Introduction

Non-medical use of ketamine was recognised over 20 years ago in the
United States when the Food and Drinks Administration (FDA) expressed
concerns about it in 1979. However, it did not come to public notice in
Europe until the 1990s. In 1995 and 1996, concern in the United Kingdom
about the prevalence of misuse and the health risks associated with ketamine
escalated following a seizure of almost 100 000 ketamine tablets. These
carried a logo commonly found on ecstasy tablets and some users suffering
anxiety attacks were hospitalised after taking large doses of ketamine believing
it to be ecstasy.

This report summarises the relevant data required by Technical Annex D of
the guidelines for the risk assessment of new synthetic drugs. In the absence
of systematic studies of non-medical use of ketamine, the epidemiological
evidence is based on information collected from:

 the Reitox national focal points in the 15 EU Member States (1);

 Europol’s contribution to the risk assessment of ketamine (2);

 the EMEA contribution to the risk assessment of ketamine (3);

 the Qualitative European Drugs Network (QED) (4);

 the literature (5);

 key European forensic scientists (6);

 key toxicologists in the United Kingdom (7);

 telephone interviews with international experts in the field of recreational
drugs (8);

 the Internet (English-language searches) (9); and

 youth and mass media (English-language searches) (10).

Table 3 presents the topics covered by this annex by briefly indicating the
extent and type of evidence that is available. The numbers in the list above
are used in the table to code the sources of information. Where information
is available, it is presented and examined under the main category headings.
In general, there is insufficient information, or too much overlap, to address
each of the subheadings in the text.

Table 3: Topics for public health risks: epidemiological evidence

Following an EMCDDA request to all 15 Reitox national focal points for
information about ketamine, five responded stating that they were unable to
provide any official evidence of non-medical ketamine use in their countries
(Denmark, Italy, Luxembourg, Austria and Portugal). Austria provided some
anecdotal reports of its use.

Forensic laboratory analysis of samples of ketamine were reported by eight
countries, either by the focal points or by Europol. The number of seizures
and quantities of ketamine identified by laboratory analysis range from 89 kg
in 1999 in Belgium to occasional small seizures in France and Sweden.

Three deaths have been reported in the European Union in which ketamine
was identified by laboratory analysis: two in Ireland in 1996 and one in
France. Ketamine was not considered to be the cause of death in the Irish
cases and few details are available about the French death. Non-fatal hospital
admissions associated with ketamine are difficult to assess in the absence of
routine screening for ketamine by hospital toxicology laboratories. Medical
staff may not distinguish symptoms of ketamine overdose from other drug
overdoses or general psychiatric symptoms, which are mainly psychological
or related to loss of physical control.

The main epidemiological indicators for ketamine use are summarised in
Table 4.

Availability and quality of product on the market

Ketamine has marketing authorisation in most countries in the EU, except
Greece, where the authorisation was recalled in 1998 (10). In human medicine,
ketamine is indicated for special situations in anaesthesia and for pain treatment.
In Ireland, ketamine is not used in human medicine and the government
plans to add it to the list under the Misuse of Drugs Act. Elsewhere in
the EU, licit use of ketamine is generally limited and is decreasing, with the
exception of Belgium, Germany, France and the United Kingdom. In Belgium,
its use has doubled in the past 10 years, although it has been controlled by
royal decree since 1976. In many countries, ketamine is subject to restricted
prescription or is regulated as a psychotropic substance so that unauthorised
supply is illegal (EMEA, 2000).

Seizures

Seizure data suggest different levels of availability of ketamine within different
Member States, with a decrease occurring in the United Kingdom and an
increase in some other Member States (Europol, 2000). A large proportion of
ketamine seizures are in tablet form and the tablets carry the same logos as
those often found on ecstasy tablets. Synonyms such as ‘K’ and ‘special K’
are used. Forensic laboratory analysis has found ketamine, in variable doses,
mixed with manitol, caffeine, ephedrine, MDMA, amphetamine and
methamphetamine.

In Belgium, 89 kg of pure ketamine in powder form was seized in September
1999 and a further 3 kg in January 2000. Some tablets seized in Belgium also
contained MDMA or amphetamine. In Denmark, no seizures have been
reported. In Greece, three seizures have been reported, the most recent of
which was from two British men on a Greek island in June 2000. They had
in their possession 56 tablets containing ketamine and caffeine and bearing
the ‘Mitsubishi’ logo. In Ireland, most seizures of ketamine took place in 1998,
including a seizure of 27 000 tablets, some of which contained a mixture of
ketamine and caffeine. One seizure was of ketamine in powder form. Since
April 1999, only four cases have been recorded and ephedrine was present
in all of these. It is believed that the vast majority of tablets seized in Ireland
originated in the Netherlands. In Spain, early seizures took place in 1995 in
the Balearic Islands and, in 1996, ketamine seized in Barcelona was found
to be mixed with manitol. Between 1995 and 1996, an English police team
visited the Balearic Islands to investigate the origin of ketamine tablets that
had been seized in discotheques and bars and were suspected to have been
manufactured in the United Kingdom. The seizures in Spain have been
mainly from foreign tourists and none have occurred in Madrid and other
major cities. In Sweden, there have been occasional small seizures of ketamine.
Ketamine is an integral part of four different medicinal products and
some years ago stolen ketamine products from the legal pharmaceutical
trade appeared on the illegal market.

In the United Kingdom, seizures climbed rapidly in the early 1990s and then
levelled out. A definite decline has occurred over the past year. In the
January to March period of 1999, ketamine constituted 10 % of all illicit
drug seizures. In the same period for 2000, ketamine dropped to 1.4 % of all
illicit drug seizures. This decrease is believed to be due to a number of
police investigations, particularly in the north-west of England. There have
been few significant customs seizures, suggesting that most, if not all, of the
tablets consumed in the United Kingdom are produced there. It is believed
that ketamine raw material is imported in bulk from legitimate suppliers in
Europe. A number of ketamine tablet manufacturers in the United Kingdom
have been successfully prosecuted for conspiracy to supply, or attempt to
supply, a controlled drug. Some dealers have been prosecuted for conspiracy
to defraud contrary to common law.

Other information sources close to ketamine users in the United Kingdom
and France suggest that there may be diversion from licit medical and
veterinary suppliers and from foreign purchases, particularly from Asia.

Dose and price

Depending on the concentration, form and method of administration, recreational
doses range from 30 to 300 mg and timing varies in both onset and
duration. For example, an average intramuscular dose is 25–50 mg with an onset
of 1–5 minutes and a duration time of 45–90 minutes. An average oral dose is
75–300 mg with an onset of 5–20 minutes and duration of 90 minutes. The
effects of nasal doses have been described as quite different from other
administration routes at low doses. An average nasal dose is 30–75 mg with
an onset of 2–25 minutes and a duration time of only 10–30 minutes.

Prices range from EUR 15 to EUR 80 per gram and anecdotal reports suggest
that, at such low prices, the illicit trade in ketamine is unlikely to be a lucrative
one. A combination of ketamine and cocaine has also been reported and
this is called ‘special CK’, with reference to Calvin Klein, the popular
American designer.

Knowledge, perceptions and availability of information

There appears to be relatively low awareness and experimentation with
ketamine in Europe compared with drugs such as cannabis, MDMA,
amphetamine and cocaine. Lack of information about the dose content of
the ketamine on the market is an important factor, according to outreach
workers. Anecdotal reports from France and the United Kingdom indicate a
growing awareness among consumers about how to manage doses to
achieve sought-after effects and avoid negative ones. At low doses, ketamine
is reported to have some stimulant effect. This could be the result of the stimulant
effect of active cutting agents or because ketamine is often sniffed with
amphetamine and/or cocaine or taken with other drugs in the ‘illicit recreational’
drug scene. Ketamine may also be administered in a series of intravenous
or intramuscular doses for a specific ketamine experience. Numerous
books and journal articles have been written concerning ketamine.
Information about the effects, supply and health risks is provided on Internet
web sites and newsgroups such as www.erowid.org and alt.drugs. Terms
such as ‘K hole’ are used by conscious consumers of ketamine to describe
and locate the effects of the drug.

Perceptions

Anecdotal reports suggest that ketamine has an upmarket image as an esoteric
drug for experienced recreational drug users. The major advantages of ketamine
from the user’s perspective are: fast onset and recovery and minimal
effect on cough and gag reflexes, thus reducing the risk of choking on saliva
or vomit (Jansen, 2000). Internet newsgroups have made comparisons
between ketamine and DXM (dextromethorphan), advising that DXM has a
considerably longer half life and worse side-effects than ketamine for most
people. Forensic scientists and toxicologists, however, have drawn attention
to close similarities to phencyclidine (a Class A controlled drug in a number
of countries) and to the (non-controlled) veterinary anaesthetic tiletamine.

Prevalence and patterns of use

The trend in non-medical use of ketamine appears to be decreasing in the
United Kingdom and increasing in France and possibly Belgium and some
other Member States. Targeted surveys of clubbers and a limited number of
school surveys are the major source of information about prevalence and
patterns of ketamine use. These have shown that a significant number of
people experiment with ketamine but that the level varies between subpopulations
and geographical areas. A London club survey in 1997 found
that up to 40 % of the 200 respondents had experimented with ketamine and
many were planning to use it that evening (Release, 1997). This survey
placed ketamine in fourth place after cannabis, amphetamine and ecstasy. A
large French survey conducted in 1997 found that 15 % of 900 respondents
in techno party settings had experimented with ketamine (Médecins du
Monde, 1999), whereas, among a matched control group of young people
who did not go to techno events, consumption of ketamine was non-existent.
Another survey targeted at a dance setting in Austria found that respondents
who were regularly taking MDMA and amphetamine considered that the
psychological risks attached to taking ketamine were very high.

Recently a large (over 1 500 respondents) school survey conducted in the
north-east of England found that 1 % of 13/14-year-old children and 2 % of
15/16-year-olds had tried ketamine compared with 2 and 5 %, respectively,
who had tried cocaine (Centre for Social Marketing, 2000). In Greece, during
1999, treatment services and telephone helplines reported some
ketamine use in the same recreational scenes as ecstasy and cocaine.

Ketamine in its pharmacological presentation is usually sniffed as a powder
or injected, but there have been reports of it being swallowed, inhaled by
‘chasing’ and inserted rectally. There are no reports of demand for treatment
of ketamine-related problems from drug treatment services in Member
States, but there appears to be a consensus among drug outreach workers,
and users themselves, that regular ketamine use may lead to psychological
dependence.

Characteristics and behaviour of users

Targeted surveys and anecdotal reports indicate that prevalence may be
higher in older, experienced MDMA users, particularly in the free-party/newage
traveller scene, among homosexual populations and among small
groups of self-exploratory individuals. A study of 100 ketamine users conducted
by the Australian National Drug and Alcohol Research Centre reported
that there appeared to be four primary user groups (Dillon et al., 2000):
injecting heroin users, members of the gay scene, regular drug users in the
dance scene, and ‘self-exploratory’ users who like to take the drug in isolation
and ‘astro travel’. Among ‘closed’ groups in Europe, initiation into ketamine
use is often ritualised. On such occasions, ketamine is given gratis.

It has been suggested by a number of different sources that the physical
clumsiness, falling asleep and blackouts that are commonly reported by ketamine
users are not tolerated in high-street and music-club settings. One outreach
worker in the United Kingdom free-party scene observed that:

‘... it’s more popular at free parties because you can lie/fall down
wherever you like and not get grief for spilling your drink all over
someone’s Pradas.’ (Telephone interview)

Among outreach workers in party settings in both London and Paris there are
reports of marked improvements among ketamine users in their ability to
manage their doses in order to avoid blackouts and other physical risks
(Dalgarno and Shewan, 1996). There are also reports of people with chronic
opiate problems using ketamine for its anaesthetic and analgesic effects.

The most vulnerable group of users are those who take ketamine under the
illusion that they are taking MDMA or some other stimulant drug. The volume
of seizures of ketamine in tablet form with ecstasy-type logos reflects the
scope for this scenario and the need for better information about drug contents
and harm reduction. Compared with the effect of stimulants, the rapid
physical incapacity rendered by ketamine consumption has serious implications
for driving.

Indicators of health consequences

In the European Union, there have been three deaths reported to the
EMCDDA in which ketamine was found by laboratory analysis. Two of these
occurred in 1996 in Ireland. In one, there was a history of ecstasy use and
ketamine and opiates were found. In the other case, ketamine, ephedrine
and pseudoephedrine were found. In neither of the Irish cases was ketamine
considered to be the main cause of death. One death of a 19-year-old male
has been reported in France in which ketamine, LSD and ecstasy were implicated.
Further details regarding this case were not available at the time of
writing (Arditti, 2000).

There has been a notable lack of reporting about hospital emergencies associated
with ketamine. A recent report prepared in France presents some data
on 17 cases of intoxication associated with ketamine. The report describes
conditions such as difficulties in walking, agitation, fever and psychological
disturbances (Arditti, 2000).

Health concerns have been expressed by drug outreach workers and music
media journalists about the anaesthetic effects of ketamine in dance settings
and sudden, unexpected, effects. Lack of information about doses and the
adoption of the same consumption patterns for ketamine as for other stimulant
drugs increase the potential for undesirable effects. In clubs, security
staff are sometimes quick to remove a person who has fallen asleep and
leave them in the street. According to outreach workers, risks such as these
could be overcome with adequate information and appropriate warnings.
A further health risk concerns the risk of tolerance and psychological dependence
resulting from regular use (Jansen, 2000a). Where there is dependence,
there may be a tendency to gravitate towards injecting ketamine.

Context of use

An important factor with regard to context of use is the lack of reliable
dosage information accompanying sales of ketamine at street level. In the
absence of advice or previous experience, first-time users of ketamine tend
to follow similar consumption patterns as for other drugs. Such uninformed
use of ketamine increases the risk of both physical and psychological
problems. Outreach workers report that ritualised care is often given to firsttime
users by others to avoid such risks. Individuals who take ketamine mistakenly
for MDMA or another stimulant may have no prior knowledge or
ameliorative support.

Short-duration effects are not generally viewed as value for money by recreational
drug users. However, in the context of ketamine’s less sought-after
anaesthetic effects, the short duration may be viewed as an advantage. One
music magazine refers to this particular ‘advantage’ of ketamine:

‘The great thing is it wears off pretty quick. If you see a girl you like,
you can give it a rest for half and hour and chat her up without making
an idiot of yourself.’ (Muzik)

Implications for the non-using population

The main implication for the non-ketamine-using population appears to be
the phenomenon of ketamine entering the recreational drug market in the
guise of ecstasy or other stimulant drugs. This means that someone expecting
to take MDMA, cocaine or amphetamine may find themselves inadvertently
taking ketamine, without warning, knowledge or support.

Table 4: Summary of key data on ketamine

(10) Classification for the supply of medicinal products for human use is regulated by Directive 92/26/EEC
of 31 March 1992. Article 12 of Directive 75/319/EEC of 20 May 1975 regulates, through the
Committee for Proprietary Medicinal Products (CPMP), the suspensions, withdrawal or variations
to the terms of the marketing authorisation, in particular to take account of the information collected
in accordance with pharmacovigilance.

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