During its meeting i n S eptember 2002, the WHO Expert Committee on Drug Dependence did
a pre-review on ketamine (WHO, 2003). Based on the available information a recommendation was given for a Critical Review of this substance. In about the same period both in The Netherlands (CAM, 2002) as well in The European Union (EMCDDA, 2002)
separate Risk Assessment procedures for Buy ketamine USA were performed, concluding that there was no need to tighten the current systems for control of this substance, i.e as a pharmaceutical product.
The information used in the three above mentioned procedures (meanwhile published) has
been the starting point for this Critical Review Report. A review of pharmacological and
toxicological data prepared by Dutch experts (Van Aerts and Van der Laan) has been used
(with their permission) for the relevant parts of this Report. In addition to these data, an online
computer search has been performed in the following databases Pubmed, Toxline, PsycINFO, and Embase.
Ketamine is an alkylamine structurally related to cyclones, like eticyclidine,
phencyclidine, procyclidine, and tenocyclidine.
It is an NMDA-receptor-antagonist used as an anesthetic in both human and veterinary
medicine. Furthermore, a number of effects on various neurotransmitter systems have been
Ketamine can produce a state of dependence as shown in various animal models. This is
supported by some human data as reported by the WHO. Although one should keep in mind
that monitoring of adverse effects in patients is quite different from monitoring effects in
recreational users. Due to its pharmacological effects, it produces depression of the central
nervous system, resulting in hallucinations, disturbances in thinking and perception, and also
in motor function.
There is evidence that ketamine is abused, but looking at the figures one can hardly consider
this to constitute a public health and social problem. Especially when comparing ketamine to
the other cyclones.
The substance is difficult to synthesize, so illegal production is unlikely. Preparations are
mainly used in hospitals and veterinary clinics, so it is not expected that diversion will take
place on a large scale.
Summarizing all the available information international control is not really necessary, but
keeping the drug under surveillance could be considered.
A specific route described on the internet involves the precursors cyclopentyl bromide, o’chlorobenzonitrile, and methylamine. A considerable amount of additional reagents and
solvents are needed for the four-step synthesis described.
At the same place it is mentioned that two ketamine analogs have been found on the black market: the compound missing the 2-chloro group on the phenyl ring, and its N-ethyl analog.
According to this internet site, both of these compounds are considered most likely more
potent and longer lasting than ketamine. Using the same synthesis route as described for
ketamine, the precursors benzonitrile and ethylamine instead of o-chlorobenzonitrile and
methylamine would be involved.
When the drug is diverted for recreational use, the original pharmaceutical form is often
abandoned. The most popular form for ketamine is a powder, which is snorted. The powder is
prepared by evaporation of the original solution. This powder is usually sold in small plastic
or paper bags. Additionally, the ketamine solution may be transferred to a vaporizer, from
which it can be administered intranasally. It may also be present in tablets for oral use. As
with all illegally sold drugs the concentration and presence of adulterants are mostly unknown
and therefore represents an additional public health risk. When tablets contain ketamine, these
tablets are often sold as ‘ecstasy’. Other substances reported to be present in ketamine containing tablets are pseudoephedrine, ephedrine, caffeine, amphetamine, methamphetamine
The pharmacology of ketamine will be described in two parts. The first one dealing with the
effects of the substance on various neurotransmitter systems and related to both its clinical use
and its use as a recreational agent. The second part dealing with the effects on various organ
systems and often wanted in clinical or veterinary practice or occurring during non-medical
use and sometimes leading to adverse reactions.
Ketamine is a dissociative anaesthetic (Domino et al, 1966). Originally, the dissociation
component refers to a functional and electrophysiological dissociation of thalamo-neocortical
and limbic systems (Reich and Silvay, 1989; Haas and Harper, 1992). Later, the nature of the
subanesthetic ketamine experience has led to the use of the term ‘dissociative’ in a more
psychological sense referring to a feeling of dissociation of the mind from the body (Jansen,
Ketamine binds to the so-called PCP-binding site of the N-methyl-D-aspartate (NMDA)-
receptor complex, located within the ion channel, thereby blocking the transmembrane ion
flux. This makes ketamine a non-competitive NMDA-receptor antagonist. NMDA-receptors
are calcium-gated channel receptors. The endogenous agonists of this receptor are the
excitatory amino acids glutamic acid, aspartic acid, and glycine. Activation of the receptor
results in opening of the ion channel and depolarisation of the neuron.