Possible Interactions Between 5-HT2A Receptors and the Endocannabinoid System in Humans: Preliminary Evidence of Interactive Effects of Ayahuasca and Endocannabinoids in a Healthy Human Subject

This open-label case study (n=1) investigated the effects of a single oral dose of ayahuasca (49.14mg DMT, 124.88mg harmine, 54.6mg tetrahydroharmine, and 2.73mg harmaline) and observed a continuous decrease in the plasma level of the endocannabinoid anandamide and late-stage increase of the endocannabinoid 2-arachidonoylglycerol.

Abstract

No abstract available

Authors: Rafael G. Dos Santos, José A. Crippa, Flávia de Lima Osório, Juliana M. Rocha, Giordano N. Rossi, Camila Marchioni, Maria E. C. Queiroz, Gabriela O. Silveira, Mauricio Yonamine, Jaime E. C. Hallak

Summary

Maria Romanos, MSc

Ayahuasca is a hallucinogenic preparation made from the bark of Banisteriopsis caapi and the leaves of Psychotria viridis. It is traditionally used for ritual and therapeutic purposes in the Northwestern Amazon Basin.

A recent randomized controlled trial with 29 patients with treatment-resistant depression showed that ayahuasca induced significant antidepressant effects 7 days after drug intake. The mechanisms behind these effects are not clear, but may involve agonism at cortical 5-HT2A receptors in brain areas related to emotional processing. Ayahuasca samples were analyzed using gas chromatography, nitrogen-phosphorus detection, and ultrahigh-performance liquid chromatography – tandem mass spectrometry.

To the Editors:

The volunteer was not taking any medication and was requested to abstain from alcohol, tobacco, and caffeinated drinks 12 hours before ayahuasca intake. A urinalysis was performed before ayahuasca intake and blood samples were collected after 5 hours of use.

The volunteer remained in the laboratory under observation for 6 hours after drug intake and was called 24 hours later to report any positive/negative effects.

Ayahuasca administration was associated with a reduction in anxiety, sedation, cognitive impairment, and discomfort, but no effects were observed in the BAI. There were also decreases in AEA and 2-AG levels, but these levels increased above baseline at 240 minutes after drug intake.

Ayahuasca was well tolerated by the volunteer, who reported mild and short-lived subjective and somatic effects.

DISCUSSION

Ayahuasca intake was associated with decreased levels of anxiety-elevating chemicals (AEA) and an increase in levels of anxiety-reducing chemicals (2-AG) in the blood. Cardiovascular measures were moderately altered, and the most relevant adverse effects were mild and transitory nausea and gastrointestinal discomfort.

The ECS modulates stress and anxiety. Although we replicated the increase in 2-AG observed in basic studies, our results regarding AEA were less consistent, because we observed a continuous decrease in AEA levels over time and not an increase.

Ayahuasca may affect the ECS, and therefore the 5-HT2A receptor, which is co-expressed in brain regions associated with emotional processing. Further research is needed to better understand the effects of ayahuasca on the ECS.