‘Paradoxical’ Reactions: Explaining Bad Responses to Benzodiazepines, Valerian, 5-HTP, Magnesium and the rest

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The problem with paradoxical reactions is twofold. Not only do you have to contend with the experience itself – a confusing and unexpected crescendo of anxiety and insomnia from an item that was meant to calm you down – then there is the search for the reason as to why this happened. This search typically involves many doctors visits, an array of blank faces and hours of internet searching. All without an answer.

Despite the lack of answers available from mainstream medicine or from Dr Google, this scenario is something that I have seen many, many occasions in my clinic. In every case, the cause was the same and originated in the central nervous system. The good news here is the reactions can be easily rectified and, just as importantly, they tell us a lot about the conditions in the central nervous system (which can allow us to construct a more suitable support package going forward).

On a basic level, a paradoxical reaction is one where you take an item and then react in the opposite manner to that you were expecting. For example, maybe you have taken a pharmaceutical item such as benzodiazepines, or perhaps a nutritional item like Valerian or 5-HTP; these items work by upregulating the activity in the GABA/serotonin pathways and should therefore calm us down. However, instead of feeling more relaxed and easing into a well-needed deep sleep, you soon find yourself wired, physically tense and moody. This is the classic paradoxical reaction and, although I have only mentioned three different agents, I also speak regularly to individuals who have reacted to Magnesium, Vitamin C, Niacin and many other items. The more ‘neurally active’ the substance is (eg. the more effect it has on neurotransmitter pathways), the more feasible a paradoxical reactions is.

What’s going on behind the scenes here? Put simply, specific neurotransmitters pathways are being stimulated at a time they are not ready to work. In other words, due to a lack of activity in brain neurons, they become ‘unfit’ (very much like a muscle that is not trained for a sustained period of time). Then, as soon as these neurons are called into action (in other words, when the pathway in question is activated) they get over-stimulated and go into ‘neural cramp’. Scientifically, this means the neurons become over-excited and this results in an excessive influx of calcium into the cell. This then triggers an array of undesirable follow-on reactions that see increases in the activation of NMDA receptors and the release of nitrous oxide and peroxynitrite. In the real word, this means you feel tired yet aggressive, wired yet unable to think clearly. Some people may notice alterations in senses (dizziness, numbness) or palpitations.

So we’ve established that there is a problem with the stamina of the neurons. But the real question is why did this occur in the first place? The answer is generally found in one of two areas:

-          Low blood supply to the central nervous system. Without sufficient blood supply, there is not sufficient oxygen for the neurotransmitters to fire. When the neurons are not sending the normal level of electrical impulses, there is less transmission emanating through the various pathways. This means they worse a lot less, and their stamina drops. This can be helped by boosting adrenal hormones (which have a big impact on circulation) but the biggest aid here is postural/chiropractic adjustment. Short-term, botanicals like Ginkgo Biloba are very useful and reliable.

-          Excess inflammation. This is another occasion where the stamina of the neurons drops, but for different reasons. Inflammation affects the synaptic fidelity (sharpness) of nervous impulses. In other words, an ‘inflammatory cloud’ descends upon the neural circuits in question and stops the electrical signals from moving in the normal fashion. While the signal may be being sent out just fine, the transmission down the pathway is compromised. As neurons are always dependent on the neurons upstream to remain active, they become more idle and stamina inevitably drops. This can be helped with glutathione (or glutathione precursors such as NAC or alpha lipoic acid) or bioflavonoids (for example, turmeric or resveratrol).


Whenever there are neural circulation issues or excess inflammation, we are likely to see suppressed activity across all the major neurotransmitter systems.  This can result in many obvious symptoms (such as reduced mental acuity, poor sleep, low energy). However, there is often one (or a couple) of neurotransmitter systems that are more suppressed than others. Sometimes, this relates to low enzyme function, which restricts the supply of a particular neurotransmitter (eg. low function of the GAD enzyme is often found following viral infections and results in low GABA levels). Sometimes, there is no obvious explanation. In any case, the end result is that individuals whose GABA circuitry has low stamina are vulnerable from any item that boosts activity here (this includes benzodiazepines like Valium, but also Magnesium and amino acids like Theanine) but may get on fine with agents that encourage the serotonin, opiate or endocannabinoid pathways. Equally, individuals may notice they have a problem with one of these latter three pathways but that the GABA pathway is fine.

Important facts to grasp is that paradoxical reactions will only occur in pathways that are underactive. Somewhat ironically, this means that the items that trigger the reactions are normally the compounds that your body needs. Equally, if the item that caused the reaction was a vitamin or mineral, the more likely it was that you were deficient in this nutrient (and the deficient you were, the bigger the bad reaction).

However, it is important that this advice not be taken out of context; for example, there are a number of items that cause bad reactions because they are simply not suitable for the individual. Having worked with many hundreds of individuals with adrenal problems, it is clear that the great majority react badly to adrenal extracts and adaptogens. These are not paradoxical reactions, just Good Ol’ Bad Reactions caused by the inappropriate stimulation that these compounds offer. If you are not sure whether you have suffered a bad reaction of this type or a paradoxical reaction, speak to a practitioner who is.

Unfortunately mainstream medicine is unlikely to provide any help in this regard. The current model of ‘put the symptoms in a box, find a name for this box, prescribe the drugs implicated’ may be profitable for those selling the drugs, but it provides no wiggle room for individuals who do not adhere to a specific syndrome or disease; it is fair to say that paradoxical reactions lie well outside the borders of standard diagnoses.

However, despite the fact that these reactions cannot be categorized or seen on X-rays, they are normally very easy to deal with. Doing so only requires that the delicate functions of the central nervous system be appreciated and assessed. This can sometimes be harder to explain than to rectify, but it always makes a huge difference. Addressing the underlying causes sees improvement in the conditions throughout the central nervous system, but also allows you to get the much-needed benefit of the item that triggered the reaction in the first place. The combined effect is a spectacular therapeutic impact.

Consequently, while paradoxical reactions can be one of the most unpleasant and confusing things to occur to an individual, the good news is that they provide us with a very solid idea of what we need to do to progress and, what’s more, dealing with these issues normally marks the ‘turning point’ in the journey towards optimal health.




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