Svensson Pharmacology of Psychedelics and Psychoactive Inhalants

Question 1

What are psychedelics?

Answer 1

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.

Question 2

Why have fallen into disfavor hallucinogens?

Answer 2

They have fallen into disfavor as these drugs rarely produce frank hallucinations at doses commonly used.

Question 3

What are delusions?

Answer 3

-Fixed, false belief unresponsive to logic
-Paranoia is a common manifestation

Question 4

What are hallucinations?

Answer 4

-A false perception arising from internal stimuli
-Creates a false reality

Question 5

What are illusions?

Answer 5

-A misperception of external stimuli
-Distorts reality

Question 6

What are the two different kinds of psychedelics?

Answer 6

-Classical psychedelics
-Dissociative psychedelics

Question 7

What are the two different kinds of classical psychedelics?

Answer 7

-Derivatives of phenethylamine
-Derivatives of tryptamine

Question 8

What are the types of dissociative psychedelics?

Answer 8

-Phencyclidine
-Ketamine
-Muscimol

Question 9

Mescaline clinical pearls

Answer 9

-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)

Question 10

Phenethylamine mechanism of action

Answer 10

-Amphetamine-like (MDMA, bath salts)
-Increase release of 5-HT > DA, NE
-Empathogens/entactogens are more hallucinogenic than stimulatory

Question 11

How can you pre-inhibit the effects of classical psychedelics?

Answer 11

-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

Question 12

Short-term physiologic adverse effects of psychedelic drug use

Answer 12

-Tachycardia
-Hypertension
-Tremors
-Dry mouth
-Nausea
-Hyperthermia

Question 13

Acute dysphoric reactions to psychedelic drug use

Answer 13

-Terrifying thoughts
-Fear of insanity
-Fear of losing control
-Fear of death

Question 14

Psychotic reactions to psychedelic drug use

Answer 14

-Flashbacks (hallucinogen persisting perception disorder)
-Enduring changes in personality
-Exacerbate underlying psychotic disorder
-Instigate prolonged psychotic disorder
-Rate of psychosis after LSD 1-5%

Question 15

How do psychedelics develop tolerance?

Answer 15

-Rapid development of tolerance - third consecutive day, marked attenuation of effect
-Frequent use can lead to mood changes
-No evidence of addictive potential

Question 16

What are the potential therapeutic uses of psychedelics?

Answer 16

-Cancer-related psychological distress
-PTSD
-Depression
-Substance use disorder (alcohol)

Question 17

Shortcomings of clinical trials into psychedelics for therapeutic use

Answer 17

-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)

Question 18

What is the difference between classical psychedelics and dissociative psychedelics?

Answer 18

In contrast to classical psychedelics, dissociative psychedelics act as antagonists of NMDA receptors

Question 19

Ketamine clinical pearls

Answer 19

-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

Question 20

Dextromethorphan clinical pearls

Answer 20

-Also serotonin reuptake inhibitor
-Abused ~4% high schoolers
-Doses for cough suppression are <60mg, while 100-600mg are used to induce “high”

Question 21

Phencyclidine (PCP) clinical pearls

Answer 21

-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

Question 22

Muscimol mechanism of action

Answer 22

Muscimol is an agonist of GABAa channels and can induce dissociative effects. In contrast, benzodiazepines and alcohol of allosteric modulators.

Question 23

How do people misuse inhalants?

Answer 23

-Sniffing
-Huffing
-Bagging
-Dusting

Question 24

Types of inhalants that are misused

Answer 24

-Volatile solvents (toluene, glue, kerosene, gasoline)
-Aerosols, gases, sprays
-Nitrites (poppers), and nitrous oxide
-Hydrocarbons, ketones

Question 25

Alkyl nitrate clinical pearls

Answer 25

-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

Question 26

Which population abuses volatile solvents the most?

Answer 26

Adolescents, especially in isolated communities

Question 27

What are the types of volatile substances?

Answer 27

-Toluene
-Acetone
-Benzene
-Butane

Question 28

Volatile substances clinical pearls

Answer 28

Liquid at room temperature and evaporate readily when exposed to air

Question 29

Acute effects of volatile solvent abuse

Answer 29

-Locomotor stimulation
-Euphoria
-Exhilaration

Question 30

Effects of high doses of volatile solvents

Answer 30

-CNS depression
-Respiratory depression
-Slurred speech
-Disorientation
-Weakness
-Sedation

Question 31

Effects of repeated exposure of volatile substances

Answer 31

lipid accumulation in adipose tissue and lipid-rich organs such as the brain, kdineys, adrenal glands, ovaries

Question 32

Risks of inhalant abuse

Answer 32

-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

Question 33

What is the number of inhalant-related fatalities in the United States [er year?

Answer 33

100-200

Question 34

What is sudden sniffing death syndrome?

Answer 34

-Development of fatal arrhythmias within minutes of inhalation
-Results from chronic use leading to neurotoxicity