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
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
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
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
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
PCP = angel dust
Diverse pharmacological mechanisms
underlying these different subclasses
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)
One of the prototypic MA-related
One of the most controversial illegal
substances in our society in recent years,
particularly because of the "double-edged
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
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.
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
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
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.
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
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
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
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,
o Remains one of the most popular recreational drugs today.
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
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-
In addition to changes in
Ecstasy can induce
damage to serotonergic
Ecstasy: Short-term effects
o Acute effect of ecstasy; pleasure, hedonic
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.
o Due to its effects on the cortex, which is involved in inhibition.
Increased sensitivity to touch
o Heightened touch sensation
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
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
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
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.
between popularity of drug
and number of emergency
room incidents related to
MDMA use, like stroke,
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