Tetrahydrofuranyl fentanyl


(3S)-3-(aminomethyl)-5-methylhexanoic acid

Year(s) and type of review / ECDD meetings
Drug Class

Recommendation (from TRS)

Substance identification
Chemically, tetrahydrofuranyl fentanyl is N-Phenylphenyl-N-[1-(2-phenylethyl) piperidin-4-yl]oxolane-2-carboxamide. Tetrahydrofuranyl fentanyl contains a stereogenic centre allowing for the existence of a pair of enantiomers, (S)- tetrahydrofuranyl fentanyl and (R)- tetrahydrofuranyl fentanyl. There is no information on the actual enantiomers found on the illicit drug market at the time of the report.

Previous review
Tetrahydrofuranyl fentanyl has not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that tetrahydrofuranyl fentanyl is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any Party. Preliminary information collected from various sources indicated that this substance may cause substantial harm and that it has no medical use.

Similarity to known substances and effects on the central nervous system
Similar to controlled opioids such as fentanyl, tetrahydrofuranyl fentanyl selectively binds to and activates the μ-opioid receptor and does so with greater potency and efficacy than with the δ- and κ-opioid receptors. A male with analytically confirmed tetrahydrofuranyl fentanyl intoxication suffered reduced consciousness, respiratory depression and miotic pupils, all effects associated with fentanyl.

Dependence potential
Currently, there are no controlled laboratory animal or human studies available that are directly pertinent to the dependence or abuse potential of tetrahydrofuranyl fentanyl.

Actual abuse and/or evidence of likelihood of abuse
Tetrahydrofuranyl fentanyl is currently sold online and through illicit markets as a nonscheduled substitute for illicit opioids and/or prescription opioids. Tetrahydrofuranyl fentanyl has been seized in the form of a liquid, in powder form and as disk-shaped tablets. Based on forensic reports and paraphernalia found at overdose sites, routes of administration appear to be intravenous, oral and as a nasal spray. Seizures of tetrahydrofuranyl fentanyl have been reported from Europe and North America. One country reported a total of 14 deaths of people with confirmed exposure to tetrahydrofuranyl fentanyl between 2016 and 2017. In at least 12 cases, tetrahydrofuranyl fentanyl was the cause of death or contributed to the death. Another country reported two confirmed deaths associated with tetrahydrofuranyl fentanyl. A number of countries in different regions have controlled tetrahydrofuranyl fentanyl under national legislation.

Therapeutic usefulness
There are currently no approved therapeutic applications or recorded medical uses for tetrahydrofuranyl fentanyl.

Controlled in vitro studies indicate that tetrahydrofuranyl fentanyl has affinity and efficacy as an agonist at the μ-opioid receptor, findings which are consistent with the pharmacological effects observed with use of controlled opioid drugs such as morphine and fentanyl. An analytically confirmed case of tetrahydrofuranyl fentanyl intoxication indicated effects that were also consistent with other opioid drugs. Several deaths have been associated with tetrahydrofuranyl fentanyl use. Seizures of the drug have occurred in at least three countries, and it is sold on the Internet.

Tetrahydrofuranyl fentanyl is a compound liable to similar abuse and with similar ill effects to controlled opioids such as fentanyl that are included in Schedule I of the Single Convention on Narcotic Drugs of 1961. It has no recorded therapeutic use, and its use has been associated with fatalities. There is sufficient evidence that it 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. Thus, because it meets the required condition of similarity, it is recommended that tetrahydrofuranyl fentanyl (N-Phenyl-N-[1- (2-phenylethyl)piperidin-4-yl]oxolane-2-carboxamide) be placed in Schedule I of the Single Convention on Narcotic Drugs, 1961, as consistent with Article 3, paragraph 3 (iii) of that Convention in that the substance is liable to similar abuse and productive of similar ill effects to drugs in Schedule I.

ECDD Recommendation

Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
MS Questionnaire Report