GABAergic SUBSTANCES (OR OTHER) THAT MAY CAUSE REACTIONS/”SETBACKS” IN THE BZ-INJURED

I have always been against supplements which are often just a money-making scam, and most have never been properly tested. Many people take so-called GABA supplements in benzodiazepine withdrawal. This is futile as there is no shortage of GABA in benzo withdrawal: the problem is the down-regulated receptors. I have always advised people withdrawing from benzos not to waste their money on supplements. – Dr. C. Heather Ashton

GABAergic means “pertaining to or affecting the neurotransmitter GABA“. A substance is GABAergic if it produces its effects via interactions with the GABA system, such as by stimulating or blocking neurotransmission. A GABAergic or GABAergic agent is any chemical that modifies the effects of GABA in the body or brain. Some different classes of GABAergic drugs include the following: GABA receptor agonistsGABA receptor antagonists, and GABA reuptake inhibitors. Some examples include gabapentinoids and GABA analogues.

When people take prescribed benzodiazepines, the body adapts to their constant presence with neuroadaptation (repeated exposure to a drug produces long-term changes in the nervous system). Neuroadaptation to the benzodiazepine’s constant presence is the reason for the development of tolerance and a sensitization of the nervous system. In other words, the continual presence of prescribed benzodiazepine causes down-regulation of the GABA receptors. This means that the GABA receptors become fewer due to the homeostatic response of the body to the constant presence of the benzodiazepines. Because the GABA receptors are fewer, due to the fact that benzodiazepines themselves enhance the actions of GABA thus making extra benzodiazepine receptors no longer necessary, when people who have benzodiazepine neuroadaptation try to withdraw, their nervous system goes into a chronic hyperactive state due to the body’s inability to properly utilize GABA because the benzodiazepine is no longer there (or is present in less and less quantity, in a taper) to enhance the actions of GABA.

When on the benzodiazepines, perhaps in tolerance withdrawal, when withdrawing from the benzodiazepines or when totally withdrawn, the nervous system can become quite destabilized. It is important to note that the withdrawal syndrome is usually more severe and long-lasting in people who withdrew from the benzodiazepine over-rapidly or who cold-turkeyed and these people also tend to have more nervous system hyperactivity as well, as a result. While the nervous system is in a hyperactive state of tolerance, toxicity, withdrawal or protracted withdrawal, people anecdotally report being more sensitive to GABAergic and even other non-GABAergic substances, even if they previously (before the benzodiazepine neuroadaptation) tolerated them. Particularly, they report having “reactions” and “setbacks”.

The term ‘reaction’ is typically used by the benzodiazepine withdrawal community to describe an increase or recurrence of withdrawal symptoms after exposure to a substance (which is sometimes GABAergic and sometimes not). The term ‘setback’ is typically used by the benzodiazepine withdrawal community to describe a recurrence of the withdrawal syndrome or symptoms after one was healed (or near-healed) from a previous withdrawal syndrome. Usually, “setbacks” occur after environmental stresses, according to Dr. Heather Ashton in her 2011 supplement to The Ashton Manual, which can include GABAergic and other substances. “Reactions” or “setbacks” can vary from short-lived and mild to severe and long-lasting, sometimes persisting for years, and sometimes even when the benzodiazepine-affected person had years of “healing” (or feeling well) under their belts (Scroll down past the below lists to continue reading about the potential reasons for “reactions” and “setbacks”).

Click on each tab in the box below to view a list of GABAergic drugs, herbs, and supplements that may interfere with GABA receptors benzodiazepine withdrawal. Some non-GABAergic substances are also listed as they have been anecdotally reported by the benzodiazepine withdrawal support communities to have caused “reactions” and/or “setbacks”.

GABAergic Substances

The following is a list of GABAergic and other non-GABAergic substances (e.g., supplements, medications, drugs, neurotoxins, etc) which one may wish to avoid during a taper, benzodiazepine withdrawal and even for a long time after healing, due to the potential for interference with recovery:

GABAergic:

  • OREGANO OIL
  • ANTICONVULSANTS (like Pregabalin, Gabapentin, Tiagabine, etc.—have similar effects to benzodiazepines)
  • LDN or LOW-DOSE NALTREXONENaltrexone and its active metabolite 6-β-naltrexol are competitive antagonists at μ-opioid and κ-opioid receptors, and to a lesser extent at δ-opioid receptors. Standard therapeutic doses of naltrexone blocks these receptors, which does two things; it prevents inhibition of GABA receptors (normally, signalling through the GABA receptors inhibits the activity of neurons; many drugs inhibit GABA and thus “free up” neuronal activation; preventing inhibition of GABA allows GABA’s normal inhibition activity to take place) and it blocks dopamine release.
  • QUININE
  • PHENIBUT (beta-phenyl-gamma-aminobutyric acid HCl) in Kavinace and other supplements.
  • LIDOCAINE Also see this abstract
  • BACLOFEN
  • PENICILLIN
  • FLUOROQUINOLONE ANTIBIOTICS
  • ASHWAGANDHA
  • EXHILARIN
  • PICAMILON
  • ALCOHOL
  • VALERIAN (Valeriana spp.) is widely used as an herbal sedative. It exact method of action is still unknown, although it definitely affects the GABA system. It contains a wide range of constituents, including alkaloids, valeric acid (which is similar in structure to both GABA and GHB), valerenic acid (which may bind to serotonin receptors), and even GABA itself. Additionally, valerian has been shown to stimulate an enzyme called glutamate decarboxylase (GAD) which creates GABA from glutamate in the brain.
  • PASSIONFLOWER (Passiflora incarnata) According to animal studies, a high potency passionflower extract has an anxiolytic effect comparable to diazepam.
  • LEMON BALM (Melissa Officinalis) This one appears to prevent the breakdown of GABA by being a potent inhibitor of the enzyme GABA transaminase.
  • SCULLCAP (Scutellaria spp.) has been used traditionally as an anxiolytic and sedative. It has a number of flavones that have been reported to selectively bind with high affinity to central benzodiazepine receptor sites.
  • KAVA (Piper methysticum) Kava, like many of these herbs, has a multi-faceted and complicated mode of action. Some research suggests that it may be a positive allosteric modulator of the GABA receptor, like benzos.
  • CHAMOMILE Traditionally, chamomile preparations such as tea and essential oil aromatherapy have been used to treat insomnia and to induce sedation (calming effects). Chamomile is widely regarded as a mild tranquilizer and sleep-inducer. Sedative effects may be due to the flavonoid, apigenin that binds to benzodiazepine receptors in the brain. Studies in preclinical models have shown anticonvulsant and CNS depressant effects respectively.
  • PROGESTERONE and/or ESTROGEN

If you have experienced a “reaction” or “setback” from something not shown on this list, please Contact Us so that we can make the list more inclusive.

GABAergic Herbs, Supplements

The following is a list of Herbs and Supplements that can cross the blood-brain barrier and affect GABA-A receptors and as such may interfere with the withdrawal and recovery process. The starred (**) ones are the most potent reactors with the same GABA-A receptors as the benzodiazepines, the others somewhat so.

  • Scute (skullcap both American and  Chinese) **
  • Salvia **
  • Polygala
  • Asaram **
  • Acorus **
  • Pueraria
  • Magnolia
  • Zizyphus **
  • White Peony
  • Schisandra
  • Ganoderma (aka reishi mushroom)
  • Dioscorea  (wild yam) (if it encourages progesterone)
  • Poria (hoelen)
  • Corydalis
  • Valerian** (binds just like a benzodiazepine)
  • Passion Flower **
  • Kava **
  • L-Theanine ** found in a lot of calming supplements like Zen Mind Progesterone meds/creams. This one is still controversial, though there is evidence that progesterone products may adversely affect benzo withdrawal in some people.
  • GABA supplements are not typically useful as they don’t cross the blood-brain barrier, but also because the problem in benzodiazepine neuroadaptation and withdrawal is not one of a lack of GABA, but one of a lack of receptors to properly utilize GABA (and it may even be more complex than that, as experts are unsure about the exact mechanism by which protracted withdrawal, “reactions,” and/or “setbacks” occur).
If you have experienced a “reaction” or “setback” from something not shown on this list, please Contact Us so that we can make the list more inclusive.

Other Substances with Interaction Potential

These herbs, supplements, drugs and other substances may result in an interaction with benzodiazepines or may aggravate benzodiazepine withdrawal and/or a  benzodiazepine-sensitized CNS. Use with caution.

  • MARIJUANA (CBD, THC, all forms—edibles, oils, smoking, etc.)
  • OPIATES
  • OTHER ANTIBIOTICS
  • OTHER HORMONES (e.g., Testosterone)
  • ANY PSYCHIATRIC DRUG (even in seemingly “low doses”; e.g., SSRIs, SNRIs, other antidepressants, stimulants, antipsychotics, antianxiety agents, mood stabilizers, other anti-anxiety agents, etc.)
  • EPINEPHRINE (e.g., lidocaine with epinephrine for dental procedures)
  • OVER-THE-COUNTER DECONGESTANT NASAL SPRAYS
  • OVER-THE-COUNTER ORAL DECONGESTANTS (e.g., Sudafed) AND MANY OTHER OTC MEDICATIONS LIKE ANTIHISTAMINES, ETC.
  • CORTICOSTEROIDS (all forms—oral, topical, nasal, etc.)
  • CAFFEINE
  • MSG AND OTHER PRESERVATIVES, FOOD DYES, ETC. MSG has been reported to have neurotoxic effects. See: Common other names for MSG
If you have experienced a “reaction” or “setback” from something not shown on this list, please Contact Us so that we can make the list more inclusive.

The potential reason(s) for these “reactions” and “setbacks”, as described by Dr. Heather Ashton:

One mechanism which might be involved in long-term (and possibly permanent) effects of benzodiazepines is an alteration in the activity of benzodiazepine receptors in brain GABA neurones. These receptors down-regulate (become fewer) as tolerance to benzodiazepines develop with chronic use. Such down-regulation is a homeostatic response of the body to the constant presence of the drugs. Since benzodiazepines themselves enhance the actions of GABA, extra benzodiazepine receptors are no longer needed, so many are, in effect, discarded. These down-regulated receptors are absorbed into neurones where, over time, they undergo various changes including alterations in gene expression. When these receptors are slowly reinstated after drug withdrawal, they may return in a slightly altered form. They may not be quite so efficient as before in increasing the actions of GABA, the natural ‘calming’ neurotransmitter. As a result, the brain may be generally less sensitive to GABA and the individual is left with heightened central nervous system excitability and increased sensitivity to stress. Molecular biologists point out that changes in gene expression can be very slow, or even unable, to reverse…

It is not unusual to experience recurrence of apparent benzodiazepine withdrawal symptoms years after a successful withdrawal and a return to normal health [“setbacks”]. This particular pattern of symptoms is unique to the individual, depending on his physical and psychological makeup, and no doubt on the innate density of his/her benzodiazepine receptors and the balance of his endozepinesThe experience of benzodiazepine withdrawal is deeply etched into the mind and memory of those who have been through it, and it is actually physically present in the strength and connections of their neural synapses, as all memories are. These recurrent symptoms are all signs of GABA underactivity with its accompanying increased output of excitatory neurotransmitters, resulting in a hyperactive, hypersensitive central nervous system. The mechanism is exactly the same as that of benzodiazepine withdrawal, which is why the symptoms are the same.

In nearly every case of apparent recurrence, the precipitating cause for the return of symptoms turns out, on close inspection, to be an increase in environmental stress. The trigger may be a new stress or worry which may be unrecognised so that the return of symptoms seems to occur out of the blue. Contributing factors can be an infection, surgery, dental problems, work problems, fatigue, bereavement, family problems, loss of sleep, adverse reaction to a drug, change of environment—almost anything.

It is not clear why many people report experiencing adverse effects from new drugs or drugs they have tolerated before taking benzodiazepines. The drugs involved are so disparate – from skin ointments to eye drops to local anaesthetics to antidepressants, steroids and many others – that it is difficult to attribute these reactions to metabolic effects, allergies or other known effects. Presumably the general hypersensitivity of the nervous system magnifies the reaction to any foreign substances, but no clear explanation has yet emerged. An exception is quinolone antibiotics which displace benzodiazepines from their binding sites and should not be taken by patients on, or recently on, benzodiazepines.

Another explanation for “reactions” and “setbacks” might be found by researching neurotoxicity. Neurotoxicity is the capacity of chemical, biological or physical agents to cause adverse functional or structural damage in the nervous system. People with chronic neurotoxic syndromes (sometimes called ‘protracted withdrawal’) often experience chemical sensitivity, even to chemicals they were never sensitive to prior to the exposure to the neurotoxin. Common symptoms of neurotoxicity can include problems with memory, concentration, learning, mental processing speed, sleep, thinking, language, as well as anxiety, depression, confusion, personality changes, fatigue, and numbness of the hands and feet. Many types of nervous system disorders can be caused by neurotoxicity, including numerous neurologic and psychiatric disorders, as well as chemical sensitivitySome experts compare head injuries to neurotoxicity, as the resulting inflammation and neurotransmitter dysfunction is similar. The same experts also believe that many manifestations of what would be labeled “mental illness” (e.g. psychiatric symptoms) are a direct result of neurotoxicity. Dr. Allen Frances, psychiatrist, Chairperson of DSM-IV Task Force. Professor Emeritus & former chair of the Department of Psychiatry at Duke University, discusses in this video how the first thing any clinician must do in evaluating psychiatric symptoms is to rule out the possibility that medications or substances may be involved in the evolution of  those symptoms (of course this almost never happens and people are misdiagnosed, mismanaged and further misprescribed drugs they don’t need or that make them worse).

The numerous anecdotal reports of “setbacks” and “reactions” in the benzodiazepine withdrawal support communities, while not studied extensively in the medical literature, are valuable anecdote that should not be ignored. Matt Samet, a very transparent journalist who suffered for many years from benzodiazepine-related damage and disability and who was near healed and then experienced a recurrence of the withdrawal syndrome years after cessation, describes his “setback” here. In Matt’s case, he reports the “setback” was initiated by a short-term, intermittent course of prescribed opiates (that he had tolerated pre-benzodiazepine injury without issue) that he took for an injury, excessive caffeine consumption, poor diet (excess refined sugar, etc.), pressures at work and climbing in the heat. Aside from Matt’s experience, there are numerous other similar cases of anecdote that can be found simply by searching the benzodiazepine support forums and groups. This interview, here on W-BAD’s blog, details a “setback” from what the previously healed benzodiazepine-injured person assumes was caused by using oregano essential oil, which is GABAergic, on the broken skin of athlete’s foot. In addition, W-BAD is aware of stories from people who used an OTC nasal decongestant spray one time, who drank alcohol socially, or who took a fraction of a prescribed dose of SSRI or SNRI (or other psychiatric drugs) while experiencing benzodiazepine withdrawal, or when near-healed or feeling totally healed from it, who experienced a “reaction” or were “setback” into a recurrence of benzodiazepine-associated illness that persisted, in some cases, for many years.

Because of the potential risk of “reactions” and “setbacks” in benzodiazepine-injured or formerly benzodiazepine-injured patients, we have composed the above lists—which are not all-inclusive of all things which could potentially cause a recurrence of benzodiazepine-associated illness—of some things that are known to be GABAergic, or that members of the benzodiazepine withdrawal support community have anecdotally reported being the supposed cause(s) of their “reactions” and/or “setbacks”. This is not to say that everyone who has taken and/or withdrawn from prescribed benzodiazepines will experience a “reaction” or “setback,” as not all will, nor is it to say that every substance on the list will cause a recurrence of withdrawal symptoms, as that won’t always be the case. The lists are solely provided for information purposes and we advise you to do your own research and to consult with a trusted pharmacist and/or medical provider as needed. It is advised that before taking anything—whether prescribed, supplement, OTC or other—one should research extensively in trusted sources and/or by searching or inquiring in online support groups for anecdotes. In the end, every decision about whether to try or take a new substance by a benzodiazepine-injured (or previously injured) person should be weighed on a risk versus benefit ratio; if the benefit outweighs the potential risk for a “reaction” or “setback” (e.g., an antibiotic for severe bacterial infection), then one may have to take their chances. After the experience of prescribed benzodiazepine-associated illness and disability, most survivors have a healthy fear of prescriptions, synthetic drugs, supplements, OTC medications, etc.—and rightfully so—and fully realize that they must be their own health advocates when making decisions about what to accept or try in the way of medical treatments.

Please also note that if an individual has taken some of the drugs and/or supplements listed above long-term they may need to be tapered to minimize withdrawal on discontinuation. Please do your own research, seek out support groups and consult with a trusted pharmacist and/or medical practitioner before making any changes.