Daytime ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers

This randomized, double-blind, active placebo-controlled, cross-over study (n=22) investigated the effects of daytime ayahuasca (DMT 70mg/70kg) consumption on sleep parameters, compared with active placebo (20mg d-amphetamine). Results showed that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an interaction between these drugs and brain circuits modulating REM- and SWS- sleep.

Abstract

“Objectives: Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilian-based religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N,N-dimethyltryptamine (DMT) and β-carboline alkaloids with monoamine oxidase-inhibiting properties that render DMT orally active. DMT interacts with serotonergic neurotransmission acting as a partial agonist at 5-HT1A and 5-HT2A/2C receptor sites. Given the role played by serotonin in the regulation of the sleep/wake cycle, we investigated the effects of daytime ayahuasca consumption in sleep parameters.

Measurements and results: Subjective sleep quality, polysomnography (PSG), and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of a placebo, an ayahuasca dose equivalent to 1 mg DMT kg−1 body weight, and 20 mg d-amphetamine, a proaminergic drug, as a positive control. Results show that ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance, in contrast with d-amphetamine, which delayed sleep initiation, disrupted sleep maintenance, induced a predominance of ‘light’ vs ‘deep’ sleep and significantly impaired subjective sleep quality. PSG analysis also showed that similarly to d-amphetamine, ayahuasca inhibits rapid eye movement (REM) sleep, decreasing its duration, both in absolute values and as a percentage of total sleep time, and shows a trend increase in its onset latency. Spectral analysis showed that d-amphetamine and ayahuasca increased power in the high frequency range, mainly during stage 2. Remarkably, whereas slow-wave sleep (SWS) power in the first night cycle, an indicator of sleep pressure, was decreased by d-amphetamine, ayahuasca enhanced power in this frequency band.

Conclusions: Results show that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an interaction between these drugs and brain circuits modulating REM and SWS.”

Authors: Manel J. Barbanoj, Jordi Riba, Susanna Clos, Sandra Giménez, Eva M. Grasa & Sergio Romero

Summary

Abstract

Ayahuasca, a traditional South American psychoactive beverage, interacts with serotonergic neurotransmission and may affect the sleep/wake cycle.

Subjective sleep quality, polysomnography and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of ayahuasca, d-amphetamine and a placebo. Ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance.

Introduction

Ayahuasca is a psychotropic plant concoction that is used in traditional medicine and magico-religious practices by the indigenous peoples of the Amazon. It has been legalized in the US and Europe by several synchretic religions.

Ayahuasca tea combines DMT from P. viridis with MAO-inhibiting -carboline alkaloids from B. caapi, and interacts mainly with serotonergic neurotransmission. It shows psychedelic and stimulatory effects compatible with 5-HT2A agonism and pro-aminergic effects.

Serotonin plays a prominent role in the regulation of sleep – wake cycles, and several serotonin receptor subtypes are involved in this regulation.

In the present study, daytime ayahuasca administration was compared with placebo and d-amphetamine as a positive control. We hypothesized that ayahuasca would deteriorate sleep initiation, maintenance and subjective quality, similar to that previously reported for d-amphetamine.

Materials and Methods

Twenty-two young healthy male volunteers were recruited. They were required to have taken psychedelics on at least ten occasions without sequelae derived thereof, to have a regular sleep – wake habit, and to not take any medications or illicit drugs during the study.

The administered drugs were a placebo, 20 mg d-amphetamine and 1 mg DMT/kg body weight of freeze-dried encapsulated ayahuasca. Each volunteer received the same number of capsules on each experimental session.

The study involved three experimental sessions, plus an adaptation night in the sleep laboratory, and involved administration of capsules containing one of the three treatments. Data were collected from 11:00 P.M. until 7:00 A.M. on the three experimental days.

Subjective effects were measured using the Hallucinogen Rating Scale and the Addiction Research Center Inventory. The HRS measures six scales: somaesthesia, affect, volition, cognition, perception, and intensity, whereas the ARCI measures five scales: euphoria, sedation, lysergic acid diethylamide, intellectual energy and efficiency, and amphetamine-like effects.

Volunteers slept in individual, sound-attenuated, temperature-regulated rooms and were supervised by qualified technical staff. They completed a self-rating scale on the subjective quality of sleep and awakening each morning.

Data were acquired by means of two different systems: the Coherence 32E-Deltamed system and the SleepLab-Aequitron Medical Recordings system. Each system recorded six EEG-channels, two electro-oculographic leads and one chin electromyographic channel.

Three channels were used to monitor the respiratory function: one for airflow signal, two for rib cage and abdominal motion, and two for limb movements. The channels were calibrated before each recording.

The sleep recordings were visually scored by two independent sleep scorers and a third expert from the same laboratory.

Sleep variables were derived by visual scoring using standard criteria. Total sleep time, total sleep period, number of awakenings, sleep efficiency index, slow-wave sleep (3+4) and REM are expressed in minutes and in percentages of the total sleep time. The latency to stages 1, 2 and 3 was measured, and the REM latency was measured as well. The number of NREM and REM periods, as well as the average duration of NREM and REM periods and of sleep cycles were computed.

Ayahuasca, d-amphetamine and placebo were tested on sleep EEG, and the spectral analysis method provided more information about the continuity of sleep stages than the conventional R&K criteria.

Slow-wave activity and spindle frequency activity were measured during whole night sleep, and delta EOG activity was measured during REM sleep. A moving average was computed to smooth the signal throughout the night.

To compensate for individual differences in the occurrence and duration of the NREM – REM cycles, the duration of each cycle was subdivided into 24 equal parts and the averaged across subjects.

A Spanish version of the Self-assessment Scale for Sleep and Awakening Quality (SSA) was used to evaluate subjective sleep quality, subjective awakening quality and the presence of somatic complaints.

Statistical Analysis

To decrease the risk of type I error, PSG variables were grouped into four clusters: sleep initiation and maintenance variables, sleep architecture variables, NREM – REM period variables, and subjective effect measures. Multivariate analysis of variance was used to assess effects on EEG power spectra and AUCs.

Results

Four subjects were excluded from the study due to technical problems, leaving 18 participants with complete PSG recordings. All participants completed the trial and were well tolerated.

Sleep initiation and maintenance

Significant results were observed for sleep initiation and maintenance variables. D-Amphetamine induced significant increases in latencies to stage 1, stage 2, and REM compared to placebo and to ayahuasca.

Sleep architecture

Significant results were observed for sleep architecture variables (Pillai’strace:1.28;F =4.60, df =20, 52; p 0.001), except for SWS in percentage of TST and movement time. D-amphetamine induced significant decreases in REM, SWS, and stage 1 sleep, but only when measured in minutes and percentage of TST.

NREM–REM periods

Significant results were observed for NREM and REM period variables, and the average duration of NREM periods and sleep cycles were increased after d-amphetamine and ayahuasca.

EEG power spectra

The power spectrum in NREM was different after d-amphetamine and ayahuasca, but the SWA spectrum showed no significant differences between placebo and the active compounds.

On all nights, SWA was higher in NREM episodes and lower in REM episodes, and a declining trend was observed over consecutive NREM episodes after all experimental interventions.

To avoid a potential bias, cycle-by-cycle comparisons should be conducted on nights with the same number of cycles. Eight subjects showed the same number of cycles after ayahuasca and placebo, and SWA showed a significant increase in activity after ayahuasca.

The typical pattern of slow activity in EOG channels during REM sleep was observed after all three treatments.

Subjective sleep and awakening quality variables significantly decreased after d-amphetamine treatment compared to placebo and ayahuasca.

Discussion

Daytime drug administration caused significant psychotropic effects as measured by self-report questionnaires. Ayahuasca showed the most relevant differences between the two drugs, with modifications in perception and increased impairment in the HRS-perception and HRS-volition subscales, respectively.

Ayahuasca did not induce a deterioration of sleep, but did increase stage 2, decreased REM stage duration and showed a trend to increase REM latency. It also increased the average duration of non-REM periods and sleep cycles.

Psychedelics have the capacity to induce increases in activation that can be measured by self-report questionnaires and by EEG. Both ayahuasca and d-amphetamine impair sleep initiation and maintenance variables and suppress REM.

The effects of ayahuasca on sleep have been studied in very few reports, most of which were published in the 1960s. Ayahuasca increases the duration of the first or second REM period and is associated with a below-normal amount of REM sleep during the second half of the night. Ayahuasca contains many alkaloids, including harmine, which undergoes intense first-pass metabolization. THH, a weaker MAO inhibitor than harmine but a stronger serotonin reuptake inhibitor, may have played a role in the effects observed on REM sleep.

Ayahuasca has MAOIs and SSRIs, but its acute pharmacological effects in humans are those of the classical serotonergic psychedelics acting at the 5-HT1A and 5-HT2A/C sites. These receptors play a role in sleep physiology, with 5-HT1A receptors being involved in REM sleep regulation and 5-HT2A/C receptors in SWS regulation.

Spectral analysis showed that d-amphetamine increased power in the high-frequency range and reduced SWA in the first night cycle, which could be explained by the alerting pattern associated with the morning intake of the d-amphetamine.

Ayahuasca showed increases in power in the high frequencies, but not in the slow-wave range, in contrast to d-amphetamine, which showed a decrease. This could be explained by activation of 5-HT1A receptors, or by a functional desensitization of 5-HT2 receptors. The acute effects of ayahuasca could cause an increase in sleep pressure, which is typical of certain situations, such as sleep deprivation and physical exercise.

Ayahuasca does not affect sleep quality, but inhibits REM sleep and increases slow-wave activity in the first night cycle.