Acute Biphasic Effects of Ayahuasca.

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered

Beta rhythm cluster.

<p>Changes in beta frequency band power spectrum over the 2 hours since ayahuasca ingestion. A) F statistics in the entire scalp revealed a significant cluster at left fronto-temporal electrodes (FT9, AF7, F7, FT7 and T7, p = 0.0260, highlighted by white *). B) Beta band increases did not survive post-hoc analysis. Inset highlights the electrodes averaged for the post-hoc analysis, in correspondence with A. Data in B is expressed as mean and standard error.</p

Concentration of chemical compounds in Ayahuasca.

<p>Concentration (mg/ml) of 13 compounds screened in the <i>Hoasca</i> tea, estimated ingested dose (mg/kg) and total amount ingested of each compound (mg).</p><p>Concentration of chemical compounds in Ayahuasca.</p

Alpha rhythm cluster.

<p>Changes in alpha frequency band power spectrum over the 2 hours since ayahuasca ingestion. A) F statistics in the entire scalp revealed a significant cluster at left parieto-occipital electrodes (P7, PO7, O1 and Oz, p = 0.0398, highlighted by white *). B) Post-hoc analysis revealed decreases in the cluster depicted at left to be significant after 50 minutes from ingestion of ayahuasca (*p<0.05, corrected). Inset highlights the electrodes averaged for the post-hoc analysis, in correspondence with A. Data in B is expressed as mean and standard error.</p

Slow-gamma rhythm clusters.

<p>Changes in slow-gamma frequency band power spectrum over the 2 hours since ayahuasca ingestion. A) F statistics in the entire scalp revealed three significant clusters at the right frontal (Fp2, AF4 and F2, p = 0.0046, highlighted by white *), left centro-parieto-occipital (C3,CP3, P5, P3, P1, PO7 and O1, p = 0.0152, highlighted by white x) and left fronto-temporal (FT9, AF7, F7, FT7, T7 and C5, p = 0.0026, highlighted by white +). B) Slow-gamma band power increases at right frontal cluster were significant only after 100 min from ayahuasca ingestion (*p<0.05, corrected). C) Slow-gamma band power increases at left centro-parieto-occipital cluster were significant only after 100 min from ayahuasca ingestion (*p<0.05, corrected). D) Slow-gamma band power increases at left fronto-temporal cluster were significant after 75, 100 and 125 min from ayahuasca ingestion (*p<0.05, corrected). Insets in B, C and D highlight the electrodes averaged for each post-hoc analysis, in correspondence with A. Data in B, C and D is expressed as mean and standard error.</p

Concentration of chemical compounds in plasma samples.

<p>Values obtained for 10 compounds detected in plasma samples. Cmax values are expressed in ng/ml, Tmax values in min, AUC in g min/ml.</p><p>Concentration of chemical compounds in plasma samples.</p

HRS subjective ratings.

<p>Subjective results as measured with the Hallucinogen Rating Scale–Brazilian Version. Int = Intensity, Som = Somaesthesia, Aff = Affect, Per = Perception, Cog = Cognition and Vol = Volition. For all six sub scales four is the maximum score possible.</p

Beta-carboline’s concentration and EEG effects.

<p>Statistical associations between plasma levels of the beta-carbolines harmine (first column from left), harmol (second column), harmaline (third column), harmalol (fourth column), THH (fifth column) and THH-OH (last column) with delta, theta (only for THH-OH) and alpha, slow- and fast-gamma frequency bands (not significant for THH-OH). A) Harmine and alpha. B) Harmol and alpha. C) Harmaline and alpha. D) Harmalol and alpha. E) THH and alpha. F) Harmine and slow-gamma. G) Harmol and slow-gamma. H) Harmaline and slow-gamma. I) Harmalol and slow-gamma. J) THH and slow-gamma. K) Harmine and fast-gamma. L) Harmol and fast-gamma. M) Harmaline and fast-gamma. N) Harmalol and fast-gamma. O) THH and fast-gamma. P) THH-OH and delta. Q) THH-OH and theta. Corresponding p values and Cohen’s <i>d</i> for each cluster are shown in the main text.</p

Tryptamine’s concentration and EEG effects.

<p>Statistical associations between plasma levels of DMT (first column from left), DMT-NO (second column), NMT (third column) and IAA (fourth column) with the delta, alpha, beta, slow- and fast-gamma frequency bands. No significant effects were found with the theta band. A) DMT and delta frequency band. B) DMT and alpha frequency band. C) DMT-NO and alpha frequency band. D) IAA and alpha frequency band. E) DMT and beta frequency band. F) NMT and beta frequency band. G) DMT and slow-gamma frequency band. H) DMT-NO and slow-gamma frequency band. I) NMT and slow-gamma frequency band. J) IAA and slow-gamma frequency band. K) DMT and fast-gamma frequency band. L) DMT-NO and fast-gamma frequency band. M) NMT and fast-gamma frequency band. N) IAA and fast-gamma frequency band. Corresponding p values and Cohen’s <i>d</i> for each cluster are shown in the main text.</p

Plasma data.

<p>Time-concentration curves for DMT, NMT and DMT-NO (A), IAA (B), THH and THH-OH (C), harmine and harmol (D), harmaline and harmalol (E) and correlation between hamaline Tmax with time for emesis. All concentration data is expressed as mean ± SD in ng/ml. All times expressed in minutes.</p