The efficacy of microdosing came under scrutiny this week, with a study co-authored by the likes of Robin Carhart-Harris, David Nutt and Amanda Feilding arguing that the “anecdotal benefits of microdosing can be explained by the placebo effect.” The research design was certainly interesting: 191 participants were asked to incorporate placebo control into their microdosing routine, however this was not supervised. Instead, the study was self-blinded, with participants instructed to place placebo and active capsules into envelopes with QR codes, before drawing the envelopes at random.

While this study is, of course, not comparable in rigour to an RCT, the authors claim that their novel self-blinding approach allows them to reach the following conclusion:

“…Our study validates the positive anecdotal reports about the psychological benefits of microdosing (significant improvements from baseline in a broad range of psychological measures); however, our results also suggest that these improvements are not due to the pharmacological action of microdosing, but are rather explained by the placebo effect (lack of significant between-groups differences).”

The full article is available here and is free to access. It was covered broadly in the media: the Guardian; FT; Science; Wired; Forbes; and others.

This is not the first research publication to raise questions regarding the practice of microdosing. While this study focuses on efficacy, other researchers have raised concerns regarding safety. The chronic administration of 5-HT2B agonists has been shown to carry some risks, as summarised on Twitter by Matthew W. Johnson:

“Many of us scientists responsible for the psychedelic research renaissance think there is realistic question about heart valve disease from chronic admin of microdoses. LSD, psilocybin, MDMA all agonize 5-HT2B receptors, a mechanism linked to valve disease.”

Several FDA-approved medications that rely on 5-HT2B agonism, such as fenfluramine/phentermine, have been withdrawn due to the risk of valvular heart disease. However, there is a dearth of longitudinal research on microdosing, and the doses involved are (unsurprisingly) small, so no firm conclusions can be drawn. Perhaps research by the likes of MindMed will give us a clearer picture of the safety profile of microdosing. In the meantime, those interested in this topic might wish to read Kelan Thomas’ article in Charcuna, published in December 2019.

Also under scrutiny this week is “the race to patent psychedelics” which, according to VICE, “is just getting started.” Shayla Love’s article explores the dizzying array of patents filed in relation to a number of psychedelics, including a number of patent applications covering DMT which were highlighted in our latest patent tracker resource.

This week has again demonstrated that a growing number of companies in the space are looking to investigate un(der)explored molecules and indications. This trend is particularly evident among smaller public companies, perhaps aware that later-stage clinical research being undertaken in popular molecules (e.g., psilocybin, MDMA, LSD) and indications (e.g., depression, anxiety, PTSD) is dominated by larger entities backed by significant funding (both for- and non-profit). As these popular areas of study and commercialisation become crowded, press releases increasingly focus on more diverse areas of purported R&D. This week, we learned that:

• PharmaTher plans to investigate neuromuscular diseases;
• Psyched Wellness is conducting preclinical trials of a Muscimol extract;
• Awakn is looking to expand its focus on the treatment of alcohol use disorder with the addition of ketamine;
• Algernon Pharmaceuticals is pressing on with its investigations of DMT for stroke;
• Silo Pharma is hoping to target rheumatoid arthritis using homing peptides as a delivery vehicle; and,
• Bright Minds Biosciences believes its proprietary 5-HT2C agonist will be effective in reducing binge eating.