Hallucinogens like LSD act on serotonin receptors in the brain and cause altered perceptual states. Their effects interfere with rational thought. LSD specifically stimulates serotonin 5-HT1 and 5-HT2 receptors. THC, the main active compound in marijuana, binds to CB1 receptors and causes euphoria, relaxation, and memory impairment. It has a wide range of effects and is metabolized and eliminated primarily through the liver. Ethanol enhances GABA and endogenous opioid effects and alters serotonin and dopamine levels. It is metabolized in the liver but chronic abuse can damage many organ systems. Withdrawal from heavy drinking can be life-threatening without medical management.

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VIJAY SALVEKAR
DEPT. OF PHARMACOLOGY
GRY INSTITUTE OF PHARMACY
Hallucinogens

2. II. Hallucinogens (psychotomimetic)
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 A few drugs have the ability to induce altered
perceptual states reminiscent of dreams, are
accompanied by bright, colourful changes in the
environment and by a plasticity of constantly changing
shapes and colour.
 The individual under the influence of these drugs is
incapable of normal decision making, because the
drug interferes with rational thought.

3. A. Lysergic acid
diethylamide
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 Multiple sites in the CNS are affected by lysergic acid
diethylamide (LSD).
 The drug shows serotonin (5-HT) agonist activity at
presynaptic 5-HT1 receptors in the midbrain, and also
stimulates 5-HT2 receptors.
 Activation of the sympathetic nervous system occurs,
which causes pupillary dilation, increased BP,
piloerection, and increased body temperature.

4. A. LSD Adverse effects:
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 include hyperreflexia, nausea, and muscular weakness.
 High doses may produce long-lasting psychotic changes
in susceptible individuals.
 Haloperidol and other neuroleptics can block the
hallucinatory action of LSD and quickly abort the
syndrome.

5. B. Tetrahydrocannabinol (THC)
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 The main psychoactive alkaloid contained in marijuana is
tetrahydrocannabinol (THC), which is available as
dronabinol.
 THC can produce euphoria, followed by drowsiness and
relaxation.
 The effects of marijuana on γ-aminobutyric acid (GABA)
in the hippocampus diminish the capacity for short-term
memory in users
 decreases muscle strength
 and impairs highly skilled motor activity, such as that
required to drive a car.
 Its wide range of effects includes: appetite stimulation,
xerostomia, visual hallucinations, delusions, and
enhancement of sensory activity

6. Mechanism of action:
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 THC receptors, designated CB1 receptors, have been
found on inhibitory presynaptic nerve terminals. CB1 is
coupled to a G protein.
 Interestingly, endocannabinoids have been identified in
the CNS.
 These compounds, which bind to the CB1 receptors, are
membrane-derived and are synthesized on demand,
and they may act as local neuromodulators.

7. Mechanism of action:
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8. Pharmacokinetics:
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 The effects of THC appear immediately after the drug
is smoked, but maximum effects take about 20
minutes. By 3 hours, the effects largely disappear.
 Dronabinol is administered orally and has a peak effect
in 2 to 4 hours. Its psychoactive effects can last up to 6
hours, but its appetite-stimulant effects may persist for
24 hours.
 It is highly lipid soluble and has a large volume of
distribution.
 THC itself is extensively metabolized by the mixed-
function oxidases.
 Elimination: is largely through the biliary route.

9. Therapeutic uses of
Dronabinol
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1. as an appetite stimulant for patients with
acquired immunodeficiency syndrome who
are losing weight.
2. It is also sometimes given for the severe
emesis caused by some cancer
chemotherapeutic agents.
Adverse effects: include increased heart rate,
decreased blood pressure, and reddening of
the conjunctiva.
 At high doses, a toxic psychosis develops.
Tolerance and mild physical dependence
occur with continued, frequent use of the
drug.

10. Rimonabant:
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Rimonabant: The CB1-receptor antagonist,
1. Obesity (decrease appetite and body weight in humans).
2. induce psychiatric disturbances, such as anxiety and
depression, during clinical trials.

11. Phencyclidine:
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 Phencyclidine (also known as PCP, or “angel dust”)
 inhibits the reuptake of dopamine, 5-HT, and
norepinephrine.
 The major action of phencyclidine is to block the ion
channel regulated by the NMDA subtype of glutamate
receptor. This action prevents the passage of critical
ions (particularly Ca2+) through the channel.
 Phencyclidine also has anticholinergic activity but,
surprisingly, produces hypersalivation.

12. Phencyclidine:
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 Phencyclidine, an analog of ketamine, causes
dissociative anesthesia (insensitivity to pain, without
loss of consciousness) and analgesia.
 At increased dosages, anesthesia, stupor, or coma
result, but strangely, the eyes may remain open.
Increased sensitivity to external stimuli exists, and the
CNS actions may persist for a week.

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14. III. Ethanol
(EtOH)
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 Alcohol is the most commonly abused substance in
modern society.
 Alcoholism decreases life expectancy by 10 to 15 years.
 Ethanol exerts its desired and toxic effects through:
 enhancing the effects of the GABA,
 inducing the release of endogenous opioids,
 and altering levels of serotonin and dopamine.
 Ethanol is a selective CNS depressant at low doses,
resulting in decreased inhibitions and the characteristic
drunken behavior.
 At high doses, it is a general CNS depressant, which can
result in coma and respiratory depression.

15. Ethanol
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Ethanol is absorbed from the stomach and duodenum, and
food slows and decreases absorption.
Peak ethanol levels are generally achieved in 20 minutes to
1 hour of ingestion.
Ethanol is metabolized by alcohol dehydrogenase to
acetaldehyde and then by aldehyde dehydrogenase to
acetate in the liver.
It is metabolized by zero-order elimination at approximately
15 to 40 mg/dL/h.
There is a constant blood-to-breath ratio of 2100:1.
Medical management of acute ethanol toxicity includes
symptomatic supportive care and the administration of
thiamine and folic acid to prevent/treat Wernicke
encephalopathy and macrocytic anemia.

16. Ethanol
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Chronic ethanol abuse can cause profound hepatic,
cardiovascular, pulmonary, hematologic, endocrine,
metabolic, and CNS damage.
Sudden cessation of ethanol ingestion in a heavy drinker
can precipitate withdrawal manifested by tachycardia,
sweating, tremor, anxiety, agitation, hallucinations, and
convulsions.
Alcohol withdrawal is a life-threatening situation that should
be medically managed with symptomatic/supportive care,
benzodiazepines, and long-term addiction treatment.

17. Drugs used in the treatment of alcohol
dependence:
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A.Disulfiram blocks the oxidation of acetaldehyde to
acetic acid by inhibiting aldehyde dehydrogenase. This
results in the accumulation of acetaldehyde in the blood,
causing flushing, tachycardia, hyperventilation, and
nausea.
B.Naltrexone Naltrexone is a long-acting opioid
antagonist that should be used in conjunction with
supportive psychotherapy. Naltrexone is better tolerated
than disulfiram.
C. Acamprosate should also be used in conjunction with
supportive psychotherapy.