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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Tuesday, April 10, 2012

Overview of the Classic Hallucinogenic-Psychedelic Family of Drugs

Introduction:

Source: NYAS.org
The term hallucinogen is a misnomer. Hallucination, by definition, describes a completely realistic encounter involving complex persons, objects, or entities that have absolutely no basis in reality (hallucinations are created out of imagination or thin air). Most so-called hallucinogenic drugs, including LSD, are not capable of producing such a phenomenon - they do however distort, alter, and enhance sensory input such as sight and sound. This may include seeming movements of objects already present (i.e. breathing or back & forth shifting of walls, vibrating ceiling), enhancement of colors, visual tracers (spots which follow from lights or bright objects when ones vision is shifted), enhancement of music or other sounds, or synesthesia (a bizzarre misprocessing of sight & sound, when one will hear colors and see noises).

A better term to describe such compounds is psychedelics, which is the term we will use in this piece. The term psychedelic is derived from the greek terms for psyche (i.e. "mind") and delein (i.e. "to manifest"); therefore, the term psychedelic essentially means "mind-manifesting", or a mind manifesting drug. Psychedelics have the potential to access and alter otherwise unused areas of the mind.

Psychedelics are distinct from other drugs such as stimulants, narcotics, or depressants in that rather than affecting a users degree or intensity of consciousness, or primitive emotional disposition at a basal-instinctual level, psychedelics modulate a users perception or quality of consciousness, at a more executive level - i.e. they alter higher brain functions such as awareness and thinking as opposed to mood and arousal. To oversimplify it; we could think of habit forming depressants or stimulants as mood altering substances, while psychedelics could be seen more as mind altering substances.

Classic Psychedelics:

The traditional family of classic psychedelics includes some of the most popular and widely studied drugs known. The "classic" psychedelics usually fall under the chemical categories of tryptamine, ergoline, or phenethylamine. Tryptamine compounds are structural analogues of serotonin (which itself is 5-hydroxytryptamine, or 5HT), while phenethylamines are structural analogues of the catecholamine transmitters dopamine and norepinephrine.

Most classic psychedelics are structurally
similar to the monoamine neurotransmitters
The "classic" sub-family of psychedelics includes the following popular drugs:

LSD - A lysergamide alkaloid with potent psychedelic properties. Derived from ergotamine. Structurally similar to tryptamines, but is a larger and more complex molecule.

Psilocybin - A tryptamine alkaloid with psychedelic properties. It is the major active constituent in most "magic mushrooms".

DMT - A tryptamine alkaloid with short acting but potent psychedelic properties. Found naturally in mammals as well as plants. It is present in the human brain as a minor neurotransmitter.

Mescaline - A phenethylamine alkaloid with psychedelic, stimulant, and empathenogen properties. It occurs naturally in some types of cacti. It is typically derived from the peyote cactus.

The aforementioned compounds are for the most part pharmacologically similar. LSD, psilocybin, and mescaline all demonstrate a degree of pharmacological cross tolerance. Such compounds are believed to exert their consciousness altering effects via their action on the central serotonergic (5HT) system. 

Main Mode of Action:

Source: Scientopia.org
The 5HT system is composed of ascending cortical pathways and descending spinal pathways which project from a central component (or hub) in the brainstem, the raphe nuclei. Serotonergic transmissions run from the raphe nuclei to areas of the cortex and the dorsal spinal cord - where they modulate a variety of neurotransmissions (via 5HT receptors).

5HT (serotonin) is known for its supposed role in modulating the extent and intensity of moods. The 5HT receptor system is believed to exert an influence biological states of anxiety, contentment, self-perception and ego, cognition, imagination, aggression, social disposition, sleep cycle, spinal pain modulation, eating habits and appetite, secretion of the hormone/neuromodulator oxytocin (5HT1A), and regulation of smooth muscle movements in the heart and digestive tract.

The 5HT receptor consists of numerous subtypes which execute a spectrum of biological functions. One subtype in particular has been implicated in the subjective & behavioral effects of psychedelic compounds, this would be the 5HT2A receptor. 

It has been observed that LSD, psilocybin, DMT, and similar compounds similarly act at the 5HT-2A receptor, with agonist or partial-mixed agonist properties. Blocking the action of 5HT-2A receptors is shown to inhibit the effects of such compounds in test subjects.

Though the intricacies of psychedelic action through this serotonergic receptor remains vague, there is a general concensus that this is the primary site of action for most classic psychedelics. 

Distribution of the 5HT-2A Receptor:

5HT2A Receptor distribution in the brain
Source: Institute of Neuroscience & Medicine
The 5HT-2A receptor is a G-protein coupled receptor. It is but one subtype of serotonergic receptor and exhibits predominantly excitatory, though some inhibitory, effects. The mapping of the 5HT2A receptor in the brain serves to further explain the effects produced by classic psychedelics. 5HT-2A receptors are widely distributed in the following areas:

Layer V pyramidial cells (Cerebral Cortex) - Awareness, cognition & thought, language, memory attention.

Prefrontal cortex - Social behavior, planning, complex cognition (i.e. critical thinking), decision making, coordination of decisions with personal desires and goals.

Parietal cortex - Navigation, spatial sense and coordination, integration of visual sense into the body's current location or direction.

Olfactory cortex (olfactory tubercle) - Sensory reception, sensory processing and responsiveness, interaction of auditory (sound) and olfactory (smell) processing.

Somatosensory cortex - Sensory perception. Receives and thus processes and integrates various types of sensory input from cortical-thalamic projections. Perceives pain and touch.

Effects of Classic Psychedelics (With LSD as a Prototypic Model):

Low doses - Mild sensory distortions.

Moderate doses - Alterations in awareness, thought, and sensory perception.

High doses - Remarkable distortions of consciousness. Fundamental changes in awareness of ones self, environment, and reality itself. Fundamental changes in sensory perception.

The effects of a psychedelic are particularly difficult to articulate, but may be best described as follows:

Enhancement or brightening of colors, radiation of light from bright objects.

Closed eyes visuals - i.e. colorful patterns seen behind closed eyelids or in the dark. Swirling patterns behind closed eyes. 

Strange sensory perceptions that cannot be classified as touch, sound, sight, etc - a bizzarre sense of ones body and surroundings taking on a single form, a sense of being dissolved & swirled or spun as part of a surface.

Distortion of visual surroundings - i.e. morphing of objects, vibration, breathing, or rippling of surfaces such as walls and ceilings, geometric patterns along surfaces.

Distortion of time - i.e. time may seem to be perpetuating itself, to be speeding up, or to be stopping altogether. Minutes seem like hours, or perhaps the reverse; hours feel like minutes.

Distorted perception of reality and self - loss of identity or ego, altered self-awareness, the alteration or loss of understanding/knowledge as to the nature of existence itself, lack of awareness regarding ones location or the current time and setting, lack of awareness that one is actually under the influence of a psychedelic.

Distortion of thought - easily identified patterns in ones thinking, analytical thinking and subsequent realizations about ones own thoughts, bizzare thoughts about ones thoughts, etc.

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