Psyc 383: Hallucinogens Insights

Psyc 383: Lecture 9 - Hallucinogens

• Psychopharmacology lecture covering hallucinogens, specifically psychedelics and dissociatives.

The Liminality Crisis

• Liminal states of mind are subjective crisis points, representing the apex of uncertainty in perception or belief.
• Individuals experience challenges to their assumptions about reality during these states.
• Questions arise such as whether the mind is perceiving or creating reality, the boundaries between self and environment, and the nature of one's identity.
• Possible outcomes of intense liminal crises include panic, paranoia, denial, surrender, (pan-)agnosticism, and courage/wisdom.

Psychedelics

• The key feature distinguishing psychedelic agents from other drugs is their reliable ability to induce altered perceptions, thoughts, and feelings, typically not experienced otherwise, except in dreams or times of religious exaltation (Jerome Jaffe, 1990).

Drugs and Dream Similarity (Sanz et al., 2018)

• Studies show similarities between drug-induced states and dream states.
• Graphs and data visualizations illustrate the degree of similarity between different substances and dream states, categorized by classes of psychedelic drugs.

Brief History of Psychedelics

• The timeline traces the isolation, synthesis and discovery of various psychedelic drugs (mescaline, psilocin/psilocybin, LSD, and ketamine)
• Key figures and dates are highlighted highlighting developments in their synthesis, initial studies, clinical trials, regulation, and their status.

History of Psychedelics

• Psychedelics have been used by indigenous cultures for millennia.
• The term "psychedelic" was coined by Humphrey Osmond and Aldous Huxley.
• Key milestones include the isolation of mescaline, the synthesis of MDMA, and LSD, as well as their history of use in therapy.

Clinical History of Psychedelics

• Early researchers termed psychedelics "psychotomimetics" due to their ability to induce schizophrenic-like symptoms.
• Clinical applications include the treatment of alcoholism and other addictions, autism, and couples counseling.

Classes of Psychedelic Drugs

• Two primary structural classes, phenethylamines and tryptamines, differ in minor functional details.

Phenethylamines: Mescaline

• Mescaline is a prototypical psychedelic phenethylamine found in cacti (peyote and San Pedro).
• It has a half-life of approximately 6 hours.
• Commonly used and legally protected in certain Native American religious practices.
• Introduced to Western society by Aldous Huxley, who described experiences of visual fractals, synaesthesia, and altered time perception.

Phenethylamines: MDMA, MDA, etc.

• Often referred to as entactogens.
• Potent releasers of monoamines (serotonin, dopamine, norepinephrine).
• Exhibit affinity for various receptors, including serotonin and dopamine receptors.
• Can be neurotoxic at high doses.
• Associated with effects like euphoria, increased empathy, and emotional contagion.

Substituted Phenethylamines

• The 2C-X family of compounds have similar structures but vary in the placement of the substituent group on the aromatic ring.
• NBOMe compounds are also in this family but have a benzyl ring, resulting in a change in affinities.

Tryptamines: Psilocybin

• Naturally derived from the psilocybe genus of mushrooms.
• Psilocybin rapidly converts to psilocin (psychoactive).
• Considered one of the least harmful illegal drugs.
• Found in various religious or cultural practices.
• About 12% of North American adults have used psilocybin.

Tryptamines: Bufotenin

• Found in the skin secretions of the Sonoran desert toad (Bufo alvarius).
• A psychedelic tryptamine.
• Similar properties to other tryptamines but less commonly used due to the difficulty in obtaining the toad.

Tryptamines - DMT, 5-MeO-DMT

• Ayahuasca is a brew used by indigenous South American peoples to induce psychedelic effects.
• Contains DMT as a primary psychoactive constituent, along with harmine/harmaline (MAO inhibitors).
• 5-MeO-DMT is also found in various plants and other species.

Lysergic Acid Diethylamide (LSD-25)

• Naturally derived from a fungus that infects rye.
• Key event: "Bicycle Day" when Albert Hofmann accidentally discovered LSD's psychedelic effects.

Bicycle Day - April 19, 1943

• Albert Hofmann's experience on April 19, 1943, when he first explored the psychedelic effects of LSD.

LSD

• The substance derived from ergot, a fungus.
• Different forms exist (e.g., crystallized, blotter paper).
• Has varied uses from a therapeutic perspective to illicit uses due to its diverse effects.

Psychological Effects of Psychedelics

• Experiences vary depending on dose, setting, and individual factors.
• Qualitative experience patterns across different psychedelic substances include peak experiences, afterglow, and residual effects.
• Many experiences are significantly related to altered states of consciousness, frequently accompanied by mystical or ecstatic states.
• Some experience anxiety and despair.

Psychological Effects: Perception

• Visual perception can be affected, including binocular rivalry, color enhancement, and changes in visual perception due to drug use.
• Changes in time perception, auditory perceptions (e.g., heightened responses to music), and sleep (including REM cycles and slow-wave sleep).

Psychological Effects: Personality

• Psilocybin use leads to significant increases in openness to experience.
• Follow-up studies show increased extraversion and conscientiousness, and some decrease in neuroticism potentially due to the substance.

Psychedelics and Nature-Relatedness

• Studies have shown a link between psychedelic use and heightened nature-relatedness.
• Psychological dimensions of nature-relatedness increased after psilocybin use.
• Authoritarianism/liberalism views also change.

Psychological Effects: "Mystical"

• Psychedelic experiences often involve a sense of profound understanding, self-transformation, and connection with a higher power/reality.
• A wide range of mystical experiences can be induced, frequently resulting in a sense of religious or spiritual significance.
• Several studies compare the mystical experience to that of non-drug users.

Mechanisms of Action

• Psychedelic drugs act as agonists for the 5-HT2A receptors.
• This action, while necessary, isn't sufficient for their effect.
• Different psychedelic classes have varying pharmacological properties affecting receptors in different ways.

Neurophysiology

• Psychedelics impact brain regions like the thalamus, ACC, PCC, and medial prefrontal cortex, influencing areas related to ego-dissolution or ego-loss.
• Functional connectivity changes.
• Patterns differ and can be measured and analyzed.

Novel Functional Dynamics

• Psychedelics fundamentally change the transition dynamics between brain states.
• A significant change in the probabilistic state transitions occur both before and after psychedelic use.

REBUS - Relaxed Beliefs Under Psychdelics

• This is a recently proposed model of how psychedelics work.
• It incorporates elements of the Free-Energy Principle, Hierarchical Predictive Coding, Bayesian Brain Hypothesis, and Entropic Brain Hypothesis.

Hierarchical Predictive Coding

• This model of brain function involves hierarchical levels processing bottom-up sensory data and top-down predictions, with psychedelics altering sensory data.

The Entropic Brain Hypothesis

• Conscious states can be placed on a spectrum from rigid to flexible, represented by entropy levels.
• Increased functional connectivity is associated with psychedelic use.

Clinical Applications: Anxiety & Depression

• Studies show significant reductions in anxiety and depression, particularly in end-of-life scenarios or treatment-resistant patients. Clinical improvements in psychological outcomes.

Clinical Applications: Depression

• Studies show significant depressive symptom reductions in treatment-resistant patients following psilocybin treatment and psychotherapy.

Clinical Applications: PTSD

• MDMA treatment is being researched and shows promise as a potential therapy for patients with PTSD where the effects persist over a long period.
• Changes in symptoms such as functional impairment, and mental wellbeing, are documented.

Biopsychosocial Healing

• Psychedelic uses are potentially linked to psychological outcomes, such as reduced crime, altered suicidality among women, and improved mental health in general.

Dissociatives

• Dissociatives are substances that produce feelings of detachment from self, environment, and reality, often characterized by significant psychological effects.

Salvia Divinorum

• A plant native to Oaxaca, Mexico, with the psychoactive compound salvinorin A, an opioid к receptor agonist.

Ibogaine

• A plant-derived compound with pharmacology in treatment-resistant addictions, often notably alcohol and opioid addictions.

Dextromethorphan (DXM)

• A common over-the-counter cough medicine with opioid-like and PCP-like characteristics and potential antidepressant effects at higher doses.

Phencyclidine (PCP)

• A potent dissociative with high abuse potential, affecting NMDA receptors and other neurotransmitter systems. Affects brain areas and associated with subjective and behavioral effects.

Ketamine

• A dissociative, often used for medical sedation.
• There is ongoing research on its potential for treating depression and other mood disorders, potentially associated with neurotoxic effects at high doses.