There are marked differences in the knowledge on the medical uses of cannabis and cannabinoids in different diseases. For nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia in HIV/AIDS, spasticity in multiple sclerosis and spinal cord injury there is strong evidence for medical benefits. For many other indications, such as epilepsy, movement disorders and depression there is much less available data.
Clinical studies with single cannabinoids or, less often with whole plant preparations (smoked marijuana, encapsulated cannabis extract) have often been inspired by positive anecdotal experiences of patients employing crude cannabis products. The anti-emetic, the appetite enhancing, relaxing effects, analgesia, and therapeutic use in Tourette's syndrome were all discovered in this manner.
Incidental observations have also revealed therapeutically useful effects in a study with patients with Alzheimer's disease wherein the primary issue was an examination of the appetite- stimulating effects of THC. Not only appetite and body weight increased, but disturbed behaviour among the patients also decreased. The discovery of decreased intraocular pressure with THC administration in the beginning of the 1970s was also serendipitous. For this reason, more surveys have been conducted in the past decade questioning individuals that use cannabis therapeutically.
(Neff et al.):
Pruritus due to cholestatic liver disease [please see below for an explanation] can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis [please see below for an explanation] because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations.
All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus.
Source: Neff GW, et al. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. Am J Gastroenterol 2002 Aug;97(8):2117-9
Explanations: What are cholestatic liver disease and plasmapheresis?
The term cholestasis originally derives from Greek and literally means "a standing still of bile." This disruption of bile flow can occur in the liver cells, in the small channels that transport the bile in the liver or in larger channels that transport the bile from the liver to the gallbladder and into the bowel. Cholestasis or cholestatic liver disease may or may not result in jaundice with yellow coloured skin. It may be accompanied by severe itching. Plasmapheresis is a method to remove certain substances from the blood plasma in a process similar to that used in an "artificial kidney," or dialysis, treatment. The procedure became known as plasmapheresis, meaning plasma separation. It is also known as plasma exchange.
In the plant the cannabinoids exist mainly in their carboxylic forms as cannabinoid acids. However, the phenolic form of THC is responsible for the psychotropic and the most medicinal effects. Decarboxylation (separation of CO2) to the phenolic form occurs readily over time, upon heating or under alkaline conditions.
The ratio of THC acids (THCA) to phenolic THC has been reported to range between 2:1 (Africa) and >20:1 (Switzerland) in leaves and flowers of Cannabis sativa. In plants grown in Middle Europe (United Kingdom) from Moroccan, Sri Lankan and Zambian seed stocks the THCA/THC ratio was 17:1 compared with 2:1 in the plants from the original areas (Africa, Asia). In hashish (cannabis resin) the THCA/THC ratio was reported to range between 6.1:1 and 0.5:1, the latter in hashish from India. Thus, the percentage of phenolic THC of all THC in cannabis products varied between less than 5% in cannabis leaves grown in Switzerland up to 65% in hashish from India.
Cannabis products with a high content of phenolic THC (e.g. hashish) may be very potent without heating, but usually the potency of cannabis products is considerably increased with heating (smoking, cooking).
Modified according to: Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics 2001, in press.