine
DMT, 5-MeO-DiPT, LSD, Ibogaine
Naturally occurring classical psychedelic drugs
Dimethyltryptamine (DMT)
5-MeODMT is a derivative of DMT that is 5-6x more potent
Psilocybin is a pro-drug of psilocin; rapid dephosphorylation of psiclocybin to psilocin
Mescaline combines mechanism of action of
LSD and MDMA; low potency drug, long lasting, cross tolerance to LSD - suspected interaction with serotonin system
from phenethylamine: amphetamine like - MDMA, bath salts; increases release of 5-HT>DA, NE; empathogens/entactogens - more hallucinogenic than stimulatory
Most classical psychedelics are agonists of
the 5-HT2A receptor
* Pretreatment with 5-HT2A antagonists blocks psychedelic effects
* Exception: MDMA stimulates 5-HT release
Dissociative psychedelics are antagonists of
NMDA receptors
inhibition of GABA release and disinhibition of glutamate release; non-competitive antagonist, enter channel when its open
NMDAR primarily postsynaptic and can also bind glycine
Prominent NMDA receptor antagonists
ionotropic glutamate receptors
ketamine
dextromethorphan
Ionotropic glutamate receptors
- NMDA receptor antagonist
- Induce anesthesia and analgesia
Ketamine
- Racemic mixture, S(+) is more active
- Fast and short acting (10-60 min)
- Esketamine recently FDA approved for treatment resistant depression
- Used in opioid tolerant patients for chronic pain
Dextromethorphan
- Also serotonin reuptake inhibitor
- Abused by ~4% high schoolers
- Doses for cough suppression are
<60 mg, while 100 – 600 mg are used to induce “high”
Phencyclidine
- NMDA antagonist: More potent than ketamine; Also dopamine D2 receptor agonist
- Cigarette dipped in liquid PCP: Nicotine or marijuana cigarette; Effect 4-6hrs
- People often unaware of cannabis laced with PCP
- Severe dissociation and analgesia: Self-mutilation without recognition (dissociation)
- Provokes psychotic reactions
- Misuse associated with violence and suicide
Muscimol
ibotenic acid –> decarboxylation to muscimol
Muscimol is an agonist of GABAA channels and can induce dissociative psychedelic effects. In contrast, benzodiazepines and alcohol of allosteric modulators
5-dimension altered states of conciousness
visionary restructuralization: sensory illusions
oceanic boundlessness: highly pleasurable state of self dissolution
anxious ego-dissolution: thought disorder leading to unpleasant state (bad trip)
Describe the acute and long-term adverse effects of psychedelic drug use
short term physiologic, acute dysphoric reaction, psychotic reaction
* Rapid development of tolerance–third consecutive day, marked attenuation of effect
* Frequent use can lead to mood changes
* No evidence of addictive potential
Short-term physiologic
Tachycardia
Hypertension
Tremors
Dry mouth
Nausea
Hyperthermia
Acute dysphoric reaction
Terrifying thoughts
Fear of insanity
Fear of losing
control
Fear of death
Psychotic reaction
Flashbacks (hallucinogen persisting perception disorder)
Enduring changes in personality
Exacerbate underlying psychotic
disorder
Instigate prolonged psychotic disorder
Rate of psychosis after LSD 1 to 5%
Describe current interest in psychedelics as psychotherapeutics
potential therapeutic uses:
* Cancer-related psychological distress
* PTSD
* Depression
* Substance Use Disorder (Alcohol)
Identify the primary psychoactive inhalants and their mechanism of action
Liquids, aerosol, gases, nitrites
inhalants can be misused in multiple ways:
* Volatile solvents (toluene, glue, kerosene, gasoline)
* Aerosols, gases, sprays
* Nitrites (poppers), and nitrous oxide.
* Hydrocarbons, ketones
sniffing, huffing, bagging, dusting
Alkyl Nitrites
- Commonly sold as ‘poppers’
- Marketed as cleaning solutions and
room deodorizers - Nitric oxide release results in smooth
muscle relaxation - Relaxes anal sphincter, enhanced
erections, euphoria - Highest abuse among gay men (25x)
- Methemoglobinemia (low oxygen) is greatest risk
Volatile Solvents
Volatile solvents are liquid at RT and evaporate readily when exposed to air
Toluene: model glues, correction fluids, lacquer thinners, plastic cements, spray paints; most characterized, alters the activity of a wide range of ion channels
Acetone: nail polish remover, model glue, rubber cements
Benzene: cleaning fluids, rubber cements, tire tube repair kits
Butane: cigarette lighters, hair spray, spray paint
Highest frequency of use among adolescents, especially in isolated communities (access driven?)
Clinical effects of volatile solvents
Acute effects: locomotor sitmulation, euphoria, exhiliration
high dose: CNS depression, slurred speech, disorientation, weakness, sedation
Describe the adverse effects of psychoactive
inhalant misuse
asphyxiation, suffocation, convulsions/seizures, coma, choking, fatal injury
Asphyxiation
from repeated inhalations that lead to high concentrations of inhaled fumes, which displace available oxygen in the lungs
Suffocation
from blocking air from entering the lungs when inhaling fumes from a plastic bag placed over the head
Convulsions/seizures
from abnormal electrical discharges in the brain
Coma
from the brain shutting down all but the most vital functions
Choking
from inhalation of vomit after inhalant use
Fatal injury
from accidents, including motor vehicle fatalities, suffered while intoxicated
Sudden sniffing death syndrome
development of fatal arrhythmias within minutes of inhalation
Compulsiveuse
Neurotoxicity - neurodegeneration with people who use it chronically
