By Sarah Hashkes
When we talk about microdosing psychedelics, it’s important we have a mutual understanding of its definition to be able to conduct accurate research, promote regulations, and educate the wider population. This article will look at three main questions and ambiguities regarding the term “microdosing psychedelics” and suggest a definition that would help promote coherence in the field.
1. What are psychedelics? In recent years, MDMA, ketamine, psilocybin, LSD, ibogaine, and other substances have all been called psychedelics, despite having very different mechanisms and risks. This has led to confusion about efficacy and side effects in the larger population. In research, the term “classic psychedelics” is used to refer to a family of chemically similar substances that activate the 5ht2a Serotonin receptor, which include LSD, psilocybin, and DMT. Classic psychedelics do not cause dependency and have a much lower risk profile than substances like MDMA or ketamine. Therefore, when we use the term “psychedelic microdosing,” it would be beneficial to limit the definition to classic psychedelics, and refer to ketamine as a dissociative, and MDMA as an entactogen.
2. What is a “micro” dose? The term “microdosing” exists in pharmaceutical and drug research, but it means something different than the common use of the word in the psychedelic context. The pharmaceutical definition of microdosing is “Less than 1/100th of the dose of a test substance calculated (based on animal data) to yield a pharmacologic effect of the test substance with a maximum dose of 100 micrograms.” This very low, subtherapeutic dose is used to study cellular response of substances. In common use, however, the term “microdosing” is usually understood in relation to a “full” dose of psychedelics, and is around 1/10 to 1/20 of such a dose. The understanding of a “full dose” can vary widely, so there is still ambiguity and potential for harm with frequent consumption of smaller doses.
Especially with respect to psilocybin, it’s important to address a potential health risk of taking “microdoses” that are too big for prolonged periods. This is because psilocybin breaks down into psilocin, which binds to the serotonin 5ht2b receptor. Research into another drug, Fen-Phen (fenfluramine/phentermine), which also activates the serotonin 5ht2b receptor, links daily over-activation of that receptor through Fen-Phen use to heart damage. Research suggests that in terms of binding affinity to the 5ht2b receptor, consumption of approximately 6 mg of Psilocin may be comparable to a 60 mg dose of Fen-Phen. Sixty mg of Fen-Phen has been found to be significantly dangerous, while about half the dose of fenfluramine (27 mg) has been shown to be safe after three months of daily use.
While research has not yet affirmatively or negatively linked psilocin to heart damage, adding a clear maximum dose as part of defining microdosing, for instance no more than 3 mg of Psilocin (or the equivalent in psilocybin), could potentially improve safety in consumers and clarity in research and regulations.
3. Is microdosing just placebo? An outdated understanding of microdosing termed the practice “sub-perceptual”. However, many participants are “breaking blind” in research, as they can feel when they are microdosing. This causes some to believe that microdosing is nothing more than a placebo. In a recent preprint that summarized 44 microdosing research papers, researchers found that microdosing is associated with identifiable subjective drug effects. Thus, the authors caution against describing microdosing as sub-perceptual. They suggest microdosing be defined as “sub-hallucinogenic with no loss of functionality.”
While we need to be careful of the hype around microdosing and acknowledge that for a healthy population that doesn’t suffer from depression or anxiety, current placebo controlled research does not show improvement in emotional scales for depression and anxiety, there is evidence from placebo controlled trials that microdosing affects the brain and can potentially be beneficial for some people including at least some patient populations.
For example, research shows that 3 mg of psilocybin activated around 40% of the brain’s 5ht2a receptors. As little as 5 micrograms of LSD enhanced sustained attention and improved positive mood and 10 micrograms increased subjective reports of “good drug effect.” Thirteen micrograms of LSD had a statistically significant stimulant effects, and altered typical brain wave patterns, in a way which suggests the brain likely is entering into a slightly extra-plastic state with diffused top-down biases.
In a placebo-controlled study with obsessive-compulsive disorder (OCD) patients, symptoms were reduced after microdosing as little as 1.7 mg of psilocybin per 70 kg. It’s also interesting to note that in an animal study using rodents, in which placebo effects are unlikely, microdosing DMT has shown positive effects on mood, anxiety, and fear.
As Oregon and potentially other states legalize psilocybin services, having a clear definition of microdosing as a classic psychedelic used in a dose that is sub-hallucinogenic with no loss of functionality, and with a clear maximum dose would allow for separate regulations that would reduce cost and increase accessibility to microdosing. This clear definition would also increase the accuracy of scientific research.
Microdoses carry potentially lower risk than higher doses and can integrate into people’s day-to-day lives to help build healthier habits. Current research is showing clear signals for microdosing being a potential stimulant and an analysis of 115 users who consented to share anonymized data on Red Light Holland’s iMicroapp reveals this is the main reason younger population is microdosing. Therefore, microdosing might help prevent stimulant misuse as well as help in other mental health conditions such as OCD. But, in order to realize this promise, first we need to agree what microdosing is.
Sarah Hashkes is the CEO of Radix Motion and CITO of Red Light Holland.