What’s the Best Way To Take 5-MeO-DMT in a Clinical Trial?
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Beckley Psytech recently announced that they have dosed the first healthy volunteers in their Phase I trial assessing the safety and efficacy of an intranasally delivered formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), named BPL-003.
5-MeO-DMT, alongside other psychedelics, has been part of a boom in research interest due to early findings suggesting such compounds may be able to help people living with mental health disorders. Until now, 5-MeO-DMT has been less well studied than other psychedelic compounds such as psilocybin.
To find out more about their trial approach and wider research into 5-MeO-DMT, we spoke to Beckley’s chief scientific offer, Dr. Steve Wooding.
Ruairi J Mackenzie (RM): BPL-003 is a benzoate formulation of 5-MeO-DMT. Is this the same molecule as naturally occurring 5-MeO-DMT, and if not, what are the practical effects of the changes?
Steve Wooding (SW): BPL-003 is Beckley Psytech’s proprietary intranasal benzoate salt formulation of 5-MeO-DMT, a synthetic psychoactive compound which binds to a variety of receptors within the brain pertaining to serotonin. The active moiety is the same as the psychedelic substance that occurs naturally in a number of plant species, as well as in the Sonoran Desert toad.
RM: You mention in your release that the dry powder formulation of BPL-003 may change users’ subjective experience. Is there previous evidence to suggest that alternative formulations can alter experiences in this way?
SW: Formulation work can often be used to change the time to peak concentration of the drug in the system and hence the timing and depth of the subjective experience. Our aim is to generate a rapid, though smooth, rise to peak and hence a positive subjective experience. At a molecular level, more research is needed to resolve the full receptor binding profile of 5-MeO-DMT and understand the functionally selective pharmacology at 5-HT2A and other receptors. Precise changes in receptor conformation result in different signaling cascades with different effects, e.g., behavioral or gene expression.
RM: 5-MeO-DMT has been less well studied in clinical trials than other classical psychedelics, such as LSD. A recent industry report from BrainFutures’ psychedelics medicine report identified only 26 randomized clinical trials for 5-MeO-DMT as compared to more than 150 for LSD. Why has it taken longer for 5-MeO-DMT’s therapeutic potential to be explored?
SW: LSD and psilocybin have been known about for longer and were considerably more researched prior to the reclassification of these substances, which made them effectively illegal and rendered further research very difficult. Attention has moved more recently to shorter acting psychedelics and hence 5-MeO-DMT has come under the spotlight.
RM: Your Phase I study will be using a double-blind randomized approach. Much interest in improving psychedelic trials currently revolves around the use of appropriate controls in research. What controls will your Phase I study use, and do you predict that participants will be able to guess which treatment they have received?
SW: This is a big topic in psychedelic research! We do have placebo volunteers in the Phase I study which will provide some basis for comparison and, as in most Phase I studies, we are primarily interested in the basic pharmacokinetic-pharmacodynamic (PK/PD) effects of the drug to determine future dosing. Going forward to Phase II, we will need to address the issue of valid controls through the use of active (low dose) placebos, blinded raters and other means to eliminate bias.
RM: What are the unique features of 5-MeO-DMT that your clinical team are excited about testing?
SW: First, 5-MeO-DMT is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences.
Second, the ongoing Phase I studies will hopefully provide invaluable information about our novel intranasal formulations of 5-MeO-DMT and its pharmacokinetics and metabolism profile. These are among the first clinical studies to measure these aspects.
References:
1. Ermakova AO, Dunbar F, Rucker J, Johnson MW. A narrative synthesis of research with 5-MeO-DMT. J Psychopharmacol. 2022;36(3):273-294. doi:10.1177/02698811211050543
Stephen Wooding was speaking to Ruairi J Mackenzie, Senior Science Writer for Technology Networks.
