This is a list of investigational hallucinogens and entactogens, or hallucinogens and entactogens that are currently under formal development for clinical use but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The list also includes non-hallucinogenic drugs related to hallucinogens, such as non-hallucinogenic serotonin 5-HT2A receptor agonists and non-hallucinogenic ketamine analogues. Cannabinoids, or cannabinoid receptor modulators, are not included in this list. Many of the indications are not for continuous medication therapy but rather are for medication-assisted psychotherapy or short-term use only.
This list was last comprehensively updated in October 2024. It is likely to become outdated with time.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
Hallucinogens are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants.
2-Bromo-LSD, also known as BOL-148, is a derivative of lysergic acid invented by Albert Hofmann, as part of the original research from which the closely related compound LSD was also derived.
1-Methylpsilocin (developmental code names CMY, CMY-16) is a tryptamine derivative developed by Sandoz which acts as a selective agonist of the serotonin 5-HT2C receptor (IC50Tooltip half-maximal inhibitory concentration of 12 nM, vs. 633 nM at 5-HT2A), and an inverse agonist at 5-HT2B (Ki of 38 nM). While 1-methylpsilocin does have higher affinity for 5-HT2C than 5-HT2A, it does produce a head-twitch response in mice that is dependent on 5-HT2A, so it is not entirely free of effects on 5-HT2Ain vivo. In contrast to psilocin, 1-methylpsilocin did not activate 5-HT1A receptors in mice.
AAZ-A-154, also known as DLX-001, is a novel isotryptamine derivative which acts as a serotonin 5-HT2A receptor agonist discovered and synthesized by the lab of Professor David E. Olson at the University of California, Davis. It is being developed for the treatment of major depressive disorder and other central nervous system disorders.
A trip killer, or hallucinogen antidote, is a drug that aborts or reduces the effects of a hallucinogenic drug experience. As there are different types of hallucinogens that work in different ways, there are different types of trip killers. They can completely block or reduce the effects of hallucinogens or they can simply provide anxiety relief and sedation. Examples of trip killers, in the case of serotonergic psychedelics, include serotonin receptor antagonists, like antipsychotics and certain antidepressants, and benzodiazepines. Trip killers are sometimes used by recreational psychedelic users as a form of harm reduction to manage so-called bad trips, for instance difficult experiences with prominent anxiety. They can also be used clinically to manage effects of hallucinogens, like anxiety and psychomotor agitation, for instance in the emergency department.
ITI-1549 is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist which is under development for the treatment of mood disorders and other psychiatric disorders. In addition to acting at the serotonin 5-HT2A receptor, it is also an antagonist of the serotonin 5-HT2B receptor and an agonist of the serotonin 5-HT2C receptor. The drug's route of administration has not been specified.
CYB003, or CYB-003, also known as deuterated psilocybin analogue, is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders. It is taken by mouth.
MSP-1014 is a serotonergic psychedelic which is under development for the treatment of major depressive disorder, other depressive disorders, and anxiety disorders.
BMB-202 is a serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of depressive disorders and post-traumatic stress disorder (PTSD). It is taken by mouth. However, BMB-202 has also been evaluated by injection in preclinical studies.
LPH-48 is a selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of alcoholism. Its route of administration has not been specified.
MYCO-005 is a serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of depressive disorders and anxiety disorders.
Regardless, a more parsimonious explanation is that certain 5-HT2 receptor-activating compounds, such as DOI and psilocin, cause specific conformations of 5-HT2 receptors that lead to LSD-like psychedelic effects.[94,232] Moreover, although the 5-HT2 agonists mCPP, lorcaserin, and quipazine, are often considered 'non-hallucinogenic', they actually do produce perceptual, cognitive, and emotional changes that may be considered 'hallucinogenic'.[15,233,234] These effects, however, are generally not considered LSD-like. Finally, it is noteworthy that novel, partial 5-HT2A/D2 receptor agonists also attenuate the DOI-elicited HTR.[235,236]
This concept is also supported by experiments on OSU-6162, a selective Sigma 1R ligand in low doses [176]. This Sigma1R ligand produced in the nucleus accumbens shell substantial increases in the density of the D2R–Sigma1R and A2AR–D2R heterocomplexes, supporting the existence of A2AR–D2R–Sigma1R trimeric complexes in which the Sigma1R agonist can strongly enhance the antagonistic allosteric A2AR–D2R interaction. This mechanism may mediate the enhanced antagonistic A2AR–D2R interaction, causing marked inhibition of cocaine reward, leading to cocaine addiction.
Author Disclosure Statement: H.K. is Vice President of Research at PharmAla Biotech and is listed as an inventor on patents related to the research in this review article. H.E.S. receives salary supported from a contract between PharmAla Biotech and UAMS. W.E.F. receives research funds and salary support from a contract between PharmAla Biotech and UAMS. The other authors have no conflicts to disclose.
MYCO - 006 and 007 represent families of molecules that are based on MDMA molecules. MYCO -006 and MYCO – 007 have been developed in order to reduce the overall acute experience time of Generation 1 MDMA by increasing the metabolism properties of the drug.
Mydecine [...] announced it has successfully synthesized multiple short-acting MDMA analogs. This family of analogs have been specifically designed by experts at Mydecine to have a shorter half life than traditional MDMA. The Company has named this family of novel molecules MYCO-006 and have applied for patent coverage with the World Intellectual Property Organization.
MYCO - 002 is an entactogenic compound that has been created with the goal of reducing harm and improving the safety profile vs. traditional MDMA.