Psychedelic Drugs Overview

Psychedelic Drugs

• Hallucinogens are a primary category of Psychedelics, causing visual hallucinations and out-of-body experiences (sensory distortions).
• Secondary effects include mood, cognitive, and physiological disturbances.
• Common hallucinogens include LSD (lysergic acid diethylamide), psilocybin (from psilocybe mushrooms), mescaline (from peyote), DMT (dimethyltryptamine), and various synthetic NBOMe analogs.
• Other hallucinogens include ololiuqui, ibogaine, Hawaiian baby wood rose seeds, salvinorin A, myristicin, bufotenine, dextromethorphan, and atropine belladonna.
• Hallucinogen use in humans dates back to religious ceremonies for communication with deities.
• LSD was synthesized in 1938 and first recognized for its potent effects in 1943 by Albert Hoffman.
• Timothy Leary's experiments with psilocybin at Harvard led to his dismissal and founding of the League of Spiritual Discovery.

LSD Pharmacokinetics (PK)

• Administered orally via blotter paper, tablets, or liquids, potentially containing additional chemicals like strychnine and amphetamines.
• A typical dose is 100 micrograms.
• Rapid absorption through the GI tract leads to effects within 30-60 minutes.
• Only about 1% of LSD reaches the brain.
• Metabolized in the liver to an inactive form with a half-life of about 3 hours.
• Effects typically last 8-12 hours.
• Eliminated via urine and feces within 72 hours.

LSD Pharmacodynamics (PD)

• Acts as a serotonin receptor agonist, with high affinity for 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors.
• Mild sympathomimetic effects (e.g., slightly increased heart rate, blood pressure, and dilated pupils).
• Potential for mild dizziness or nausea.
• Common subjective effects include pseudo-hallucinations, visual and auditory disruptions, time distortion, body distortion, synesthesia, and hyper-suggestibility.
• Enhanced emotionality and mood changes are possible.
• Little psychological dependence, with no effects on the reward pathway.
• Tolerance develops but recovers quickly after abstinence.
• Cross-tolerance with other hallucinogens is observed.

Adverse Reactions to LSD

• "Bad trips" or distressing experiences are possible, often linked to amplified emotional states.
• Panic reactions can occur due to altered perceptions and intense fear or sadness.
• Flashbacks, short recurrences of previous drug experiences, are possible.
• Hallucinogen persisting perception disorder can result in the lingering of unpleasant aspects (often visual) after abstinence.
• Effects can be mitigated with serotonin antagonists or antipsychotics like chlorpromazine.

Mixed Stimulant Psychedelics

• Drugs like MDMA (3,4-methylenedioxymethamphetamine) possess both stimulant and hallucinogenic properties.
• Other related drugs include MDEA, AMT, and 5-MeO-DIPT.

MDMA Pharmacokinetics (PK)

• Readily absorbed through the GI tract, reaching peak levels after approximately two hours.
• Metabolized in the liver with a half-life of about 9 hours, primarily converted to MDA.
• SSRI use can inhibit MDMA metabolism.

MDMA Pharmacodynamics (PD)

• Acts as a serotonin releaser and inhibits serotonin reuptake.
• Also increases dopamine release, though to a lesser extent.
• Classified as an enactogen (sense of warmth and well-being) and an empathogen (enhanced empathy).
• Causes mild sensory distortions and heightened tactile sensations.
• Rapid heart rate is a potential adverse effect.

MDMA Adverse Effects

• Neurotoxicity is a concern, particularly in animals, shown to decrease serotonin levels and 5-HIAA (serotonin metabolite) concentrations.
• 5-HT reuptake site reductions suggest serotonin neuron degradation.
• Potential effects in humans include decreased 5-HIAA levels, reduced 5-HT transporter numbers, and certain 5-HT receptor upregulation.
• Possible MDMA rebound effects, including depression and lethargy, lasting for days after use.
• Potential for longer-lasting chronic effects, including sleep disorders, depression, anxiety, impulsiveness, and memory impairment lasting up to six months.

Dissociative Anesthetics

• These drugs produce a sense of detachment from the body, including depressant and stimulant effects.
• Examples include PCP (angel dust) and ketamine.

PCP Pharmacokinetics (PK) and Pharmacodynamics (PD)

• Administered via IV, inhalation, or insufflation.
• Peak effects are dependent on administration route (5-30 minutes).
• Elimination takes 18-51 hours.
• Acts as a serotonin, dopamine, and acetylcholine noncompetitive agonist, and glutamate agonist.
• Potential side effects include amnesia, numbness, perceptual disturbances, hallucinations, and paranoia.

Ketamine

• Used as an anesthetic in animals.
• Classified as a schedule III drug in 1999.

Mental Health Disorders

• Included are anxieties (fear, worry, and distress about potential events), specific phobias, agoraphobia, panic disorder, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD).

Anxiety Disorders

• Anxiety becomes a disorder when it's maladaptive and negatively impacts daily life.
• Structures involved in fear and anxiety responses include the amygdala, prefrontal cortex, and locus coeruleus.
• Fear conditioning involves connecting stimuli to fearful events.
• Amygdala and MGN lesions impede fear responses.

Anxiolytic Drugs (Anxiety-Reducing Drugs)

• Barbiturates were early anxiolytic options, acting as positive GABA modulators, but have high risk of overdose and dependence.
• Benzodiazepines, including Diazepam (Valium) and Alprazolam (Xanax), are widely prescribed positive GABA modulators but carry risks of dependence and withdrawal.
• Z-drugs (e.g., Zolpidem, Zaleplon) are widely used for sleep and have similar GABA-enhancing mechanisms, with sleep-related complex behaviors as a risk.

Other Treatments for Anxiety and Depression

• Anticonvulsants can facilitate GABA transmission and treat seizures.
• Antidepressants, especially SSRIs and SNRIs, are a common first-line treatment for depression, but not all patients respond.
• Buspirone is a partial serotonin agonist.

Depressive Disorders

• Major depressive disorder involves five or more symptoms over two weeks.
• Persistent depressive disorder (dysthymia) has a lower severity but lasts at least two years.
• Brain alterations in depression include overactive amygdala, hippocampal volume reduction, prefrontal cortex underactivity, and nucleus accumbens underactivity.
• The monoamine hypothesis suggests insufficient monoaminergic neuron activity contributes to depression.

Antidepressant Drugs

• Monoamine oxidase (MAO) inhibitors block MAO to increase monoamines.
• Tricyclic antidepressants inhibit NE and 5-HT reuptake.
• SSRIs (e.g., Fluoxetine) block serotonin reuptake.
• SNRIs (e.g., Venlafaxine) enhance 5-HT and NE.
• Atypical antidepressants (e.g., Bupropion) have different mechanisms.
• Limitations include treatment resistance and response time (2-4 weeks).

Bipolar Disorder

• Characterized by fluctuations between depression and mania.
• Mania includes elevated mood, increased arousal, and energy.
• Treatments include mood stabilizers, such as lithium, and anticonvulsants.

Schizophrenia Spectrum & Other Psychotic Disorders

• A severe chronic disorder characterized by positive (delusions, hallucinations) and negative (flat affect, avolition) symptoms.
• The dopamine and glutamate hypotheses attempt to explain the mechanisms.
• Antipsychotics, including typical (e.g., chlorpromazine, haloperidol) and atypical (e.g., quetiapine), are used to manage symptoms.
• Third-generation antipsychotics (e.g., aripiprazole) offer a potentially lower risk profile.

This quiz explores the fascinating world of psychedelic drugs, focusing on hallucinogens and their effects. Learn about common substances like LSD and psilocybin, historical use, and key figures in psychedelics research such as Timothy Leary. Test your knowledge on the pharmacokinetics and cultural significance of these compounds.