March 27, 2018

I realize I've been talking a lot about supplements lately, but as a big fan of better living through science and the use of targeted micronutrients to satisfy specific physiological desires or address specific biological issues, whenever I discover something interesting, I consider it my duty to share it with you.

…and today is just such a case. I’ve recently been experimenting with a fringe, little known, but entirely natural nootropic for everything from lucid dreaming to memory recall to mental fatigue.

It was introduced to me by the brilliant minds over at Neurohacker Collective, and the results in the past week I’ve been using it have been quite notable, so I figured I’d share with you this substance I’ve been tweaking my brain with of late. If you have questions, just leave them in the comments section below!

Here we go…

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Celastrus Paniculatus – “The Intellect Tree”

The official title for this particular nootropic is “Celastrus paniculatus”.

Celastrus paniculatus is a woody climbing shrub that grows throughout India at elevations up to 5,900 ft (1,800 m). Celastrus paniculatus, also known as Jyotishmati and “intellect tree”, is widely used in traditional Indian Unani and Ayurvedic medicine. Ayurvedic medicine has used Celastrus seeds for their potent medicinal properties for thousands of years.

In Ayurveda, oil from its seeds, known as Celastrus oil or Malkanguni oil, is used to enhance memory and comprehension. Traditional healers have administered Celastrus oil as a brain tonic for centuries, using it to help overcome physical weakness and mental fatigue, increase mental acuity, improve memory retention and recall, reduce headaches, reduce stress and alleviate arthritic joint pain. People using the oil used to call it ‘magzsudhi’ or brain clearer. Small quantities of the oil have also long been consumed as a supplement in healthy diets to improve dream recall and to help induce lucid dreams.

The seeds contain around 45% of fatty oil, mainly palmitic, oleic, linoleic and linolenic acids and their glycerol esters; seeds also contain sesquiterpene polyesters, the most abundant being malkangunin, sesquiterpene alkaloids (celapanin, celapanigin, celapagin) and triterpenoids.

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Effects & Mechanisms Of “The Intellect Tree”

Findings from experimental research support the purposes and reported effects of Celastrus paniculatus use in Ayurvedic medicine: Celastrus seed oil/extract has shown nootropic, anxiolytic, neuroprotective and antioxidant properties. Celastrus paniculatus seems to act on multiple neurotransmitter systems and to affect multiple mechanisms of cellular protection.

Nootropic effects

In healthy rats, oral administration of Celastrus seed oil was shown to be effective in improving 24h memory retention after a single administration. This effect was accompanied by a reduction in the concentration of central monoamines (norepinephrine, dopamine and serotonin) and their metabolites (MHPG, HVA and 5-HIAA) in the brain, indicating a decreased turnover of these neurotransmitters.

Also in healthy rats, after continued administration of the aqueous seed extract for 14 days, a significant improvement in learning and memory was observed; and after 30 days, enhanced cognitive function was reported.

In rats subjected to chronic-restraint stress, Celastrus seed oil administration for 14 days reversed stress-induced spatial learning and memory impairment and restored working memory.  Celastrus seed oil also attenuated aluminum-induced memory loss in rats. As an aqueous seed extract, Celastrus was also able to reverse sodium nitrite-induced amnesia in mice.

Celastrus seed oil was also effective in reversing scopolamine-induced memory deficits in rats after a single oral administration, but it was most effective in doing so following a chronic treatment for 14 days. In mice with scopolamine-induced memory deficits, Celastrus also improved both spatial and fear memory. Scopolamine’s effects on memory are due to its action as an acetylcholine muscarinic receptor antagonist. Therefore, Celastrus’s ability to restore the memory deficits induced by scopolamine indicates an effect on the cholinergic system, which may underlie its memory-enhancing activity. This is supported by the finding that Celastrus seed extract administered for 30 days to healthy rats induced a dose-dependent inhibition of acetylcholinesterase activity in the brain, the enzyme responsible for the breakdown of acetylcholine and for the termination of acetylcholine signaling.

Celastrus’s nootropic effects may also be linked to an increase in the brain content of total lipids and phospholipids, observed in healthy rats after continued administration, possibly due to increased myelination.

Anxiolytic and antidepressant effects

Celastrus showed an anxiolytic activity in multiple studies in rats and mice.6,10,11 Such effects were observed following seed oil administration for 14 days both in healthy rats10 and in rats subjected to chronic-restraint stress.

Celastrus seed oil oral administration to mice for 14 days was also shown to have an antidepressant-like activity comparable to that of fluoxetine.

Celastrus’s anxiolytic and antidepressant activity has been attributed to a probable interaction with dopamine-D2, serotonergic, and GABAB receptors, to MAO-A inhibition and to a reduction in plasma corticosterone levels.

Neuroprotective effects

The neuroprotective effects of Celastrus seed oil were assessed in rats with aluminum-induced neurodegeneration; Celastrus attenuated aluminum-induced cellular changes in the hippocampus and motor cortex, memory loss, motor function loss, acetylcholinesterase activity loss in blood and brain, and oxidative changes.

Celastrus seed extract also reduced 3-nitropropionic acid (3-NP)-induced neurotoxicity in rats, manifested as cognitive dysfunctions, behavioral alterations and oxidative damage.

Celastrus aqueous seed extract protected forebrain primary neuronal cell cultures from glutamate-induced toxicity and from H2O–induced oxidative injury. Celastrus seed oil also protected embryonic rat forebrain neuronal cells from glutamate-induced and H2O2-induced neuronal death.

Antioxidant effects

The antioxidant activity of Celastrus was shown in healthy rats, in which the aqueous seed extract administered orally for 14 days was effective in decreasing lipid peroxidation and free radical generation.

This antioxidant activity is likely mediated by the increased production of the antioxidant molecules glutathione, superoxide dismutase (SOD) and catalase, observed both in healthy rats after chronic administration and in young adult rats with gastric ulcers after a single administration of the seed oil. In the latter, decreased lipid peroxidation was also observed. This was confirmed in vitro, where Celastrus seed oil was also able to increased catalase activity and decrease the levels of malondialdehyde (a lipid peroxidation product) in adult and embryonic rat forebrain neuronal cells.

As also shown in adult and embryonic rat forebrain neuronal cells in vitro, Celastrus’s antioxidant action may also be due to a free radical scavenging capacity: it scavenged reactive oxygen species, including the superoxide anion and the hydroxyl radical, as well as the stable radical DPPH.

Analgesic and anti-inflammatory effects

Celastrus paniculatus has shown analgesic effects in healthy rats and mice, likely linked to its anti-inflammatory activity. A single oral dose of Celastrus seed extract showed analgesic effects in the hot plate and tail immersion tests (indicating a central nervous system effect) and inhibited visceral pain induced by acetic acid administration into the peritoneal cavity (indicating a peripheral nervous system effect); it also inhibited carrageenan-induced paw inflammation in mice.

In young adult rats with gastric ulcer, Celastrus seed oil increased the levels of IL-10 (an anti-inflammatory molecule) and reduced levels of TNF-α (a pro-inflammatory molecule).

Other effects

Celastrus’s cytoprotective effects extend beyond neurons, as seen when administered to human fibroblast cells in vitro, in which Celastrus reduced H2O2-induced cytotoxicity and DNA damage. Celastrus seed oil’s cytoprotective effects were also evidenced by its gastroprotective activity and improved ulcer healing observed in young adult rats with gastric ulcer. In muscle cells in vitro, Celastrus seed extract inhibited tertiary butyl hydroperoxide (t-BHP)-induced muscle cell cytotoxicity, apoptosis, mitochondrial and DNA damage, and restored the antioxidant status, indicating a possible application to treat strenuous exercise/fatigue-induced oxidative damage of muscle cells.

In opposition to its cytoprotective effects in healthy cells, when a bioactive compound isolated from the whole plant was administered to MCF-7 breast cancer cells, apoptosis and autophagy were induced through a pleiotropic mode of action.

A hypocholesterolemic and hypolipidemic effect has also been described following oral administration of Celastrus seed extract for 6 weeks to healthy rats on a high-fat diet: it considerably decreased total cholesterol, triglycerides, LDL and VLDL cholesterol levels and increased HDL; liver weight was also significantly lower suggesting decreased cholesterol and fat deposition in the liver; cholesterol deposition in the aorta decreased three-fold. This effect was found to be due to a reduced activity of glucose 6-phosphate dehydrogenase and malate dehydrogenase (lipogenic enzymes), and to increased activities of plasma lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (associated with lipoprotein synthesis); an enhanced rate of degradative processes and a reduction in intestinal absorption of free cholesterol and other lipids was also observed.

Other effects reported for Celastrus paniculatus also include intestinal relaxation, observed in isolated preparations of human and rat ileum, and anti-fungal and anti-bacterial activity.

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Safety

Despite centuries of therapeutic use in Ayurvedic medicine, there are no published human studies (in English) on Celastrus paniculatus. Therefore, there are no controlled clinical trials that substantiate Celastrus’s accepted safety. Support for its tolerability is given by the fact that Celastrus paniculatus seed oil is a natural product that has been extensively used in Ayurvedic medicine for centuries, often as part of a regular healthy diet. Celastrus’s tolerability and low toxicity are also evidenced by the multiple oral toxicity studies that have been performed in rodents, even at high doses.

Celastrus paniculatus ethanolic seed extract was shown to be well tolerated in healthy mice following a single oral administration at doses ranging from 300 to 5000 mg/kg (Human Equivalent Dose of 24.4 to 406.5 mg/kg); no changes were observed in body weight, food, water intake and sleep; in skin and fur, eyes, and mucous membranes; in the respiratory, circulatory, autonomic, and central nervous systems; in somatomotor activity and behavior pattern; tremors, convulsions, salivation, diarrhea, lethargy, or coma were never observed.

When administered orally to healthy rats at a single dose of up to 5 g/kg (Human Equivalent Dose of 806.4 mg/kg), Celastrus seed oil showed no toxic effects on the normal behavior or on motor coordination at any dose level, thereby showing no neurotoxic effects. Likewise, when continuously administered orally to rats for 14 days at dosages ranging from 50 to 400 mg/kg (Human Equivalent Dose of 8.06 to 64.6 mg/kg), Celastrus seed oil had no significant effects on body weight or behavior, and no signs of cholinergic toxicity (tremor, convulsions, salivation, fasciculations, lacrimation, etc.).

When applied to human fibroblast cells in vitro, Celastrus’ methanolic extract had no cytotoxic effects. There was in fact only one study that reported undesired effects following intraperitoneal administration of 0.2 ml Celastrus seed oil to healthy rats every alternate day for 30 days. This study reported regressive changes in the histomorphology of the testis tubules, including vacuolization, germ cell depletion, desquamation of the germinal epithelium, shrinkage and an arrest in spermatogenesis; necrotic foci were found in the liver, but changes were reversed after cessation of treatment.

Given that such effects were only reported following continued intraperitoneal administration, that no toxic effects were observed upon oral administration to rodents, and that no cytotoxic effects were observed in human fibroblast cells in vitro, it is likely that these undesired effects occurred as a direct consequence of the intraperitoneal injection of the oil. To avoid undesired effects, compounds injected intraperitoneally should be sterile, isotonic, non-irritating and close to neutral pH; intraperitoneal injections are also inadequate for continued administration. Furthermore, intraperitoneal injection is regarded as an inherently unreliable technique, with a failure rate in the order of 10–20%. When the administration is not properly performed, compounds may be inadvertently injected into an organ, abdominal fat or subcutaneous tissues, as occurs with relative frequency.

Therefore, based on the relative unreliability of intraperitoneal injections and on the lack of indications of toxicity following oral intake of Celastrus paniculatus seed extracts, and given the long history of human consumption, the oral intake of Celastrus paniculatus by healthy adults should be well tolerated. This is supported by users’ accounts in online forums that report good tolerability and an absence of undesired effects.

Finally, if you check out the featured image for this blog post, it even looks like a little brain, doesn't it? Funny how nature gives us clues like that.

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Summary

Want to try Celastrus paniculatus for yourself?

I did.

Here's how: I recently got my hands on a tiny black bottle emblazoned made by same folks at Neurohacker Collective who make the smart drug “Qualia” (which I reported on in my notorious God pill article here). This new formulation is called “Qualia Mind”.

Allow me to give you a bit of background here. For thousands of years, humanity has been trying to deal with these needs.  And we haven’t been very good at it.

We discovered the power of coffee beans: great for bursts of energy, not so great hours later when we’re crashed and braindead. We learned to ferment alcohol: great for briefly raising mood and lowering social anxiety, but not so great for work production or feeling fresh the next morning.  We discovered cannabis and psilocybin mushrooms, along with lots of other substances frowned upon by law and employers. Some are highly dangerous. Others are relatively safe, but put you at risk of prosecution or termination from work. And the black market status of most of these substances means questionable safety regarding their purity, sourcing, or handling.

But then the internet age began linking information to everyday citizens about legal, little-known plants and herbs with nootropic properties. Nutritionists and chemists began sharing information to develop “nootropic stacks”, where taking these substances together could deliver great results for people: greater focus, mood, creativity, and mental energy.

But who has time to cobble together 20 or 30 ingredients from all around the world?

This created a market for what I call “premade nootropic stacks”.

Dozens of startup companies tried their hand at the complex neuroscience behind nootropic formulations. Many barely worked at all. A few delivered decent results, but could not come close to comprehensive benefits, because it takes a massive manufacturing operation to combine dozens of rare and premium ingredients from all around the world into a single premade dietary product.

Then came a San Diego startup called Neurohacker Collective (I interviewed their founder in this podcast about 42 ways to build a better brain). With a team of renowned complex systems science visionaries and neuroscientists, Neurohacker Collective didn’t compete for the lowest price-point. They wanted to make the flat-out best and most comprehensive nootropic stack available, and they quickly cornered the market on premium nootropics with their first offering: “Qualia”.

And Qualia worked amazingly well for a large number of people, including myself (as I wrote about here) But the catch? Qualia was hard to use with two different steps to take the product each day- some ingredients on an empty stomach and some with food- and with expensive manufacturing, it originally cost 149 dollars to even try the product for a month.

However, Neurohacker Collective just launched this new second product – Qualia Mind – this may be the product that marks the beginning of widespread use of comprehensive nootropic stacks.  Over a year in the making, Neurohacker Collective has carefully trimmed the original ingredient list in the original formulation Qualia from 42 down to 28, and formulated the product into one mighty step that does not require a “Step 1” and “Step 2” dose like the original Qualia. This has resulted in a drastically lower price-point and a far easier to use product than original Qualia.

They’ve also – you guessed it – added into Qualia Mind potent amounts of extract from the Indian plant Celastrus paniculatus that you’ve just read about. In my opinion, as coffee gave way to first generation nootropic stacks that were either far from comprehensive or complicated to use, Qualia Mind is the next step in the evolution of how human beings enhance daily mental performance. This stuff represents the first comprehensive nootropic stack that:

A) has a price within range of many consumers;

B) takes only ONE step to use each day and;

C) is designed to radically enhance mental and emotional functioning across a wide array of capacities.

You can click here to Qualia Mind today here with a 100-Day money back guarantee, and be among the first people in the world to experience the next evolution in the history of mental enhancement. Neurohacker Collective is also offering coupon code “GREENFIELD2018” for an additional 15% off your first purchase of Mind, lowering the cost for the first month of product to less than 76 bucks, with a cancel-anytime subscription. That's about half the cost of trying the original Qualia when it debuted (and this is despite Qualia Mind having tested just as effective in Neurohacker's customer surveys). 

So there you have it. Enjoy the feeling of the intellect tree, and in the meantime, leave your questions and comments about Celastrus paniculatus and Qualia Mind below and I will reply!