Drugs of Abuse: Psychedelic Agents

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Drugs of AbusePsychedelic Agents

• By Nima Deljavan
• Medicinal Chemistry
• Dr. John Buynak
• March 29, 2007

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Hallucinogens

• Hallucinogenic drugs are among the oldest drugs
  used by humankind. They naturally occur in
  mushrooms, cacti, and various other plants.
• hallucinogens can be divided into three broad
  categories
• psychedelics,
• dissociatives,
• deliriants

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Psychedelics

• These classes of psychoactive drugs can cause
  subjective changes in perception, thought,
  emotion and consciousness.
• Unlike other psychoactive drugs, such as
  stimulants and opioids, psychedelics do not
  merely amplify familiar states of mind, but
  rather induce experiences that are different from
  those of ordinary consciousness.

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History and Use

• Various cultures have endorsed the use of
  hallucinogens in medicine, religion, and
  recreation to varying extents, and some have
  regulated or outright prohibited their use
• Starting in the mid-20th century, psychedelics
  have been explored as potential therapeutic
  agents in treating depression,post-traumatic
  stress disorder,alcoholism, cluster headaches,
  and other ailments
• Today, in most countries, the possession of many
  hallucinogens, even those that are common in
  nature, is considered a crime and punished by
  fines, imprisonment, or even death.

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History continued

• Starting in the mid-20th century, psychedelics
  have been the object of extensive attention in
  the Western world. They have been explored as
  potential therapeutic agents in treating
  depression, post-traumatic stress
  disorder,alcoholism, cluster headaches, and other
  ailments.
• Early military research focused on their use as
  incapacitating agents and or interrogation.
• The most popular, and at the same time most
  stigmatized, use of psychedelics in Western
  culture has been associated with the search for
  direct religious experience, enhanced creativity,
  personal development, and "mind expansion".
• The use of psychedelic drugs was a major element
  of the 1960s, where it got associated with
  various political movements, rebellion, and
  strife between generations.

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Types of Psychedelics

• Commonly applied to any drug with
  perception-altering effects such as
• LSD (derived from grain fungus that typically
  grows on rye)
• Psilocybin (present in fungi)
• Dimethyltryptamine (DMT) chemically synhesized in
  1931/occurs in plants naturally
• 2C-B (chemically synthesized)
• Mescaline (occurs naturally in the peyote
  cactus,the San Pedro cactus, and the Peruvian
  Torch cactus
• DOM (chemically synthesized)
• as well as an array of other tryptamines,
  phenethylamines and yet more exotic chemicals,
  all of which appear to act mainly on the 5-HT2A
  receptor

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Chemical Structures
2C-B
DMT
DOM
Mescaline
Psilocybin
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LSD Blotter Paper and Structure
Source www.DEA.gov
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Mushrooms
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5-HT2A Receptor

• The mammalian 5-HT2A receptor is a subtype of the
  5-HT2 receptor which belongs to the Serotonin
  receptor family and is a G-protein coupled
  receptor(GPCR).
• This is the main excitatory receptor subtype
  among the GPRC for serotonin(5-HT), although
  5-HT2A may also have an inhibitory effect on
  certain areas such as the visual cortex.
• Necessary for mechanism of the action of
  hallucinogens
• Inhibition of the firing of neurons in the visual
  cortex, which are normally involved in the
  perception of the objects, is thought to be the
  cause of the visual hallucinations produced.

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How It All Works

• As the 5-HT2A receptor is G-protein linked, the
  first step in its signaling cascade (after it is
  stimulated by an agonist) is activation of its
  associated G-protein.
• The 5-HT2A receptor has been shown to be linked
  to most major G-protein systems, but classically
  it linked to the G(q) G-protein.
• Activation of this receptor stimulates
  phospholipase C (PLC) activity, which
  subsequently promotes the release of
  diacylglycerol?(DAG) and inositol
  triphosphate?(IP3), which in turn stimulate
  protein kinase C?(PKC) activity and Ca(2)release.

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Signaling Cascade
Source Hefter Review of Psychedelic Research
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General Subjective Effects

• Many of the tryptamines and phenethylamines cause
  remarkably similar effects, despite their
  different chemical structure. However, most users
  report that the two families have subjectively
  different qualities in the "feel" of the
  experience which are difficult to describe.
• At lower doses, sensory distortions such as the
  warping of surfaces, shape shifting, and color
  variations. Users often report intense colors
  that they have not previously experienced, and
  repetitive geometric shapes are common.
• Higher doses often cause intense distortions of
  sensory perception such as synesthesia or the
  experience of additional spatial or temporal
  dimensions.
• 2C-B has extremely tight "dose curves," meaning
  the difference between a non-event and an
  overwhelming disconnection from reality can be
  very slight.

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Medicinal Possibilities and Uses

• University of Baltimore scientists are examining
  LSD as a possible treatment for addiction to
• heroin
• opium
• alcohol
• sedative hypnotics.
• University of Miami researchers are studying the
  psychedelic drug ibogaine to treat cocaine
  addiction.
• Other scientists are focusing their psychedelic
  research on learning more about the human brain,
  discovering antidotes to drug overdoses, and
  relieving pain in cancer patients.
• It's still too early to say whether the drugs
  have medicinal uses or not.

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Thank You!