Svensson Pharmacology of Psychedelics and Psychoactive Inhalants Flashcards
What are psychedelics?
Agents that produce non-ordinary and variable forms of conscious experiences. These include changes in mood, thoughts, and distorted perceptual sensations generally only experienced in dreams.
Why have fallen into disfavor hallucinogens?
They have fallen into disfavor as these drugs rarely produce frank hallucinations at doses commonly used.
What are delusions?
-Fixed, false belief unresponsive to logic
-Paranoia is a common manifestation
What are hallucinations?
-A false perception arising from internal stimuli
-Creates a false reality
What are illusions?
-A misperception of external stimuli
-Distorts reality
What are the two different kinds of psychedelics?
-Classical psychedelics
-Dissociative psychedelics
What are the two different kinds of classical psychedelics?
-Derivatives of phenethylamine
-Derivatives of tryptamine
What are the types of dissociative psychedelics?
-Phencyclidine
-Ketamine
-Muscimol
Mescaline clinical pearls
-Mescaline combines the mechanism of action of LSD and MDMA
-Lowest potency (~500 mg)
-Long lasting 10-12 hrs
-Cross tolerance to LSD (suspected interaction with serotonin system)
Phenethylamine mechanism of action
-Amphetamine-like (MDMA, bath salts)
-Increase release of 5-HT > DA, NE
-Empathogens/entactogens are more hallucinogenic than stimulatory
How can you pre-inhibit the effects of classical psychedelics?
-Pretreatment with 5-HT2A antagonists block psychedelic effects because classical psychedelics are agonists for the 5-HT2A receptor
-The exception is MDMA because it stimulates 5-HT release
Short-term physiologic adverse effects of psychedelic drug use
-Tachycardia
-Hypertension
-Tremors
-Dry mouth
-Nausea
-Hyperthermia
Acute dysphoric reactions to psychedelic drug use
-Terrifying thoughts
-Fear of insanity
-Fear of losing control
-Fear of death
Psychotic reactions to psychedelic drug use
-Flashbacks (hallucinogen persisting perception disorder)
-Enduring changes in personality
-Exacerbate underlying psychotic disorder
-Instigate prolonged psychotic disorder
-Rate of psychosis after LSD 1-5%
How do psychedelics develop tolerance?
-Rapid development of tolerance - third consecutive day, marked attenuation of effect
-Frequent use can lead to mood changes
-No evidence of addictive potential
What are the potential therapeutic uses of psychedelics?
-Cancer-related psychological distress
-PTSD
-Depression
-Substance use disorder (alcohol)
Shortcomings of clinical trials into psychedelics for therapeutic use
-Small sample size
-Lack of inadequate controls (hard to do blinded studies)
-What is the proper control group?
-Selection bias (those experienced with or comfortable with psychedelic drug use are more likely to do the study)
What is the difference between classical psychedelics and dissociative psychedelics?
In contrast to classical psychedelics, dissociative psychedelics act as antagonists of NMDA receptors
Ketamine clinical pearls
-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 clinical pearls
-Also serotonin reuptake inhibitor
-Abused ~4% high schoolers
-Doses for cough suppression are <60mg, while 100-600mg are used to induce “high”
Phencyclidine (PCP) clinical pearls
-NMDA antagonist
-More potent than ketamine
-Also dopamine D2 receptor agonist
-Cigarettes are often dipped with PCP and can cause effects that last 4-6 hrs
-People are often unaware of cannabis-laced with PCP
-Severe dissociation and analgesia (self-mutilation without recognition)
-Provokes psychotic reactions
-Misuse associated with violence and suicide
Muscimol mechanism of action
Muscimol is an agonist of GABAa channels and can induce dissociative effects. In contrast, benzodiazepines and alcohol of allosteric modulators.
How do people misuse inhalants?
-Sniffing
-Huffing
-Bagging
-Dusting
Types of inhalants that are misused
-Volatile solvents (toluene, glue, kerosene, gasoline)
-Aerosols, gases, sprays
-Nitrites (poppers), and nitrous oxide
-Hydrocarbons, ketones
Alkyl nitrate clinical pearls
-Commonly sold as poppers
-Marketed as cleaning solutions and room deodorizers
-Nitric oxide release results in smooth muscle relaxation
-Relaxes anal sphincter, enhances erections, and euphoria
-Highest abuse is among gay men (25x)
-Methemoglobinemia is the greatest risk
Which population abuses volatile solvents the most?
Adolescents, especially in isolated communities
What are the types of volatile substances?
-Toluene
-Acetone
-Benzene
-Butane
Volatile substances clinical pearls
Liquid at room temperature and evaporate readily when exposed to air
Acute effects of volatile solvent abuse
-Locomotor stimulation
-Euphoria
-Exhilaration
Effects of high doses of volatile solvents
-CNS depression
-Respiratory depression
-Slurred speech
-Disorientation
-Weakness
-Sedation
Effects of repeated exposure of volatile substances
lipid accumulation in adipose tissue and lipid-rich organs such as the brain, kdineys, adrenal glands, ovaries
Risks of inhalant abuse
-Asphyxiation - from repeated inhalations that lead to a high concentration 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 over the head
-Convulsions and 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
What is the number of inhalant-related fatalities in the United States [er year?
100-200
What is sudden sniffing death syndrome?
-Development of fatal arrhythmias within minutes of inhalation
-Results from chronic use leading to neurotoxicity
