Research from the University of California published in the journal Nature has found that tabernanthalog (TBG), an analogue of the plant-based substance ibogaine, has anti-addictive and antidepressant effects on rats.
These promising results suggest that TBG, which is a non-hallucinogenic, safer form of ibogaine, could be useful in treating addiction and depression in humans. Scientists hope that the substance could also lead to anti-addictive and antidepressant effects in humans, validating TBG for therapeutic use.
With 2.8 million people accessing NHS mental health services from 2019 to 2020 (NHS Mental Health Services Statistics, June 2020), there is a clear need for further development of our understanding of mental health problems and how to treat them.
While many people think that mental health problems such as depression and anxiety are just caused by the levels of the neurotransmitter serotonin, more recent research pioneered in part by researchers from the University of Oxford suggests that these mental illnesses have more complicated biological roots. In particular, serotonin levels play a role in neural plasticity, which can be broadly described as the ability of the brain’s neural connections and behaviour to be modified in response to new information, as well as playing a role in neurogenesis (the generation of new neurons in the brain), with Glover and colleagues’ 2017 work at the University of Oxford discussing the role of neurogenesis in anxiety in rodents.
Antidepressants are thought to regulate neural plasticity within the brain, as well as stimulating neurogenesis, thus increasing the capacity for recovery from depression (for example, see Santarelli and colleagues, 2003). Crucially though, this does not guarantee recovery, as there is a global increase in sensitivity to the environment’s effects on mood whether positive or negative, which could explain why some patients do not benefit from antidepressant treatment.
Current treatments for depression, such as Cognitive Behavioural Therapy (CBT) and antidepressants like Prozac, often reduce the symptoms experienced by patients, but some people do not benefit from them. Alternative treatments are therefore being explored, such as using psychedelic substances like ketamine. This substance has proven effectiveness from research, as it demonstrates a rapid and long-lasting antidepressant effect mere hours after being administered, as well as being effective in reducing symptoms for those with treatment-resistant depression.
Similarly, pioneering research from Lindsay Cameron and colleagues published in Nature on the 9th of December 2020 explores the potential therapeutic use in treating depression for another psychedelic substance: ibogaine (IBG). The researchers report that IBG is subject to safety concerns due to its toxicity, hallucinatory properties, and recorded induction of cardiac arrhythmia, so despite its beneficial anti-addictive and antidepressant properties, it is not safe for therapeutic use in humans. They therefore aimed to harness IBG’s therapeutic properties while reducing safety concerns, which they achieved by creating an analogue of IBG named tabernanthalog (TBG).
This non-hallucinogenic, psychedelic substance has a very similar chemical structure to IBG, but was without IBG’s safety concerns when administered to rodents. Crucially, the researchers found that there was increased structural neural plasticity, reduced alcohol- and heroin-seeking behaviour (thus potential to treat addiction), and an antidepressant-like effect in the rodents who were given TBG.
These results suggest that if the use of this substance is extended to human trials and the researchers find similar therapeutic effects, TBG may be useful for treating depression and addiction in humans. A particular benefit of this analogue, should it be found safe for human use, is that it is produced in a single step so can be easily synthesised, allowing large quantities to be produced rapidly.
TBG could be another tool in psychology’s arsenal of treatments to address mental health issues like depression, with promising potential to help those who are resistant to the treatments currently in use. These are only preliminary results as rodents were the participants in this study, so there is no guarantee of efficacy in humans yet. However, there is certainly potential for TBG to be used as a treatment for depression and addiction should these antidepressant and anti-addictive effects be found in later research involving human participants.
Image Credit: Marco Schmidt on Wikimedia Commons