Natural Highs


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Whether initiated by stimulants such as caffeine or alcohol, or stronger substances such as recreational drugs, most “highs” are swiftly followed by a state of imbalance and depression. In his latest research, Patrick Holford BSc, Dip.ION analyses brain chemistry during these “peak” experiences, and reveals how specific herbs and nutrients can create similar mood-enhancing states, without the side effects

I have always been fascinated by peak experiences. Those transcendent moments when everything falls into place, when you know the meaning of it all, when you know there is a unity, a connection, between everything.

The psychologist Abraham Maslow was the first to give peak experiences a context in modern psychology. He studied what he called “actualisers”, people who really made a contribution to humanity - great scientists, artists, teachers and so on, and found that such transcendent and guiding experiences played a fundamental role in their lives. All mystical traditions describe similar experiences, the hallmark of which is that the three fundamental pillars of normality, our sense of self, time and space, undergo transformation. Our feeling of separation disappears, replaced by an understanding that we and others, and everything, are interconnected. Time both stops and reaches into eternity. Space becomes vast. In this place, the contradictions and paradoxes in life dissolve as a bigger picture, a greater meaning, emerges.


While the desire to permanently have such a clear perspective has been a major driving force in my personal life, in my professional life I have delved deeply into the chemistry of the body and mind. The bridge, the question that has most intrigued me, is what is the chemistry of such expanded states of consciousness? It is well known that transcendent experiences that carry all the hallmarks described above, not only occur as a consequence of spiritual practices, such as meditation, but also in scientists (and artists) who are absorbed in some worthy enquiry, in near-death experiences, and under the influence of certain drugs.

These psychoactive drugs, collectively known as “entheogens”, or “substances that take you towards unity” include Ecstasy (MDMA), psilocybin mushrooms (psilocin), peyote (mescaline) and LSD. It is often this search for greater meaning, a hallmark of adolescence, that leads people to experiment with entheogens, so named because they do sometimes induce such peak experiences. The fact that there are chemicals that can induce such expanded states of awareness is, of course, a vital clue, an in-road into unraveling the chemistry of consciousness and, for that reason alone, I'd like to explore their chemistry. But first, some background.

In case you think the use of entheogens is a minority activity of little relevance to humanity’s quest for meaning, take a look at history. Virtually every culture throughout history has used these substances. In India almost 4,000 years ago, the Vedas – Hindu philosophical texts – extol a plant potion called soma, considered to be God in plant form. Although the magic formula of soma is lost, it is highly likely to have included Syrian rue. The ancient Greeks, from Aristotle to Plato, took part in an initiation called the Eleusian mysteries that involved consuming a rye-based drink. Historians believe this contained the ergot-rye fungus, a natural source of LSD. Egyptian cultures used the blue lily, henbane and mandrake, which were also favourites of European witches.

In the Americas, the Mayans discovered that certain mushrooms, and the skin of certain toads, contained powerful hallucinogens. Some native American tribes use the San Pedro and peyote cactus to this day, which is a natural source of mescaline. Probably the earliest use of “magic” mushrooms predates even this, back to the Siberian peoples of north-east Asia who later crossed the Bering Strait to colonise the Americas. They revered the highly toxic Amanita muscaria, or fly agaric, a red and white spotted mushroom. To this day a herbal brew known as yage or ayahuasca is still used widely by South American shamans. In the West, the most widely used entheogens are “designer drugs”, manufactured compounds such as MDMA (Ecstasy) and LSD, tried by an estimated one quarter of all 16 to 24 year olds. But what is going on at a chemical level? How do they work and what can they tell us about the chemistry of expanded states of consciousness?


Our brains filter out the vast majority of information that comes in through our senses. This presumably allows us to make sense of the world and also has survival value. Our awareness seems to work much like a lighthouse, always scanning our world for potential danger. We see what we need to see for our survival. And this is a mere fraction of what is actually “out there”.

When an entheogen is taken, and indeed in any peak experience, it appears that this filter is suspended. The person under the influence is seeing a bigger picture, and makes bigger connections. (Of course, this all sounds amazing, however there are dangerous downsides to entheogens: many of them are extremely toxic, the experiences aren't always good and a small number of people, perhaps those who are inherently or biochemically less stable, develop mental illness.)

The vast majority of entheogens are tryptamines, which are chemical cousins of a key brain chemical, di-methyl tryptamine (DMT), itself closely related to the “happy” neurotransmitter serotonin.


In a chemical sense, all roads lead to DMT, a mind-expanding substance in its own right, that is produced in our brain and acts much like a neurotransmitter. It is thought to be produced primarily in the pineal gland, along with serotonin and melatonin. The pineal, which is at centre stage in the brain, is light sensitive in many animals, and is necessary for them to be connected to the environment and the ebb and flow of day and night, as well as seasonal changes. The Indian mystics consider the pineal to be our “third eye”, an antenna, if you like, for inner light. (Have you ever thought where the light comes from when you dream?) As you can see in Figure 1, entheogens all have profound effects on the neurotransmitter serotonin and, perhaps most importantly, on DMT.
Almost all psychoactive substances that stimulate the release of, or mimic the effects of a neurotransmitter, generally lead to a state of imbalance known as “downregulation”, which creates a state of deficiency and hence craving. In other words, you get the high, followed by the low. This is exactly what happens with most entheogens: you don’t feel so good the next day (and may lead to depression in the long term).

If DMT is the key in the equation of consciousness and connection, then we need to investigate which nutrients support the chemistry of connection as opposed to drugs which disrupt normal brain chemistry and hence have downsides But just like the neurotransmitters dopamine, serotonin or acetylcholine, DMT works every time. This suggests that we all have within us the chemistry that is associated with expanded awareness, all the time. We know far too little about what DMT does and how it works, mainly because funding for research was shut down in the backlash against LSD in the seventies. In fact, only one scientist, Dr Rick Strassman, Clinical Associate Professor of Psychiatry at the University of New Mexico, USA has been sanctioned to research the effects of DMT. The whole story and the results of his research, which was carried out in the nineties, are published in his extraordinary book DMT: The Spirit Molecule (Park Street Press).





I have long thought that the malaise of 21st century living, with its ever-increasing incidence of depression, divorce, social isolation and violence, is associated with vast chunks of humanity losing its sense of “connection”. Connection with nature, connection with the divine, connection with family and friends, connection with culture, with community, with the body and with the act of nourishment.

In the same way that we have asked, and answered, the question “Which optimal intake of nutrients facilitates health?” we are now asking, and answering the question “Which optimal intake of nutrients facilitates a sense of connection; an expanded state of consciousness?” If DMT is the key in the equation of consciousness and connection, then we need to investigate which nutrients support the chemistry of connection as opposed to drugs which disrupt normal brain chemistry and hence have downsides. We are interested in which nutrients enhance an expanded state of awareness, working with our bodymind's design, not against it. (There are many non-chemical ways to enhance the sense of connection, such as meditation, which we may assume have an impact on our chemistry; however, discussing these is not within the brief of this article.)

This has led me to research how the body makes DMT and serotonin (which appear to be the key chemicals of connection), out of amino acids such as tryptophan and 5-hydroxytryptophan; together with methylating agents such as SAMe (S-adenosyl methionine), TMG (trimethylglycine) and certain B vitamins (see Figure 2 - Natural Connectors). I have also been exploring how certain herbs, such as kava from the Pacific Islands, or sceletium from Africa support and enhance this process, and testing what happens when people supplement such nutrients in combination in certain doses.


The amino acid tryptophan, a normal constituent of food, is the basic building block not only of serotonin, but also of tryptamines, such as DMT. As such, tryptophan is critical to the chemistry of connection. Tryptophan deficiency leads to depression, while supplementing tryptophan has proven an effective antidepressant. The only trouble is that tryptophan is not available as a supplement.

More effective and more readily available than tryptophan, 5-hydroxytryptophan (5-HTP), is a more biologically active form of it. While 5-HTP is not a direct precursor for DMT, it is the most effective precursor for serotonin. By providing the brain with the raw material to make serotonin this spares dietary tryptophan for producing other important tryptamines, such as DMT.

Described by one magazine as “Hawaii in a bottle”, 5-HTP can have profound mood-lifting effects. Here’s what happened to Alex after he took 5-HTP.

“I had recently ended a long-term relationship and often felt lonely and a bit down, missing that company and connection. On good days I felt fine, looking forward and getting on with life, but they were few and far between. I started supplementing 200mg of 5-HTP a day. Within a couple of days I felt much more “up”, in the moment and basically happier. I had more of an enjoyable, warm sense of detachment, that everything was all right, rather than a kind of gloomy seriousness. I don’t take it all the time but when I’ve “lost the plot” I include this in my daily supplement regime.”

5-HTP is ten times more powerful than tryptophan, so the dose needed for a psychoactive effect is a tenth. Like tryptophan it has proven to be at least as effective as the best antidepressant drugs, but without the same high risk of side effects. 5-HTP occurs naturally in an African plant, Griffonia simplifica, and is available as a nutritional supplement. Because 5-HTP doesn’t compete for absorption with other amino acids, it is well absorbed both with food and without. The amount needed to promote a sense of connection is 100mg a day, or less if taken in combination with other “connecting” nutrients. 5-HTP should not be taken with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants unless under medical guidance.

S-ADENOSYL METHIONINE (SAMe): the master tuner

As far as the chemistry of connection is concerned, SAMe is the master tuner. SAMe donates “methyl” groups and helps to make naturally occurring tryptamines – part of the brain’s well-tuned chemistry. The methylation of tryptamine, for example, results in DMT. The body can and does make SAMe from the constituent of protein, methionine. Having enough vitamin B6, B12 and folic acid helps the body maximise its production of SAMe.
SAMe also helps neurotransmitters deliver their messages to the receptor sites by sharpening up their activity. By methylating phospholipids, from which nerve cell membranes are made, SAMe improves cellular communication between nerve cells. SAMe can also help you get a good night’s sleep, and promotes dreaming. This is because the brain’s manufacture of melatonin, a key neurotransmitter for sleep and dreaming, from serotonin, depends on SAMe.

Although SAMe has been proven to be an antidepressant, it can enhance a feeling of well-being and connection. While a positive response is often felt within a few days, it may take as long as four weeks. In general, the longer SAMe is used, the more beneficial the results. SAMe should be taken on an empty stomach, preferably one hour away from food. Build up to a dosage of 200mg twice daily.

Unfortunately, SAMe is expensive, and also relatively unstable as a supplement – it should be kept refrigerated whenever possible. Pharmaceutical-grade SAMe comes in two forms, tosylate and a newer, more stable form called butanedisulfonate. The former quickly degrades upon exposure to heat and/or moisture and if improperly handled during manufacture can be worthless. Both forms are relatively stable in enteric coated tablets. A word of caution: although it’s not reported in the literature, higher doses may lead to irritability and anxiety.


Until stable SAMe supplements become widely available, your best bet is to supplement trimethylglycine (TMG). The body can make SAMe directly from TMG, which is both stable and much less expensive. While it has not been as extensively researched as SAMe, the fact that it is a direct precursor of SAMe may indicate that its effect would be very similar. Also, TMG helps the body to make more SAMe from dietary protein. TMG is extracted from sugar beets and is also found in broccoli and spinach. It has no reported side effects other than brief muscle tension headaches if it is taken in very large quantities without food. Optimal doses needed to raise SAMe levels in the body are 1,000 to 3,000mg a day. A 500mg dose is sufficient enough when combined with other connectors.

VITAMINS B3, B6, B12 AND FOLIC ACID: a brain’s best friends

If SAMe is the source of the methyl groups that transform one brain chemical into another, B vitamins are the delivery boys who can accept or donate methyl (carbon-based) groups. They are the real workers in the enzymes that turn one brain chemical into another and keep you feeling connected. For some enzymes you need vitamin B3, for others B6, B12 or folic acid. Not surprisingly, deficiency of any one of these leads to disconnection, and is associated with depression, mental illness, schizophrenia and unpleasant hallucinations. Supplementing these has the reverse effect, and has been shown to improve a person’s mental and emotional well-being dramatically. Optimal intakes are in the region of niacin (B3) 50mg, pyridoxine (B6) 50mg, cyanocobalamine (B12) 50µg, and folic acid 500µg.


From Hawaii to Papua New Guinea, kava has been at the core of life for centuries, as a wonderful connector. Taking kava opens you to an experience of heightened awareness and empathy, of enhanced “being” and freedom from “doing”. Traditionally, the feel-good staple of the South Sea islands, has two main uses: first, a personal experience of peace, relaxation, ease, well-being, even euphoria; and secondly, a social context, often with a sense of ritual or ceremony.

When you take kava, at least in the manner and doses used regularly in the South Pacific, your consciousness is unmistakably altered. Referring to its subtlety, islanders say: “Kava doesn’t come to you. You go to kava.” Terence’s description of his experience on kava explains its role as a natural connector:

“Over the next several minutes, at least four things seem to happen fairly simultaneously. A wave of relaxation rolls through my body. The effects of kava are immediate, but they are not abrupt. The second thing is an emotional release, perhaps even more subtle than the physical. I don’t notice the change as it happens, but I find I’m feeling at ease, comfortable in my skin, but again very awake. Finally I’m aware of a feeling of easy connectedness and relationship with others in the room.”

Kava definitely affects consciousness and thinking. In studies, memory actually seems to be enhanced. Perception is heightened, and so is sensitivity to stimuli such as noises or bright lights. Unlike alcohol, with kava you’re likely to experience no loss of mental sharpness. (In some studies kava actually enhanced it.) But don’t be fooled. Kava can deeply relax muscles, almost to the point of numbness. You can still function, but coordination is not as good. So, definitely do not drive or operate heavy machinery under the relaxing influence of kava. Other than this there appears to be no downside to using kava as a connector.

Kava works by enhancing GABA activity, the relaxing neurotransmitter that also modulates dopamine, adrenalin and noradrenalin. As a relaxant, the normal dosage is approximately 75mg of kavalactones; as a connector, 250 to 500mg.

SCELETIUM: South African gem

According to Dr Nigel Gericke, who is spearheading research into sceletium at the University of Natal’s department of botany in South Africa:

“Sceletium is one of the most ancient of mind-altering substances, and it is likely to have had a profound influence on the evolution of human consciousness. People interested in consciousness will find that sceletium is a key, but it needs to be used wisely. It is not a quick-fix, and after ten years of use I’m still learning about it.”

An unfamiliar herb to most of us, this native South African creeper, also called kougoed, has been used by hunter-gatherer tribes since prehistoric times. It lessens anxiety, stress and tension, raises the spirit and enhances the sense of connection. If you take a very large dose you may even feel euphoric, then taken over by a sense of drowsiness. It does not cause hallucinations. Nor do nearly 400 years of documented use reveal many serious adverse effects, either.

Traditionally, sceletium is chewed or brewed as a tea. If enough is chewed, it has a mild anaesthetic effect in the mouth, much like kava, and is used by the San people of South Africa for tooth extractions, or is given in minute doses to children with colic. A tea made from sceletium is used to wean alcoholics off their tipple. In this way the recovering alcoholic can avoid withdrawal symptoms.

People have reported that sceletium-induced relaxation has helped them to focus on inner thoughts and feelings, or to have a heightened experience of the beauty of nature. Some have reported an increased sensitivity of the skin as well as sexual arousal, while others have said it leaves them feeling free of fear and stress. Lewin, in his 1934 book Phantastica, reports mesembrine – one of the active chemicals in the plant – to induce a meditative state of mind.

While no clinical trials have been published yet, a number of doctors and psychiatrists have reported a wide range of positive uses for sceletium, from treating anxiety and depression to alleviating alcohol, cocaine and nicotine addiction. Moreover, by promoting a sense of empathy and connection, it has also been reported to help couples in therapy.

How does it work? The active constituents of the plant are alkaloids, including mesembrine, mesembrone, mesembrenol and tortuosamine. According to laboratory studies sponsored by the National Institute of Mental Health near Washington DC, its major alkaloid, mesembrine, acts as a serotonin-uptake inhibitor. Like Prozac, it helps to keep more serotonin in circulation. It also appears to have a harmonising and balancing effect on the other feel-good neurotransmitters, dopamine and noradrenalin, as well as on adrenalin.

An effective dose is 50mg a day, although some doctors report needing to use 100 to 200mg a day for those with chronic depression or anxiety.

Twenty-eight-year-old Jonathan is a new advocate of sceletium.

“I used to drink on Friday nights to unwind after my stressful week. Now I prefer sceletium. I combine 100mg of sceletium with 400mg of kava and 1g of TMG. This not only chills me out but it makes me feel very connected and “present” and able to really enjoy my friend’s company. It’s a bit like the buzz you get sitting on the beach watching the waves rolling in. What’s more, there’s no hangover.”


The following nutrients are worthy additions to a supplement programme designed to enhance connection. Here's a selection of comments from volunteers in our first pilot study: “I feel alert but not anxious… It's like caffeine without the anxiety…. More present and clear…. It's mellow and expansive…. It’s like the edge of life was softened…. Time is altered…. There is more light…. Everything is sharper.” These nutrients are likely to improve meditation, dreaming, insights and understanding, as well as your mood and ability to relate.

5-HTP* 50mg 200mg
SAMe+ or 200mg 400mg
TMG 600mg 1800mg
Kava (standardised extract)^ 100mg 250mg
Sceletium 100mg 200mg
Niacin (B3) 100mg 500mg
Pyridoxine (B6) 50mg 100mg
Cyanocobalamine (B12) 50ug 100ug
Folic acid 500ug 1000ug


*Do not supplement 5-HTP with antidepressant medication. One supplies the precursor to make serotonin. The other prevents the breakdown of serotonin. Taking both could lead to serotonin overload.

+SAMe can be substituted by its precursor, TMG, which is more stable and less expensive, in which case you need triple the dose.

^The kava dosage given here relates to the actual amount of kavalactones in the product, be it powder,capsules or tincture.

So, to sum up, you should take the following to get connected:

A good all-round multivitamin and mineral supplying optimal amounts of B vitamins and the minerals zinc, manganese and magnesium.
A “connector nutrient” formula providing 5-HTP, SAMe or TMG, sceletium, kava and additional B vitamins to achieve the levels shown above. SAMe is unstable, needs to be refrigerated and supplemented away from food, and for these reasons is often supplemented separately.

ION Comment

ION is not responsible for the views asserted by individual authors. Before embarking on a supplement programme such as the one suggested in this article, we strongly advise that you consult a nutritionist or other health professional.

This feature is adapted from Patrick Holford's forthcoming book, Natural Highs, (Piatkus £14.99), co-authored with Dr Hyla Cass, Associate Clinical Professor of Psychiatry at UCLA School of Medicine, LA, USA. Natural Highs is due to be published in September. For references and resources visit


To coincide with the launch of his new book, Patrick Holford will be visiting 20 cities in the UK during October. If you'd like to find out how to increase your energy, improve your mood, relax, beat stress, and get connected come and meet him on tour.


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