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Drugs of Abuse: Psychedelic Agents By: Nima Deljavan Medicinal Chemistry Dr. John Buynak March 29, 2007 By: Nima Deljavan Medicinal Chemistry Dr. John.

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Presentation on theme: "Drugs of Abuse: Psychedelic Agents By: Nima Deljavan Medicinal Chemistry Dr. John Buynak March 29, 2007 By: Nima Deljavan Medicinal Chemistry Dr. John."— Presentation transcript:

1 Drugs of Abuse: Psychedelic Agents By: Nima Deljavan Medicinal Chemistry Dr. John Buynak March 29, 2007 By: Nima Deljavan Medicinal Chemistry Dr. John Buynak March 29, 2007

2 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, Fdeliriants  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, Fdeliriants

3 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.  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.

4 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.  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.

5 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.  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.

6 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  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

7 Chemical Structures 2C-BDMT Psilocybin DOM Mescaline

8 LSD Blotter Paper and Structure Source:

9 Mushrooms

10 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.  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.

11 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 ハ (DAG) and inositol triphosphate ハ (IP3), which in turn stimulate protein kinase C ハ (PKC) activity and Ca(2+)release.  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 ハ (DAG) and inositol triphosphate ハ (IP3), which in turn stimulate protein kinase C ハ (PKC) activity and Ca(2+)release.

12 Signaling Cascade Source: Hefter Review of Psychedelic Research

13 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.  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.

14 Medicinal Possibilities and Uses  University of Baltimore scientists are examining LSD as a possible treatment for addiction to … Fheroin Fopium Falcohol Fsedative hypnotics. F University of Miami researchers are studying the psychedelic drug ibogaine to treat cocaine addiction. FOther scientists are focusing their psychedelic research on learning more about the human brain, discovering antidotes to drug overdoses, and relieving pain in cancer patients. FIt's still too early to say whether the drugs have medicinal uses or not.  University of Baltimore scientists are examining LSD as a possible treatment for addiction to … Fheroin Fopium Falcohol Fsedative hypnotics. F University of Miami researchers are studying the psychedelic drug ibogaine to treat cocaine addiction. FOther scientists are focusing their psychedelic research on learning more about the human brain, discovering antidotes to drug overdoses, and relieving pain in cancer patients. FIt's still too early to say whether the drugs have medicinal uses or not.

15 Thank You!


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