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. [1]
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. The section that the drug is in corresponds to its highest developmental phase, not its phase for all listed indications.
This list was last comprehensively updated in October 2024. It is likely to become outdated with time.
The company also hopes to improve tolerability with its program combining MDMA with citalopram, a selective serotonin reuptake inhibitor (SSRI) used to treat depression, for PTSD. Baggott anticipates beginning Phase II trials with the combo in 2025. [...] "The fact that Lykos didn't get their NDA approved on this cycle means that we are seriously considering prioritizing our novel compounds and waiting to move forward with our MDMA product," Baggott said. Tactogen's pipeline includes a number of preclinical molecules that Baggott said he believes will be superior to MDMA.
"There are several studies that gave MDMA and an SSRI to healthy volunteers and compared the effects to MDMA alone. These studies show that even a single dose of an SSRI can reduce the psychological effects of MDMA by as much as 80 percent," says Matt Baggott, an MDMA research heavyweight and CEO of Tactogen, which develops MDMA-like compounds for medicinal use. [...] Interestingly, Baggott tells VICE that taking an SSRI after a MDMA roll "probably works" in alleviating a comedown. He points to animal studies that suggest SSRIs given shortly after MDMA may protect the brain from the negative effects of this overstimulation. He also ran a small, unpublished study with people who typically recorded a comedown post-MDMA, and did not normally take SSRIs. "When I gave them MDMA in a laboratory setting, they performed worse at a demanding cognitive task at both five and 26 hours after MDMA." In a separate session he gave them MDMA, followed three hours later by the SSRI citalopram. He says that this "prevented MDMA-induced performance difficulties without noticeably changing the main emotional effects of MDMA. This supports the idea that SSRIs can reduce the undesirable after-effects of MDMA."
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.
{{cite web}}: |author= has generic name (help)MYCO - 002 is an entactogenic compound that has been created with the goal of reducing harm and improving the safety profile vs. traditional MDMA.
[ARIADNE] had been explored rather extensively as a potential psychotherapeutic ally by a friend of mine. He said that there seemed to be some value in a few of his patients who had some underlying depression, but not much of anything with the others. So, I decided to call it an anti-depressant. I had mentioned some of this history one time when I was giving an address at a conference on the East Coast, and my host (who happened to be the research director at a large pharmaceutical house) asked if I would send him a sample. His company did many animal tests, one of which showed that it was not hallucinogenic (a cat whose tail erected dramatically with DOM did nothing with ARIADNE) and another that showed re-motivation (some old maze-running monkeys who had decided not to run any more mazes changed their minds with ARIADNE). So patents were obtained for the "R" isomer, the more effective isomer, covering its use for such things as the restoring of motivation in senile geriatric patients. And a tradename of Dimoxamine was assigned it, despite several voices that held out for Ariadnamine. But it didn't have what was needed to make it all the way to the commercial market.
The drug MDA (3,4-methylenedioxy-amphetamine), which is in some respects similar to MDMA, played a significant role in the pre-history of MDMA (Beck and Rosenbaum 1994). In the 1950s and 1960s, MDA was tested for selected medical indications by pharmaceutical companies, but it was abandoned due to unwanted "central side-effects" (Smith, Kline & French Laboratories 1957; Friedhoff et al. 1958; Cook and Fellows 1961). [...] Smith, Kline & French Laboratories. 1957. Report on clinical evaluation of SKF #5 (Amphedoxamine). Philadelphia, PA: Smith, Kline & French Laboratories.
There have been a number of medical explorations [of MDA]. Under the code SKF-5 (and trade name of Amphedoxamine) it was explored as an anorexic agent. It has been found promising in the treatment of psychoneurotic depression. [...]
During the early 1960s, α-ethyltryptamine [(AET)] (Monase®, Upjohn Company) was marketed in the United States as an antidepressant and stimulant, but the drug was removed shortly after introduction because of the occurrence of serious blood disorders. [...] [α-Methyltryptamine (AMT)] (Indopan) was marketed in the Soviet Union during the 1960s as an antidepressant.