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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

They are also found in Atropa belladonna (deadly nightshade), Datura
stramonium (jimsonweed), and several related species throughout the world.
Cannabis is also classified as a hallucinogen, but is considered separately
in this chapter.

Behavioural effects

These drugs produce increased heart rate and blood pressure, elevated body
temperature, reduced appetite, nausea, vomiting, abdominal discomfort, rapid
reflexes, motor incoordination and pupillary dilatation (Jacobs & Fehr, 1987).
The hallucinatory effects are related to dose, and distortions of any of the
sensory modalities can occur. The melding of two sensory modalities is also
possible (e.g. music being “seen”), and is called synaesthesia (Jacobs & Fehr,
1987). These drugs also affect thought processes and memory.
The intensity of the effects, and the emotional reaction to them, differ from
person to person. Reactions can range from joy and euphoria to fear and
panic. There can be a sense of deep insight, as well as psychotic episodes.
The effects of hallucinogens are quite similar between classes of drugs
within this category, and range from excitation or depressant effects, analgesic
and anaesthetic effects, depending on the dose taken and the situation. PCP
and ketamine can produce hallucinations at very low doses.

Mechanism of action

LSD acts on the serotonin system, and is an autoreceptor agonist in the raphe
nucleus. An autoreceptor is a receptor on a neuron for the transmitter that
neuron releases. Activation of an autoreceptor acts as a negative feedback
mechanism to turn down the firing of the neuron. This helps to regulate
neuronal firing and to prevent overactivation of neurons. LSD also acts as a
serotonin-2 agonist, or partial agonist (Jaffe, 1990). It is taken orally, and doses
as low as 20–25 µg can produce effects.
PCP is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA)
receptor (Lodge & Johnson 1990). PCP-induced psychosis can last for weeks
despite abstinence from substance use (Allen & Young 1978; Luisada 1978).
Similarly to PCP, ketamine, a PCP analogue that is also a non-competitive
NMDA receptor antagonist that exhibits higher selectivity than PCP for the
NMDA receptor (Lodge & Johnson 1990), also induces psychotomimetic
effects in healthy volunteers (Newcomer et al., 1999), and exacerbates
symptoms in patients with schizophrenia (Lahti et al., 1995).
The atropinic class of hallucinogens are antagonists of muscarinic
cholinergic receptors.

Tolerance and withdrawal
Tolerance develops rapidly to both the physical and psychological effects of
the hallucinogens. The psychoactive effects will no longer occur after 3–4 days

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