New Study on Yohimbine for Working Memory Enhancement
Does the noradrenergic drug yohimbine have nootropic effects?
Posted Jun 26, 2020
A study titled “(Lack of) Effects of noradrenergic stimulation on human working memory performance”  was published on the 25th of June 2020 in the journal (Springer) Psychopharmacology. The effects of 20 mg and 40 mg doses of yohimbine on working memory performance compared with placebo in healthy humans were examined.
Purpose of the Study
Previous research suggests noradrenaline may be involved in human working memory performance. But it has previously been unclear if the relationship is linear or u-shaped. Perhaps an optimal level of noradrenaline could be conducive to increased working memory capacity, with higher or lower levels having detrimental effects.
This study was aimed at elucidating how pharmacological manipulation of noradrenaline levels with yohimbine affected working memory performance in healthy humans.
There was also a secondary purpose of the study, the authors note:
”Second, we aimed to test whether noradrenaline modulates working memory performance after exposure to controllable vs. uncontrollable aversive events.”
A working memory (WM) task was used to assess the difference in baseline WM performance between groups. Several subjective self-report assessments were also used to assess baseline differences between groups. The WM task, called adaptive n-back, was administered again around 70 minutes after drug administration to test for the effects of yohimbine (20 or 40mg) compared with placebo on WM.
The researchers also aimed to find out if the effects of control of negative stressors on WM performance was affected by yohimbine. To test this, participants underwent an electric shock experiment, in which they either had control or not of the shocks. The participants in the group that received electric shocks without control over them were told they had control over the shocks.
The researchers lied to participants, which may raise doubts as regards the ethics of the study. The shocks were considered unpleasant but painful, which means participants probably didn’t suffer tremendously. They were also informed after the experiment that they had no control over the shocks during the experiment and received a monetary reward for their time and effort. The ethics committee of the Hamburg Medical Association approved the study protocol, which shows us as readers of the study that there was an independent party verifying the research was ethically conducted.
Grouping of participants was randomized. The study was placebo-controlled, with three dosage groups, two of which received 20 mg and 40 mg of yohimbine respectively. For each of the dosage groups, the participants were further divided into three sub-groups, resulting in nine final study groups. The three sub-groups of each dosage group were in different electric shock conditions (in the second test).
Participants that finished the study (8 dropped out due to yohimbine side effects) had an average age of around 25, and around half of them were female. In the final data analysis of the study, 121 participants were included.
No baseline differences were found between any of the nine study groups. This makes the working memory and electric shock test results after yohimbine or placebo consumption and any inferences made about the effects of yohimbine on WM performance more reliable.
Objective controllability increased the subjective controllability of the shocks and objective learning of how to control shocks. This means that the participants that had the ability to control shocks also experienced a greater degree of control of the shocks and learned to control the shocks more effectively. These findings were expected by the researchers.
The effects of either 20 mg or 40 mg of yohimbine on WM performance were slightly more surprising. No significant effects were found on the n-back task, and shock control response learning was unaffected, compared to placebo.
Because of the apparent lack of effects from yohimbine, the researchers conducted further statistical analysis, which confirmed that yohimbine didn’t have any effect on WM performance.
The findings of the study do not support the idea that noradrenaline manipulation positively or negatively influences working memory performance.
The researchers also concluded:
“Moreover, yohimbine did not affect the acquisition of instrumental control over aversive events, the subjective sense of helplessness after exposure to uncontrollable aversive events, or the relation between uncontrollability and working memory performance.”
Most other studies showing positive effects from noradrenergic manipulation have assessed the visuospatial aspect of working memory. The present study used the n-back task which does not test visuospatial WM. The n-back test assesses other aspects of working memory and fluid intelligence . This could be the reason for the lack of effects on working memory as tested in this study.
It is unclear what the side effects that made 8 participants drop out were, and side effect information was lacking in general in this study.
It can be concluded that yohimbine did not affect working memory in this well-designed healthy human placebo-controlled study. The use of yohimbine as a drug for cognitive enhancement, specifically for working memory enhancement, is therefore not recommended.
This article was originally published at blog.nootralize.com; it is not a substitute for professional medical advice diagnosis or treatment.
 Wanke, N., Müller, J.C., Wiedemann, K. et al. (Lack of) Effects of noradrenergic stimulation on human working memory performance. Psychopharmacology (2020). https://doi.org/10.1007/s00213-020-05590-0