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University of Toronto Scarborough
Suzanne Erb

PSYC62: Drugs and the Brain Lecture 9: Dissociative Anesthetics, Psychedelics, & Hallucinogens  Hallucinogens is the most commonly used name for this class of drugs  Refer to the fact that they can produce hallucinations and other alterations in perception and sensory alterations.  Advocates of hallucinogenic use referred to them as psychedelics (like LSD) to refer to their mind- expanding or altering properties, but whether these drugs have these properties is controversial, so we don't use this term anymore  Some would argue that even the term hallucinogen is misleading because they produce other effects, like profound effects on mood, on thinking processes, on some physiological processes, not just hallucinations. But inducing hallucinations is the hallmark characteristic Dissociative Anesthetics, Psychedelics, Hallucinogens  These drugs are capable of inducing hallucinations, and have consciousness-altering and perception-altering properties o More than 90 different plants and many more synthetic agents that can produce these hallucinations, this is why we subdivide them into different organizations/classification  Four major classes of hallucinogens (Grilly, 2002): 1. Monoamine-related substances (e.g., LSD, MDMA, mescaline, and psilocybin)  LSD is a synthetic drug, prototypic hallucinogens  aka serotonergic hallucinogens (because the primary MA system they affect is the 5HT system)  Mescaline an psolcybin are LSD-like 2. Cannabinoids (e.g., marijuana, hashish)  Not always considered as a subclass, sometimes considered a family of their own 3. Anticholinergics (e.g., atropine, scopalamine, belladonna)  Less familiar to most people than the previous two. Act on cholinergic receptors in the brain and their hallmark effect is to produce a dream-like trance from which the user awakens with very little recollection of the experience. Messes with systems involved with memory 4. Dissociative anesthetics (e.g., PCP, ketamine)  Ability to produce surgical anesthesia without the patient losing complete consciousness  They maintain a semi-conscious state with these drugs. Affect receptors in the glutamate system  PCP = angel dust  Diverse pharmacological mechanisms underlying these different subclasses Figure 1  Monoamine hallucinogens are mostly schedule I drugs  LSD is schedule III in Canada  Canabinoids are schedule II in Canada and I in the US (1) Monoamine-related substances (e.g., LSD, MDMA, mescaline, and psilocybin) Ecstasy  One of the prototypic MA-related substances drug.  One of the most controversial illegal substances in our society in recent years, particularly because of the "double-edged sword" properties.  In the past it has been considered for its potential therapeutic purposes for treatment of anxiety and PTSD  However it has mood altering and dependence properties, and toxic effects  Also part of the controversy is the fact that it's such a new drug, not enough time to characterize and understand its effects  It's a relatively new drug in that it was not popular at all before the late 1990s. At that time there was a huge increase in popularity.  Figure on the right is the percentage of high school students reporting MDMA use  in their senior year. In 1996, more than 4%, and then a fairly big increase in the next few years until 2001.  After 2001 usage declined to the same level as that in the late 90s  One of the reasons for this decline is the advertising of the dangers of MDMDA, such as claims of brain damage and death, although these claims are controversial.  It is generally recognized that it is a drug that is prevalent in college and university campuses. Ecstasy  Lots of young people in Canada at least experiment with this drug, warrants research into the effects of the drug.  SOME RECENT STATISTICS FOR CANADA 1  According to the 2004 CAS survey , 4.1% of Canadians aged 15 and older had used ecstasy at least once in their lifetime. That represents over 990,000 people.  According to a 2002 survey, 65.2% of those attending raves in Montreal reported having used ecstasy at least once in their lifetime.  According to a survey of street youth in sentinel sites across Canada conducted in 2003 , 10 approximately 5% of youth not using injection drugs had used ecstasy (MDMA) during the three preceding months.  According to the 2004 CAS survey , 1.1% of Canadians aged 15 and older had reported having used ecstasy in the course of the preceding year. That represents over 260,000 people. 4  According to the national 2002 survey, Health Behaviour in School-Aged Children , held in Canadian schools, 8% of boys and 5% of girls among Grade 10 students had used ecstasy during the 12 preceding months.  Statistical trend : 3% from 1998 to 2002 for boys and 3% for girls Figure 2: Ecstasy  Ecstasy is one of a group of drugs known as the methaylated amphetamines  Often categorized together as the serotonergic hallucinogens  DOM resembles mescaline in structure and produces similar effects like vivid hallucinations.  MDA, MDMDA, and MDE are more similar to amphetamine in structure and effects than DOM. The primary effects are inducing a mild state of euphoria (pleasure) accompanied by feelings of openness, empathy, lack of defensiveness, ability to identify with others' feelings and emotions.  These properties are what lead therapists to advocate use of MDMDA as an adjunct to treatment of anxiety and other psychological disorders. Figure 3 & 4: Ecstasy  Some classify this along with the hallucinogens, others with psychostimulants, because the molecular structure also very closely resembles amphetamines and have similar effects to the psychostimulants  Others group them as hallucinogens because they are unique - they do produce these hallucinations.  Ecstasy = MDMA (3,4-methylenedioxymethamphetamine) o Derivative of the amphetamine molecule.  Most typically taken orally, in tablet form. Can be injected or snorted.  Absorbed very rapidly, very long lasting (6-8 hours).  Ecstasy is unlike many of the other drugs of abuse that are often derived from plants  Ecstasy is synthesized in illegal, underground labs and involves altering the structure of the amphetamine molecule. Since it is synthesized in labs, its purity can vary from lab to lab and other compounds (contaminants) can be diluted into the tablets (like caffeine, ketamine, sometimes methamphetamines). Users can't be sure what they are consuming. It's considered a party drug, but its abuse has expanded to include other settings outside the rave scene, such as college campuses. Ecstasy: Historical perspective  It's history is quite a bit shorter than other drugs. Other drugs used for centuries with in ancient civilizations. This was not, very new.  MDMA was patented in 1914 by Merck Pharmaceuticals in Germany, but not marketed or studied until many years later o Relatively unknown until 1970s.  In the1970‟s and 80‟s, there was growing interest in the potential value of MDMA in psychotherapy o Publicity about therapeutic benefits made it attractive, and the fact that it was named 'ecstasy' was good for PR  Until 1985, MDMA was a legal drug; at this time became a Schedule I drug in U.S. o Also schedule I in Canada, prior to 1985 people perceived it wasn't as bad? But due to animals testing it's moved to schedule I on an emergency classifications? Then in 1986 it permanently moved to schedule 1.  MDMA grew in popularity in the 1990‟s, as it became associated with the “rave” scene o Alcohol isn't really involved in the rave scene, mostly MDMDA and related drugs.  By early 2000‟s, MDMA was considered fastest growing elicit drug in North America, Europe, and Australia o Remains one of the most popular recreational drugs today. Ecstasy: Pharmacology  Serotonin is a classic NT system in the mammalian CNS, cell bodies originate in the raphe nuclei in the base of the brain and project diffusely throughout the brain to a variety of limbic structures deep in the brain, the hypothalamus, into the cortex, and into the spinal cord  The system is pervasive throughout the mammalian brain and alters almost every aspect of psychological and motivational function.  MDMA exerts its effects primarily by stimulating the release of serotonin  Acts to block reuptake of serotonin and reverses serotonin transporter to stimulate release  Also stimulates the release of dopamine and noradrenaline and blocks their reuptake  Acts in a very similar way to amphetamines  Blocks reuptake of 5HT and reverses the 5HT transporter to stimulate release, all in all more 5HT available in synapse for postsynaptic binding  Binds to transporters on presynaptic terminal to prevent transporters from carrying back into terminal, and causes the transporters to work in 'reverse' mode - causes direct released of 5HT from the presynaptic cell  5HT system is the primary target of MDMA, but it has similar effects on the dopamine system and this is what causes reinforcement due to its effect on the reward system. Ecstasy: Short- and long- term effects  In addition to changes in brain chemistry.  Ecstasy can induce damage to serotonergic neurons. Ecstasy: Short-term effects  Euphoria o Acute effect of ecstasy; pleasure, hedonic  Elevated mood  Increased empathy o Very characteristic, real hallmark feature of this drug. Ability to induce feelings of empathy and warmth, identify with others' feelings and emotions o This characteristic is what lead therapists to be interested in this drug in therapy.  Decreased inhibitions o Due to its effects on the cortex, which is involved in inhibition.  Increased sensitivity to touch o Heightened touch sensation  Reduced appetite o Typical of amphetamine-like drugs (amphetamines and cocaine do this as well) Ecstasy: Short-term effects  Projection targets of 5HT neurons, effects overlap with 5HT projection pattern.  Basal ganglia, coordination of movement  Hypothalamus regulates all the vital systems of the body, MDMA has big effects on this.  Hippocampus, involved in memory and other limbic effects related to regulation of emotion Ecstasy: Short-term effects  The ability to induce empathy is missing in this slide,  because although we know the drug has the profound ability to induce empathy, research in this field is new  and we haven't shown where these effects come from.  Probably the frontal cortex which is involved in executive type functions  Could also be the limbic system, which is directly related to regulation of emotions Ecstasy: Short-term effects  Is ecstasy toxic? YES,  Especially under conditions where people take multiple doses over the course of a night, like 3 or more tablets at once called "stacking" or taking tablets in rapid succession called "piggybacking".  People do this to intensify the effects, but this increased dose also results in increased toxic effects, can cause death  Cause heat injury due to hyperthermia, hypertension (high BP), arrhythmias in heart beat, muscle and renal failure  A lot of these effects come from the effects of ecstasy on the hypothalamus which is involved in regulating many of these body functions. Ecstasy: Toxicity?  Clear correspondence between popularity of drug and number of emergency room incidents related to MDMA use, like stroke, seizure, hyperthermia, muscle/renal failure, these usually happen with high doses being ingested. Although in some individuals these effects may happen with lower doses. Ecstasy: Short-term “after” effects  MDMA not associated with dramatic physical withdrawal, but DOES produce a degree of physical and psychological dependence  Not as much physical as opiates, and not like methamphetamines which only produces psycholog
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