LPH-5 (drug)

LPH-5, also known as (S)-3-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)piperidine or as (S)-2C-TFM-3PIP, is a psychedelic drug of the phenethylamine, 2C, and 3-phenylpiperidine families which is under development for potential medical use. It is a cyclized phenethylamine and is the derivative of 2C-TFM in which the β position has been connected to the amine to form a piperidine ring.

Interactions

Pharmacology Pharmacodynamics LPH-5 acts as a potent partial agonist of the serotonin 5-HT2A receptor (Ki = 1.3nM, = 2.1–25nM, = 56–94%). It shows 10- to 100-fold selectivity for the 5-HT2A receptor over the serotonin 5-HT2B and 5-HT2C receptors in terms of affinity and activational potency. Along with related compounds like 25CN-NBOH, DMBMPP, and TGF-8027, LPH-5 is said to be one of the few truly selective serotonin 5-HT2A receptor agonists.

The drug robustly induces the head-twitch response as well as persistent and robust antidepressant-like effects in rodents. Owing to its high selectivity for the serotonin 5-HT2A receptor, LPH-5 is expected to avoid the cardiac and other risks of serotonin 5-HT2B receptor activation.

Chemistry Analogues LPH-5's analogue LPH-48 is likewise a selective serotonin 5-HT2A receptor agonist and psychedelic with similar characteristics. However, this drug has a shorter duration of action than LPH-5. As with LPH-5, LPH-48 is also under development by Lophora for potential medical use.

Another analogue of LPH-5 is 2T-2CTFM-3PIP (2-thio-LPH-5).

History LPH-5 was patented in 2021 and was first described in the scientific literature by Emil Märcher-Rørsted and colleagues in 2024. These researchers are affiliated with the Danish pharmaceutical company Lophora. In late 2025, LPH-5 was suggested as a possible alternative and replacement of DOI for use in scientific research.

Society and culture Legal status Canada LPH-5 is not an explicitly controlled substance in Canada as of 2025. However, as a derivative of 2Cs, it might fall under phenethylamine blanket-ban language, although as a cyclized phenethylamine this is unclear.

United States LPH-5 is not an explicitly controlled substance in the United States. However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

Research LPH-5 is under development by Lophora and Atai Beckley (formerly Atai Life Sciences and Beckley Psytech) for the potential treatment of major depressive disorder. As of May 2025, it is in phase I clinical trials for this indication.

LPH-5 (drug)

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