Macrodosing to microdosing with psychedelics: Clinical, social, and cultural perspectives

This paper (2022) explores the influence of macrodosing and microdosing on various clinical, social and cultural perspectives. The influence of microdosing is relatively unexplored in a formal context, but informal accounts propose that microdosing plays an important role as both therapeutic intervention and a cognitive enhancement tool.

Abstract

“To date, the clinical and scientific literature has best documented the effects of classical psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), in typical quantities most often associated with macrodosing. More recently, however, microdosing with psychedelics has emerged as a social trend and nascent therapeutic intervention. This variation in psychedelic practice refers to repeat, intermittent ingestion of less-than-macrodose amounts that do not cause the effects associated with full-blown “trips”. Microdosing paves the road to incorporating psychedelic drugs into a daily routine while maintaining, or even improving, cognitive and mental function. Unlike macrodosing with psychedelics, the influence of microdosing remains mostly unexplored. And yet, despite the paucity of formal studies, many informal accounts propose that microdosing plays an important role as both a therapeutic intervention (e.g., in mental disorders) and enhancement tool (e.g., recreationally—to boost creativity, improve cognition, and drive personal growth). In response to this relatively new practice, we provide an integrative synthesis of the clinical, social, and cultural dimensions of microdosing. We describe some of the overarching context that explains why this practice is increasingly in vogue, unpack potential benefits and risks, and comment on sociocultural implications. In addition, this article considers the effects that macro- and microdoses have on behavior and psychopathology in light of their dosage characteristics and contexts of use.”

Authors: Ayse Kaypak & Amir Raz

Summary

Microdosing with psychedelics is a social trend that has emerged as a nascent therapeutic intervention. It is still mostly unexplored, but many informal accounts propose that microdosing plays an important role as both a therapeutic intervention (e.g., in mental disorders) and enhancement tool (e.g., to boost creativity, improve cognition, and drive personal growth).

Introduction

Psychedelic substances produce mind-altering experiences that may have therapeutic and recreational value. They mainly work through 5-HT2A receptor agonism, affecting perception, mood, and thought.

Microdosing has emerged as a modern practice with illegal substances, with great differences in substance, dose, frequency, and duration.

Microdosing is the frequent use of psychedelic substances in low doses, with many individuals reporting benefits in creativity and productivity. However, there is sparse scientific support from controlled studies.

Macrodoses

Psychedelics have been used by indigenous healers for centuries, but were not used in modern medicine until the isolation of mescaline from the peyote cactus and the synthesis of LSD from ergot fungus. Several clinical trials have been published showing promising results, but the majority of these trials were criticized as methodologically weak and suboptimal. In addition, public opinion concerning psychedelics responded to media sensationalism, lack of information, and cultural biases, rather than evidence-based harm assessments.

Although conventional clinical wisdom has confirmed that LSD and psilocybin rank as some of the least harmful recreational drugs, population studies have found no association between psychedelic use and negative mental health outcomes.

After a lacuna in psychedelic research from the 1970s to the 1990s, a renaissance is underway with studies on depression, end-of-life distress, alcohol dependence, tobacco dependence, and obsessive-compulsive disorder.

Microdoses

Unlike the vast literature addressing macrodoses and megadoses, the effects of low doses of psychedelics remain underexplored. However, anthropological accounts mention the use of psychedelic substances in low doses for a variety of therapeutic effects, including to increase libido, reduce appetite, increase courage, and treat some inflammatory and infectious disorders.

Following Fadiman’s book, many stories on microdosing appeared in the popular media. Individuals reported improvement in creativity and productivity, and preferred microdosing to psychostimulants as a cognitive enhancer.

In psychedelic literature, microdose is defined as a dose range that does not cause marked perceptual alterations (such as hallucinations). It is typically taken every few days, rather than daily, and the effects last for only the dosing day.

Preclinical studies with microdosing of LSD report a mixed bag of effects, from anxiogenic to anxiolytic and antidepressant. Males gain weight whereas females do not, and female rats display a decrease in dendritic spine density whereas males do not.

In online surveys and observational studies, microdosing has been reported to improve creativity, mood, and cognition, increase sociability, lower dysfunctional attitudes, lower negative emotionality, higher wisdom, and open-mindedness. However, the first double-blind, placebo-controlled trial of microdosing found no significant changes in perception, concentration, and consciousness.

Discussion

Recent systematic reviews have reported that psychedelics have immediate, substantial, and sustained outcomes when administered in supportive and controlled settings, even after a single dose. They have also been dubbed “psychoplastogens” and may be good candidates for treating neurodegenerative disorders.

According to anecdotal reports and preliminary evidence, microdosing with psychedelics can be a psychostimulant, antidepressant, and psychoplastogen, with its own clinical benefits. However, these relative merits come with related risks.

The illegality of psychedelics increases health risks, but Portugal decriminalized illicit drugs in 2001 and saw a decrease in problematic drug use.

Research with psychedelics faces many challenges, including problems with drug purity, concomitant drug use, precise dosing, and screening for psychiatric and medical conditions. However, microdosing is an advantageous focus for such research.

Future research might benefit from comparing data from psychedelic-naive participants with that of experienced individuals, and microdosing offers a safer and gentler entry point by largely bypassing the stigma and fear around these substances, especially for those new to them.

Many sources suggest that the effects of psychedelics may be context-dependent, including psychological factors, environmental context, and cultural elements. Additionally, the cultural discourse differs between psychedelic substances, and this would further constitute the context-dependent effects of psychedelics.

Psychedelic-assisted psychotherapy has benefited from increased awareness of the importance of cultural factors. However, when contextual factors are neglected, psychedelic experience has been found to be clinically ineffective.

Set and setting theory and placebo response theory consider how non-pharmacological/biological factors related to cognition and meaning modulate and shape the response to a given therapy. Placebo effects are further conceptualized as contextual factors.

Psychedelics have been framed as meaning-response magnifiers, or as hyperactive placebo catalysts, perhaps by amplifying contextual factors and expectations. Positivity bias and positive reports and media headlines may also shape and amplify response expectancies associated with microdosing.

Microdoses can have minimal, subtle, and ambiguous effects, and users may interpret small changes as being in line with their expectations. However, the jury is still out on whether users should subjectively detect a microdose for its beneficial effects.

In high doses, psychedelics can cause acute psychological distress and prolonged psychosis, especially for patients with pre-existing psychological problems. There are also ethical concerns regarding cultural appropriation, commercialization, and extraction of pristine cultural heritage without consent. Ethical concerns regarding microdosing include lack of adequate controlled studies concerning efficacy and safety, as well as therapeutic value and associated risks. In addition, microdosing may incite social competition and perfectionism, and may receive the same label as doping in sports.

Conclusion

The benefits and risks of microdosing are unclear at this time, but informal accounts and early research suggest that microdosing is likely beneficial both clinically and socially. More rigorous investigation into the effectiveness and safety of short- and long-term use is the only responsible course of action to take.

Study details

Topics studied
Microdosing

Study characteristics
Theory Building

Participants
0 Humans