Psychedelic drugs

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states-psychedelic experiences or psychedelic trips, and/or an apparent expansion of consciousness.

The most popular names—hallucinogen, psychotomimetic, and psychedelic are often used interchangeably. 

Psychedelics are scheduled 1 controlled substances. 

Considered to have no currently accepted medical use and a high potential for abuse.

Psychedelics produce changes in cognition, perception, and affect. 

Psychedelics may be synthesized, such as LSD, and others may be botanical drugs, consisting of plant or fungal material, such as psilocybin producing mushrooms. 

Psychedelics have a potential risk of valvular disease with the drugs having a high affinity for serotonin receptors. 

Psychedelics are also called classic hallucinogens, serotonergic hallucinogens, or serotonergic psychedelics, and may include various types of hallucinogens or those which are atypical or adjacent to psychedelia such as salvia and MDMA.

Psychedelics cause specific psychological, visual, and auditory changes, and may a substantially altered the state of consciousness.

Psychedelics with the largest scientific and cultural influence, are mescaline, LSD, psilocybin, and DMT.

In particular, LSD has long been considered the paradigmatic psychedelic compound.

Psychedelic drugs fall into one of the three families of chemical compounds: tryptamines, phenethylamines, or lysergamides.

LSD is considered both a tryptamine and lysergamide.

They act via serotonin 2A receptor agonism.

These compounds bind to serotonin 5-HT2A receptors, and modulate the activity of key circuits in the brain involved with sensory perception and cognition. 

The psychedelic experience is often compared to non-ordinary forms of consciousness:meditation, mystical experiences,  and near-death experiences, which also appear to be partially underpinned by altered default mode network activity.

A key feature of the psychedelic experience is ego death.

Studies show that psychedelics are physiologically safe and rarely lead to addiction.

Studies using psilocybin in a psychotherapeutic setting reveal that psychedelic drugs may assist with treating depression, alcohol addiction, and nicotine addiction.

Psychedelics could be effective treatments for certain forms of psychopathology.

A 2022 survey found that 28% of Americans had used a psychedelic at some point in their life.

Psychedelic therapy is the proposed use of psychedelic drugs to treat mental disorders.

Ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder, anxiety and depression linked to terminal illness.

The FDA  has granted breakthrough therapy status to psilocybin therapy for treatment-resistant depression and major depressive disorder.

Recreational use of psychedelics is common.

Psychedelic microdosing is using microdoses of psychedelics in an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction.

Psychedelics show affinities for various 5-HT (serotonin) receptors in different ways.

 Psychedelics may be classified by their activity at different 5-HT sub-types, particularly 5-HT1A, 5-HT2A, and 5-HT2C.

Psychedelics produce their effect by acting as strong partial agonists at the 5-HT2A receptors,  likely acting by increasing excitation in the cortex, by facilitating input from the thalamus, the major relay for sensory information input to the cortex.

Psychedelics are also potent psychoplastogens, compounds capable of promoting rapid and sustained neural plasticity.

Tryptamine, along with other trace amines, is found in the central nervous system.

Tryptamine is hypothesized to play a role as a neuromodulator on classical monoamine neurotransmitters, such as dopamine, serotonin, and norepinephrine, epinephrine.

Tryptamine acts as a non-selective serotonin receptor agonist to activate serotonin receptors, and a serotonin–norepinephrine–dopamine releasing agent to release more monoamine neurotransmitter.

Mescaline is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class.

Phenethylamine acts as a neurotransmitter in the human central nervous system (CNS), regulating monoamine neurotransmission playing a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS.

 It inhibits vesicular monoamine transporter 2 (VMAT2) in monoamine neurons such as dopamine, which cannot be released into the synapse via typical release mechanisms.

Amides of lysergic acid are lysergamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors. 

Lysergamides contain both Tryptamine and Phenethylamine structures.

At low doses, psychedelic experiences include sensory alterations, such as the warping of surfaces, shape suggestibility, pareidolia, color variations, intense colors that they have not previously experienced, and repetitive geometric shapes or form constants are common as well. 

Higher doses often cause alterations of sensory, visual perception, spatial or temporal dimensions.

Tryptamines cause classic psychedelic states, such as increased empathy, visual distortions, auditory hallucinations, ego dissolution or ego death with high enough dose, mystical, transpersonal and spiritual experiences, autonomous encounters, time distortion, closed eye hallucinations and complete detachment from reality with a high enough dose.

Negative experiences, known as “bad trips,” is associated with dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation.

Psychedelics are considered to be those found in nature like psilocybin, DMT, mescaline, and LSD which is derived from naturally occurring ergotamine.

Non-classic psychedelics are considered to be newer analogs and derivatives of pharmacophore lysergamides, tryptamine, and phenethylamine structures.

Many psychedelics cause similar effects, despite their different chemical structure. 

Psychedelic drugs are not addictive and are physiologically safe, with few or any deaths due to overdose of LSD, psilocybin, or mescaline.

However, risks exist during an unsupervised psychedelic experience, there is a range of negative reactions: fear, a prolonged sense of dread, or full panic, driving or even walking in public can be dangerous during a psychedelic experience because of impaired hand-eye coordination and fine motor control, performance of dangerous or fatal acts because they believed they possessed superhuman powers.

Psycodelic-induced states of mind share features with states experienced in psychosis, however there no evidence that psychedelic use is associated with increased prevalence of any mental illness.

Using psychedelics poses certain risks of re-experiencing of the drug’s effects, including flashbacks and hallucinogen persisting perception disorder (HPPD), but the permanent symptoms/endless trip are considered to be rare.

Serotonin syndrome can be caused by combining psychedelics with other serotonergic drugs, including certain antidepressants, opioids, CNS stimulants, 5-HT1 agonists and herbs.

Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline: obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), alcoholism, depression, and cluster headaches.

Psychedelics promote neurite growth and neuroplasticity and are potent psychoplastogens, and can induce molecular and cellular adaptations related to changing neurons and that these could potentially underlie therapeutic benefits.

Psychedelics have anti-inflammatory activities and therapeutic effects in animal models of inflammatory diseases including asthma, and cardiovascular disease and diabetes.

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