Fluoroamphetamine - Expert Committee on Drug Dependence Information Repository (2024)

Substance identification
The chemical name of 4-FA is 1-(4-Fluorophenyl)propan-2-amine. The presence of a chiral centre at the α-carbon of the side chain gives rise to the enantiomeric pair of (S)-4-FA and (R)-4-FA. 4-FA is most likely to be available as the racemic mixture.

Previous review
4-FA underwent a critical review by the ECDD in 2015. At that time, the Committee recommended that 4-FA not be placed under international control due to insufficient evidence regarding dependence, abuse and risks to public health. However, it was kept under surveillance. Preliminary information collected from various sources indicated that this substance may cause substantial harm and that it has no medical use, thereby warranting an updated critical review.

Similarity to known substances and effects on the central nervous system
4-FA is a ring-substituted derivative of amfetamine, which is listed in Schedule II of the United Nations 1971 Convention on Psychotropic Substances. 4-FA shares some effects of psychostimulants and of the entactogens. Similar to amfetamine- like stimulants, 4-FA releases dopamine, noradrenaline and serotonin, and displays amfetamine-like features in a number of in vivo and in vitro assays, including the induction of locomotor activity and associated dopamine release in the striatum and nucleus accumbens (regions of the brain linked to the rewarding effects of drugs). 4-FA differs from (+)-amfetamine in its ability to increase extracellular serotonin concentrations in the rat nucleus accumbens.

Some users report that 4-FA promotes pro-social effects that might overlap with those of 3,4-methylenedioxy-methamphetamine (MDMA). Recent studies, including a systematic survey of users, confirmed that the effects of 4-FA were consistent with a psychom*otor/entactogen stimulant profile. Some adverse reactions in users have been reported that required hospitalization and others have resulted in death. The clinical features associated with 4-FA intoxication include agitation, tachycardia, hypertension, hyperthermia, cardiovascular toxicity and cerebrovascular complications such as severe headaches and cerebral haemorrhage.

Dependence potential
No reports from controlled, experimental studies pertinent to the possible physical dependence effects of 4-FA in laboratory animals and humans are available.

Actual abuse and/or evidence of likelihood of abuse
In nonclinical studies in rodents, 4-FA shows classic features associated with amfetamine-like stimulants that are predictive of abuse liability. These include release of dopamine, induction of locomotor activity and substitution for the discriminative stimulus effects of (+)-amfetamine. It is also self-administered by rhesus monkeys.

The presence of 4-FA in Europe has been observed at least since 2007. Over the years, it has been found in products sold as "ecstasy"/MDMA tablets, amfetamine powder and also as an adulterant present in other controlled substances. 4-FA is also available online or from offline retailers as a single substance under its own name. 4-FA can be taken orally or insufflated. It is rarely injected.

Most reports of 4-FA use so far are from European countries. Seizures have been documented in a number of European countries and 4-FA is controlled through national legislation in several countries.

Therapeutic usefulness
There are no known approved medical or veterinary applications of 4-FA.

Recommendation
4-FA is a ring-substituted derivative of amfetamine, which is listed in Schedule II of the United Nations Convention on Psychotropic Substances of 1971. In nonclinical studies, 4-FA has been found to share several effects produced by psychostimulants that are predictive of abuse liability. These include activation of locomotion, substitution for the amfetamine discriminative stimulus, and self-administration. Users report effects of 4-FA that are consistent with a psychom*otor/entactogen stimulant profile. It has been found in products sold as "ecstasy"/MDMA tablets, amfetamine powder, as an adulterant present in other controlled substances, and is sold in its own right. Seizures of 4-FA have occurred in more than 20 countries, and several countries have placed it under national control. Some adverse reactions have been reported that required hospitalization and others that have resulted in death.

The Committee considered that the degree of risk to public health and society associated with the abuse of 4-FA is substantial. Therapeutic usefulness has not been recorded. The Committee recognized that 4-FA has similar abuse potential 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 4-FA 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. The Committee recommended that 4-FA (1-(4-Fluorophenyl)propan-2-amine) be placed in Schedule II under the UN Convention on Psychotropic Substances of 1971.

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