Using personality, psychopathology, and neuropsychological assessment instruments, our team assessed the therapeutic effects of an ayahuasca ritual treatment. Data was collected at the Institute of Applied Amazonian Ethnopsychology (IDEAA), in the Brazilian Amazon Basin. Psychological assessments were obtained both before and at the end of the treatment. The ayahuasca treatment lasted between 3 and 9 months and included biweekly ayahuasca consumption. The sample consisted of 13 patients (8 men, 5 women) with a mean age of 35 years. Nine had a diagnosis of drug abuse and/or dependence; one of borderline personality disorder, and 3 were at IDEAA for personal growth. Results showed that the “Impulsiveness,” “Disorderliness,” “Anticipatory Worry,” and “Shyness with Strangers” subscales of the Temperament and Character Inventory presented statistically significant reductions after treatment, while the “Self-Directedness,” “Responsibility,” “Purposefulness,” and “Congruent Second Nature” subscales presented significant increases. The psychopathology subscales “Positive Symptoms,” “Obsessive–Compulsive,” and “Anxiety” of the Symptom Check-List-90-Revised, were significantly diminished after treatment, as well as all subscales of the Frontal Systems Behavior Scale: “Total,” “Apathy,” “Disinhibition,” and “Executive Dysfunction.” In addition, the “Resistance to Interference” measure of the Stroop Color and Word Test, the Purpose in Life Test, and the “Transcendent Dimension,” “Meaning and Purpose in Life,” “Mission in Life,” and “Material Values” subscales of the Spiritual Orientation Inventory presented statistically significant increases after treatment. Despite important limitations, such as the small sample size and the lack of a control group, the present pilot study provides preliminary evidence suggesting psychotherapeutic effects of ritual ayahuasca treatment in drug-related disorders.