B. disticha (Figure 2) is regarded as a visionary plant called leshoma in Sesotho (Pasquali, 2021). It is used as a divinatory “bioscope”, giving the ability to see things that ordinary people cannot see during consultation, by Zulu, Xhosa, Shona, and San TMPs. Each ethic group has a particular name for it.

During consultation with a traditional healer, a preparation of B. disticha is administered to the enquirer. This causes a visionary cataleptic state during which they can “see” the person responsible for their misfortune”. Over the years, such activities have been kept secret by TMPs, but now it is common knowledge in some communities. As a result, careless consumption by adolescents of a B. disticha decoction made from the bulb, both for therapeutic and intoxicating purposes—a herbal high—is now reported to be common in some communities (Laing, 1979).

The route of administration is as a liquid preparation of the bulb, usually administered orally.

The decoction from the bulb must be carefully prepared by boiling it at least thrice and discarding the boiled water containing toxic constituents. The last boil is then left to stand over night before being used (Nyazema, 1984).

To date, the presence of 11 alkaloids—including buphanidrine 13 (19.4%), undulatine 14 (18.6%), buphanisine 15 (16.9%), buphanamine 11 (14.1%), nerbowdine 12 (11.1%), crinine 3 (7.2%), distichamine 16 (5.4%), crinamidine 17 (1.2%), acetylnerbowdine 18 (0.6%), lycorine 2 (0.4%), and buphacetine (0.3%)—has been identified and described (Nair and Staden, 2014) with their respective contribution percentage. There is uncertainty over which of the 11 alkaloids is affected by the boiling of the bulb, which thereby influences the “entourage effect” described by observed symptoms including unconsciousness, dilated pupils, tachycardia, raised blood pressure, slightly raised temperature, laboured respiration, psychosis, drunkenness, and visual disturbances (Laing, 1979).

Stafford et al. (2008) reported that B. disticha can be used for phytotherapy for mental disorders such as anxiety, depression, epilepsy, and age-related dementia.

All the alkaloids mentioned above produced by B. disticha are of the crinane series. As shown in Figure 3, nerbowdine, previously called “haemathamine” (Gelfand and Mitchell, 1952), was thought to be responsible for effects similar to those of anti-cholinergic scopolamine.

Several areas of B. disticha use in traditional medical practice still require pharmacological validation because the plant is regarded as poisonous. There is a need for rigorous investigation to reduce harm that may be caused by the use and abuse of B. disticha (Stafford et al., 2008).

There are no legal sanctions in southern African countries, which opens the drug to possible abuse.

C. sativa is not indigenous to southern Africa, as believed by many people. A more in-depth analysis of the issue of cannabis diffusion in Africa versus its possible status as a native plant has been extensively reviewed in a brief agricultural history of Africa by Duvall (2019). Linguistic evidence indicates that it was introduced into the sub-continent from Asia (Crampton, 2015; du Toit, 1996). Be that as it may, Cannabis is now reported to be used by many TMPs (Sobiecki, 2008). Illegal use by non-healers for recreation and ritual is widespread throughout southern Africa. However, South Africa is moving towards the decriminalization of its cultivation for possession personal use. Figure 4 shows a female and a male plant in a household backyard, which is now permitted.

The major route of administration is smoking as a cigarette. It is believed that cannabis may be mixed with N. tabascum and other plants to aid divination and its psychotropic effects. Vaporization is another commonly used route of administration. Inhalation is believed to be quickest for onset of action and shortest duration (Iversen, 2001).

C. sativa is used for religious purposes as a sacred herb entheogen by southern African Rastafarians who call it ganja (ganga), a word derived from Indian plantation workers in Jamaica (Booth, 2005; Crampton, 2015). It is mainly used for its THC (tetrahydrocannabinol) content, which is responsible for its intoxicating effects. More than 100 other cannabinoids including, CBD (cannabidiol), are non-intoxicating (Figure 5) (Russo, 2017).

Cannabis grown in different conditions can produce different phytochemical profiles which may not be known by its users. Studies have shown that handling of the plant can cause the oxidation and degradation of cannabinoids, resulting in adverse or unknown biological effects. This is critical information of primary importance for its medical and recreational use (Zandkarimi, Decatur, Casali, Gordon, Skibola, et al., 2023).

There are cannabinoid-like substances in the brain that can interfere with or modulate neurotransmission. This is because cannabinoid-like substances bind to CB1 receptors on the pre-synaptic neuron found in the brain. Depending on the neurotransmitter released as a result of the binding, this can result in different psychotropic effects, depending on the part of the central nervous system (Mouhamed et al., 2018).

There is continued research into the psychological effects of cannabis . An interesting recent study has shown that the volume of the grey matter of the brain increased following a couple of uses of marijuana by some adolescents, resulting in increased risk of anxiety, and decreased ability to think and memory (Orr, Spechler, Cao, Albaugh, Chaarani et al., 2019). The genetic basis for cannabis use and its psychiatric disorders has been published in Lancet Psychiatry, indicating that a subset of the population is at high risk (Cheng, Parker, Karadag Koch, Hindley et al., 2023).

The early Sanskrit word dustura or dahatura means “divine” inebriation, from which D. stramonium derives its name. This explains why, for approximately 400 years, solanaceous plants were regarded as “diabolic incarnations”. Consequently, Datura has been referred to as “devil’s apple”, “mad apple”, and “devils work” due to its ability to cause visionary dreams and assist in the foretelling of the future and revealing the causes of disease (Busia and Heckles, 2006).

In southern Africa D. stramonium has been reported to be used in traditional medical practice (Figure 6) (Sobiecki, 2008). It is thought that the use of its leaves can relieve headache, and vapours from a leaf infusion can relieve the pain of rheumatism and gout. The smoke of the leaf can be inhaled to relieve asthma and bronchitis.

The name of H. odoratissimum is derived from the Greek word heliscryson, a compound of the word for “sun” plus chryos, which means “gold,” referring to the golden flowers which are characteristic of the genus (Figure 8). “Odoratissimum” refers to the strong odour of the plant. The plant is commonly termed “African incense”, and perhaps this is why it is used as a calmative for insomnia and ritual incense (Maroyi, 2019; Serabele, Chen and Combrinck, 2023). Recently, it has been reported that another species in the Helichrysum genus, H. umbraculigerum, which is not commonly used, produces phytocannabinoids such as cannabigerol and CBG but not THC and CBD (Benson, 2023). TMPs in southern Africa have their own ways of distinguishing the different Helichrysum species, in spite of their florescence being almost identical (Figure 8) (Viljoen et al., 2022).

The principal route of administration is the inhalation of smoke from burnt parts of the plant or direct smoking. It can, however, also be taken as herbal tea.

According to the phytochemical studies of Viljoen et al. (2022), 4,5-dicaffeoylquinic acid and dicaffeoylquinic acid, also found in coffee beans (Mondolot et al., 2006) (Figure 9), consistently appear to be possible markers for the species. This has also been confirmed by Serabele, Chen and Combrinck (2023), who used high-performance-thin-layer-chromatograph (HPTLC) coupled with mass spectrometry (UPLC-MS) analysis. What is interesting, however, is that essential oils such as α-pinene-containing oils and neryl acetate also may be possible markers of the species, using the method of analysis of Tundis, Statti, Conforti, Bianchi, Agrimonti et al. (2005). Their study of Helichrysum italicum showed that environmental factors influenced the phytochemistry (volatile constituents) and biological effects (antibacterial activity) of the plant. Interestingly, H. italicum is commonly used as a herbal medicine in Mediterranean regions (Appendino et al., 2015).

There are no legal restrictions on its use.

L. leonurus, although often referred to as “wild dagga,” an Afrikaans word for cannabis, is not related to true dagga (C. sativa). Leonotis is a Greek word meaning “lion ear”.

In traditional medical practice, its dried leaves and pink or brilliant orange flowers, (Figure 10) are used to treat many ailments, including epilepsy. Non-healers use it for its calming effect.

Route of administration: The leaves and flowers are smoked for mild euphoric effect less potent than cannabis.

Terpenoids with the main compounds (mono-, sesqui-, and diterpenoids) have been reported to be biologically active. Labdane diterpenes (Figure 11) were found to be more abundant compounds by Nsuala, Enslin and Viljeon (2015).

However, a phytocannabinoid-like compound, adrenoyl-EA (adronyl-ethanolamine), (Figure 12) has recently been identified in the flowers. The compound has the same structure as endocannabinoid anandamide (N-acylethanolamine) (Figure 13) which is also found in cocoa beans. Anandamide is as an agonist of the CB1 and TRPV1 receptor proteins in humans, whose other agonists are ideal candidates for the development of anti-inflammatory, neuroprotective, and anticancer drugs (Hunter, Stander, Kossman, Chakraborty, Prince et al., 2020).

There are other compounds that have been isolated from the plant. However, according to Nsuala, Enslin and Viljeon (2015), leonurine (Figure 14) has been reported in the popular literature. Interestingly there has been no scientific analysis of extracts of L. leonurus that have reported leonurine.

Legal status: no restrictions on its use.

P. cubensis is a fungus with neurotropic (hallucinogenic or psychotropic) properties, also referred to as narcotic, magic, sacred, psychedelic entheogenic mushrooms; they have been reported as found all over the world, including southern Africa (Matsushimaet al., 2009). Because of the legal status of mushrooms use, coupled with continued secrecy surrounding some traditional medical practices, it was difficult to obtain information on how P. cubensis (Figure 15) is actually employed in culturally sanctioned visionary experiences in ritual or religious contexts.

Its route of administration is oral.

This is also the case in West Africa (Osemwegjie, Okhuoya and Dania, 2014). Ethnomycological studies in some parts of Africa have been found to be varied, incoherent, skewed, and not balanced in terms of information on mushrooms of unknown use.

However, information obtained about the collection and uses of mushrooms indicate that there is community knowledge about which mushrooms can be eaten, which can be used for medicinal purposes, and which are poisonous. There are beliefs such as the following: 1) any wild mushroom attacked by insects, rodents, and other animals where they are growing can be classified as edible; 2) any mushroom given to a live chicken, pig, dog, and which does not die is regarded as edible; 3) brightly coloured and pleasantly smelling mushrooms could be edible and associated with spirituality. Such human experiments provide more knowledge about the better use of wild mushrooms in general, leading to their acceptance as food, medicine, or poison.

P. cubensis, which is reported to grow on cow and wildlife dung in Zimbabwe (van der Horst, 2018), is similar to that which grows on Asian elephant dung in India. Psilocybin, psilocin (Supplementary Figure S1), and baeocystin are reported to be the biologically active substances in the mushroom. Of these biologically active substances, psilocybin is the most stable. It is found in some of the mushrooms and is converted to psilocin, which produces the psychoactive effect (Stamets, 1996). The activity produced by the mushrooms depends on the species and variety and where it grows and is subsequently harvested for use. The same is true with any of the psychoactive plants. There are currently several clinical trials with psilocybin (University of San Francisco, 2023). Previous studies at the Johns Hopkins Centre for Psychedelic and Consciousness Research showed that psilocybin could be effective for therapeutic purposes, such as for depression, drug abuse, and end-of-life mental disorders (Ziff et al., 2022). Despite this, “magic mushrooms” are easily accessible to the general public.

S. tortuosum L.) N.E. Br. and S. expansum L. Bolus were formerly known as Mesembryanthemum tortuosum L. and Mesembryanthemum expansum L. (Supplementary Figure S3). Sceletus is a Latin word that describes the plant’s prominent leaf veins (Supplementary Figure S4).

A number of habitats have been found suitable for the growth of different genera of its family. It is found in south-west Africa, including Angola, South Africa, Zimbabwe, Botswana, and Namibia (Supplementary Figure S4) (Faber, Laubscher and Jimoh, 2021).

Traditionally, S. tortuosum was reported to be useful for toothache and abdominal pain. Furthermore, it is thought to elevate mood, suppress hunger and thirst, induce analgesia, aid hypnosis, reduce anxiety, is used as an intoxicating/euphoric substance (Olatunji et al., 2021), and is sometimes used together with cannabis to enhance the latter's intoxicating effect (Michell, 2004).

The route of administration is mainly oral by mastication, and by inhalation through smoking the dried plant material or snorting the root powder.

The plant contains different types of mesembrine alkaloids (Supplementary Figure S5) which are found in a few plant genera, Sceletium being one (Faber, Laubscher and Jimoh, 2020).

Mesembrine is a serotonin re-uptake inhibitor and is also thought to act as a monoamine-releasing agent (Coetzee et al., 2016). Historical use of different extracts of the plant by the San and Khoi people has been shown to have various biological properties (Manganyi et al., 2021).

It can therefore be argued that S. tortuosum has both pharmaceutical and economic significance because it contains mesembrenone and mesembrine, which can be developed as useful products that promote health and/or to treat some psychological disorders.

According to anthropologist Manton Hirst, S. capensis has been used for hundreds of years. It is a stringy, leafy green plant found near rivers that produces a fragrant white flower that only blooms at night, hence perhaps its name as the “African dream herb” (Hirst, 2005). It is believed that S. capensis is used to heighten one’s intuitive capacity to extract wisdom from the dream realm and apply it the waking state. Details of how S. capensis is used depend on the Bantu ethnic group, including how the plant material preparation is consumed.

The plant’s route of administration is oral, by chewing the root bark, or scooping or sipping the foam that it produces during preparation.

S. capensis is used in ritual ceremonies; hence, the potential for abuse because information on accessibility and availability is now public knowledge. Perceptions regarding its value and potential harm have been reported to be transformed by those participating in ceremonies.

Most Silene species are hermaphrodite, and more than 400 bioactive compounds have been isolated, including phytoecdysteroids, the predominant constituents (Mamadalieva, 2012). Supplementary Figure S6 shows the general chemical structure of phytoecdysteroids, and Supplementary Figure S7 gives the structure of 20-hydroxyecdysone.

Ecdysteroids can be used for chemotaxonomy in this genus because many Silene species contain complex ecdysteroid cocktails (Zibareva et al., 2009). Despite what is now known about the responsibility of 20-hydroxyecdysone for genomic biological effects manifested in different animal models (Dinan, Dioh, Veillet, and Lafont, 2021), ecdysteroids are thought not to be responsible for CNS effects.

According to Sparg, Light, & van Staden, (2004), the frothing and foam formation associated with preparation for use could be explained by the presence of saponins— oleanane-type aglycone moieties. Supplementary Figure S8 shows the basic structure of a saponin said to be commonly present in the Caryophyllacae order. Since the foam is generally consumed during the ceremonies, it is therefore assumed that its psychoactive effects are due to the saponin content rather than the phytoecdysteroids.

Observations made by Hostettmann & Marston (1995) confirm that cleavage of the saponins aglycone moiety can serve as a useful substance for the synthesis of hormones such as progesterone in industry. The amphiphilic nature of saponins is useful in soap manufacture and surfactants for the cosmetic industry (Guclu-Ustundag and Mazza, 2007).

Ground root is now commercially available in gel capsules which contain approximately 500 mg of ground powder of the root. It is promoted for lucid dreams as well as enhancing the quality of sleep, with a maximum daily dose of 30 g (Sumpter, 2021).

There are no legal restrictions on its use

D. dregeana (wild yam) (Supplementary Figure S9) grows naturally in Eswatini, Mozambique, and South Africa. It is mainly used as a sedative, depending on the mental disorder (Maroyi, 2022).

Its route of administration is oral as a weak decoction which is a more vigorous extraction of the active ingredient from the plant’s tuber.

The tubers of D. dregegeana contain the following compounds: sitosterol, stigmasterol, dodecanosyl 3-[4′-hydroxy, 3′-methoxyphenyl] propenoate, 3, 4′,5-trihydroxybibenzyl, crinamine, and dioscorine. Of these phytochemicals, dioscorine (Supplementary Figure S10) has intoxicative and soporific effects. On the other hand, crinamine (Supplementary Figure S11) is a selective monoamine B inhibitor (Naidoo et al., 2020).

An animal study found that a combination of the psychoactive principles in the tuber produced central nervous system depressant/sedative and anxiolytic effects (Patel and Galani, 2017). Bio-prospecting of D. dregeana and wild tubers in the food and pharmaceutical industries can benefit from the observed effects.

There are no legal restrictions on its use.

Over the years, the commercialization of tradition African medicinal plants has increased as a result of interest in and knowledge of their use. For example, the economic value of indigenous medicinal plants in South Africa now represents 5.69% of the national health budget, and the plant trade is a key rural industry and business stimulant (Rispel and Setswe, 2007). It is therefore necessary to investigate ethno-psychoactive plant use for their psychotropic actions.

These plants contain secondary metabolites including terpenoids, flavonoids, and alkaloids. These metabolites feature various chemical structures and produce a variety of beneficial biological which are a valuable source of compounds that the pharmaceutical, nutraceutical, cosmetic, and fine chemical industries can use. The present study shows that ethno-psychoactive plants are a major source of many drugs that can be developed for therapeutic purposes. Many of these plants contain useful substances, either in the whole plant or in some parts that can used be for therapeutic purposes in disease, diagnosis, and prevention. It has been estimated that 84% of drugs or their structures now used for mental disorders have been obtained from natural sources (Bharate et al., 2018). According to Halilu (2022), medicinal plants can be a significant source of income for research in pharmaceutical science and socio-economic development. B. disticha is certainly a plant from which neuro-protective products can be developed for Alzheimer’s and Parkinson’s diseases, epilepsy, depression, and anxiety. The crinamine contained in B. disticha has been demonstrated to be a selective inhibitor of monoamine oxidase B, which is useful in the treatment of Parkinson’s disease. Another plant which contains crinamine, Crossyne guttata, is used by Rastafarian bush doctors for alcoholism, which is accentuated by MAO (Naidoo et al., 2020).

Research on treatments for depression, post-traumatic stress disorder, and other psychiatric conditions using psychedelics has been brought closer to legalization (Krediet et al., 2020).

Another group of psychoactive plants, the Silene genus, has been exploited as an industrial source of phytoecdysteroids that can be used to develop anabolic steroids. S. capensis, the dream root, is another source of hallucinogens that can be developed for specific mental disorders and to improve the quality of sleep. C. sativa (THC), D. stramonium, N. tabacum, and P. cubensis can be exploited just as C. sinensis and N. tabascum have been by industry. The recent discovery that non-cannabis plants such as H. umbraculigerum have cannabis qualities opens new avenues for the development of products of medical use, particularly psychiatrics (Berman et al., 2023). This species has been shown to have a parallel evolution of cannabinoid biosynthesis which can be exploited to produce botanicals for medicinal use.

On the other end of the spectrum, psychosis—a collection of symptoms affecting the mind, where there has been some loss of contact with reality—can be treated and managed in traditional medical practice. Psychosis in traditional medical practice is regarded as a disequilibrium that results from psychological or spiritual factors or both. It is also referred to as a collection of symptoms that affect the brain, causing a loss of contact with reality. The healing of such patients emphasizes correcting this disequilibrium by using C. sativa, D. dregeana, S. tortuosum, L. leonurus, and H. odoratissimum. Unfortunately, little is being done to authenticate their effects within a scientific paradigm because they do not contain a simple ingredient, making them more complex than conventional pharmaceutical products like prochlormazine. The many substances that may be contained in a plant responsible for beneficial effects may act synergistically and produce what is known as “entourage effect” (Ferber, Namdar, Hen-Shoval, Eger, Hinanit Koltai, et al., 2020). This synergistic interaction may be a strength for medicinal plants, but unfortunately it is also an obstacle to standardizing research, which is a concern for those trying to develop pharmaceutical products from medicinal plants. It should be a concern for TMPs, conventional healthcare providers, and consumers. Such complexity requires psycho-pharmacological and social pharmacological information on the value of botanicals used for mental problems, diagnosed in traditional medical practice, in the assessment of a risk-effective balance.