Psychedelic Drugs Overview

Psychedelic Drugs

• Psychedelic drugs are psychoactive substances that cause perceptual changes, visual hallucinations, altered awareness of the mind and body, and cognitive distortions, without toxic delirium.
• Many are synthesized from plants or plant-derived compounds.
• Examples include LSD, mescaline, psilocybin, bufotenine, DMT, 5-MeODMT, salvinorin (from Salvia), and ibogaine.

Mescaline

• Mescaline is found in the peyote cactus.
• Peyote buttons (dried tops) are chewed raw or cooked.
• Native Americans use peyote in religious and healing rituals.
• Pure mescaline can be synthesized, becoming popular in the 1960s.

Psilocybin

• Psilocybin is an alkaloid found in various mushroom species.
• It's consumed dried and raw, or as a tea.
• Psilocybin converts to psilocin (the psychoactive compound) in the body.
• The use of psilocybin dates back thousands of years.
• The Harvard Marsh Chapel Experiment used psilocybin to induce profound religious experiences in graduate students.

DMT and Ayahuasca

• DMT, 5-MeO-DMT, and bufotenine are found in South American plants.
• When smoked or snorted, DMT produces a brief (30-minute) intense hallucinatory experience.
• Synthetic DMT analogs are orally active.
• Ayahuasca is a hallucinogenic drink made from plants containing DMT and alkaloids (β-carbolines) that inhibit MAO activity.
• Ayahuasca use dates to pre-Columbian times, used in spiritual/religious ceremonies.

Lysergic Acid Diethylamide (LSD)

• LSD is a synthetic drug derived from ergot alkaloids (in the parasitic rye fungus).
• Long-term ergot poisoning causes ergotism (convulsions and gangrene).
• Ergot alkaloids can also trigger labor and reduce post-birth uterine hemorrhage.
• LSD was initially synthesized in search for circulatory and respiratory stimulants.
• Some researchers explored LSD in psychotherapy and psychoanalysis.

Ibogaine

• Ibogaine comes from the bark and roots of a West African shrub.
• It's chewed or made into a powder.
• Low doses are psychostimulants (increasing energy, reducing hunger, creating euphoria).
• High doses induce psychedelic effects.
• Ibogaine, under controlled conditions, can counteract opioid withdrawal symptoms and cravings.

Salvinorin A and Ketocyclazocine

• Salvinorin A is a psychoactive compound found in Salvia divinorum (sage of the diviners).
• It's historically used in religious rituals by Mazatec shamans.
• The leaves are chewed or extracted, absorbed orally or smoked.
• Salvinorin A is inactivated in the gastrointestinal tract.
• Salvinorin A and ketocyclazocine produce vivid hallucinations, out-of-body experiences, and similar effects to other hallucinogens.
• They act through kappa opioid receptors.

General Psychedelic Effects

• Potency varies among types.
• Oral effects begin in 30-90 minutes, lasting from minutes to hours.
• A "trip" involves four phases: onset, plateau, peak, and comedown.
• Users experience visual hallucinations, altered time perception, depersonalization, strong emotions, and disrupted logic.
• Synesthesia (crossing of senses) is possible.
• Trips can be mystical or disturbing.

Altered States of Consciousness (ASC) Rating Scale

• The ASC scale measures five dimensions of experience: oceanic boundlessness, ego-disintegration anxiety, visionary restructuralization, reduced vigilance, and auditory alterations.
• Subdimensions provide more detailed analysis of drug-induced reactions.

Physiological Responses

• Physiological responses include sympathetic nervous system activation, dizziness, nausea, and vomiting (possible with mushrooms and peyote).

Chemical Structures

• Many psychedelic drugs share a serotonin-like (indolamine) molecular structure (LSD, psilocybin, psilocin, DMT, 5-MeO-DMT, ibogaine).
• Some have a catecholamine-like structure (mescaline, synthetic phenethylamines).

Neurobiology Mechanisms

• 5-HT2A receptor activation is crucial for many effects.
• Psychedelics activate a trigger population of glutamatergic neurons, disrupting a brain loop.
• Some hallucinogens act on opioid pathways.

Medical Uses

• LSD was previously studied as an alcohol treatment.
• Recent research explores long-term psychological effects and potential for treating depression, OCD, and PTSD.

Adverse Reactions

• Psychedelics are not typically addictive but a few users may meet diagnostic criteria for hallucinogen use disorder.
• Tolerance develops with repeated use, potentially leading to receptor downregulation.
• Adverse effects include bad trips, flashbacks, and hallucinogen persisting perception disorder (HPPD).
• High doses can cause toxic reactions.

Dissociative Anesthetics (PCP and Ketamine)

• PCP and ketamine are uncompetitive NMDA antagonists.
• PCP was initially developed as an anesthetic but has significant adverse effects.
• Ketamine is a safer alternative, used clinically and in veterinary medicine.
• Both produce a "dissociated state" at anesthetic doses.
• Subjective experiences include light, visions, loss of time sense, body distortions, and feelings of detachment.

Pharmacology of PCP and Ketamine

• They block ion flow in NMDA receptors.

Models of Schizophrenia

• LSD and PCP/ketamine models have been developed to study schizophrenia.
• The glutamate hypothesis suggests that hypofunction of the glutamatergic system contributes to schizophrenia.

Recreational Use and Chronic Effects

• PCP and ketamine have potential for recreational use.
• Chronic use can lead to urological issues, GI disturbances, cognitive impairment, and possible psychosis.
• Alternative uses for chronic pain/depression.

Cannabis

• Cannabis exhibits stimulant and depressant effects, with potential for hallucinogen-like effects.
• Medicinal uses vary depending on cannabinoid composition (THC, CBD).
• Consumption produces dose-dependent intoxication with a series of stages.
• Cannabis impairment of learning/memory is related to effects on the glutamatergic system.

Cannabis Use Disorder (CUD)

• Regular users exhibit tolerance and cognitive impairment.
• Mechanisms may include CB1 receptor desensitization, reduced glutamate, striatal dopaminergic dysfunction, and withdrawal symptoms (similar to nicotine).

Long-Term Cannabis Use Effects

• Long-term use can impact cognitive domains, especially if initiated in adolescence.
• Possible link between early cannabis use and reduced educational/occupational achievement.

Brain Changes with Long-Term Use

• Cannabis use is associated with changes in brain structure (volume) and function.

Psychoses and Antipsychotic Medications

• Psychoses are conditions involving difficulty distinguishing reality.
• Antipsychotic medications treat disorders of the schizophrenia spectrum.
• Schizophrenia features both positive (delusions, hallucinations) and negative (reduced emotional expression) symptoms.

Diagnosing Schizophrenia

• Diagnoses can be challenging due to varied symptom patterns.
• Symptoms change over time and intensity.

Schizophrenia Brain Abnormalities

• Brain imaging shows structural changes (atrophy, ventricle enlargement).
• Functional changes exist, such as reduced prefrontal cortex activity or changes in abnormal activation.
• Possible associations between immune dysfunction and schizophrenia.

Genetic and Developmental Aspects

• Strong genetic component in schizophrenia.
• Early life stress can lead to epigenetic changes.
• Neurodevelopmental factors are crucial (e.g., prenatal inflammation, viral infections).

Models of Schizophrenia

• Animal models investigate specific aspects of the disorder.

Dopamine Hypothesis

• The dopamine imbalance hypothesis suggests positive symptoms relate to excessive mesolimbic dopamine activity; negative symptoms are due to reduced mesocortical dopamine.

Glutamate and Other Neurotransmitters

• The glutamate hypothesis points to inadequate glutamate levels.

Neuroleptics and Antipsychotics

• Antipsychotics are used to treat schizophrenia, with differing effects on individuals.
• Classic neuroleptics (phenothiazines, butyrophenones) have significant side effects.
• Newer atypical antipsychotics are sometimes more effective with fewer side effects.

Antipsychotic Mechanisms

• Dopamine receptor antagonism is a key mechanism of antipsychotic action.
• Antipsychotics affect several neurotransmitter receptors.

Antipsychotic Side Effects

• Side effects, such as Parkinsonian symptoms, neuroendocrine effects, and tardive dyskinesia, can be significant.

Atypical Antipsychotics

• Atypical antipsychotics have different mechanisms and/or affect other receptors.

Clinical Trials

• Pragmatic clinical trials offer real-world insights.
• Some trials have found limitations in effectiveness of newer antipsychotics.

Potential New Approaches

• There are a range of research directions attempting to address the challenges of treating schizophrenia.

Explore the fascinating world of psychedelic drugs, including their effects on perception and cognition. Learn about well-known substances like mescaline and psilocybin, their sources, uses in rituals, and historical significance. This quiz provides insights into these mind-altering compounds and their cultural contexts.