Specific Medicinal Uses of Cannabis: Anticonvulsant Activity

As early as 1890, the use of cannabis was advocated for the suppression of convulsions in man. While there are some reports of the effects of smoking cannabis in this area, most effort has focused on synthetic cannabinoid derivatives. Cannabis Two reports indicate that regular cannabis smoking contributes to better control of seizures in epileptic patients whose disease is refractory to conventional therapy. These studies were not controlled and contained few patients. THC There have been no reports of the use of THC in epileptics; this compound has induced or exacerbated seizure activity in animal studies. Cannabidiol (CBD) Carlini and Cunha added CBD, 200–300 mg daily, to the anticonvulsant regime of eight patients with generalised secondary seizures, refractory to antiepileptic drugs. Over the 5-month observation period, improvement was noted in seven. Very similar results were reported in an earlier trial by Karler and Turkanis. In a placebo controlled study in patients with grand mal seizures, CBD produced improvement in seizure control in 7 patients, three of these showing great improvement. One patient showed some improvement on placebo however. Summarising, there seems to be little to recommend the Read more […]

Stress: Rhaponticum

R. carthamoides has been used for centuries in Siberia as a folk medicine for the treatment of fatigue, anemia, and impotence, as well as for convalescence after illness. In 1961 the liquid extract (1:1) was officially recognized and included in the Soviet Pharmacopoeia as a natural agent for overcoming fatigue, improving physical and mental productivity and stamina, and shortening recovery time after illness. The roots and rhizomes are considered the plant’s medicinal parts; the active ingredients are primarily phytoecdysterones (especially ecdysterone), although the plant also contains a number of other biologically active compounds, including flavonoids, sesqui-terpene lactones, and polyines. R. carthamoides extract standardized to 5% ecdysterone is considered the most potent form. Several decades of research have demonstrated numerous pharmacologic effects in animal models and human studies. It is a classic adaptogen with a wide range of activities, including normalizing effect on the central nervous and cardiovascular systems, sleep, appetite, moods (neurotic, asthenic, depressive, hypochondriac), mental and physical state, and the ability to function well under stress. It has marked anabolic activities, building Read more […]

Herb-Drug Interactions: Cannabis

Cannabis sativa L. (Cannabaceae) Synonym(s) and related species Bhang, Dagga, Ganja, Hashish, Indian hemp, Marihuana, Marijuana. Cannabis indica Lam. Constituents Cannabis herb contains a wide range of cannabinoids, which are the major active compounds. The main psychoactive constituent is delta9-tetrahydrocannabinol (THC; dronabinol), and it is the cause of many of the pharmacological effects elicited by the consumption of cannabis. However, other cannabinoids, which do not possess psychoactive properties, such as cannabidiol, cannabinol (a decomposition product of delta9-tetrahydrocannabinol), cannabigerol and cannabichromene, are increasingly being investigated for their pharmacological and therapeutic properties. Cannabinoids are often found in the plant as their acid metabolites, e.g. ll-nor-9-carboxy-delta9-tetrahydrocannabinol, cannabidiol acid and others, especially if the plant has been grown in a cooler climate. These decarboxylate to the parent cannabinoid at high temperatures, such as during smoking. Most medicinal cannabis products have been heat treated to ensure that the cannabinoids are present only in the non-acid form. Use and indications Cannabis has no current established use in herbal Read more […]

CNS DEPRESSANTS

CNS DEPRESSANTS depress the CNS. In practice, very diverse agents can be grouped under this heading and it does not describe any specific type of drug action. Most of the agents that depress neuronal activity in the brain or spinal cord are dealt with under specific headings. The properties of some of these classes will be summarized here. GENERAL ANAESTHETICS are either inhaled or injected agents and produce insensibility, mostly to alleviate pain during surgical procedures (e.g. halothane, thiopentone sodium). HYPNOTICS induce sleep and a wide range of chemical types may be used. The older agents, such as the barbiturates, were often SEDATIVE agents used at a higher dose, but they readily produced dangerous respiratory depression and are now much less commonly used (e.g. amylobarbitone, chloral hydrate, chlormethiazole, triclofos). Increasingly, the drugs of choice are anxiolytic/minor tranquillizers at a somewhat higher dosage (vide infra). Tranquillizers depress the CNS. The need for the term came with the introduction of drugs having rather more subtle effects on mood and behaviour than the barbiturates. However, it soon became necessary to divide the category into minor tranquillizers and major tranquillizers. Read more […]

BENZODIAZEPINE BINDING-SITE AGONISTS

BENZODIAZEPINE BINDING-SITE AGONISTS act not at a distinct receptor-effector entity (and cannot be cloned as independent receptors) but rather have a (normally positive) allosteric interaction at ‘modulatory’ binding-sites on GABAA receptors. GABAA receptors are of the heteromeric intrinsic-ion-channel superfamily, and these ligand-gated channels are permeant to chloride ions, so their effect on membrane excitability is normally inhibitory (see CHLORIDE-channel activators, gaba receptor agonists ). GABA (γ-aminobutyric acid) is thought to be the major inhibitory neurotransmitter within the CNS, and GABA receptors have a wide distribution within the body. The key feature of this benzodiazepines-GABAA interaction is a positive allosteric modification both of binding and action of GABA at its main ‘competitive site’ which is concerned with the gating of ion channel opening. Benzodiazepine agonists and GABA, mutually enhance binding at the GABAA receptors; the former increase the number of channels that are opened by a given concentration of GABA (rather than increasing the average open channel time or channel conductance). The molecular basis of these modulatory interactions of benzodiazepine and the GABAA receptor is Read more […]

Herb-Drug Interactions: St John’s wort

Hypericum perforatum L. (Clusiaceae) Synonym(s) and related species Hypericum, Millepertuis. Hypericum noeanum Boiss., Hypericum veronense Schrank. Pharmacopoeias St John’s Wort (British Ph 2009, European Ph 2008, US Ph 32); St John’s Wort Dry Extract, Quantified (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4). Constituents The main groups of active constituents of St John’s wort are thought to be the anthraquinones, including hypericin, isohypericin, pseudohypericin, protohypericin, protopseudohypericin and cyclopseudohypericin, and the prenylated phloroglucinols, including hyperforin and adhyperforin. Flavonoids, which include kaempferol, quercetin, luteolin, hyperoside, isoquercitrin, quercitrin and rutin; biflavonoids, which include biapigenin and amentoflavone, and catechins are also present. Other polyphenolic constituents include caffeic and chlorogenic acids, and a volatile oil containing methyl-2-octane. Most St John’s wort products are standardised at least for their hypericin content (British Pharmacopoeia 2009), even though hyperforin is known to be a more relevant therapeutic constituent, and some preparations are now standardised for both (The United Read more […]

Herb-Drug Interactions: Passiflora

Passiflora incarnata L. (Passifloraceae) Synonym(s) and related species Apricot vine, Maypop, Passion flower, Passion vine. Note that Passiflora edulis Sims is the source of the edible passion fruit. Pharmacopoeias Passion Flower (British Ph 2009, European Ph 2008); Passion Flower Dry Extract (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4). Constituents The major constituents of passiflora leaf and flower are C-glycosides of flavonoids based on apigenin and luteolin, to which it may be standardised. Other flavonoids present include chrysin (5,7-hydroxyflavone), quercetin and kaempferol. The indole alkaloids of the P-carboline type (e.g. harman, harmol and others) are minor constituents or may not even be detectable. Other minor constituents include a cyanogenic glycoside gynocardin, gamma-benzopyrones maltol and ethylmaltol, a polyacetylene passicol and an essential oil. Use and indications Passiflora is used as a sedative, hypnotic and anxiolytic and has been reported to have antiepileptic and anti-inflammatory effects. Some clinical studies in patients appear to support the anxiolytic and sedative effects of passiflora, and animal data suggest that some of the flavonoid Read more […]

Herb-Drug Interactions: Ginkgo

Ginkgo biloba L. (Ginkgoaceae) Synonym(s) and related species Fossil tree, Kew tree, Maidenhair tree. Salisburia adiantifolia Sm., Salisburia biloba Hoffmanns. Pharmacopoeias Ginkgo (US Ph 32); Ginkgo capsules (US Ph 32); Ginkgo dry extract, refined and quantified (British Ph 2009, European Ph 2008); Ginkgo leaf (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4); Ginkgo tablets (US Ph 32); Powdered ginkgo extract (The United States Ph 32). Constituents Ginkgo leaves contain numerous flavonoids including the biflavone glycosides such as ginkgetin, isoginkgetin, bilobetin, sciadopitysin, and also some quercetin and kaempferol derivatives. Terpene lactones are the other major component, and these include ginkgolides A, B and C, and bilobalide, Ginkgo extracts may be standardised to contain between 22 and 27% flavonoids (flavone glycosides) and between 5 and 12% terpene lactones, both on the dried basis. The leaves contain only minor amounts of ginkgolic acids, and some pharmacopoeias specify a limit for these. The seeds contain ginkgotoxin (4-O-methylpyridoxine) and ginkgolic acids. Use and indications The leaves of ginkgo are the part usually used. Ginkgo is often used Read more […]

Herb-Drug Interactions: Evening primrose oil

Oenothera biennis L. (Onagraceae) Synonym(s) and related species Common evening primrose, King’s cureall, Sun drop, Tree primrose. Oenothera lamarkiana, Onagra biennis (L.) Scop. Pharmacopoeias Evening primrose oil (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4). Constituents The oil from evening primrose seeds contains the essential fatty acids of the omega-6 series, linoleic acid (about 65 to 85%) and gamolenic acid (gamma-linolenic acid, about 7 to 14%). Other fatty acids include oleic acid, alpha-linolenic acid, palmitic acid and stearic acid. Use and indications Evening primrose oil is used as a food supplement to provide essential fatty acids. It is also used for atopic eczema and mastalgia; however, in the UK licences for two prescription products containing gamolenic acid derived from evening primrose oil were withdrawn in 2002, due to lack of evidence in support of efficacy. Other conditions for which it is used include rheumatoid arthritis, premenstrual syndrome, menopausal symptoms, chronic fatigue syndrome and attention deficit hyperactivity disorder. Evening primrose oil has also been used topically as a cream, for the relief of dry or inflamed skin. Read more […]

ANTICONVULSANTS

ANTICONVULSANTS are drugs used to treat convulsions of various types, for instance, in drug or chemical poisoning, e.g. chlorpromazine, diazepam. However, these anticonvulsants are not necessarily effective or suitable for epilepsy. In practice, the antiepileptic drugs are the more used, especially for prolonged treatment, and these agents have extensive usage in preventing the occurrence of epileptic seizures. The drug of choice depends on the type and severity of the epilepsy. For tonic-clonic seizures (Grand Mai) as part of a syndrome of primary generalized epilepsy the drugs of choice are carbamazepine and phenytoin. For absence seizures (Petit Mai), sodium valproate and ethosuximide. For myoclonic seizures, sodium valproate, clonazepam and ethosuximide. For other types of seizure, such as atypical absence, atonic and tonic seizures (often in childhood), phenytoin, sodium valproate, clonazepam, phenobarbitone, or ethosuximide are valuable. These all appear to work by stabilizing membranes and decreasing excitability, though with differing profiles of activity and mechanisms of action. Phenobarbitone, though a barbiturate, is more of an anticonvulsant than expected from its sedative actions, and it resembles Read more […]