Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant

Abstract

Rationale: Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase inhibitors that render DMT orally active. Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention, with individuals reporting altered somatic perceptions and intense emotional modifications, frequently accompanied by visual imagery. Despite recent advances in the study of ayahuasca pharmacology, the neural correlates of acute ayahuasca intoxication remain largely unknown. Objectives: To investigate the effects of ayahuasca administration on regional cerebral blood flow. Methods: Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double-blind clinical trial. Regional cerebral blood flow was measured 100-110 min after drug administration by means of single photon emission tomography (SPECT). Results: Ayahuasca administration led to significant activation of frontal and paralimbic brain regions. Increased blood perfusion was observed bilaterally in the anterior insula, with greater intensity in the right hemisphere, and in the anterior cingulate/frontomedial cortex of the right hemisphere, areas previously implicated in somatic awareness, subjective feeling states, and emotional arousal. Additional increases were observed in the left amygdala/parahippocampal gyrus, a structure also involved in emotional arousal. Conclusions: The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes.

Psychedelics

“…Psychedelics may alter thalamocortical transmission by stimulating 5-HT 2A receptors located in several key components of the CSTC loops Geyer and Vollenweider, 2008). This interpretation is consistent with the neuroimaging studies showing that oral administration of psilocybin, mescaline, and DMT alter neuronal activity during their peak effects in the frontomedial and frontolateral cortices ("hyperfrontality"), basal ganglia, and thalamus (Hermle et al, 1992(Hermle et al, , 1998Gouzoulis-Mayfrank et al, 1999;Riba et al, 2006), variously correlating with different dimensions of psychedelic states (Vollenweider and Geyer, 2001).…”

“…To examine the neural correlates of acute ayahuasca effects, Riba et al (2006) used single-photon emission tomography to study regional CBF after acute administration of ayahuasca to 15 healthy volunteers. Ayahuasca administration led to bilateral activation of the anterior insula/inferior frontal gyrus, with greater intensity seen in the right hemisphere.…”

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

“…Although nonsignificant, in the present study these effects were observed during a period ranging from 80 to 140 min after AYA administration, which is the time point when the subjective effects of AYA are peaking, as are DMT plasma levels. [8][9][10][11][12] The absence of statistically significant effects on BPRS-TD scores could be explained by the DMT concentration found in our AYA batch (0.08 mg/mL), which is lower than DMT doses used in previous studies that reported significant psychotropic effects of AYA (0.53 mg/ mL DMT). 9,12 The nonsignificant effects of AYA on the BPRS-TD subscale suggest that changes in sensory perception and thought content may not be essential for therapeutic effects.…”

“…6,[8][9][10][11] The psychoactive effects of AYA are produced by a combined action of peripheral (gastrointestinal and liver) monoamine oxidase A (MAO-A) inhibition by harmine and central 5-HT 1A/2A/2C agonist action of DMT on frontal and paralimbic brain areas. 8,9,12 Studies conducted among long-term (i.e., years or decades) members of religious groups that use AYA ritually suggest that this population does not present evidence of psychological, neuropsychological, or psychiatric harm caused by AYA. [13][14][15] In fact, there are several reports describing reduced mental health problems in AYA users.…”

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

“…Self-report questionnaires demonstrated somatic, perceptual and cognitive modifications, together with increases in positive mood and activation (Riba et al 2003). Electroencephalography measures during wakefulness indicated reductions in slow (delta and theta) and alpha-2 activity (Riba et al 2002) and measures of regional cerebral blood flow showed increased perfusion in paralimbic and frontal brain regions (Riba et al 2006). Sleep disturbances have been described for recreational drugs acting on serotonergic neurotransmission, such as 3,4 methylenedioxymethamphetamine (Morgan 2000).…”