Zembrin Reviews

Another study featured the use of quantitative electroencephalogram (EEG) monitoring of subjects using Zembrin. The study showed efficacy of Zembrin seen from three levels of evidence: psychometric tests (CPT and NCT), questionnaire (HAMA), and on the electrical activity of the brain.


Stress takes a toll on everyone it touches – contributing to health problems, poor relationships and lost productivity at work. It can also affect our ability to perform at our best.

Zembrin can help give people power over their lives by introducing a sense of calm serenity or alert focus. Clinically-studied, it has been shown to start working in as little as 2 hours and is safe enough to be used every day for months.

Zembrin is not an anti-depressant, but it helps with calmness and serenity. It’s not a stimulant, but it helps with alertness and focus. It doesn’t cause drowsiness. It has no harmful side effects and does not present addiction potential – unlike many pharmaceuticals that may offer the same benefits.

PLT works with some of the most innovative, socially-committed companies in the world in bringing our solutions for health & wellness to market. HG&H Pharmaceuticals from South Africa is a unique company with a fascinating story to tell your customers.

Active/Sports Nutrition

Motivation is considered by many to be the single most important element of any training program. If you’re not out there, you’re not improving. At the same time, loving every minute of training, every day can be a challenge. Training requires focus and overcoming the stresses of everyday life. That’s where adding Zembrin to your sports formulation can help.

Cognitive & Mood

Zembrin has been clinically demonstrated to improve cognitive function – specifically cognitive flexibility and executive function. Additionally, tests have shown reduction of stress and improvement of mood, manifested through statistically significant improved quality of sleep, less fatigue, enhanced work performance, enhanced interest in daily activities and lower levels of irritability, worry and insecurity. One of the most intriguing aspects of Zembrin is that it is experiential – users “feel” its benefits.

Weight Management

Experts are increasingly recognizing the role of cognitive support in long-term weight management programs. Zembrin can help make the long road to weight loss success seem just a little less long.

One of the industry’s most advanced science programs

Zembrin has been the subject of one of the most extensive and forward-thinking clinical science programs in the nutraceutical industry.

One study of Zembrin featured functional Magnetic Resonance Imaging (fMRI) technology to examine the effects of acute supplementation on the “threat circuitry” of the human brain. That study showed that 25 mg of Zembrin reduced anxiety-related activity of the amygdala and its associated anxiety circuitry within 2 hours of administration.

Another study featured the use of quantitative electroencephalogram (EEG) monitoring of subjects using Zembrin. The study showed efficacy of Zembrin seen from three levels of evidence: psychometric tests (CPT and NCT), questionnaire (HAMA), and on the electrical activity of the brain.

Zembrin’s clinical program has traveled the journey from mechanistic understanding of Zembrin’s function to relevant clinical endpoints in humans, supporting consumer communications about improved well-being. The present indications for Zembrin, as a dietary supplement are to elevate mood, relieve stress and improve cognition (focus). Adjectives like “anti-stress, calmness, focused, serenity, motivated, energy, improves sleep” are often used to describe the experiential effects of Zembrin.

How does Zembrin work?

In the body, Zembrin functions as both a serotonin reuptake inhibitor and a phosphodiesterase 4 inhibitor. SRIs are used predominantly as antidepressants and are also commonly used in the treatment of other psychological conditions such as anxiety disorders and eating disorders. Zembrin’s unique dual mode of action is patented, and it is the dual inhibition of 5-HT uptake and PDE4 is rapid onset of action and the synergistic activity allowing low doses to be used with excellent tolerability.

Zembrin is Experiential

One of the most intriguing aspects of Zembrin is that it is experiential – users “feel” its benefits. It is also fast acting. A published study that used functional Magnetic Resonance Imaging (fMRI) technology to examine the effects of short term supplementation with Zembrin on the “threat circuitry” of the human brain showed statistically-significant reductions in anxiety-related activity of the amygdala and its associated anxiety circuitry within 2 hours of administration.

Cognitive Support for Peak Performance

At PLT Health Solutions, we have been focusing on what we consider to be an underserved demographic – the 18-54 age range. Within this group, we see intense interest in issues such as ‘peak performance’, ‘well-being’ and ‘quality of life’. The market opportunity with this group is massive. Peak performers including knowledge workers and students make up 40% of the US population and is growing. Stress affects 75 million people in this group. And the impact of cognitive performance on other aspects of life is becoming better understood by this demographic– as evidenced by the introduction of ingredients to improve mental performance in exercise via sports nutrition products as well as easier weight management.

Cognitive Support for Sports & Weight Management

Increasingly, PLT is seeing the adoption of Zembrin as part of multi-ingredient formulations where cognitive support is desired to help achieve specific goals. The sports nutrition community has discovered Zembrin and is using it in workout products with the goal of providing cognitive support leading to enhanced focus and better workouts. Recently, there has been a good deal of discussion of the potential role of cognitive support in the weight management sector. The concept is two-fold. The first area has to do with the notion that weight loss can be a stressful time and that cognitive support can help maintain compliance with a weight management program. The second has to do with providing daily, experiential support. Successful weight management involves diet, exercise and slow, consistent weight loss. Weight management ingredients are studied over periods of 16 weeks and longer. The idea is that the use of an experiential ingredient like Zembrin can give immediate positive reinforcement and enhanced mood every day over this process.

Zembrin is Ethically-Sourced

As part of its development program, Zembrin was awarded the first ever Export and Bioprospecting permit to be issued by the South African government, #001, which was issued compliant with the National Environmental Management; Biodiversity Act, Act 10 of 2004 (NEMBA) and its associated Bioprospecting, Access and Benefit Sharing or BABS Regulations of 2008.

Zembrin is the impetus for Africa’s first prior-informed consent benefit-sharing agreement, signed with the South African San Council after 2 years of negotiation, to formally recognize the primary indigenous knowledge holders of Sceletium. The beneficiaries of the bioprospecting project include the South African San Council (San).

Whole-brain FWE-corrected positive main effects of CONDITION (emotion>shape) were observed bilaterally in the fusiform and temporal cortices, cerebellum, frontal inferior PFC, amygdala, and hippocampus (see Table 1 and Figure 4a ). No main effect of DRUG or interaction was observed using this or a more liberal (FWE-corrected cluster threshold P<0.05, cluster-defining threshold P<0.001 uncorrected) statistical threshold. ROI analysis on the threat circuit shows reliable activation in the midbrain, hypothalamus, amygdala, and vmPFC/OFC on the emotion>shape-matching contrast (see Table 1 ), again with no main or interaction effects of DRUG. A 2 × 2 repeated-measures ANOVA on the extracted mean signal in the bilateral amygdala, with DRUG and CONDITION as within-subject factors, revealed a marginally significant interaction effect (F(1,14)=3.13, P=0.099, partial η 2 =0.18) indicating marginally stronger amygdala activity on the emotion>shape-matching contrast in the Zembrin (percentage of signal change; 0.61, SD=0.53) compared with placebo (0.38, SD=0.23) condition.


The South African endemic plant Sceletium tortuosum (L.) N.E. Br. (synonym Mesembryanthemum tortuosum L.), of the succulent family Mesembryathemaceae, has a long history of traditional use by San and Khoikhoi people as a masticatory and medicine (Smith et al, 1996) and later by colonial farmers as a psychotropic in tincture form (Pappe, 1868). Over the past 15 years, the plant has attracted increasing attention for its hypothesized applications in promoting a sense of wellbeing and relieving stress in healthy individuals and for treating anxiety and depression in clinically anxious and depressed patients (Gericke and Viljoen, 2008). A recent in vivo study in rats demonstrated a positive effect of an extract of S. tortuosum on restraint-induced anxiety (Smith, 2011), and a small series of case reports described preliminary evidence for antidepressant and anxiolytic activity in patients suffering from major depression who were treated with tablets of milled S. tortuosum raw material (Gericke, 2001).

The mechanisms of action on the central nervous system (CNS) of a standardized extract of S. tortuosum (Zembrin) were recently identified as comprising blockade of the serotonin (5-HT) transporter and selective inhibition of the phosphodiesterase-4 (PDE4) enzyme (Harvey et al, 2011). 5-HT reuptake inhibitors (SSRIs) are widely used for the treatment of anxiety disorders and depression (Pringle et al, 2011). However, a combination of SSRIs with a PDE4 inhibitor has been argued to have synergistic therapeutic potential in CNS disorders by providing greater symptomatic efficacy and broader therapeutic utility than either as a drug on its own. In particular, repeated treatment with SSRIs can upregulate PDE4 (Ye et al, 2000), which in turn reduces the sensitivity to SSRIs in response to long-term treatment, suggesting that dual treatment with SSRIs and PDE4 inhibitors may be a promising approach (Cashman et al, 2009).

Cyclic nucleotide PDEs comprise a diverse group of enzymes that are important regulators of signal transduction. PDEs are classified into 11 families based on sequence homology, substrates and regulation by modulators. Enzymes in the PDE4 family catalyze the hydrolysis of cyclic AMP (cAMP) and have a critical role in controlling the intracellular concentration of cAMP and increasing phosphorylation of cAMP-response element-binding protein (Li et al, 2009). PDE4s are found throughout the brain (Perez-Torres et al, 2000), but their levels are decreased in unmedicated depressed individuals (Fujita et al, 2012). This reflects a downregulation of the cAMP cascade that can potentially be restored using PDE4 inhibitors (Duman et al, 1999), an idea which is supported by an increasing number of animal studies that indicate the potential of PDE4 inhibitors for novel treatments of anxiety and depression (Halene and Siegel, 2007; Li et al, 2009). Indeed, the prototypical PDE4 inhibitor rolipram has been shown in both animal (Saccomano et al, 1991) and clinical (Fleischhacker et al, 1992) studies to have antidepressant activity.

A consistent challenge in translating these pre-clinical studies of PDE4s into clinical practice has been the side effects (Duman et al, 1999); in particular nausea and vomiting (Rock et al, 2009). The combination of SSRIs and PDE4 inhibitors might therefore not only have synergistic therapeutic potential but may allow for lower PDE4 doses that are better tolerated. Zembrin has been found to be safe and well-tolerated at doses of 8 and 25 mg taken orally once a day in a randomized, double-blind, parallel-group, placebo-controlled clinical trial, supporting the ethnobotanical record of safe use of S. tortuosum (Nell et al, 2013). Here, we report a functional magnetic resonance imaging (fMRI) study that is the first to test the activity of S. tortuosum (Zembrin) in the human brain and is thereby also the first study on the effects of a dual PDE4 and 5-HT reuptake inhibitor in humans. The present study was designed to test the effects of a single administration of Zembrin (25 mg) on anxiety-related activity in the human brain. A reliable and often used index of fear responsivity and anxiety in the human brain is the blood oxygenation level-dependent (BOLD) response to facial threat in the bilateral amygdala as measured with fMRI (Freitas-Ferrari et al, 2010). The amygdala can be considered a hub in the brain’s threat system involved in threat detection and subsequent promotion and regulation of defensive reactions in the subcortical threat circuit, particularly the hypothalamus, midbrain, and brainstem (Davis and Whalen, 2001; Walker et al, 2003). Moreover, the amygdala relays threatening information to the cortex and orchestrates, together with cortical structures, the regulation of fear and anxiety (Kim et al, 2011; Terburg et al, 2012). Given this diverse role in threat processing, we used two fMRI experiments to independently assess anxiety-related amygdala activation (Bishop et al, 2007) and functional connectivity of the amygdala with the threat circuit of the brain (Fisher et al, 2011; Hariri et al, 2002; Kirsch et al, 2005; van Wingen et al, 2010; van Wingen et al, 2008). As the amygdala is involved in the regulation of fear responsivity in the subcortical threat circuit (hypothalamus and midbrain), as well as with controlling mechanisms in the prefrontal cortex (PFC), we specifically focused the latter analysis on these areas. We hypothesized that administration of Zembrin would reduce anxiety-related amygdala activity as well as functional connectivity of the amygdala with the cortical and/or subcortical threat circuit.

Products shown in the section titled ‘Our Top Products’ are those that we promote as the owner and/ or reseller and does not represent all products currently on the market or companies manufacturing such products. In order to comply fully with FTC guidelines, we would like to make it clear that any and all links featured in this section are sales links; whenever a purchase is made via one of these links we will receive compensation. Health Web Magazine is an independently owned website and all opinions expressed on the site are our own or those of our contributors. Regardless of product sponsor relations, all editorial content found on our site is written and presented without bias or prejudice.

Zembrin contains ingredients that are supposed to combat emotional and mental conditions by enhancing the mood, fighting off restlessness/anxiety, and improving cognitive function.

While the brand claims that when used as directed, the formulation may be safe and free of adverse effects, unlike many other formulations, the claim may not be entirely accurate as some of the ingredients, such as the magnesium stearate, are known to cause side effects.

The key ingredient Sceletium Tortuosum may also require more studies to fully evaluate its effects.

According to the manufacturers of Procera Mood, this ingredient “is a clinically studied plant extract that supports neural circuits involved in processing emotions.”

Risks of Taking Zembrin

The Natural Medicines Comprehensive Database has not given Zembrin a safety rating due to a lack of reliable research information available to assess health risks. [2]

The use of Zembrin in pregnant women and women who are nursing is not recommended due to uncertainty about the effects of this product. Consumers should see a doctor before using Zembrin.

Although the results of a 2013 study that appeared in the Journal of Alternative and Complementary Medicine indicated that Zembrin was generally well tolerated when used in healthy adults for 3 months, it can produce mild side effects. [5]

Both user reviews and research studies indicate that these possible side effects include appetite loss, headaches and respiratory issues. In some individuals, Zembrin was associated with depression.

Those who take Zembrin for depression should note that this product has the potential to cause harmful effects when taken with antidepressants that act as selective serotonin reuptake inhibitors (SSRIs).

This combination can lead to high levels of serotonin and increase the risk of serotonin syndrome. Supplements with sedative properties, including 5-HTP and kava, might cause increased drowsiness when used with Zembrin.

Consumers who take antidepressants or supplements should consult their doctor before taking Zembrin or any other products that have Sceletium as an ingredient.

Quipped Dr Roger Chennels, a veteran human rights lawyer and San expert who brokered the deals, ‘when something’s been tested for over 10 000 years, it really works. We all chewed it during our negotiations which led to things going very smoothly and a happy outcome’.

Sceletium tortuosum is magic ingredient in Zembrin and Elev8

A highly effective, fast-acting, mood-lifting and anxiety-reducing indigenous plant extract called Zembrin® has hit the complementary medicine shelves in South Africa, marketed locally as packs of Elev8 tablets.

The South African produced and patented Zembrin® is an extract of a cultivated elite selection of the Namaqualand plant Sceletium tortuosum – for centuries used and traded by San hunter-gatherers and Khoi Khoi pastoralists for medicinal, social and spiritual purposes.

Zembrin® has been researched and developed for more than a decade and is presently being marketed in South Africa and the United States as a safe over-the-counter remedy for healthy people to enhancing mood, decreasing anxiety, and to reduce stress.

Huge potential

Zembrin® has been clinically tested for safety and efficacy in three rigorous placebo-controlled clinical studies. There is preliminary clinical evidence that the extracts effect, described by the excited researcher as “experiential”, which can be felt two hours after oral ingestion (versus up to two to three weeks with some well-known pharmaceutical anti-depressive drugs). This has huge global market potential.

Prozac and newer mainstream drugs, such as Cymbalta and Effexor, are routinely provided to around 40 million patients by doctors in the United States and Europe for a wide variety of mood disorders including major depression, obsessive-compulsive disorder, anxiety and severe premenstrual syndrome.

Zembrin®’s team of developers are however taking a conservative approach initially, by marketing Zembrin® for use in lower doses as health supplement products for people who are not clinically depressed or anxious.

HG&H Pharmaceuticals (Pty) Ltd, the research-based company that developed Zembrin®, is actively looking for a large pharmaceutical company to partner with for the development of higher dose products for registration as botanical medicines for the treatment of mental health diseases.

This development has taken place just as the United States Federal Drug Administration (FDA) approved its first-ever orally ingested botanical medicine, known as Crofelemer. The precedent-setting FDA registration is also the ultimate goal for HG&H Pharmaceuticals. Like Zembrin®, Crofelemer (trade name Fulyzaq) is a poly-molecular botanical medicine, but developed from the latex of an Amazonian tree. Crofelemer was approved in January by the FDA for the treatment of Aids-related diarrhoea.

Hard science

The Research and Development team’s excitement over Zembrin® is anything but hype. Already, an initial brain imaging study led by Professor Dan Stein, Head of the Department of Psychiatry and Mental the Health at the University of Cape Town, shows that a single 25mg dose of Zembrin® has ‘effects on neural circuits involved in processing emotions’.

This study, due for peer review and publication later this year, focuses on activity in the amygdala and its connected neuro-circuitry and is characterised by Stein as; ‘important in beginning to understand exactly how Zembrin® exerts its effects’.

The full details of the study will be released in due course. Two earlier randomized, double-blind studies with groups of healthy adults, one in Cape Town and the other in Canada, show Zembrin® to be safe and well-tolerated. The first study, purely a safety study, reported unsolicited positive effects on wellbeing, including improved coping with stress and enhanced sleep in subjects taking once-daily doses continually for three months.

The second study, presented at the World Psychiatric Association Congress in Prague in 2012, concluded that Zembrin® significantly improved cognitive flexibility and executive function, suggesting that the extract may also have therapeutic potential in cognitive ageing.

The Canadian clinical investigators believe that Zembrin® should be studied as a treatment for neurodegenerative disorders, including Alzheimer’s disease.

Elev8 tablets containing 25mg Zembrin® were approved for sale as complementary medicine by the South African Medicines Control Council (MCC) and have been available through most pharmacies since September 2012.

In March 2013, Zembrin® was recognised as the ‘most sustainable ingredient’ at the prestigious annual Natural Products Expo West held in Anaheim, USA. Zembrin was noted as one of the leading ingredients pioneering the next great foundation of new product development.


South African medical practitioner, botanist and ethnopharmacologist Dr Nigel Gericke together with Deon Hofmeyr, a horticulturalist and entrepreneur, with backing from H.L. Hall and Sons, developed Zembrin® by directing an international multidisciplinary team effort.

According to Gericke, ‘For now we’re promoting the use of Zembrin® as a botanical supplement for self-medication for healthy people suffering from stress, low mood and mild anxiety, who need a clinically studied product with a rapid onset of tangible activity.

However, our pharmacological research and clinical studies have been so encouraging that we believe Zembrin® has the potential to be developed into a blockbuster botanical medicine for treating serious mental health conditions, which meets a need for a rapidly acting, safe, effective, natural medicine.

Gericke came across Sceletium in 1986 during a gap year after his medical studies when he read a book in Australia on psychoactive plants from around the world. There was a brief mention of an obscure South African plant called Sceletium without much known about its effect – which he found intriguing, and determined to investigate on his return home.

Gericke and a small group of friends consisting of ethnobotanists, doctors and psychiatrists then experimented with various doses of the plant. It was immediately apparent that low doses of the plant had a subtle effect, providing ‘a sense of alert serenity’, while excessive doses caused a transient euphoria.

These observations and comparisons with the side-effects of high doses with those of mainstream anti-depressives made by Gericke’s psychiatrist wife Olga, ultimately led them to confirm that some of the plants compounds are potent serotonin re-uptake inhibitors (Prozac-like activity).

The research team then hunted for an explanation for the surprisingly rapid onset of action, finally discovering that Zembrin® is also a potent PDE4 inhibitor, a very current research target of pharmaceutical companies for treating anxiety, depression and neurodegenerative diseases such as Alzheimer’s disease.

Addictive potential ruled out

To evaluate possible addictive effects at the outset of the project, in 1995 Dr Gericke took one of the country’s leading addiction specialists at the time, psychiatrist Dr Greg McCarthy, with him on a field trip to the Namaqualand villages of Paulshoek and Nourivier to interview local people about the use of Sceletium, known locally as “kougoed” and to evaluate additional potential. McCarthy, (who rehabilitated drug addicts in Cape Town) and Gericke interviewed many elders and shepherds from the community, some of whom had been using the plant on a daily basis for over 40 years and found them to be ‘in perfect health’.

Gericke noted that elderly Sceletium users were surprisingly lucid in spite of advanced age. McCarthy was unable to find any folk who were socially dysfunctional as a result of Sceletium use.

Social responsibility

The Zembrin® founders are also the first local developmental entrepreneurs to sign Africa’s first “prior informed consent benefit-sharing agreement” with a South African indigenous community. In terms of this agreement they will share six percent of all income from Zembrin® with the San Council which generously agreed, and formalized, to allocate 50% of their share with the villagers of Paulshoek and Nourivier. The villagers’ input on what plants to use, doses, and participation in the addiction study were pivotal to the initial research and development on Zembrin®.

Quipped Dr Roger Chennels, a veteran human rights lawyer and San expert who brokered the deals, ‘when something’s been tested for over 10 000 years, it really works. We all chewed it during our negotiations which led to things going very smoothly and a happy outcome’.

All the raw plant material for Zembrin® comes from 10 hectares of Sceletium grown outside Nelspruit, (half under shade cloth and half on open land) belonging to the company’s major shareholders, HL Hall and Sons. Another large tranche comes from a huge fruit farming operation near Tzaneen.