Ibogaine is a naturally occurring psychoactive substance derived from the roots of the iboga plant, a species native to central Africa. For centuries, this powerful psychedelic has played a crucial role in the spiritual and medicinal practices of African shamanistic rituals, where it is believed to facilitate healing and personal transformation.
During the late 19th century and early 20th century, doctors in Europe and the United States used ibogaine to treat various ailments. And while ibogaine has garnered interest in the Western medical community for its potential to treat addiction and depression, its complex pharmacological profile and numerous interactions with human biology have hindered its widespread acceptance.
One reason for its limited use is its interference with numerous biochemical processes in the body. Ibogaine binds to hERG (human ether-a-go-go-related gene), which can lead to heart arrhythmias, and is considered a “dirty” drug due to its binding to multiple targets beyond SERT. Despite these challenges, ibogaine’s unique impact on SERT continues to inspire the development of new drug candidates that could help millions of patients suffering from these debilitating conditions.
The Crucial Role of Serotonin Transporter (SERT) in Mental Health
Serotonin, a neurotransmitter, is an essential chemical messenger in the human brain responsible for regulating various physiological and psychological functions, including mood, appetite, and sleep. It contributes significantly to our overall well-being and emotional stability. An imbalance in serotonin levels has been strongly associated with depression, anxiety, and other mood disorders, making the regulation of this neurotransmitter critical in mental health treatments.
The serotonin transporter (SERT) is a protein found in the membranes of nerve cells that plays a pivotal role in regulating serotonin levels in the brain. Its primary function is to transport serotonin across the synaptic cleft, the passageway between nerve cells where neurotransmitters are released, back into the presynaptic neuron. This process, known as reuptake, effectively terminates the action of serotonin and helps maintain a balanced level of the neurotransmitter in the brain.
Given the importance of SERT in managing serotonin levels, it has become a key target for many antidepressant medications, specifically selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro).
Innovative Study Approach: Harnessing Virtual Screening and Docking Techniques
A collaborative effort between researchers from the University of California, San Francisco (UCSF), Duke, and Yale universities aimed to discover novel drug leads capable of blocking SERT similarly to ibogaine.
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The team utilized computer-aided molecular docking techniques to examine a staggering 200 million molecular structures virtually. Docking is a process that entails methodically evaluating chemical structures to determine their ability to bind with a specific protein, allowing scientists to identify potential new drug candidates without the need to create them in laboratory settings.
Developing New Drug Candidates
The virtual-reality-assisted “docking parties” allowed researchers to identify the top five molecules for further refinement. The two most powerful SERT inhibitors were then sent to other research groups for thorough evaluation using animal models of depression, anxiety, and addiction. The outcomes demonstrated that these novel medications were more potent than paroxetine (Paxil) while still maintaining a high degree of selectivity.
The Promising Results and Next Steps
Researchers utilized cryo-electron microscopy (cryo-EM) to verify that one of the two novel drugs, referred to as ‘8090, influenced SERT at the atomic level in a strikingly similar manner to the computer-generated forecasts. There was a reduction in SERT activity with these drugs in a way that was comparable to ibogaine, yet with considerably enhanced potency and selectivity.
In contrast to ibogaine, the new drug candidates did not exhibit any unintended effects on a broad range of transporters and receptors. The creation of these potentially innovative medications offers promising prospects for improved therapeutic results without accompanying side effects.
Brian Shoichet, a principal investigator in the project, has provided the structural details of both drugs to Sigma Aldrich, a company specializing in chemical manufacturing. This move aims to enable other scientists to conduct additional tests on these compounds. Meanwhile, the research team remains committed to identifying even more accurate molecules for potential therapeutic applications.
In conclusion, exploring nature’s hidden treasures, such as the African iboga plant, can transform our understanding of mental health treatment. By harnessing the power of traditional psychedelic plant medicines like ibogaine and employing cutting-edge scientific techniques, researchers are unlocking new pathways to tackle depression and addiction.
The development of these novel drug candidates highlights the importance of interdisciplinary collaboration and the role of “chance” in scientific discovery. As we continue to delve into the mysteries of the natural world, we open up new horizons for healing, offering hope and better therapeutic options for millions of individuals suffering from these debilitating conditions.
Note: The content on this page is for informational purposes only and is not intended to be professional medical advice. Do not attempt to self-diagnose or prescribe treatment based on the information provided. Always consult a physician before making any decision on the treatment of a medical condition.
Veriheal does not support illegally consuming therapeutic substances such as psychedelics but acknowledges that it transpires because of the current illicit status, which we strive to change by advocating for research, legal access, and responsible consumption. Always consult a physician before attempting alternative therapies.
Lemetria Whitehurst is a cannabis nurse educator and writer specializing in cannabis science and culture. Her career in the medical industry spans more than two decades where she began her career as a pharmacy technician before becoming a registered nurse. As an avid reader
and researcher, she is passionate about educating others about cannabis’ medicinal properties.
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