The induction of synaesthesia with chemical agents: a systematic review

This review (2013) investigates how psychedelics (serotonin agonists) elicit synaesthesia (merging of senses) and what neurological mechanisms may underlie these effects.

Abstract

“Despite the general consensus that synaesthesia emerges at an early developmental stage and is only rarely acquired during adulthood, the transient induction of synaesthesia with chemical agents has been frequently reported in research on different psychoactive substances. Nevertheless, these effects remain poorly understood and have not been systematically incorporated. Here we review the known published studies in which chemical agents were observed to elicit synaesthesia. Across studies there is consistent evidence that serotonin agonists elicit transient experiences of synaesthesia. Despite convergent results across studies, studies investigating the induction of synaesthesia with chemical agents have numerous methodological limitations and little experimental research has been conducted. Cumulatively, these studies implicate the serotonergic system in synaesthesia and have implications for the neurochemical mechanisms underlying this phenomenon but methodological limitations in this research area preclude making firm conclusions regarding whether chemical agents can induce genuine synaesthesia.”

Authors: David P. Luke & Devin B. Terhune

Summary

Introduction

Synaesthesia is an unusual condition in which a stimulus will consistently and involuntarily produce a second concurrent experience. It is believed to have a genetic basis, but is also shaped by the environment.

Despite the consensus regarding the developmental origins of synaesthesia, there has been scant systematic quantitative research conducted to explore the phenomenon of transient induction of synaesthesia with chemical agents. This research may lend insights into the neurochemical basis of this condition.

Despite the potential value of studying synaesthesia with chemical agents, there is a relative paucity of research on this topic. The present review summarizes research studies investigating the induction of synaesthesia with chemical agents.

Literature Search and Inclusion Criteria

A literature search was conducted using relevant databases to find studies describing the induction of synaesthesia using psychoactive substances. Four direct experimental attempts were made, but many other studies describe the experience of synaesthesia in the context of other studies.

Drug Types

Most studies and case reports relate to three psychedelic substances, but some also mention ketamine, ayahuasca, MDMA, 4-HO-MET, ibogaine, Ipomoea purpurea,amyl nitrate, Salvia divinorum, and buproprion.

Direct experiments

In four published experimental studies, participants who had previously experienced tone-color associative training but had not experienced synaesthesia took 15 g of dried peyote cactus and experienced various types of synaesthesia, including haptic-visual, kinaesthetic-visual (especially color), and algesic-color.

In the second study, two congenital synaesthetes were administered mescaline doses between 0.3 and 0.5 g on separate occasions. Both groups reported several distinct types of novel synaesthesias, with a relatively equal ratio of novel synaesthesias between synaesthetes and non-synaesthetes.

A third study compared the effects of mescaline, psilocybin, and LSD, administered under blind conditions. Participants experienced more colors and other auditorily-driven visual effects whilst under the influence of mescaline and LSD, but not psilocybin.

Masters and Houston (1966) conducted an informal study with 214 participants in 204 sessions in which psychedelic drugs were consumed. They reported successfully intentionally inducing color-sound and auditory-gustatory synaesthesia with LSD.

Four studies suggest that synaesthesia can be induced in a controlled environment using chemical agents. However, they suffer from a large number of limitations including a lack of placebo control, double-blinds, and randomized allocation.

Indirect experiments

Despite the lack of direct experiments in the last 50 years, nine studies investigated the psychological effects of psychedelic drugs under controlled conditions, including placebo controls. The prevalence of induced auditory-visual synaesthesia was high for psilocybin, and linear dose-synaesthesia relationship was demonstrated for psilocybin.

Studies have found that individuals high in absorption are more prone to drug-induced synaesthesia, including auditory-visual synaesthesia, with substances such as ketamine, psilocybin, ayahuasca, Salvia divinorum, andIpomoea purpurea.

Indirect experimental studies largely corroborate the results of the experimental studies, but they have a number of limitations. Some studies benefit from the inclusion of placebo controls.

Case Reports

We identified 17 case reports exploring the apparent induction of synaesthesia with chemical agents. The phenomenological characteristics of synaesthesia vary among individuals, and one subset of grapheme-color synaesthetes experiences colors as mental representations whereas another subset experiences colors as spatially co-localized with the inducing grapheme.

Case reports describing the modulation of congenital synaesthesias with chemical agents are of special interest. These reports provide further support for the role of serotonin in the modulation of synaesthesia.

Chemically-induced synaesthesia is typically of the auditory-visual variety, particularly auditory-shape and auditory-color, and is sometimes dynamic in nature fluctuating with the sounds as they change.

Surveys

A few surveys report on the prevalence and type of chemically-induced synaesthesias, and most report auditory-visual synaesthesia. The most common type of synaesthesia is music-color synaesthesia, which is also found in cannabis users.

We found one study that surveyed synaesthetes regarding the impact of chemical agents on congenital synaesthesia. Alcohol and caffeine enhanced or reduced synaesthesia to comparable degrees, but LSD had stronger effects.

Types of Synaesthesias

Most studies reporting induction of synaesthesia in non-synaesthetes specified the inducer-concurrent associations. Auditory-visual synaesthesia was the most commonly reported type, but other inducer-concurrent associations were also reported.

Discussion

Here we reviewed the known studies describing the apparent induction and modulation of synaesthesia with chemical agents. We concluded that there is preliminary evidence that these drugs have compatible effects on congenital synaesthesia.

Study Limitations

Despite the importance of convergent results, this research literature suffers from a number of substantial limitations, including a paucity of experimental studies and the absence of placebo controls. Furthermore, there is little information available regarding dosage or the time course of the phenomenon.

The reviews of studies on synaesthesia relied on self-reports, and some forms of synaesthesia resemble states of absorption. Further studies with stronger experimental controls are needed to confirm the reports of non-synaesthetes.

Types of Chemical Agents

The studies reviewed here suggest that a wide range of drugs can produce synaesthesia-like experiences, even in controlled settings. Serotonin agonists are the most common cause of synaesthesia, although non-serotonergic substances such as ketamine and Salvia divinorum have also been reported to induce synaesthesia.

Nevertheless, non-serotonergic compounds can also induce synaesthesia, although most are psychedelic in character. These chemicals all act on different neurochemical systems to each other, yet they all elicit profound changes in consciousness and somewhat similar phenomenological syndromes.

Types of Synaesthesia

The most common form of synaesthesia under the influence of drugs is auditory-visual synaesthesia, which is induced by auditory stimuli and concurrent with visual experiences. However, there is considerable variability across studies in the types of chemically-induced synaesthesias reported by participants.

The present review only partly supports the conclusion that drug-induced synaesthesias tend to differ from congenital synaesthesias in terms of the complexity and types of inducer-concurrent associations. However, there are reports of well-documented types of induced synaesthesia such as spatial-sequence synaesthesia.

Criteria of Synaesthesia

Open question: Are chemically-induced synaesthesias equivalent to congenital synaesthesias? Consensus has yet to emerge regarding the principal characteristics of synaesthesia and the ways by which ostensible synaesthesias can be confirmed as genuine.

There is no clear evidence that chemically-induced synaesthesias are automatic, and there is only one study that confirmed the consistency of melatonin-induced grapheme-color synaesthesia. However, the studies that have attempted to validate induced synaesthesias have produced mixed results.

Congenital synaesthesias tend to be simple associations, whereas chemically-induced synaesthesias are often complex and reflect inducer-concurrent associations not observed in congenital synaesthesias. There is considerable heterogeneity in the types of chemically-induced synaesthesias, and the complexity of the visual concurrent experience is related to dose and time from dosing.

Similarities between chemically-induced synaesthesias and congenital synaesthesias include individual differences in the visuospatial phenomenology of color concurrents, and a tendency for individuals high in absorption to be more prone to chemically-induced synaesthesias.

Future Dir

Future research on chemically-induced synaesthesia will need to utilize up-to-date methodologies and include established measures to verify the occurrence of synaesthesia. This will require placebo-controlled, double-blind studies and consideration of the fact that inducer-concurrent associations may be strengthening over time. Future studies should include more comprehensive phenomenological inventories and use transcranial magnetic stimulation to determine whether chemically-induced synaesthesias are dependent upon similar cortical structures as congenital synaesthesias.

Summary and Conclusions

Although there is consistent evidence that a variety of chemical agents, particularly serotonergic agonists, produce synaesthesia-like experiences, research on this topic remains in its infancy.