Clinical Pharmacology and Therapeutics

DRUGS THAT ALTER PERCEPTION 437
which provide anonymized data to the appropriate national or
regional Drug Misuse Database (DMD).
Key points
Prescription of controlled drugs
Preparations which are subject to the prescription
requirements of the Misuse of Drugs Regulations 2001 are
labelled CD. The principal legal requirements are as follows:
Prescriptions ordering Controlled Drugs subject to
prescription requirements must be signed and dated by
the prescriber and specify the prescriber’s address. The
prescription must always state in the prescriber’s own
handwriting in ink or otherwise so as to be indelible:
• the name and address of the patient;
• in the case of a preparation, the form and, where
appropriate, the strength of the preparation;
• the total quantity of the preparation, or the number of
dose units, in both words and figures;
• the dose.
Prescriptions ordering ‘repeats’ on the same form are not
permitted.
It is an offence for a doctor to issue an incomplete
prescription (see the British National Formulary for full
details).
DRUGS THAT ALTER PERCEPTION
Cannabis (marijuana) is the most widely used illicit drug in the
UK. The most active constituent is Δ-9-tetrahydrocannabinol,
which produces its effects through actions on cannabinoid CB1
receptors. It is most commonly mixed with tobacco and
smoked, but it may be brewed into a drink or added to food.
The pleasurable effects of cannabis include a sensation of relaxation,
heightened perception of all the senses and euphoria. The
nature and intensity of the effects varies between individuals,
and is related to dose, and to the mood of the subject. The effects
usually occur within minutes and last for one to two hours.
Conjunctival suffusion is common. Tetrahydrocannabinol and
other cannabinoids are extremely lipid soluble and are only
slowly released from body fat. Although the acute effects wear
off within hours of inhalation, cannabinoids are eliminated in
the urine for weeks following ingestion. It is claimed that
cannabis may be of value in the symptomatic management
of multiple sclerosis, particularly if nausea is a prominent
symptom. It has no approved medicinal use in the UK.
Acute adverse effects include dysphoric reactions, such as
anxiety or panic attacks, the impairment of performance of
skilled tasks, and sedation. This may lead to road traffic accidents.
Chronic use has been associated with personality
changes, including ‘amotivational syndrome’ which is characterized
by extreme lethargy. The association of chronic
cannabis use with onset of schizophrenia is unproven. A physical
dependence syndrome has been reported for cannabis, but
only after extremely heavy and frequent intake. Dependence on
cannabis as a primary problem is rare and there are no specific
treatments for cannabis dependence. Similarly, there are no
treatments for cannabis intoxication, although dysphoric
reactions may require brief symptomatic treatment (e.g. with
benzodiazepines).
LYSERGIC ACID DIETHYLAMIDE AND OTHER
PSYCHEDELICS
Psychedelics produce hallucinations (e.g. visual, somatic, olfactory)
and other changes in perception, e.g. feelings of dissociation
and altered perception of time. Psychedelics can be divided
into serotonin- or indoleamine-like psychedelics (e.g. lysergic
acid diethylamide (LSD) and psilocybin) and phenylethylamines
(e.g. mescaline, phencyclidine – angel dust – and
methylenedioxymethylamphetamine – MDMA or ‘ecstasy,
XTC’). These are agonists at the serotonin 5-HT 2 -receptor and
their potency as hallucinogens is closely correlated with their
affinity for this receptor. Some phenethylamine psychedelics
stimulant properties and can produce feelings of increased
energy and euphoria and heightened perception.
MDMA is the most commonly abused recreational hallucinogenic
central stimulant in the UK. The most common
users are adolescents.
In high-dose hyperpyrexia, trismus, dehydration, hyponatraemia,
rhabdomyolysis, seizures, coma, hepatic damage and
death have been reported. Interactions with antidepressants
are life-threatening. Impulsivity and impaired memory are
serious long-term effects. Chronic MDMA usage produces
degeneration of serotonergic neurones. MDMA is metabolized
via the CYP 2D6 system and is a potent CYP 2D6 inhibitor. The
elimination kinetics are saturable.
Psychedelics were used historically as adjunctive treatment
in psychotherapy, but were subsequently found to be of
no benefit. Most are taken orally and perceptual changes
occur approximately one hour later. The duration depends on
dose and clearance, and is often several hours to one day.
Tolerance to behavioural effects can occur, but no withdrawal
syndrome has been demonstrated.
In addition to the uncommon life-threatening adverse
effects caused by MDMA, physicians come into contact with
psychedelic drug abusers when they contact emergency services,
e.g. as a result of dysphoric reactions or ‘bad trips’. These
symptoms can respond to reassurance and quiet surroundings,
although chlorpromazine (which has 5-HT 2 -antagonist
effects) or diazepam may be of benefit.
Phencyclidine (‘PCP’, ‘angel dust’) was originally developed
as an injectable anaesthetic. It binds to the glutamate ion channel.
Its therapeutic use in humans was stopped after early clinical
studies showed that it produced confusion, delirium and
hallucinations. It is used for anaesthetic purposes by veterinarians.
Patients may show extreme changes in behaviour and
mood (e.g. rage and aggression, lethargy and negativism,
euphoria), hallucinations, autonomic arousal (hypertension,
hyperthermia) and, in extreme cases, coma and seizures.
Symptoms of PCP intoxication should be treated symptomatically.
PCP abuse is rare in the UK.