Ethylphenidate

Substance identification
Chemically, ethylphenidate is ethyl phenyl(piperidin-2-yl)acetate.

Previous review
Ethylphenidate has not previously been pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to the attention of WHO that ethylphenidate is clandestinely manufactured, poses a serious risk to public health and society, and has no recognized therapeutic use by any Party.

Similarity to known substances and effects on the central nervous system
Ethylphenidate is a structural analogue of methylphenidate, which is controlled as a Schedule II substance under the UN Convention on Psychotropic Substances of 1971. Ethylphenidate can be converted into methylphenidate and vice versa. Ethylphenidate is also produced as a metabolite from the co-ingestion of methylphenidate and alcohol (ethanol), and it has been suggested as one determinant of co-abuse of these substances. Ethylphenidate is a selective and potent dopamine uptake inhibitor. It is more potent than cocaine in inhibiting dopamine uptake, and also more selective than cocaine for the dopamine relative to the noradrenergic or serotonergic transporters. Similar to psychostimulants, it increases locomotor activity in rodents and can induce stereotypies. Ethylphenidate has clinical effects typical of amphetamine-like stimulants, including tachycardia, hypertension, dilated pupils, palpitations, fever, anxiety, agitation, paranoia and tremor. Ethylphenidate use has been associated with deaths due to mixed drug toxicity, and in one documented instance, ethylphenidate alone was detected.

Dependence potential
No controlled studies in humans or laboratory animals regarding the potential physical dependence effects of ethylphenidate have been reported. One brief case study has been published describing an individual who developed dependence on ethylphenidate purchased from the Internet. The subject had previously been dependent on cannabis, heroin/morphine and had occasionally used stimulants.

Actual abuse and/or evidence of likelihood of abuse
Ethylphenidate is sold over the Internet and discussed on drug-user websites, and has been identified in confiscated material. Routes of administration reported by users include nasal insufflation, oral, anal, vapour inhalation and intravenous injection. Users report an immediate and intense rush of pleasurable stimulation, which is characterized by alertness and a general mood lift. Other effects reported include increased self-confidence, improved ability to focus and concentrate, and enhanced social interaction and social skills. The pro-social effects appear similar to those reported by users of MDMA. Users on Internet forums report tolerance to some of its effects, leading to use of a higher drug dose to achieve the same effect and also describe a strong urge to re-dose. Ethylphenidate has been placed under national control in several countries in different regions.

Therapeutic usefulness
There are currently no known therapeutic applications for ethylphenidate.

Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of ethylphenidate (ethyl phenyl(piperidin-2-yl)acetate) is substantial. Therapeutic usefulness has not been recorded. It recognized that ethylphenidate has similar abuse and similar ill-effects to substances in Schedule II of the UN Convention on Psychotropic Substances of 1971. The Committee considered that there is sufficient evidence that ethylphenidate is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. As per the Guidance on the WHO review of psychoactive substances for international control (2), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness. The Committee recommended that ethylphenidate be placed in Schedule II under the UN Convention on Psychotropic Substances of 1971.