Mental effects and potential therapeutic use of kratom/mitragynine

Kratom (Mitragyna speciosa) is a traditional plant of the (sub)tropical regions of Southeast Asia, where it has been widely used since the 19th century for medicinal applications. In recent decades, kratom products containing leaf extracts have become increasingly available in Europe and the US. Such products are classified by the Food and Drug Administration (FDA) as “new dietary ingredients” with inadequate information on their safety. Despite this, kratom is used worldwide for self-medicating some conditions (e.g., pain, substance use disorder, and psychiatric symptoms) outside clinical settings. In addition, there is anecdotal evidence that kratom is being used for performance enhancement and recreational purposes. One of the main active and most studied alkaloids present in kratom is mitragynine (MG), which acts on opioid (mu-, delta- and kappa) and non-opioid (e.g., α-adrenergic, dopamine, and serotonin) receptors. Serious safety issues linked to kratom use have often been explained by drug-drug interactions and have been mainly described in case reports from the West. Despite the global spread of kratom for recreational and medical purposes, as shown in case reports, drug fora and surveys, clinical and toxicological data from controlled studies on kratom and mitragynine exposure in humans are quite limited. Therefore, the knowledge about kratom and mitragynine use (e.g., safety and motivations), their behavioral effects, and the balance between therapeutic benefits and addictive potential need to be further investigated. This dissertation aimed to enhance understanding of kratom/mitragynine use and their behavioral effects through two literature reviews, a netnographic analysis, online research on the darkweb, a placebo-controlled single-blind experimental study, and a survey. Findings in this dissertation contributes to the intense debate on kratom use as therapeutic aid in some conditions and to the knowledge base of clinicians in the field of psychiatry and addiction medicine. Further tolerability and safety studies, including randomized-controlled trials, are necessary to evaluate kratom’s potential therapeutic benefits and safety issues, for which studies in this dissertation offer a potential basis.