Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, Durban, South Africa, 2016. / There are now several thousand remedies available to a homoeopath and this number is continually increasing with the increase in homoeopathic research and provings. This growing wealth of data does, however, make choosing a homoeopathic remedy difficult and some homoeopaths argue that the essence of homoeopathic remedies are being lost in this excess of data. In an attempt to more accurately see a remedy’s ‘picture’ and gain deeper insight into remedies, Scholten (1993), Sankaran (2005a) and Mangialavori (2010) developed different methods which can now be collectively referred to as “group analysis”. The aim of group analysis is to find symptoms, sensations and pathological tendencies that are common to all remedies within a group. This study involved applying Sankaran’s group analysis approach to the psychoactive plant drug remedies with the rationale of filtering and organizing the mass of data we now have available on this group. This will enable both students and professionals of homoeopathy to develop a deeper understanding, and hence greater utilization, of the psychoactive plant drug remedies. The following five homoeopathic remedies were chosen for this study on the grounds that they have all been extensively proved through both homoeopathic provings and cured clinical cases and there is a vast amount of literature available on these remedies in materia medica and repertories: • Anhalonium lewinii (Cactaceae family) • Cannabis indica (Hamamalidae family) • Coffea cruda (Rubiaceae family) • Nux moschata (Magnolianae family) • Opium (Papaveraceae family) A computer repertory search was conducted using RadarOpus (Archibel, 2014) to extract all rubrics containing the selected remedies. Parameters were set to retain only rubrics that have less than 50 remedies and at least two of the selected psychoactive plant remedies in them. This was to ensure that only well-defined, characteristic remedies were looked at. The rubrics were visually analyzed, compared and contrasted to determine the common sensations within them and mental, general and particular symptoms were analyzed in terms of Sankaran’s model of Vital Sensation (2005a). The vital sensation of the psychoactive plant drug remedies was found to be that of horror, fear or fright. All the remedies belonging to this group experience the sensation of horror either through their perception of pain or through dreams, visions, hallucinations or anxiety. This sensation pervades all these remedies which are constantly trying to escape this sensation by either increasing or decreasing their activity and sensitivity. The active reaction to the sensation of horror is to increase activity. This is expressed through increased sensitivity; mental clarity; sensations of contraction, fullness, heaviness, heat or moisture; delirium, hallucinations and instability. The passive reaction to the sensation of horror is to decrease activity. This is expressed through insensitivity; lack of mental clarity; sensations of expansion, emptiness, lightness, cold or dryness; sleep, stupor and unconsciousness. The compensation, or coping mechanism that psychoactive plant drug remedies develop, is a transcendence of their condition: they transcend, or escape, their condition by no longer feeling or doing anything, by becoming numb and insensitive. The researcher suggests that although the remedies of the psychoactive plant drug group can be classified according to different miasms, the over-riding miasm of this group is the sycotic miasm with its fundamental sense of having a ‘fixed weakness’ within themselves. The researcher also proposes that the psychoactive plant remedies have an affinity for the central nervous system and for ailments caused by strong emotions such as joy, anger, excitement, fear or fright. These remedies tend to produce pathologies of the central nervous system and sleep including increased reflexes, involuntary motions, trembling, jerking; weakness, atrophy, slowness, paralysis; unconsciousness; catalepsy; Autism Spectrum Disorders; hypersensitivity; insensitivity or absence of sensitivity; pain; formication; mental confusion, poor comprehension, nonsensical speech; memory disorders; delirium, hallucinations, schizophrenia; mood disorders; behavioural disorders; anxiety; insomnia, narcolepsy and nightmares. The researcher found group analysis to be a powerful methodology that, if employed correctly, can aid homoeopaths to learn and understand remedies in their ‘totality’. / M

In this investigation the chemistry of three southern African plants used for medicinal purposes was investigated. The plants were Dioscorea dregeana, Avonia rhodesica and Equisetum ramossisimum. Extracts of all three of these plants have been found to be active on the central nervous system. The structures of the compounds isolated were determined by using 1H and 13C n.m.r., i.f., UV-VIS, - mass spectroscopy and chemical methods. D. dregeana yielded two alkaloids and three aromatic compounds. A. rhodesica contained a large amount of wax which was analysed by GC-MS and its distribution and physical nature on the surface of the leaves was determined by SEM (scanning electron microscopy). This plant also contained two sterols. Equisetum ramossisimum extracts contained a carotenoid and several porphyrins, as well as large amounts of silica. A DTSA X-ray microanalysis system (which was a component of the scanning electron microscope) was used to determine the distribution of silica in the stem. / Thesis (M.Sc.)-University of Natal, Durban, 1998.

The majority of the population in South Africa use traditional health care to treat various mental conditions. This thesis has two main objectives; to bring together a comprehensive and detailed record of psychotropic plants used in southern Africa by indigenous peoples for medicinal or cultural purposes. Secondly, this research attempts to investigate the validity and rationale of the use of these plants by screening them in various biological assays for psychotropic activity. Plants were selected, based on their traditional use and availability, and were screened in four assays, which detect biological activity of a useful nature. A number of in vitro enzymatic and neuronal signal transduction assays were employed in this thesis, the inhibition of the serotonin reuptake transporter protein (SERT); inhibition of catabolic enzymes (e.g. acetylcholinesterase, monoamine oxidase); GABAA- benzodiazepine receptor binding. The influence of legislation, past and present, on the state of traditional medicine is highlighted. Aspects of the philosophies and practises of the various practitioners of South African traditional medicine will be discussed. An annotated list compiled from available ethnobotanical literature of plants traditionally used for central nervous system-related purposes is provided. It contains more than 330 species, from 94 families, which are currently used or have been used for cultural, medicinal and recreational purposes related to the central nervous system (CNS). Where available, information pertaining to plant part used, preparation method, dosage, route of administration, known and potentially active constituents are included. Seventy five extracts from 34 indigenous plant species used in South African traditional medicine or taxonomically related to these were investigated for their affinity to the serotonin reuptake transport protein, making use of an in vitro [3H]-citalopram serotonin reuptake transport protein binding assay. Aqueous and 70% ethanolic extracts of various plant parts were screened and 45 extracts derived from 15 plant species showed affinity. The affinity of 12 extracts from four plants was characterized as high (more than 50% inhibition at 5, 1, and 0.5 mg/ml). Plant species with high affinity to the serotonin reuptake transport protein included Agapanthus campanulatus, Boophone disticha, Datura ferox and Xysmalobium undulatum. Agapanthus campanulatus yielded high activity in aqueous extracts from leaves and flowers. B. disticha showed high activity both in aqueous and ethanolic extracts of leaves and bulbs. D. ferox showed high activity in aqueous extracts from the seeds and X. undulatum showed high activity in the ethanolic extract of the whole plant. Two compounds, buphanadrine and buphanamine, were isolated by bioassay-guided fractionation on vacuum-liquid-chromatography (VLC) and preparative thin-layer-chromatography (TLC) from B. disticha. The structures of the compounds were determined by 1H and 13C NMR. Fractions were tested for affinity to the serotonin transporter in a binding assay using [3H]-citalopram as a ligand. The IC50 values of buphanidrine and buphanamine were 274 ìM (Ki = 132 ìM) and 1799 ìM (Ki = 868 ìM), respectively. The two alkaloids were also tested for affinity to the 5HT1A receptor, but only showed slight affinity. Aqueous and ethanol extracts of 43 plants that are traditionally used to treat against epilepsy and convulsions were initially tested in the GABAA-benzodiazepine receptor binding assay, where the binding of 3H-Ro 15-1788 (flumazenil) to the benzodiazepine site is measured. The GABAA-benzodiazepine receptor complex is involved in epilepsy and convulsions. Out of the 118 extracts tested, one aqueous and 18 ethanol extracts showed activity. The most active extracts were the ethanolic leaf extracts of Searsia tridentata, Searsia rehmanniana and Hoslundia opposita and the ethanolic corm extract of Hypoxis colchicifolia, which all showed good dose-dependent activity. A further forty-six ethanol extracts from another 35 species, both indigenous and exotic that are traditionally used predominantly as sedatives or to treat various CNS-related ailments were tested in the GABAA-benzodiazepine receptor-binding assay. Out of the 46 extracts tested, seven showed good activity and 10 showed moderate activity. The most active extracts were the ethanolic leaf extracts of Arctopus echinatus, Artemisa afra, four Helichrysum species and Mentha aquatica which all showed good dose-dependent activity. Two biflavonoids with activity in the 3H-Ro 15-1788 (flumazenil) binding assay were isolated by high pressure liquid chromatography (HPLC) fractionation of the ethanol extract of the leaves from Searsia pyroides. The structures of the two biflavonoids were elucidated by nuclear magnetic resonance spectroscopy (NMR) to be agathisflavone and amentoflavone. Agathisflavone and amentoflavone competitively inhibited the binding of 3H-Ro 15-1788 with a Ki of 28 and 37 nM, respectively. Extracts of Searsia dentata and Searsia pentheri were not as active as the extract from Searsia pyroides; both were found to contain apigenin and agathisflavone. The monomer apigenin, agathisflavone and amentoflavone were fitted into a pharmacophore model for ligands binding to the GABAA receptor benzodiazepine site. This reflected the affinities of the compounds in the [3H]-flumazenil binding assay. Mentha aquatica, a mint that is found in Europe and Africa, is used in Zulu traditional medicine for spiritual purposes. The ethanolic leaf extract showed a strong affinity to the GABA-benzodiazepine receptor. Viridiflorol from the essential oil and (S)-naringenin from an ethanolic extract was isolated by bioassay-guided fractionation using binding to the GABA-benzodiazepine site. Viridiflorol had an IC50 of 0.19 M and (S)-naringenin of 0.0026 M. Twenty plants used in Zulu traditional medicine for several CNS-related ailments were screened for MAO inhibition and specific MAO-B inhibition activity. MAO-B inhibitors are currently employed in the treatment of neurodegenerative related illnesses such as Parkinson's and Alzheimer's diseases. A photometric peroxidase linked assay was used to determine the inhibition of the oxidative deamination of tyramine by MAO isolated from rat liver. Ruta graveolens exhibited the best MAO inhibitory activity (ethyl acetate leaf extract = IC50 5 ± 1 ìg/ml, petroleum ether extract = 3 ± 1 ìg/ml) and specific MAO-B inhibition (ethyl acetate leaf extract = IC50 7 ± 6 ìg/ml petroleum ether extract = 3 ± 1 ìg/ml). Schotia brachypetala, Mentha aquatica and Gasteria croucheri also exhibited good MAO-B inhibition activity. Six extracts of varying polarity of Mentha aquatica were tested in a photometric peroxidase linked MAO bioassay. The 70% ethanol extract had highest inhibitory activity. (S)-Naringenin was isolated from the extract by bioassay guided fractionation on VLC and preparative TLC. The structure of the compound was determined by 1H, 13C and 13C-DEPT NMR and optical rotation. The IC50 values for MAO inhibition by naringenin were 342 ± 33 ìM for the rat liver mitochondrial fraction, 955 ± 129 ìM for MAO-A and 288 ± 18 ìM for MAO-B respectively. South African traditional medicine clearly utilizes many botanical species with CNS-related activity. Only a small number of the more than 330 southern African plant species reported to treat or alter the CNS have been scientifically evaluated. To date very few of the active compounds have been isolated and identified. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.