disorder. Ayahuasca has also been studied for the treatment of addictions and shown to be effective, with lower Addiction Severity Index scores seen in users of ayahuasca compared to controls. Ayahuasca users have also been seen to consume less alcohol. Both in vitro and in vivo experiments have shown the DMT component of ayahuasca may induce the production of new neurons in the hippocampus. Murine test subjects performed better on memory tasks compared to a control group. Future research may lead to treatments for psychiatric and neurological disorders. Ayahuasca has been reported to have been successfully used to treat SUNCT, an excruciating headache disorder, and relieve the symptoms for three weeks at a time. Chemistry and pharmacology Harmala alkaloids are MAO-inhibiting beta-carbolines. The three most studied harmala alkaloids in the B. caapi vine are harmine, harmaline and tetrahydroharmine. Harmine and harmaline are selective and reversible inhibitors of monoamine oxidase A (MAO-A), while tetrahydroharmine is a weak serotonin reuptake inhibitor (SRI). This inhibition of MAO-A allows DMT to diffuse unmetabolized past the membranes in the stomach and small intestine, and eventually cross the blood–brain barrier (which, by itself, requires no MAO-A inhibition) to activate receptor sites in the brain. Without RIMAs or the non-selective, nonreversible monoamine oxidase inhibition by drugs like phenelzine and tranylcypromine, DMT would be oxidized (and thus rendered biologically inactive) by monoamine oxidase enzymes in the digestive tract. Individual polymorphisms of the cytochrome P450-2D6 enzyme affect the ability of individuals to metabolize harmine. Some natural tolerance to habitual use of ayahuasca (roughly once weekly) may develop through upregulation of the serotonergic system. A phase 1 pharmacokinetic study on ayahuasca (as Hoasca) with 15 volunteers was conducted in 1993, during the Hoasca Project. A review of the Hoasca Project has been published. The compound N,N-dimethyltryptamine (DMT) found in ayahuasca has been shown to be immunoregulatory by preventing severe hypoxia and oxidative stress in in vitro macrophages, cortical neurons, and dendritic cells by binding to the Sigma-1 receptor. In vitro co-treatment of monocyte derived dendritic cells with DMT and 5-MeO-DMT inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10 by activating the Sigma-1 receptor. Neurogenesis Several studies have shown the alkaloids in the B. caapi vine promote neurogenesis. More specifically, in vitro studies showed that harmine, tetrahydroharmine and harmaline, stimulated neural stem cell proliferation, migration, and differentiation